Ischemic Stroke Subtypes Research Articles

Inflammation biomarkers in acute ischemic stroke according to different etiologies.

High throughput technologies provide new opportunities to further investigate the pathophysiology of ischemic strokes. The present cross-sectional study aimed to evaluate potential associations between the etiologic subtypes of ischemic stroke and blood-based proteins. We investigated the associations between ischemic stroke subtypes and a panel of circulating inflammation biomarkers in 364 patients included in the Stroke Cohort Augsburg (SCHANA). Stroke etiologies were categorized according to the TOAST (Trial of Org 10172 in Acute Stroke Treatment) classification. Serum concentrations of 52 biomarkers were measured using the Bio-Plex Pro™ Human Cytokine Screening Panel, ICAM-1 set and VCAM-1 set, plus the Pro™ Human TH17 cytokine sCD40L set and IL31 set (all Bio-Rad, USA). Multivariable linear regression models were used to examine associations. Point estimates were calculated as the mean difference in -standardized cytokine levels on the log2 -scale. Stromal-cell-derived-factor 1 alpha (SDF-1a) showed significantly higher serum levels in cardioembolic compared with large vessel atherosclerotic stroke (β = 0.48; 95% CI 0.22; 0.75; Padj = 0.036). Significantly lower levels of interleukin-6 (IL-6) (β = -0.53; 95% CI -0.84; -0.23; Padj = 0.036) and macrophage migration inhibitory factor (MIF) (β = -0.52; 95% CI -0.84; -0.21; Padj = 0.043) were found in the small vessel versus large vessel stroke subtype. Immune dysregulations observed in different stroke subtypes might help uncover pathophysiological mechanisms of the disease. Further studies are needed to validate identified biomarkers in diverse study populations before they can potentially be used in clinical practice to further improve stroke management and patient outcomes.

Autism Spectrum Disorder in Children With Perinatal Ischemic Stroke Varies by Stroke Type.

Background and Objectives: Perinatal stroke leads to significant morbidity over a child's lifetime, including diagnosis of various neurodevelopmental disorders. Specific studies examining the prevalence of autism spectrum disorder in children with perinatal stroke are scarce. Following the clinical observation of autism spectrum disorder in a pediatric referral stroke center, we evaluated the rate of autism spectrum disorder diagnosis after perinatal ischemic stroke, including analysis by subtypes of perinatal ischemic stroke. Methods: We retrospectively examined all children diagnosed with perinatal ischemic stroke, who were ≥18 months old at the time of last follow-up at a single institution from 2008 through 2021. We classified patients as having autism spectrum disorder if they were diagnosed by a neurologist, neuropsychologist, clinical psychologist, or developmental pediatrician. Multivariable logistic regression was performed to examine the association between ischemic stroke subtype and autism spectrum disorder. Results: Among 260 children with perinatal stroke, 19 children (7.3%) also had autism spectrum disorder. Children with perinatal venous stroke had 3-fold higher odds of autism spectrum disorder compared to those with perinatal arterial ischemic stroke (adjusted odds ratio: 3.01, 95% confidence interval: 1.07-8.47). Conclusion: In our perinatal ischemic stroke population, children with venous stroke had higher odds of autism spectrum disorder compared to those with arterial ischemic stroke alone. Prospective studies are needed to further investigate the role of perinatal stroke in autism spectrum disorder development.

Tricuspid regurgitation: a hidden risk factor for atrial fibrillation related stroke?

Tricuspid regurgitation (TR) is a common but overlooked valvular disease, and its association with the etiologic subtypes of ischemic stroke is unclear. We explored the relationship between TR and atrial fibrillation (AF) in patients with acute ischemic stroke. This retrospective analysis of ongoing stroke registry assessed 6,886 consecutive acute ischemic stroke patients who underwent transthoracic echocardiography during their in-hospital care. Multivariable logistic regression models adjusted for age, sex, stroke characteristics, and echocardiographic indices were used to investigate the association between TR and total AF, and newly diagnosed AF during hospitalization and a 1-year follow-up period, respectively. TR was present in 877 (12.7%) patients (mild, 9.9%; moderate, 2.4%; severe, 0.5%). AF was identified in 24.1% (medical history, 11.1%; first detected in the emergency room, 6.6%; newly diagnosed after admission, 6.4%). TR was associated with AF [adjusted odds ratio (aOR) 4.87 (95% confidence interval (CI), 2.63-9.03)], compared with no/trivial TR. The association between TR and AF was consistent regardless of severity (aOR [95% CI], 4.57 [2.63-7.94] for mild and 7.05 [2.57-19.31] for moderate-to-severe TR) or subtype of TR (5.44 [2.91-10.14] for isolated and 3.81 [2.00-7.28] for non-isolated TR). Among the AF-naïve patients at admission, TR was associated with newly diagnosed AF during hospitalization and a 1-year follow-up period (aOR [95% CI], 2.68 [1.81-3.97]). TR is associated with AF in acute ischemic stroke patients regardless of severity and subtypes of TR. TR is also associated with newly diagnosed AF after stroke.

