Clinical Stroke Research Articles

Identifying at-risk patients for atrial high-rate episodes by machine learning

Abstract Background Current evidence suggests that atrial high rate episodes (AHRE)/subclinical atrial fibrillation (AF) are associated with increasing risk of clinical AF, and subsequently, ischaemic stroke and other adverse cardiovascular events. Purpose To construct a high-performance model by machine learning (ML) for the prediction of AHRE detected by a cardiac implantable electronic device (CIED) capable of atrial sensing in a European cohort. Methods We utilized data from a prospective cohort of patients with CIED. AHRE was defined as an episode lasting at least 5 minutes with atrial rate ≥ 175 beats per minute. We divided the cohort into training and internal validation cohorts in 7:3 and used 5-fold cross-validation in the training cohort to assess model performance and prevent model overfitting. Pre-selected features were imported into eight common ML algorithms to predict AHRE, including light gradient boosting machine (LightGBM), random forest (RF), logistic regression, support vector machine, multiple perceptron, eXtreme gradient boosting machine (XGBoost), Gaussian naïve Bayes, and K nearest neighbours. The importance ranking of the features was interpreted by calculating the SHapley Additive exPlanationation (SHAP) value for each feature within the optimal model. Results A total of 500 consecutive patients with CIEDs (mean age 70.2±13.3; 39.2% female) were included. Of these, 164 patients (32.8%) were found to have AHRE. Among all ML models, RF was the best performing model, which obtained the highest AUC (0.738), recall (0.673) and F1-score (0.584) in the internal validation cohort. The results of SHAP showed that antiplatelet, statin, age, white blood cell count, and cardiomyopathy were the first five important features, indicating that the RF model had good interpretability and reliability. Conclusion Our study is the first to demonstrate in a European cohort the effectiveness and feasibility of ML algorithms in predicting AHRE in patients detected by CIEDs. The best RF models require further external validation to assess generalizability to other cohorts.Figure 1Figure 2

How vaccination affects clinical outcomes of COVID-19 positive revascularized patients?

Abstract Background/Introduction Several vaccines are now available under emergency use authorization in globe and have demonstrated efficacy against COVID-19 positive patients. Our investigation centers on understanding the correlation between COVID-19 vaccine status and an extensive spectrum of risk factors, clarifying their impact on clinical outcomes in COVID-positive revascularized populations. Purpose This study clarified the multifaceted impact of the COVID-19 vaccine on individuals with a history of revascularization, highlighting the relationship between vaccination status and clinical outcomes. Methods We conducted a retrospective a cohort study COVID-19 positive (n=620) patients with revascularized two years prior to the pandemic, was categorized into unvaccinated (n=359) and vaccinated (n=261) groups. Comprehensive retrospective data on various risk factors, including hypertension, diabetes, smoking, stroke history, family history were collected. Clinical outcomes, intently documented, encompassed hospitalization, mortality, stroke and mechanical ventilation. Statistical analyses, including correlation assessments, were conducted, focusing on the COVID-positive subgroup. Results During the analysis of risk factors, between the unvaccinated and vaccinated groups the prevalence of smoking (32% vs. 31.4%, p=0.871), hypertension (81.3% vs. 78.2%, p=0.329), DM (42 .9% vs. 43.3%, p=0.921), HLP (14.8% vs. 13%, p=0.539), family history (21.7% vs. 17.6%, p=0.208)were not significantly different (Table 1). It showed a significant association with increased hospitalization(14.6% vs. 24.8%, p = 0.002) and death (2.3% vs. 8.1%, p = 0.002)rates in the unvaccinated group. In addition, it was associated with higher rate of mechanical ventilation in the unvaccinated group (2.6% vs. 10.1%, p = 0.153).Also, no significant difference was found between the two groups according to the type of revascularization, PCI (70.2% vs. 75.1%, p = 0.179), CABG (29.8% vs. 24.9%, p = 0.179) (Table 2). Conclusion(s) Our analysis within the COVID-positive subgroup of 620 revascularized patients revealed a significant correlation between COVID-19 vaccination status and clinical outcomes. Thus, a significant reduction in hospitalizations and deaths was recorded in the vaccinated group. This supports a potential positive effect of the vaccine on cardiovascular events in patients with COVID-19.Table 1Table 2

Prediction of cardiovascular outcomes by subtle changes in the peripheral immune cell landscape - insights from the LURIC single cell RNA-sequencing study (LuRNA)

