Ischemic Stroke Subtypes Research Articles

The Untargeted Metabolomics Reveals Differences in Energy Metabolism in Patients with Different Subtypes of Ischemic Stroke.

Ischemic stroke (IS) is the most common subtype of stroke. The risk factors and pathogenesis of IS are complex and varied due to different subtypes. Therefore, we used metabolomics technology to investigate the biomarkers and potential pathophysiological mechanisms of different subtypes of IS. We included 126 IS patients and divided them into two groups based on the TOAST classification: large-artery atherosclerosis (LAA) group (n = 87) and small-vessel occlusion (SVO) group (n = 39). Plasma metabolomics analysis was performed using liquid chromatography-high-resolution mass spectrometry (LC-HRMS) to identify metabolic profiles in LAA and SVO subtype IS patients and to determine metabolic differences between patients with the two subtypes of IS. We identified 26 differential metabolites between LAA and SVO subtype IS. A multiple prediction model based on the plasm metabolites had good predictive ability for IS subtyping (AUC = 0.822, accuracy = 77.8%), with 12,13-DHOME being the most important differential metabolite in the model. The differential metabolic pathways between the two subtypes of IS patients included tricarboxylic acid (TCA) cycle, alanine, aspartate and glutamate metabolism, and pyruvate metabolism, mainly focused on energy metabolism. 12,13-DHOME emerged as the primary discriminatory metabolite between LAA and SVO subtypes of IS. In LAA subtype IS patients, energy metabolism, encompassing pyruvate metabolism and the TCA cycle, exhibited lower activity levels when compared to patients with the SVO subtype IS. The utilization of targeted metabolomics holds the potential to improve diagnostic accuracy for distinguishing stroke subtypes.

Patient Readmission for Ischemic Stroke: Risk Factors and Impact on Mortality.

Patient readmission for ischemic stroke significantly strains the healthcare and medical insurance systems. Current understanding of the risk factors associated with these readmissions, as well as their subsequent impact on mortality within China, remains insufficient. This is particularly evident in the context of comprehensive, contemporary population studies. This 4-year retrospective cohort study included 125 397 hospital admissions for ischemic stroke from 838 hospitals located in 22 regions (13 urban and 9 rural) of a major city in western China, between January 1, 2015 and December 31, 2018. The Chi-square tests were used in univariate analysis. Accounting for intra-subject correlations of patients' readmissions, accelerated failure time (AFT) shared frailty models were used to examine readmission events and pure AFT models for mortality. Risk factors for patient readmission after ischemic stroke include frequent admission history, male gender, employee's insurance, advanced age, residence in urban areas, index hospitalization in low-level hospitals, extended length of stay (LOS) during index hospitalization, specific comorbidities and subtypes of ischemic stroke. Furthermore, our findings indicated that an additional admission for ischemic stroke increased patient mortality by 16.4% (P < .001). Stroke readmission contributed to an increased risk of hospital mortality. Policymakers can establish more effective and targeted policies to reduce readmissions for stroke by controlling these risk factors.

Ischemic stroke in men 18-50 years of age

To evaluate the main modifiable risk factors for ischemic stroke (IS) and features of the course in atherothrombotic, cardioembolic, and lacunar subtypes of IS in men aged 18-50 years. The study included 125 men (the mean age was 42.6±5.3 years) who were admitted to the Vascular department before the COVID-19 pandemic and survived for the first 30 days after IS. Information on patients' baseline characteristics, traditional vascular risk factors, and lifestyle risk factors was systematically collected. Neuroimaging, ultrasound and laboratory tests were performed. Atherothrombotic subtype was identified in 60 patients, lacunar subtype in 46 patients and cardioembolic subtype in 19 patients. In the group as a whole, major risk factors included arterial hypertension (83.2%), dyslipidemia (50.4%), smoking (67.2%), alcohol consumption (29.6%), obesity (16.8%), heart rhythm disorders (12%), and diabetes mellitus (8%). The study revealed the main risk factors, the frequency of which differed depending on the stroke subtype and the age of the patients.

Genetically predicted small dense low-density lipoprotein cholesterol and ischemic stroke subtype: multivariable Mendelian randomization study.