Stroke in women: experience in a developing country

BackgroundSeveral studies have addressed gender differences in stroke. Yet, results are diverse, and research is still required in different populations. So, this study investigates variation in stroke according to gender in a developing country.MethodsThis is a registry-based, retrospective observational cross-sectional study comparing men and women as regards age, risk factors, stroke severity, quality of services, and stroke outcome.ResultsData analyzed comprised 4620 patients. It was found that men outnumbered women, while women had an older age, more prevalence of hypertension and atrial fibrillation, with severer strokes and worse outcomes. However, there was no gender difference in promptness nor frequency of administration of revascularization therapies.ConclusionDespite the gender difference in risk factors and stroke severity, we could not detect any significant disparity in acute stroke services provided to either gender. Among age categories in women, we identified differences in acute ischemic stroke subtypes, and acute management in favor of older age.

The value of serum Lp-PLA2 combined with MPO in the diagnosis of cerebral infarction caused by large artery atherosclerosis

ObjectiveTo explore the value of serum lipoprotein-associated phospholipase A2（Lp-PLA2）combined with myeloperoxidase（MPO）for the diagnosis of large artery atherosclerosis(LAA) cerebral infarction. MethodsBaseline data were collected from patients with first-ever acute cerebral infarction, serum Lp-PLA2 and MPO levels were measured. The etiology of cerebral infarction was classified according to the Chinese Ischemic Stroke Subtype Classification Standard. The risk factors associated with LAA cerebral infarction were identified by univariate and multivariate regression analysis. The diagnostic value of serum Lp-PLA2 and MPO for LAA cerebral infarction was assessed by the area under the receiver-operating characteristic (ROC) curve. ResultsOverall 368 patients were involved, 148 patients (40.22 %) were LAA. The serum La-PLA2 and MPO levels were higher in the LAA group than those in non-LAA group (23.06 ± 3.39 ng/mL versus 17.48 ± 3.26 ng/mL; 93.60 ± 9.58 ng/mL versus 75.98 ± 15.53 ng/mL; P < 0.001 for both). Multivariate analysis showed that elevated levels of serum Lp-PLA2 (OR 1.742, 95 %CI 1.499–2.025; P < 0.001) and MPO (OR 1.060, 95 % CI 1.026–1.096; P = 0.001) were the independent risk factors of LAA cerebral infarction. The area under curve of the serum Lp-PLA2 combined with MPO for the diagnosis of LAA cerebral infarction was 0.896 [0.866 ∼ 0.927] (P < 0.001). ConclusionSerum Lp-PLA2 combined with MPO could be valued as a predictor of acute cerebral infarction caused by large artery atherosclerosis.

Estimated Burden and Risk Factors of Ischemic and Hemorrhagic Strokes in a Tertiary Hospital, Mogadishu-Somalia: A Cross-Sectional Study

Objective: In Somalia, a country in East Africa, no data is available about key features of stroke such as incidence, prevalence, mortality, or stroke subtypes. The objective of this study is to show the burden of stroke, both ischemic and hemorrhagic stroke, and its risk factors in Somalia. Materials and Methods: We conducted a hospital-based retrospective study. Patients were recruited from January 1, 2019, to December 31, 2019, at the Mogadishu Somali Turkey Recep Tayyip Erdogan Training and Research Hospital. Results: A total of 292 participants with stroke (65.4% male and 34.6% women) were analyzed. The prevalence of ischemic and hemorrhagic strokes was 66.8% and 33.2%, respectively. A system for categorization of subtypes of ischemic stroke mainly based on etiology has been developed for the Trial of Org 10172 in Acute Stroke Treatment (TOAST). The most prevalent was a stroke of other determined etiology (28.7%), while the least common were lunar stroke (11.3%) and cardio-embolic (13.3%). The most prevalent hemorrhagic strokes were in the basal ganglia. Conclusions: In Somalia, there is no previous data on the prevalence and risk factors of stroke. We concluded that the prevalence of hemorrhagic stroke in Somalia is higher compared to other countries in the region. Key words: Cardio-embolic, Basal ganglia, Computed tomography, Lacunar, Thalamus

Intravenous Thrombolysis for Central Retinal Artery Occlusion: A Look at the Literature for the Emergency Medicine Physician.