Abstract Background and Aims Atherosclerosis and its clinical sequelae, myocardial infarction and stroke, represent the main causes of death worldwide. Although preclinical evidence has suggested the existence of an inflammatory response driving disease, the extend of cellular alterations in human atherosclerosis remains enigmatic. Here, we employ single cell RNA-sequencing (scRNA-seq) on peripheral blood mononucleated cells (PBMCs) in a well-defined cardiovascular risk cohort from the "Ludwigshafen Risk and Cardiovascular Health (LURIC) trial" to define changes in the immune cell landscape in atherosclerotic patients. Methods and Results Of 3317 patients enrolled in the LURIC trial between 1997 and 2000, we selected individuals with stable coronary-artery disease (CAD) (n=31) and healthy patients (no CAD) (n=16) by propensity score matching, adjusted for CRP, NTproBNP, Troponin T, LDL-C, and Cystatin-C, in a case-control design. scRNA-seq was performed by droplet sequencing on PBMCs stored in liquid nitrogen. Individual data sets were integrated and changes between healthy individuals and patients with CAD were evaluated on numeric and transcriptional level. Single cell transcriptomes were annotated using an established CITE-seq reference atlas. While bulk RNA-sequencing of PBMC preparations revealed only minor changes between both conditions, we identified several leukocyte populations on a single cell level with specific transcriptomes that were differentially regulated between both conditions. Interestingly, we found that several subsets of Natural Killer (NK) cells, T cells with an enrichment of proliferation-associated pathways, and a population resembling hematopoietic stem cells were more frequent in patients with CAD, while naïve phenotypes of B and T cells were overrepresented in the absence of CAD. Consistently, most T and B cell populations in patients with CAD were enriched in pathways associated with cell activation, immune receptor signalling, and differentiation. In addition, we detected restricted repertoires of T cell receptor sequences in several adaptive immune cell subtypes from patients with CAD, suggestive of increased cellular clonality and antigen-specificity. Finally, in a comparison of cellular frequencies with cardiovascular outcomes over more than 15 years, several immune cell subsets and cell-type specific transcriptional programs predicted cardiovascular death in this case-control scenario in multi-variate adjusted regression analysis. Notably, addition of scRNA-seq derived parameters was superior to traditional risk prediction with clinical characteristics and soluble biomarkers alone. Conclusion Employing scRNAseq, we demonstrate that atherosclerosis is associated with a profound change in the circulating immune cell landscape even in the absence of measurable differences in inflammatory biomarkers. These findings propose the usage of scRNAseq for the discovery of outcome-relevant cellular biomarkers in the future.

Echocardiographic signs of atrial cardiopathy and MRI-detected silent brain infarcts in a middle-aged cohort: the Akershus Cardiac Examination 1950 Study

Abstract Background Atrial fibrillation (AF) is linked to clinical stroke and silent brain infarction (SBI). In the majority of AF patients, there exists a recognized form of atrial cardiopathy, and it is suggested that atrial cardiopathy, even in the absence of AF, may serve as a risk factor for stroke. However, existing evidence is limited, and it remains unclear whether atrial cardiopathy indeed poses a risk for stroke and SBI. Purpose We aimed to investigate the association between echocardiographic signs of atrial cardiopathy and the detection of SBI through magnetic resonance imaging (MRI) in a middle-aged cohort from the general population. Methods In the prospective Akershus Cardiac Examination (ACE) 1950 Study conducted within the general population in Norway, cardiovascular risk assessment including transthoracic echocardiography, was undertaken at study inclusion between 2012 and 2015. We assessed body surface area-indexed left atrial (LA) maximum and minimum volume, as well as LA reservoir and contractile strain. Subsequently, brain MRI was conducted in a subset of the cohort between 2017 and 2023. SBI was defined as presence of neuroimaging sign of infarcts, including lacunes, in individuals without a history of stroke. Logistic regression analyses were performed to explore the associations between echocardiographic measures of atrial cardiopathy and SBI on MRI, adjusting for sex, age, hypertension, and diabetes. Results A total of 397 out of 3706 (10.7%) participants in the ACE 1950 study underwent MRI examination and were included in this analysis. At the time of MRI, the mean age was 70.0±2.2 years, with 157 (40%) women, 248 (62%) with hypertension, and 36 (9%) with diabetes at study inclusion. SBI was present in 51 (13%), of which only 1 (2%) had known AF. After excluding 18 participants with pre-existing AF, no significant difference were observed in LA volumes or LA strain between participants with or without SBI (Figure 1). In unadjusted and adjusted logistic regression analyses, neither LA volume nor LA strain were associated with SBI (Table 1). Conclusion Echocardiographic signs of atrial cardiopathy were not associated with silent brain infarcts in a middle-aged cohort from the general population.