Small dense low-density lipoprotein cholesterol (S-LDL-C) has been suggested as a particularly atherogenic factor for ischemic stroke (IS) in observational studies, but the causality regarding the etiological subtype remains unclear. This study aims to explore the causal effects of small dense low-density lipoprotein cholesterol (S-LDL-C), medium (M-LDL-C) and large (L-LDL-C) subfractions on the lifetime risk of ischemic stroke (IS) and main subtypes using two-sample Mendelian randomization (TSMR) design. We identified genetic instruments for S-LDL-C, M-LDL-C and L-LDL-C from a genome-wide association study of 115 082 UK Biobank participants. Summary-level data for genetic association of any ischemic stroke (AIS), large artery stroke (LAS), small vessel stroke (SVS) and cardioembolic stroke (CES) were obtained from MEGASTROKE consortium. Accounting for the pleiotropic effects of triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C), we conducted multivariable TSMR analysis. In univariable TSMR, we found a causal association between genetically predicted S-LDL-C and LAS (IVW-FE: odds ratio (OR) = 1.481, 95% confidence interval (CI): 1.117-1.963, P = 0.006, q = 0.076) but not AIS, SVS or CES. No causal effects were observed for M-LDL-C or L-LDL-C in terms of AIS and IS subtype. In multivariable analysis, the causal association between S-LDL-C and LAS remained significant (IVE-MRE: OR = 1.329, 95% CI: 1.106-1.597, P = 0.002). Findings supported a causal association between S-LDL-C and LAS. Further studies are warranted to elucidate the underlying mechanism and clinical benefit of targeting S-LDL-C.

Ischemic Stroke During the Pandemic in a Secondary Care Hospital: COVID-19 and Its Collateral Effects

Aim: Ischemic stroke is among the leading causes of death and disability. Although recent studies have&#x0D; shown a possible relationship between COVID-19 and ischemic stroke, the effect of the pandemic period,&#x0D; which may be another factor in the increase of ischemic stroke risk factors, has not been investigated.&#x0D; Therefore, in current study, we assessed how the COVID-19 pandemic affected ischemic strokes.&#x0D; Material and Methods: Patients were divided as two years before and after the first COVID-19 case&#x0D; in Turkey, and their COVID-19 history, demographic characteristics and clinical features (comorbid&#x0D; diseases, etc.) were obtained.&#x0D; Results: There were 588 ischemic stroke patients pre-pandemic and 694 ischemic stroke patients&#x0D; post-pandemic. In post-pandemic periods, 322 patients were vaccinated, and 288 patients were not.&#x0D; No significant difference in ischemic stroke was found between vaccinated and unvaccinated groups&#x0D; (p = 0.168) and between different vaccine-type groups (p = 0.873). Partial anterior circulation infarct&#x0D; (PACI) was the most common ischemic stroke subtype in both groups; there was no difference between&#x0D; them (p=0.719). The number of ischemic stroke were significantly increased in the post-pandemic&#x0D; period (p

Causal Effect of Lipoprotein-Associated Phospholipase A2 Activity on Ischemic Stroke: A Mendelian Randomization Study

Background: The relationship between ischemic stroke (IS) and lipoprotein-associated phospholipase A2 (Lp-PLA2) activity is still unclear, and there is a dearth of stratified research on the relationship between Lp-PLA2 activity and different IS subtypes. Therefore, Mendelian randomization (MR) was used in this study to examine the relationship between genetically proxied Lp-PLA2 activity and the risks of IS and its subtypes. Methods: Based on information from a meta-analysis of genome-wide association studies, which included 13,664 European people, five single nucleotide polymorphisms related to Lp-PLA2 activity were chosen as instrumental variables. Summary statistics information about the MEGESTROKE consortium with the European group (40,585 cases and 406,111 controls) include any IS (AIS; n = 34,217), large-artery stroke (LAS; n = 4,373), cardioembolic stroke (CES; n = 7,193), and small-vessel stroke (SVS; n = 5,386). In order to determine the causal relationships between Lp-PLA2 activity and IS as well as its subtypes, the inverse-variance-weighted (IVW) approach was chosen as the primary analysis. Significant estimates were then tested by sensitivity analysis to rule out heterogeneity and pleiotropy. Results: IVW showed that Lp-PLA2 activity was causally associated with LAS (odds ratio = 3.25, 95% confidence interval = 1.65–6.41, p = 0.0007) but not with other subtypes of stroke. Sensitivity analysis for causal estimates between Lp-PLA2 activity and LAS showed no significant heterogeneity or pleiotropy. Conclusions: These MR analyses support a causal effect of Lp-PLA2 activity on LAS but not on AIS, CES, or SVS, which suggests that serum Lp-PLA2 activity might be a biomarker for prediction of LAS.

Hospital-Level Variability in Reporting of Ischemic Stroke Subtypes and Supporting Diagnostic Evaluation in GWTG-Stroke Registry.