Central retinal artery occlusion (CRAO) is a subtype of ischemic stroke and true ocular emergency presenting with acute, painless, monocular vision loss. Typical findings include poor visual acuity (VA), impaired color vision, relative afferent pupillary defect, and on fundoscopic evaluation, retinal edema, cherry red spot, and occasionally visualization of retinal artery emboli. While there are no proven treatments for CRAO, options include orbital massage, hyperbaric oxygen therapy, and intra-arterial or intravenous thrombolysis (IVT). This study reviews the current literature on the efficacy of IVT for patients affected by acute, symptomatic CRAO and provides an up-to-date, evidence-based background for emergency physicians (EPs) who evaluate and manage these patients.

A Nomogram for Predicting the Recurrence of Acute Non-Cardioembolic Ischemic Stroke: A Retrospective Hospital-Based Cohort Analysis.

Non-cardioembolic ischemic stroke (IS) is the predominant subtype of IS. This study aimed to construct a nomogram for recurrence risks in patients with non-cardioembolic IS in order to maximize clinical benefits. From April 2015 to December 2019, data from consecutive patients who were diagnosed with non-cardioembolic IS were collected from Lanzhou University Second Hospital. The least absolute shrinkage and selection operator (LASSO) regression analysis was used to optimize variable selection. Multivariable Cox regression analyses were used to identify the independent risk factors. A nomogram model was constructed using the "rms" package in R software via multifactor Cox regression. The accuracy of the model was evaluated using the receiver operating characteristic (ROC), calibration curve, and decision curve analyses (DCA). A total of 729 non-cardioembolic IS patients were enrolled, including 498 (68.3%) male patients and 231 (31.7%) female patients. Among them, there were 137 patients (18.8%) with recurrence. The patients were randomly divided into training and testing sets. The Kaplan-Meier survival analysis of the training and testing sets consistently revealed that the recurrence rates in the high-risk group were significantly higher than those in the low-risk group (p < 0.01). Moreover, the receiver operating characteristic curve analysis of the risk score demonstrated that the area under the curve was 0.778 and 0.760 in the training and testing sets, respectively. The nomogram comprised independent risk factors, including age, diabetes, platelet-lymphocyte ratio, leukoencephalopathy, neutrophil, monocytes, total protein, platelet, albumin, indirect bilirubin, and high-density lipoprotein. The C-index of the nomogram was 0.752 (95% CI: 0.705~0.799) in the training set and 0.749 (95% CI: 0.663~0.835) in the testing set. The nomogram model can be used as an effective tool for carrying out individualized recurrence predictions for non-cardioembolic IS.

Association Between Ischemic Stroke Subtype and Stroke Severity: The Atherosclerosis Risk in Communities Study.