Changing Landscape of Randomized Clinical Trials in Stroke: Explaining Contemporary Trial Designs and Methods.

Evidence generated from randomized clinical trials (RCTs) plays an indispensable role in advancing clinical stroke care. Although the number of stroke-related RCTs published every year has grown exponentially over the past 25 years, the execution and completion of RCTs, particularly those conducted in a hyperacute setting, have grown more complicated and challenging over the years. In addition to the practical challenges associated with conducting a clinical trial, like obtaining human subjects approval, identifying clinical sites, training trial personnel, and enrolling the target number of patients within the available funding and timeline, the complexity of contemporary RCT designs and analyses has become much more exacting. It is no longer sufficient to have a decent understanding of the 2-arm, placebo-controlled RCT, combined with a rudimentary grasp of the P value; things are now much more complicated. Innovations in trial design and analysis, including adaptive, Bayesian, platform, and noninferiority designs, have occurred to address the problems of poor trial efficiency. However, these advances require the end user to have a much greater level of understanding regarding the rationale, conduct, analysis, and interpretation of each design. While these newer designs seek greater efficiency, there are inevitably tradeoffs that need to be understood. In this month's edition of Stroke, we introduce a new series designed to help fill in these knowledge gaps. Over the next few months, 4 papers will be published that address major design innovations (adaptive, Bayesian, platform, and noninferiority) with the aim of illustrating how these approaches can make trials more efficient (where efficiency is defined as getting to the right answer, sooner, with a potentially lower sample size). In addition to introducing this series, this current article also reviews traditional hypothesis testing and the common misinterpretations of the P value; fortunately, new philosophical schools of inference are beginning to vanquish the overreliance on the P value. We are excited about the opportunity to educate the Stroke readership about these new trial designs and the profound implications that they bring.

Adaptive Clinical Trials in Stroke.

Designing a clinical trial to evaluate the efficacy of an intervention is often complicated by uncertainty over aspects of the study population, potential treatment effects, most relevant outcomes, dropouts, and other factors. However, once participants begin to be enrolled and partial trial data become available, this level of uncertainty is reduced. Adaptive clinical trials are designed to take advantage of the accumulating data during the conduct of a trial to make changes according to prespecified decision rules to increase the likelihood of success or statistical efficiency. Common adaptive rules address early stopping for benefit or futility, sample size reestimation, adding or dropping treatment arms or altering randomization ratios, and changing the eligibility criteria to focus on responder patient subgroups. Adaptive clinical trials are gaining popularity for clinical stroke research. We provide an overview of the methods, practical considerations, challenges and limitations, and potential future role of adaptive clinical trials in advancing knowledge and practice in stroke.

Enhancing Blood-Brain Barrier Integrity in Patients With Acute Ischemic Stroke Via Normobaric Hyperoxia.

Recent advancements in animal studies have demonstrated the potential of normobaric hyperoxia (NBO) as a promising intervention for preserving the integrity of the blood-brain barrier (BBB). However, there is still limited understanding of the effects of NBO on BBB function in patients with clinical stroke. Therefore, the objective of this study was to investigate the efficacy of NBO therapy in attenuating BBB damage and reducing brain injury in individuals undergoing endovascular treatment (EVT) for acute stroke. This study enrolled patients from the OPENS-1 (Normobaric Hyperoxia Combined With Reperfusion for Acute Ischemic Stroke) study, with 43 patients receiving NBO combined with EVT and 43 patients receiving EVT alone. The main outcome measures included serum levels of occludin, MMP-9 (matrix metalloproteinase-9), NSE (neuron-specific enolase), and S100b at 24 hours and 7 days, as well as the intracranial extravasation rate at 24 hours. Serum markers were assessed using ELISA, and intracranial contrast extravasation was visualized using dual-energy computed tomography scan. We analyzed a total of 86 patients and found that the 24-hour serum markers levels of BBB damage and brain injury were significantly lower in the group receiving NBO therapy combined with EVT compared with the group receiving EVT alone. Similarly, at 7 days, the levels of occludin, MMP-9, and NSE were lower in the NBO+EVT group. We also found that the 24-hour serum levels of occludin and MMP-9 were correlated with intracranial contrast extravasation. Additionally, the incidence of intracranial contrast extravasation was lower in the NBO+EVT group compared with the EVT group (35.9% versus 60.5%, P=0.031). This study offers valuable insights into the positive impact of NBO on maintaining BBB integrity and reducing brain injury in patients with acute stroke undergoing EVT.