Secondary prevention of ischemic stroke (IS) requires adequate diagnostic evaluation to identify the likely etiologic subtype. We describe hospital-level variability in diagnostic testing and IS subtyping in a large nationwide registry. We used the GWTG-Stroke (Get With The Guidelines-Stroke) registry to identify patients hospitalized with a diagnosis of acute IS at 1906 hospitals between January 1, 2016, and September 30, 2017. We compared the documentation rates and presence of risk factors, diagnostic testing, achievement/quality measures, and outcomes between patients with and without reported IS subtype. Recording of diagnostic evaluation was optional in all IS subtypes except cryptogenic, where it was required. Of 607 563 patients with IS, etiologic IS subtype was documented in 57.4% and missing in 42.6%. Both the rate of missing stroke pathogenesis and the proportion of cryptogenic strokes were highly variable across hospitals. Patients missing stroke pathogenesis less frequently had documentation of risk factors, evidence-based interventions, or discharge to home. The reported rates of major diagnostic testing, including echocardiography, carotid and intracranial vascular imaging, and short-term cardiac monitoring were <50% in patients with documented IS pathogenesis, although these variables were missing in >40% of patients. Long-term cardiac rhythm monitoring was rarely reported, even in cryptogenic stroke. Reporting of IS etiologic subtype and supporting diagnostic testing was low overall, with high rates of missing optional data. Improvement in the capture of these data elements is needed to identify opportunities for quality improvement in the diagnostic evaluation and secondary prevention of stroke.

Thrombolytic Therapy for Central Retinal Artery Occlusion in an Academic Multi-Site Stroke Centre

ABSTRACT Central retinal artery occlusion (CRAO) is a subtype of acute ischaemic stroke leading to severe visual loss. A recent American Heart Association scientific statement proposed time-windows for thrombolysis in CRAO similar to acute ischaemic cerebral strokes. We aimed to review our academic multi-site stroke centre experience with intravenous (IVT) and intra-arterial thrombolysis (IAT) in CRAO between 1997 and 2022. Demographic, clinical characteristics, thrombolysis timeline, concurrent therapies, complications, and 3-month follow-up visual acuity (VA) were collected. The thrombolysed cohort follow-up VA was compared with an age, gender and baseline VA matched cohort of CRAO patients that received conservative therapies. Thrombolytic therapy was administered to 3.55% (n = 20) of CRAO admissions; 13 IVT (mean age 68, 61.5% male, 12 alteplase and 1 tenecteplase, all embolic aetiology, 1 CRAO mimic) and 7 IAT (mean age 55, 85.7% male, 3 post-operative and 3 embolic). Additional conservative CRAO-targeting therapies was received by 60%. The median time from onset of visual loss to IVT was 158 minutes (range 67–260). Improvement by at least two Snellen lines was achieved by 25% with 12.5% improving to 20/100 or better. Intracranial haemorrhage post IVT occurred in 1/13 (7.6%). The median time from onset of visual loss to IAT was 335 minutes. Improvement by at least two Snellen lines was achieved by 42%. No difference in 3-month VA was noted between patients that received thrombolysis, either alone (n = 8) or combined with other therapies, and those that received conservative therapies. Our results suggest that the management of acute CRAO remains heterogeneous. The lack of obvious benefit of thrombolysis in our small series supports the need for randomizsd clinical trials comparing thrombolysis to placebo to guide hyperacute CRAO management.

Neuroprotective effects of oral metformin before stroke on cerebral small-vessel disease

BackgroundMetformin (MET) treatment prior to stroke might have neuroprotective effects other than hypoglycemic effects. This study evaluated whether MET treatment prior to stroke is associated with neurological severity and functional outcome in patients with stroke who were not indicated for endovascular treatment and whether the effects of MET differ for each ischemic stroke subtype. MethodsWe investigated 160 type 2 diabetes mellitus patients with ischemic stroke without endovascular treatment who were taking some oral antidiabetic agents prior to stroke in two tertiary hospitals. Lower neurological severity was defined as a National Institutes of Health Stroke Scale score of 3 or lower on admission, and favorable functional outcome was defined as a modified Rankin Scale score = 0–2 at discharge. We analyzed the effects of MET on the neurological severity and functional outcome in each ischemic stroke subtype on logistic regression analysis with adjustments for multiple confounding factors. ResultsMET treatment prior to stroke was associated with lower stroke severity and favorable functional outcome. In the stroke subtypes, MET use affected both neurological severity (P = 0.037) and functional outcome (P = 0.041) in only patients with small-vessel disease (SVD). ConclusionsMET may be useful to improve the outcome of patients with SVD.