Disability after stroke occurs across ischemic stroke subtypes, with a suggestion that embolic strokes are more devastating. Whether this difference is as a result of differences in comorbidities or differences in severity at the time of the stroke event is not known. The primary hypothesis was that participants with embolic stroke would have more severe stroke at the time of admission and a higher risk of mortality, compared with thrombotic stroke participants even with consideration of confounders over time, with a secondary hypothesis that this association would differ by race and sex. Atherosclerosis Risk in Communities (ARIC) study participants with incident adjudicated ischemic stroke, stroke severity and mortality data, and complete covariates were included. Multinomial logistic regression models determined the association between stroke subtype (embolic vs thrombotic) and admission NIH Stroke Scale (NIHSS) category (minor [≤5], mild [6-10], moderate [11-15], severe [16-20], and very severe [>20]) adjusted for covariates from visits most proximal to the stroke. Separate ordinal logistic models evaluated for interaction by race and sex. Adjusted Cox proportional hazard models estimated the association between stroke subtype and all-cause mortality (through December 31, 2019). Participants (N = 940) were mean age 71 years (SD = 9) at incident stroke, 51% female, and 38% Black. Using adjusted multinomial logistic regression, the risk of having a more severe stroke (reference NIHSS ≤5) was higher among embolic stroke vs thrombotic stroke patients, with a step-wise increase for embolic stroke patients when moving from mild (odds ratio [OR] 1.95, 95% CI 1.14-3.35) to very severe strokes (OR 4.95, 95% CI 2.34-10.48). After adjusting for atrial fibrillation, there was still a higher risk of having a worse NIHSS among embolic vs thrombotic strokes but with attenuation of effect (very severe stroke OR 3.91, 95% CI 1.76-8.67). Sex modified the association between stroke subtype and severity (embolic vs thrombotic stroke, p interaction = 0.03, per severity category, females OR 2.38, 95% CI 1.55-3.66; males OR 1.75, 95% CI 1.09-2.82). The risk of death (median follow-up 5 years, interquartile range 1-12) was also increased for embolic vs thrombotic stroke patients (hazard ratio 1.66, 95% CI 1.41-1.97). Embolic stroke was associated with greater stroke severity at the time of the event and a higher risk of death vs thrombotic stroke, even after careful adjustment for patient-level differences.

Prediction of restoration of swallowing function in patients with ischemic stroke and neurogenic dysphagia

Objective: to determine prognostic characteristics of the restoration of swallowing function in patients with ischemic stroke (IS) of various pathogenetic subtypes.Material and methods. The study included 110 patients (64 men and 46 women aged 44–89 years) with dysphagia in the acute period of IS. The SSS-TOAST criteria were used to diagnose the pathogenetic subtype, and the MASA scale was used to determine the presence and severity of dysphagia. To predict the probability of switching to self-feeding depending on the severity of dysphagia, a non-linear regression method was used using the least squares method.Results. Patients with cardioembolic stroke subtype were initially characterized by a greater degree of dysphagia in comparison with patients with atherothrombotic stroke subtype in groups comparable in severity (p&lt;0.05). In the cardioembolic subtype of IS, the probability of switching patients to self-feeding on the 21st day in groups with dysphagia severity from 105 to 135 points on the MASA scale was lower than in the atherothrombotic subtype of IS (p&lt;0.05).Conclusion. Patients with cardioembolic strokes are characterized by more severe initial dysphagia and a worse prognosis for recovery of swallowing function compared to patients with atherothrombotic strokes.

CLINICAL CHARACTERISTICS OF LACUNAR ISCHEMIC STROKE PATIENTS

Background: Stroke is the leading causes of death and disability in the world. Ischemic stroke covered 85% of stroke types. Based on the subtypes of ischemic stroke, lacunar ischemic stroke encompassed 20% of them. Knowing the characteristics help physicians to diagnose patients clinically and offer management to treat risk factors. Objective: This study aimed to know the characteristics of lacunar ischemic stroke based on patients risk factors, ischemic location on CT-scan, clinical syndrome, and NIHSS score. Methods: Using retrospective analytical study with cross sectional approach, medical record data from 2019-2022 were collected from RSUP DR. Hasan Sadikin Bandung. Results: From 60 patients, 35% (21) are 55-64 years old. Both sexes are equally distributed. 50 patients (83.3%) have multiple risk factors. Out of 60 patients, 57 (95%) have hypertension, 8 (13.3%) have diabetes mellitus, 44 (73.3%) have dyslipidemia, 6 (10%) have hyperuricemia, and 14 (23.3%) smoke. On admission, out of 60 patients, 34 (56.7%) have mild stroke, 23 (38.3%) have moderate stroke, 2 (3.3%) have moderate to severe stroke, and 1 (1.7%) has severe stroke. 44 (73.3%) out of 60 patients have pure motor hemiparesis. 41 (68.3%) out of 60 patients have basal ganglia ischemic. Conclusion: Lacunar ischemic stroke patients were equally distributed in sex with peak incidence occur between 55-64 years old. Most patients have multiple risk factors, basal ganglia lesion, pure motor hemiparesis, and history of hypertension, dyslipidemia, and smoking. On admission, most patients have mild stroke, followed by moderate stroke.

Prediction of subjective cognitive decline after corpus callosum infarction by an interpretable machine learning-derived early warning strategy.