Cerebrovascular Events in Patients Undergoing Transcatheter Aortic Valve Replacement: A Review.

Cerebrovascular events (CVEs) are a dreaded complication of transcatheter aortic valve replacement (TAVR). They are associated with significant mortality, morbidity, and reduced quality of life and impose a significant burden to health care systems. Although the rates of clinical stroke have reduced since the advent of TAVR, it remains an important complication, particularly as TAVR is increasingly utilized. CVE may occur at the time of the TAVR, as a direct consequence of the procedure, or may occur later, related to thrombosis of the prosthetic valve, atrial fibrillation, and other comorbidities. Imaging of the brain has revealed a high prevalence of subclinical cerebral infarcts (68%-98%) associated with the TAVR procedure. Although their clinical significance has not been fully established, clinically evident CVE ranges between 3% and 5% in patients considered at high operative risk to between 1% and 3% in low operative risk patients. Periprocedural CVEs are largely the result of embolization of the thrombus and tissue derived from the valve, vasculature, or myocardium. Cerebral embolic protection devices have been studied in multiple trials, with some evidence supporting a reduction in new cerebral lesion volume, number, and potentially disabling strokes. However, thus far, there is no robust evidence that they reduce the overall stroke rate. The number and severity of comorbidities, in particular, new-onset atrial fibrillation, are associated with CVEs. Valve thrombosis diagnosed using computed tomography as areas of hypoattenuated leaflet thickening has been identified in 10% to 15% of patients. This is a dynamic process associated with an increase in CVEs, but that resolves with anticoagulation or sometimes without it. Routine use of anticoagulation compared with a single antiplatelet agent is associated with an increased risk of bleeding, without any additional alleviation in risk of thromboembolism. Future studies to improve risk stratification could facilitate the tailoring of preventive therapies to patients at high risk of CVE, who stand to gain the most benefit.

Recurrent Ischemic Stroke and Transient Ischemic Attack: Risk of Single and Multiple Recurrence.

Background/Objectives: Efforts have been made toward primary or secondary stroke or transient ischemic attack (TIA) prevention. However, little attention has been paid to recurrent stroke or TIA. This study investigated risk factors for multiple or single recurrent stroke or TIA. Methods: Data from 3646 patients with ischemic stroke or TIA were obtained from the Korea University Ansan Hospital Stroke Center between March 2014 and December 2021, using the prospective institutional database of the Korea University Stroke Registry. The associations between clinical features and recurrent stroke or TIA were assessed using bivariable and multivariable Cox models. Results: Recurrent stroke or TIA was associated with male sex (adjusted hazard ratio (HR) 1.95, 95% confidence interval (CI) 1.42-2.80), hypertension (HR 1.49, 95% CI 1.00-2.23), diabetes mellitus (HR 1.54, 95% CI 1.13-2.13), an etiologic subtype of transient ischemic attack (HR 1.88, 95% CI 1.09-3.16), white matter changes (HR 1.62, 95% CI 1.05-2.38), and cerebral microbleeds (HR 1.79, 95% CI 1.26-2.59). Multiple recurrent stroke or TIA was associated with male sex (HR 3.86, 95% CI 1.94-11.55), diabetes mellitus (HR 2.40, 95% CI 1.31-4.53), and anemia (HR 4,58, 95% CI 2.31-10.44). Conclusions: Given the risk factor profiles for recurrent stroke or TIA, risks differed among patient subgroups and were based on multiple or single recurrences. It may exert an effect as a prognostic indicator in the high risk of recurrences.

MRI-based Quantitative Collateral Assessment in Acute Stroke : AComparison with Single-phase CTA in Drip-and-ship Patients with Serial Imaging.