Clonal Hematopoiesis of Indeterminate Potential (CHIP) Related to the Etiology of Ischemic Stroke

Introduction: Clonal Hematopoiesis of Indeterminate Potential (CHIP) is associated with cardiovascular disease, including acute myocardial infarction and ischemic stroke, due to immune system dysregulation leading to increased atherosclerotic plaque formation and inflammation. Approximately 25-40% of ischemic strokes have an unknown cause even after a comprehensive etiological study and are eventually categorized as cryptogenic strokes. Our hypothesis is that the presence of CHIP could represent a biomarker for atherosclerotic or cardioembolic ischemic stroke and help to clarify the origin of cryptogenic strokes. Therefore, the objective of this study was to analyze the prevalence of CHIP in patients with different subtypes of ischemic stroke and its prognostic impact on cardiovascular risk. Methods: This prospective observational study included consecutive patients over 60 years of age with no prior history of neoplasia or cytotoxic treatment, who experienced embolic ischemic stroke between September 2021 and August 2022. Ischemic strokes were classified into cardioembolic (CE), atherothrombotic (AT) or cryptogenic (CRYP) etiologies after performing a systematic etiological study. During the stroke admission, peripheral blood samples were obtained in order to analyze the 13 genes most frequently associated with CHIP ( DNMT3A, TET2, ASXL1, JAK2, PPM1D, TP53, SF3B1, GNB1, SRSF2, CHEK2, CBL, GNAS, NRAS) through targeted next generation sequencing. Libraries were prepared using the KAPA HyperPlus capture chemistry (Roche) and were sequenced on a MiSeq platform (Illumina) following a 2x150bp paired-end read standard protocol, allowing the detection of variants with a variant allelic frequency (VAF) of ≥1%. The analysis was conducted using an in-house developed pipeline. Patients with one or more mutations in these genes with a VAF ≥2% were considered CHIP carriers. Cardiovascular risk factors including: hypertension, diabetes mellitus, dyslipidemia, smoking and obesity, were also analyzed. Results: Seventy-eight patients with stroke were included (50% female, median age 72 years (range: 59-90). Ischemic strokes were classified etiologically as: 36 CE (46.2%), 34 AT (43.6%) and 8 CRYP (10.3%) (Table 1). CHIP was detected in 21/78 (31.3%) patients, with the following gene mutation frequencies among CHIP carriers: DNMT3A (47.6%), TET2 (28.5%), SRSF2 (14.2%), PPM1D (9.5%), ASXL1 (4.8%), CBL (4.8%), CHEK2 (4.8%) and JAK2 (4.8%). The median VAF detected was 4.85% (range: 2.1%-43.7%), and 23.8% (5/21) of cases presented more than one mutation. The incidence of CHIP varied according to stroke etiology: CE etiology: 38.9% (14/36); AT etiology: 17.6% (6/34) and CRYP etiology: 12.5% (1/8) (p=0.046) (Figure 1). Moreover, only CE strokes showed mutations in TET2 (16.7% (6/36)) compared to AT (0/34) and CRYP (0/8) (p=0.015). No significant differences were observed in the blood counts (Hb, MCV, RDW, neutrophil count, monocytes, platelets or PCR) between stroke patients with CHIP and non-CHIP (Table 1). Finally, in the multivariate analysis, TET2 mutations were associated with CE stroke independently of age, coronary artery disease and classic cardiovascular risk factors (OR 8.1; Cl: 1.35-48.47; p=0.012). Conclusions: Our findings identify that CHIP is common in patients with ischemic strokes, especially in those of cardioembolic etiology, with TET2 being the most frequently mutated gene. The presence of CHIP TET2 could represent a novel cardiovascular risk factor, contributing to a more precise etiological distinction between the different etiologies of ischemic stroke. Funding source: this project is supported by health research fund of Carlos III health institute. FIS PI20/00881

Association between internal carotid artery kinking and ischemic stroke: A population-based cross-sectional study