Corpus callosum (CC) infarction is an extremely rare subtype of cerebral ischemic stroke, however, the symptoms of cognitive impairment often fail to attract early attention of patients, which seriously affects the long-term prognosis, such as high mortality, personality changes, mood disorders, psychotic reactions, financial burden and so on. This study seeks to develop and validate models for early predicting the risk of subjective cognitive decline (SCD) after CC infarction by machine learning (ML) algorithms. This is a prospective study that enrolled 213 (only 3.7%) CC infarction patients from a nine-year cohort comprising 8,555 patients with acute ischemic stroke. Telephone follow-up surveys were carried out for the patients with definite diagnosis of CC infarction one-year after disease onset, and SCD was identified by Behavioral Risk Factor Surveillance System (BRFSS) questionnaire. Based on the significant features selected by the least absolute shrinkage and selection operator (LASSO), seven ML models including Extreme Gradient Boosting (XGBoost), Logistic Regression (LR), Light Gradient Boosting Machine (LightGBM), Adaptive Boosting (AdaBoost), Gaussian Naïve Bayes (GNB), Complement Naïve Bayes (CNB), and Support vector machine (SVM) were established and their predictive performances were compared by different metrics. Importantly, the SHapley Additive exPlanations (SHAP) was also utilized to examine internal behavior of the highest-performance ML classifier. The Logistic Regression (LR)-model performed better than other six ML-models in SCD predictability after the CC infarction, with the area under the receiver characteristic operator curve (AUC) of 77.1% in the validation set. Using LASSO and SHAP analysis, we found that infarction subregions of CC infarction, female, 3-month modified Rankin Scale (mRS) score, age, homocysteine, location of angiostenosis, neutrophil to lymphocyte ratio, pure CC infarction, and number of angiostenosis were the top-nine significant predictors in the order of importance for the output of LR-model. Meanwhile, we identified that infarction subregion of CC, female, 3-month mRS score and pure CC infarction were the factors which independently associated with the cognitive outcome. Our study firstly demonstrated that the LR-model with 9 common variables has the best-performance to predict the risk of post-stroke SCD due to CC infarcton. Particularly, the combination of LR-model and SHAP-explainer could aid in achieving personalized risk prediction and be served as a decision-making tool for early intervention since its poor long-term outcome.

Association of Homocysteine with Acute Stroke and Its Subtypes in the Chinese Population.

Homocysteine (Hcy) is recognized as a risk factor for stroke. Our study examined the relationship between plasma Hcy levels and stroke, along with its subtypes, among Chinese patients who experienced an acute stroke episode. We retrospectively enrolled patients with acute stroke and age- and sex-matched healthy controls admitted to the First Affiliated Hospital of Xi'an Jiaotong University from October 2021 to September 2022. Ischemic stroke subtypes were classified using the modified TOAST criteria. Multivariate logistic regression models were employed to probe the associations of plasma Hcy levels with total stroke, ischemic stroke and its subtypes, and hypertensive intracerebral hemorrhage (HICH), and the correlation between plasma Hcy levels and the National Institute of Health Stroke Scale (NIHSS). The mean age of the total group was 63 years, with women representing 30.6% (246 individuals). Elevated Hcy levels were significantly associated with total stroke (OR 1.054, 95% CI: 1.038-1.070), HICH (OR 1.040, 95% CI: 1.020-1.060), ischemic stroke (OR 1.049, 95% CI: 1.034-1.065), and the TOAST subtypes of ischemic stroke in large-artery atherosclerosis (LAA) (OR 1.044, 95% CI: 1.028-1.062) and small-artery occlusion (SAO) (OR 1.035, 95% CI: 1.018-1.052), but not with cardioembolic (CE) stroke. Moreover, only in the case of SAO stroke were the Hcy levels positively correlated with the NIHSS score (B=0.030, 95% CI: 0.003-0.056, P=0.030). Plasma Hcy levels were found to be positively correlated with the risk of stroke, particularly in the context of LAA, SAO stroke, and HICH. Additionally, Hcy levels demonstrated a positive correlation with stroke severity in patients presenting with SAO stroke. These findings suggest potential clinical implications in stroke prevention, particularly for ischemic stroke (LAA, SAO subtypes) and HICH by employing homocysteine-lowering therapies. Future investigations are warranted to fully elucidate these associations.

Amide proton transfer-weighted MRI features of acute ischemic stroke subtypes.