In acute ischemic stroke with large-vessel occlusion (LVO), collateral assessment with single-phase computed tomography angiography (CTA) might underestimate pial collateral supply in aconsiderable proportion of patients. We aimed to compare time-resolved magnetic resonance imaging (MRI)-based quantitative collateral mapping to conventional collateral imaging with CTA. This retrospective single-center study covering aperiod of 6years (2012-2018) included drip-and-ship LVO patients who underwent MR imaging after initial imaging evaluation with CT. For MRI-based collateral assessment, T2*-weighted time series from perfusion-weighted imaging (PWI) were processed to compute aquantitative collateral vessel index (CVIPWI) based on the magnitude of signal variance across the entire acquisition time. CTA-based collateral scores (Tan and Maas) and CVIPWI were investigated in terms of inter-modality associations between collateral measures, as well as their relationships with stroke severity, infarct volume and early functional outcome. The final analysis included n = 56patients (n = 31female, mean age69.9 ± 14.21 years). No significant relationship was found between MR-based quantitative collateral supply (CVIPWI) and CT-based collateral scores (r = -0.00057, p = 0.502 and r = -0.124, p = 0.797). In contrast to CVIPWI, CTA-based collateral scores showed no significant relationship with clinical stroke severity and infarct volume. While MR-based CVIPWI was independently associated with favorable early functional outcome in multivariate analysis (OR 1.075, 95% CI 1.001-1.153, p = 0.046), CTA-based collateral scores were not significantly associated with outcome. Since collateral scores based on single-phase CTA do not accurately reflect infarct progression and might underestimate pial collateralization in arelevant proportion of patients, they are not associated with early functional outcome in LVO patients. In contrast, CVIPWI represents arobust imaging parameter of collateral supply and is independently associated with functional outcome.

SIRT-1/RHOT-1/PGC-1α loop modulates mitochondrial biogenesis and transfer to offer resilience following endovascular stem cell therapy in ischemic stroke

Current clinical interventions for stroke majorly involve thrombolysis or thrombectomy, however, cessation of the progressive deleterious cellular cascades post-stroke and long-term neuroprotection are yet to be explored. Mitochondria are highly vulnerable organelles and their dysfunction is one of the detrimental consequences following stroke. Mitochondria dysregulation activate unfavourable cellular events over a period of time that leads to the collapse of neuronal machinery in the brain. Hence, strategies to protect and replenish mitochondria in injured neurons may be useful and needs to be explored. Stem cell therapy in ischemic stroke holds a great promise. Past studies have shown beneficial outcomes of endovascularly delivered stem cells in both pre-clinical and clinical settings. Intra-arterial (IA) administration can provide more cells to the stroke foci and affected brain regions than intravenous administration. Supplying new mitochondria to the stroke-compromised neurons either in the core or penumbra by infused stem cells can help increase their survival and longevity. Previously, our lab has demonstrated that IA 1∗105 mesenchymal stem cells (MSCs) in rats were safe, efficacious and rendered neuroprotection by regulating neuronal calcineurin, modulating sirtuin1(SIRT-1) mediated inflammasome signaling, ameliorating endoplasmic reticulum-stress, alleviation of post-stroke edema and reducing cellular apoptosis. To explore further, our present study aims to investigate the potential of IA MSCs in protecting and replenishing mitochondria in the injured neurons post-stroke and the involvement of SIRT-1/RHOT-1/PGC-1α loop towards mitochondria transfer, biogenesis, and neuroprotection. This study will open new avenues for using stem cells for ischemic stroke in clinics as one of the future adjunctive therapies.

Incident Infarcts in Patients With Stroke and Cerebral Small Vessel Disease: Frequency and Relation to Clinical Outcomes.

Factors associated with cerebral small vessel disease (SVD) progression, including incident infarcts, are unclear. We aimed to determine the frequency of incident infarcts over 1 year after minor stroke and their relation to baseline SVD burden, vascular risks, and recurrent stroke and cognitive outcomes. We recruited patients with lacunar or nondisabling cortical stroke. After diagnostic imaging, we repeated structural MRI at 3-6 monthly intervals for 12 months, visually assessing incident infarcts on diffusion-weighted imaging or FLAIR. We used logistic regression to determine associations of baseline vascular risks, SVD score, and index stroke subtype with subsequent incident infarcts. We assessed cognitive and functional outcomes at 1 year using Montreal Cognitive Assessment (MoCA) and modified Rankin scale (mRS), adjusting for baseline age, mRS, MoCA, premorbid intelligence, and SVD score. We recruited 229 participants, mean age 65.9 (SD 11.1). Over half of all participants, 131 of 229 (57.2%) had had an index lacunar stroke. From baseline to 1-year MRI, we detected 117 incident infarcts in n = 57/229 (24.8%) participants. Incident infarcts were mainly of the small subcortical (86/117 [73.5%] in n = 38/57 [66.7%]) vs cortical infarct subtype (n = 19/57 [33.3%]). N = 39/57 participants had incident infarcts at 1 visit; 18 of 57 at 2 or more visits; and 19 of 57 participants had multiple infarcts at a single visit. Only 7 of 117 incident infarcts corresponded temporally to clinical stroke syndromes. The baseline SVD score was the strongest predictor of incident infarcts (adjusted odds ratio [OR] 1.87, 95% CI 1.39-2.58), while mean arterial pressure was not associated. All participants with incident infarcts were prescribed an antiplatelet or anticoagulant. Lower 1-year MoCA was associated with lower baseline MoCA (β 0.47, 95% CI 0.33-0.61), lower premorbid intelligence, and older age. Higher 1-year mRS was associated with higher baseline mRS only (OR 5.57 [3.52-9.10]). Neither outcome was associated with incident infarcts. In the year after stroke in a population enriched for lacunar stroke, incident infarcts occurred in one-quarter and were associated with worse baseline SVD. Most incident infarcts detected on imaging did not correspond to clinical stroke/transient ischemic attack. Worse 1-year cognition and function were not associated with incident infarcts.

Clinical and subclinical microemboli following neuroangiography in children

BackgroundTo assess the frequency, imaging appearances, and risk factors of brain microemboli following pediatric neuroangiography, as assessed by early diffusion-weighted MRI imaging (DWI).MethodsThis single-center, retrospective analysis investigated early DWI post-pediatric...

Arterial blood pressure monitoring in stroke cohorts: the impact of reduced sampling rates to optimise remote patient monitoring.

Remote patient monitoring (RPM) beat-to-beat blood pressure (BP) provides an opportunity to measure poststroke BP variability (BPV), which is associated with clinical stroke outcomes. BP sampling interval (SI) influences ambulatory BPV, but RPM BP SI optimisation research is limited. SI and RPM device capabilities require compromises, meaning SI impact requires investigation. Therefore, this study assessed healthy and stroke subtype BPV via optimised BP sampling, aiding sudden BP change identification and potentially assisting cardiovascular event (recurrent stroke) prediction. Leicester Cerebral Haemodynamic Database ischaemic [acute ischaemic stroke (AIS), n = 68] and haemorrhagic stroke (intracerebral haemorrhage, n = 12) patient and healthy control (HC, n = 40) baseline BP data were analysed. Intrasubject and interpatient SD (SDi/SDp) represented individual/population variability with synthetically altered SIs. Matched-filter approaches using cross-correlation function detected sudden BP changes. At SIs between 1 and 180 s, SBP and DBP SDi staticised while SDp increased at SI < 30 s. Mean BP and HR SDi and SDp increased at SI < 60s. AIS BPV, normalised to SI1s, increased at SI30s (26%-131%) and SI120s (1%-274%). BPV increased concomitantly with SI. Cross-correlation analysis showed HC and AIS BP sudden change detection accuracy reductions with increasing SI. Positive BP deviation detection fell 48.48% (SI10s) to 78.79% (SI75s) in HC and 67.5% (SI10s) to 100% (SI75s) in AIS. Negative BP deviation detection fell 50% (SI10s) to 82.35% (SI75s) in HC and 52.27% (SI10s) to 95.45% (SI75s) in AIS. Sudden BP change detection and BPV are relatively robust to SI increases within certain limits, but accuracy reductions generate unacceptable estimates, considerable within RPM device design. This research warrants further SI optimisation.

Cognitive Impairment in Atrial Fibrillation Patients: A Literature Review

Introduction: Atrial fibrillation (AF) has become one of the most significant health problems worldwide, warranting urgent answers to currently pending questions on the effects of AF on brain function. Recent evidence has emerged to show an association between AF and an increased risk of developing dementia and worsening of stroke outcomes. In the last two decades several reports have shown an association between AF and cognitive function, ranging from impairment to dementia. Purpose: To present data on cognitive impairment in atrial fibrillation patients. Materials and methods: The study material consisted of reviewed articles on the topic found on the globally accepted electronic databases, PubMed, Medline, Google Scholar, regarding cognitive decline in atrial fibrillation patients. The study material consisted of scientific books, reviews and research papers published online. Results: In the absence of clinical stroke, people with incident atrial fibrillation are likely to reach thresholds of cognitive impairment or dementia at earlier ages than people with no history of atrial fibrillation. Results in a large sample of patients show that AF may be associated with higher risk for both cognitive impairment and dementia in patients with preexisting stroke, even if there was significant heterogeneity in the analysis for cognitive impairment. Adequate oral anticoagulation and improved management of the overall cardiovascular risk profile in individuals with AF offer the promise of reducing the impact of AF on cognitive decline and dementia. Conclusion: AF is associated with higher risk of developing AD and dementia. Future studies should examine whether specific treatments, including optimal anticoagulation, can decrease this risk.