Stroke is a highly heterogeneous disorder with distinct subtypes, and the stroke subtype influences the outcome. Amide proton transfer-weighted (APTW) MRI has been demonstrated to be promising in stroke patients, but the image characteristics of stroke subtypes have not been sufficiently investigated. The purpose of this study was to investigate the APTW MRI features of different subtypes of acute ischemic stroke (AIS). Ninety-two AIS patients presenting within 96 h of symptom onset were enrolled and examined with a 3.0-T MRI system. Patients were grouped into four subtypes: lacunar circulation infarcts (LACI, n = 33); total anterior circulation infarcts (TACI, n = 9); partial anterior circulation infarcts (PACI, n = 28); and posterior circulation infarcts (POCI, n = 22). APTW values in the lesion (APTWlesion ) and the contralateral normal-appearing region (APTWcontral ) were measured. The change in APTW values between the acute ischemic lesion and the contralateral normal-appearing region (APTWles-con ) was calculated. A two-sample t-test, one-way ANOVA, and the Chi-square method were used. There were significant differences between APTWlesion and APTWcontral in the three categories of nonlacunar strokes (TACI, PACI, and POCI, all p < 0.01), but not for lacunar strokes (LACI, p = 0.080). TACI patients had the lowest APTWlesion and APTWles-con in all groups (p < 0.05). In the POCI group, patients with supratentorial infarcts showed significant differences between APTWlesion and APTWcontral (p = 0.001), while the differences were not significant for infratentorial infarcts (p = 0.135). Our results suggest that the APT effect was heterogeneous in different stroke subtypes, and that APTW MRI gave an excellent performence in depicting nonlacunar AIS in supratentorial locations.

Ischemic stroke subtypes in subjects with and without diabetes: data from two hospitals in Mongolia

According to the World Health Organization report in 2020, the number of stroke deaths in Mongolia has reached 4,401, accounting for 19.84% of the total deaths, ranking as the second leading cause of death in Mongolia. Furthermore, the prevalence of diabetes has been steadily increasing for the last 20 years. In this case-control study (80 diabetic and 160 non-diabetic subjects), we analyzed data from two tertiary stroke centers over the past six months (June-December 2022). Inclusion criteria included patients over 18 years who presented to the emergency department with an acute ischemic stroke (I63 according to ICD 10). We reviewed and compared the data on clinical assessments such as the National Institutes of Health The Stroke Scale (NIHTSS), Glasgow Coma Scale and Modified Rankin Score, laboratory parameters, and TOAST classification of ischemic stroke between diabetic and non-diabetic patients in Mongolia. The mean age was 39.2±15.2, and 33.2% (n = 392) were male. The duration of diabetes in patients ranged from 0 to 23 years, and the median was 5.0. Mean glycated haemoglobin in subjects was 9.75±2.49%, and only 27.5% (n = 22) had HbA1c below 7.5%. Only BMI was significantly different in patients with diabetes compared to patients without diabetes (27.2±4.4 vs. 28.6±5.2). However, for other parameters, no significant difference was observed, but the NIHTSS at discharge was significantly higher in patients with diabetes. According to the TOAST classification, the risk of ischemic stroke caused by microangiopathy (18% vs 33.8%, p=0.142) and macroangiopathy (44.4% vs 57.5%, p=0.192) was 13-15% higher in people with diabetes than in people without diabetes. In regression analysis, patients with diabetes had a six times greater risk of ischemic stroke caused by atherosclerosis than non-diabetic patients. Most subtypes of stroke that occur in people with diabetes are caused by atherosclerosis, both large and small vessels.

Association of oral bisphosphonates with cardioembolic ischemic stroke: a nested case-control study.