Huanglian Jiedu decoction alleviates ischemia-induced cerebral injury in rats by mitigating NET formation and activiting GABAergic synapses.

Huanglian Jiedu decoction (HLJD) has been used to treat ischemic stroke in clinic. However, the detailed protective mechanisms of HLJD on ischemic stroke have yet to be elucidated. The aim of this study is to elucidate the underlying pharmacological mechanisms of HLJD based on the inhibition of neuroinflammation and the amelioration of nerve cell damage. A middle cerebral artery occlusion reperfusion (MCAO/R) model was established in rats and received HLJD treatment. Effects of HLJD on neurological function was assessed based on Bederson's score, postural reflex test and asymmetry score. 2, 3, 5-Triphenyltetrazolium chloride (TTC) staining, Hematein and eosin (HE) and Nissl staining were used to observe the pathological changes in brain. Then, transcriptomics was used to screen the differential genes in brain tissue in MCAO/R model rats following HLJD intervention. Subsequently, the effects of HLJD on neutrophil extracellular trap (NET) formation-related neuroinflammation, gamma-aminobutyric acid (GABA)ergic synapse activation, nerve cell damage and proliferation were validated using immunofluorescence, western blot and enzyme-linked immunosorbent assay (ELISA). Our results showed that HLJD intervention reduced the Bederson's score, postural reflex test score and asymmetry score in MCAO/R model rats. Pathological staining indicated that HLJD treatment decreased the cerebral infarction area, mitigated neuronal damage and increased the numbers of Nissl bodies. Transcriptomics suggested that HLJD affected 435 genes in MCAO/R rats. Among them, several genes involving in NET formation and GABAergic synapses pathways were dysregulated. Subsequent experimental validation showed that HLJD reduced the MPO+CitH3+ positive expression area, reduced the protein expression of PAD4, p-P38/P38, p-ERK/ERK and decreased the levels of IL-1β, IL-6 and TNF-α, reversed the increase of Iba1+TLR4+, Iba1+p65+ and Iba1+NLRP3+ positive expression area in brain. Moreover, HLJD increased GABA levels, elevated the protein expression of GABRG1 and GAT3, decreased the TUNEL positive expression area and increased the Ki67 positive expression area in brain. HLJD intervention exerts a multifaceted positive impact on ischemia-induced cerebral injury in MCAO/R rats. This intervention effectively inhibits neuroinflammation by mitigating NET formation, and concurrently improves nerve cell damage and fosters nerve cell proliferation through activating GABAergic synapses.

Stroke in sickle cell patients, epidemiology, pathophysiology, systemic and surgical treatment options and prevention strategies

AbstractBackgroundA hereditary haemoglobinopathy known as sickle cell disease (SCD) affects over 100 000 people in the United States severely. Cerebrovascular disease is a prominent consequence of SCD. By the age of 30, 53% of patients have silent cerebral infarcts (SCIs) (a stroke that occurs without any obvious symptoms because it damages a small part of the brain that isn't responsible for any essential functions), and by the age of 40, 3.8% have overt strokes.Main bodyThe multidimensional burden of cerebrovascular illness in SCD is reviewed in detail in this article, which includes both clinical strokes and the frequently asymptomatic SCIs. The intricate pathophysiology of SCD and stroke is explored. With SCD, there are currently very few methods for preventing primary and secondary stroke; the most common ones are hydroxyurea and blood transfusion. Nevertheless, not enough research has been done on the possible contributions of anticoagulation and aspirin to strokes linked to SCD. Promising evidence is also highlighted in the study, suggesting that new drugs intended to treat SCD may be able to alleviate leg ulcers and renal impairment in addition to reducing unusually high transcranial Doppler flow velocity – a crucial component of cerebrovascular events. Given that these novel medications specifically target haemolysis and vaso‐occlusion, the two main causes of strokes in this population, more research is desperately needed to determine whether they are effective in avoiding strokes in people with SCD. The literature review also emphasizes how common healthcare inequities are and how they hinder advancements in SCD research and management in the United States.ConclusionTo successfully address these inequities, the evaluation recommends more funding for both SCD management and research, as well as for patient and clinician education. This multimodal viewpoint highlights the intricate terrain of cerebrovascular problems associated with SCD and the urgent need for all‐encompassing and fair strategies to improve patient outcomes and advance research.