Background: Bisphosphonates have been reported to increase the risk of atrial fibrillation. Therefore, it is conceivable that they may increase the risk of cardioembolic ischemic stroke (IS). However, most epidemiological studies carried out thus far have not shown an increased risk of IS, though none separated by the main pathophysiologic IS subtype (cardioembolic and non-cardioembolic) which may be crucial. In this study, we tested the hypothesis that the use of oral bisphosphonates increases specifically the risk of cardioembolic IS, and explored the effect of treatment duration, as well as the potential interaction between oral bisphosphonates and calcium supplements and anticoagulants. Methods: We performed a case-control study nested in a cohort of patients aged 40-99years, using the Spanish primary healthcare database BIFAP, over the period 2002-2015. Incident cases of IS were identified and classified as cardioembolic or non-cardioembolic. Five controls per case were randomly selected, matched for age, sex, and index date (first recording of IS) using an incidence-density sampling. The association of IS (overall and by subtype) with the use of oral bisphosphonates within the last year before index date was assessed by computing the adjusted odds ratios (AOR) and their 95% CI using a conditional logistic regression. Only initiators of oral bisphosphonates were considered. Results: A total of 13,781 incident cases of IS and 65,909 controls were included. The mean age was 74.5 (SD ± 12.4) years and 51.6% were male. Among cases, 3.15% were current users of oral bisphosphonates, while among controls they were 2.62%, yielding an AOR of 1.15 (95% CI:1.01-1.30). Of all cases, 4,568 (33.1%) were classified as cardioembolic IS (matched with 21,697 controls) and 9,213 (66.9%) as non-cardioembolic IS (matched with 44,212 controls) yielding an AOR of 1.35 (95% CI:1.10-1.66) and 1.03 (95% CI: 0.88-1.21), respectively. The association with cardioembolic IS was clearly duration-dependent (AOR≤1year = 1.10; 95% CI:0.82-1.49; AOR>1-3years = 1.41; 95% CI:1.01-1.97; AOR>3years = 1.81; 95% CI:1.25-2.62; p for trend = 0.001) and completely blunted by anticoagulants, even in long-term users (AOR>1year = 0.59; 0.30-1.16). An interaction between oral bisphosphonates and calcium supplements was suggested. Conclusion: The use of oral bisphosphonates increases specifically the odds of cardioembolic IS, in a duration-dependent manner, while leaves materially unaffected the odds of non-cardioembolic IS.

Identification and cross-validation of autophagy-related genes in cardioembolic stroke.

Cardioembolic stroke (CE stroke, also known as cardiogenic cerebral embolism, CCE) has the highest recurrence rate and fatality rate among all subtypes of ischemic stroke, the pathogenesis of which was unclear. Autophagy plays an essential role in the development of CE stroke. We aim to identify the potential autophagy-related molecular markers of CE stroke and uncover the potential therapeutic targets through bioinformatics analysis. The mRNA expression profile dataset GSE58294 was obtained from the GEO database. The potential autophagy-related differentially expressed (DE) genes of CE stroke were screened by R software. Protein-protein interactions (PPIs), correlation analysis, and gene ontology (GO) enrichment analysis were applied to the autophagy-related DE genes. GSE66724, GSE41177, and GSE22255 were introduced for the verification of the autophagy-related DE genes in CE stroke, and the differences in values were re-calculated by Student's t-test. A total of 41 autophagy-related DE genes (37 upregulated genes and four downregulated genes) were identified between 23 cardioembolic stroke patients (≤3 h, prior to treatment) and 23 healthy controls. The KEGG and GO enrichment analysis of autophagy-related DE genes indicated several enriched terms related to autophagy, apoptosis, and ER stress. The PPI results demonstrated the interactions between these autophagy-related genes. Moreover, several hub genes, especially for CE stroke, were identified and re-calculated by Student's t-test. We identified 41 potential autophagy-related genes associated with CE stroke through bioinformatics analysis. SERPINA1, WDFY3, ERN1, RHEB, and BCL2L1 were identified as the most significant DE genes that may affect the development of CE stroke by regulating autophagy. CXCR4 was identified as a hub gene of all types of strokes. ARNT, MAPK1, ATG12, ATG16L2, ATG2B, and BECN1 were identified as particular hub genes for CE stroke. These results may provide insight into the role of autophagy in CE stroke and contribute to the discovery of potential therapeutic targets for CE stroke treatment.

Causal relationship between ischemic stroke and its subtypes and frozen shoulder: a two-sample Mendelian randomization analysis.

Previous epidemiological and other studies have shown an association between ischemic stroke (IS) and frozen shoulder (FS). However, the causal relationship between them remains unclear. Therefore, the present study aimed to investigate the causal relationship between IS and FS using a two-sample Mendelian randomization method. Our research was divided into two stages: discovery and replication. The data were extracted from publicly available genome-wide association studies (GWAS). We selected a large sample of IS (n = 440, 328) and its subtypes (large-artery atherosclerotic stroke (LAS), cardioembolic stroke (CES), and stroke caused by small-vessel disease (SVS) and lacunar stroke (n = 254, 959) as exposure data. Additionally, we selected a large sample of FS as outcome data (n = 451, 099). Inverse variance weighting (IVW) was applied as the primary analysis method. The weighted median, MR-Egger, simple model, and weighted model were used as complementary analysis methods to assess causal effects. Moreover, heterogeneity was analyzed using Cochran's Q-test with IVW and MR-Egger. The MR-Egger intercept and MR-PRESSO analysis methods were used for pleiotropy testing. The stability of the results was also assessed using a leave-one-out analysis. In the discovery stage, the IVW approach revealed an odds ratio (OR) of 1.207 with a 95% confidence interval (CI) of 1.027-1.417 and a P-value of 0.022. This suggests a causal association between IS levels and an increased risk of FS. In the subtype studies of IS, the findings were negative. However, during the replication stage, a significant causal link was found between selected lacunar strokes and FS with an OR of 1.252, a 95% CI of 1.105-1.419, and a P-value of 0.0004. All studies had no pleiotropy or heterogeneity, and the findings were robust. Our study confirmed the causal relationship between any IS level and increased risk of FS. Furthermore, the same results were obtained in the replication stage with lacunar stroke as an exposure factor. However, there was no direct causal relationship between the subtypes of IS and FS. Our study provides theoretical support for shoulder care for patients with IS.

B-Type Natriuretic Peptide Can Distinguish Ischemic Stroke Subtypes Better than Other Cardiac Biomarkers.

BACKGROUND The primary benefit to patients of being able to distinguish among subtypes of ischemic stroke (IS) is creation of a better treatment decision-making process. Current classification methods are complex and time-consuming, requiring hours to days. Blood-based cardiac biomarker measurements have the potential to improve mechanism classification of ischemic stroke. MATERIAL AND METHODS In this study, 223 patients with IS were selected as the case group and 75 healthy people who underwent physical examination at the same time were selected as the control group. The chemiluminescent immunoassay (CLIA) method established in this study was used to quantitatively detect plasma B-type natriuretic peptide (BNP) levels in subjects. All subjects were assessed for serum creatine kinase isoenzyme-MB (CK-MB), cardiac troponin I (cTnI), and myoglobin (MYO) after admission. We investigated the effectiveness of BNP and other cardiac biomarkers in the diagnosis of different subtypes of IS. RESULTS The levels of the 4 cardiac biomarkers were increased in IS patients. BNP could better diagnose different types of IS compared to other cardiac biomarkers, and BNP combined with other cardiac biomarkers was better than a single indicator in diagnosing IS. CONCLUSIONS Compared with other cardiac biomarkers, BNP is a better marker for the diagnosis of different subtypes of ischemic stroke. Routine screening for BNP in IS patients is recommended to improve the treatment decision-making process and minimize the time to thrombosis, thereby providing a more precise treatment for patients with different subtypes of stroke.

Prevalence and Clinico-Radiologic Spectrum of Intracranial Atherosclerotic Disease-Related Stroke: An Observation from a Single Center in Saudi Arabia.

Intracranial atherosclerotic disease (ICAD) is an important etiologic subtype of acute ischemic stroke (AIS). However, little direct evidence is available regarding ICAD-related stroke in Saudi Arabia (SA). This study aimed to identify the prevalence and describe the clinico-radiological spectrum of ICAD-related AIS in a SA cohort. This was a hospital-based retrospective study enrolling patients with ICAD-related AIS between 2017 and 2020. The electronic charts were reviewed. The mechanisms of stroke were identified as artery-to-artery embolization (AAE), in situ thrombotic occlusion, hypoperfusion, or perforator branch occlusion. Pearson's χ2 test was performed to calculate the P values to establish the statistical significance of factors that could correlate with the mechanisms of stroke and functional outcome. ICAD was found in 133 of AIS comprising 26% of total. Data from all patients were reviewed. Left ICA (25%) was the most frequently affected vessel. Territorial pattern (63.9%) was the most common infarct pattern, and AAE (44.3%) was the most common underlying mechanism. Perforator branch occlusion was more prevalent in women than in men. Malignant and hemorrhagic transformation (P=0.00) were more prevalent in the AAE group. Left-sided vascular involvement was statistically associated with unfavorable outcomes than the right (P=0.019). The prevalence of ICAD in our cohort from Western Asia did not differ from that in Southern Asia. ICA involvement was observed more frequently than previously reported. Further research from SA is required to better understand ICAD-related strokes in this region.