Oral condition at admission predicts functional outcomes and hospital-acquired pneumonia development among acute ischemic stroke patients

IntroductionOral care is crucial for the prevention of cardiovascular events and pneumonia. However, few studies have evaluated the associations between multidimensional assessments of oral status or functional outcomes and hospital-acquired pneumonia (HAP).MethodsConsecutive patients with acute ischemic stroke (AIS) were retrospectively analyzed. We evaluated the modified oral assessment grade (mOAG) and investigated its association with a modified Rankin scale (mRS) score of 0‒2 (good stroke outcome) and HAP. The mOAG was developed to evaluate 8 categories (lip, tongue, coated tongue, saliva, mucosa, gingiva, preservation, and gargling) on a 4-point scale ranging from 0 to 3. We analyzed the effectiveness of the mOAG score for predicting stroke outcome or HAP using receiver operating characteristic (ROC) curve analysis.ResultsIn total, 247 patients with AIS were analyzed. The area under the ROC curve of the mOAG for predicting poor outcomes was 0.821 (cutoff value: 7), and that for HAP incidence was 0.783 (cutoff value: 8). mOAG (a one-point increase) was associated with poor stroke outcome (odds ratio [OR] 1.31, 95% confidence interval [CI] 1.17‒1.48, P < 0.001) and HAP (OR 1.21, 95% CI 1.07‒1.38, P = 0.003) after adjusting for baseline clinical characteristics, including age and stroke severity.ConclusionsLower mOAG scores at admission were independently associated with good outcomes and a decreased incidence of HAP. Comprehensive oral assessments are essential for acute stroke patients in clinical settings.

A meta-analysis of animal studies evaluating the effect of hydrogen sulfide on ischemic stroke: is the preclinical evidence sufficient to move forward?

Hydrogen sulfide (H2S) is a gasotransmitter that has been studied for its potential therapeutic effects, including its role in the pathophysiology and treatment of stroke. This systematic review and meta-analysis aimed to determine the sufficiency of overall preclinical evidence to guide the initiation of clinical stroke trials with H2S and provide tailored recommendations for their design. PubMed, Web of Science, Scopus, EMBASE, and MEDLINE were searched for studies evaluating the effect of any H2S donor on in vivo animal models of regional ischemic stroke, and 34 publications were identified. Pooling of the effect sizes using the random-effect model revealed that H2S decreased the infarct area by 34.5% (95% confidence interval (CI) 28.2-40.8%, p < 0.0001), with substantial variability among the studies (I2 = 89.8%). H2S also caused a 37.9% reduction in the neurological deficit score (95% CI 29.0-46.8%, p < 0.0001, I2 = 63.8%) and in the brain water content (3.2%, 95% CI 1.4-4.9%, p = 0.0014, I2 = 94.6%). Overall, the studies had a high risk of bias and low quality of evidence (median quality score 5/15, interquartile range 4-9). The majority of the included studies had a "high" or "unclear" risk of bias, and none of the studies overall had a "low" risk. In conclusion, H2S significantly improves structural and functional outcomes in in vivo animal models of ischemic stroke. However, the level of evidence from preclinical studies is not sufficient to proceed to clinical trials due to the low external validity, high risk of bias, and variable design of existing animal studies.

Prolonged and repeated microemboli detection in acute ischemic stroke – The Norwegian Microemboli in Acute Stroke Study (NOR-MASS)

ObjectivesCerebral microemboli can be detected by transcranial Doppler monitoring (TCDM) and may elucidate stroke etiology, the effect of preventive therapy, and the risk of stroke recurrence. Microemboli detection is usually performed for up to 60 minutes, but due to temporal variability, microembolization may be missed if the monitoring time is too short. We aimed to assess the time course of microembolization in acute ischemic stroke and explore the utility of prolonged and repeated microemboli detection. Materials and MethodsPatients with suspected ischemic stroke and symptom onset within 24 hours were examined with bilateral, stationary TCDM for one hour followed by unilateral, ambulatory TCDM for two hours. Unilateral TCDM was repeated for the following two days and after three months. ResultsWe included 47 patients, of which 41 had ischemic stroke, five had transient ischemic attack, and one had amaurosis fugax. Microemboli were detected in 60 % of patients. The occurrence was highest within 24 hours after onset and significantly lower at three months. Prolonged and repeated microemboli detection yielded only one additional microemboli-positive patient. Hence, patients who initially were microemboli negative tended to remain negative. We could not demonstrate an association between microemboli occurrence and clinical outcome or stroke recurrence. ConclusionsMicroembolic signals are frequent within 24 hours after ischemic stroke onset, but prolonged and repeated microemboli detection did not increase the yield of MES positive patients. Clinical Trial Registration-URLhttp://www.clinicaltrials.gov. Unique identifier: NCT03543319.