AimEvidence for an association between Internal carotid artery (ICA) kinking and ischemic stroke has been controversial. We aimed to examine the association between ICA tortuosity and risk of ischemic stroke and specific ischemic stroke subtypes (large artery atherosclerosis, LAA; small artery occlusion, SAO). MethodsA total of 419 outpatients were included in this cross-sectional study. ICA kinking was objectively assessed by head and neck computed tomography angiography (CTA). The risk of ischemic stroke for each patient was evaluated according to the Essen Stroke Risk Score (ESRS). Ischemic stroke subtypes (LAA and SAO) were measure with head magnetic resonance imaging (MRI). ResultsThe average age of patients was 59.1 years (SD = 13.25) and 264 (63.0 %) were males. The prevalence of ICA kinking in this sample was 31.5 % (132 out of 419). Individuals with ICA kinking was associated with 0.55-points increase in ESRS score than those without ICA kinking (95 % CI, 0.28–0.81, p < 0.001) among patients over 50 years. In addition, right ICA kinking or left ICA kinking were associated with 0.35-points (95 % CI, 0.08–0.63) and 0.49-points (95 % CI, 0.23–0.76) increase in ESRS score, respectively. For specific ischemic stroke subtypes, individuals with ICA kinking had a 10.34-fold increased risk of SAO compared to those without ICA kinking (95 % CI, 6.22–20.68). Individuals with right ICA kinking had a 4.51-fold risk of SAO than those without kinking (95 % CI, 2.64–7.71), and had an 8.86-fold risk of SAO than those without kinking in the left ICA kinking (95 % CI, 4.97–15.79). ConclusionOur findings support the role of ICA kinking on ischemic stroke. Early screening and proper treatment of carotid artery tortuosity could be a potential intervention strategy for the prevention of ischemic stroke later on.

Differential impacts of admission LDL-cholesterol on early vascular outcomes by ischemic stroke subtypes

Because ischemic stroke is heterogeneous, the associations between low-density lipoprotein (LDL)-cholesterol levels and early vascular outcomes might be different according to the stroke subtype in acute ischemic stroke patients. This study was an analysis of a prospective, multicenter, stroke registry. Acute ischemic stroke patients previously not treated with statins were included. Admission LDL-cholesterol levels were divided into 7 groups at 20 mg/dl intervals for comparison. The primary early vascular outcome was a composite of stroke, myocardial infarction (MI) and all-cause mortality within 3 months. A total of 38,531 patients (age, 68.5 ± 12.8 yrs; male, 59.6%) were analyzed for this study. The 3-month cumulative incidences of the composite of stroke, MI, and all-cause mortality significantly differed among the LDL-cholesterol level groups, with the highest event rate (11.11%) in the lowest LDL-cholesterol group (<70 mg/dl). After adjustment, the U-shaped associations of LDL-cholesterol levels with primary outcome and all-cause mortality were observed. For the stroke subtypes, there were substantial interactions between the LDL-cholesterol groups and stroke subtype and all-cause mortality (Pinteraction=0.07). Different patterns, with higher risks of all-cause mortality in the lower LDL-cholesterol in the large artery atherosclerosis subtype (adjusted hazard ratio [aHR] 1.29, 95% confidence interval [CI] 0.98-1.69), but in the higher LDL-cholesterol in the cardioembolism subtype (aHR 1.71 95% CI [1.28-2.29]), were observed among stroke subtypes. We found that there were differential associations of admission LDL-cholesterol levels with all-cause mortality within 3 months among stroke subtypes. These results suggest that admission LDL-cholesterol and early vascular outcomes had complex relationships in patients with ischemic stroke according to the stroke subtypes.

Excessive Sedentary Time Is Associated with Cognitive Decline in Older Patients with Minor Ischemic Stroke.

Cognitive impairment is commonly seen after acute ischemic stroke (AIS). Sedentary behaviors increase the risk of dementia among community dwelling population. This study aims to investigate the association of sedentary behaviors with poststroke cognitive impairment among older adults of minor AIS. This cohort study recruited 594 older subjects with minor AIS from three hospitals in China during February 1, 2016, and December 31, 2018. Participants were followed up for two years and the sedentary time per day was self-reported at the endpoint of follow-up. Cognitive functions were assessed by Mini-Mental State Examination (MMSE). Participants were categorized into the high and low sedentary time group according to the median sedentary time of the participants. At two years of follow-up, the long sedentary time group had significantly lower MMSE scores than the short sedentary time group [median, (95% CI): 21 (18 to 25) versus 22 (18 to 25), p = 0.368]. The long sedentary time group had a higher speed of cognitive decline than the short sedentary time group. Excessive sedentary time was associated with a higher risk of longitudinal cognitive decline (OR: 2.267, 95% CI: 1.594 to 3.225), adjusting for age, sex, education, body mass index, APOE genotype, comorbidities, symptoms of depression, anxiety, and insomnia, baseline MMSE scores and National Institute of Health Stroke Scale scores, cognitive therapy, and TOAST ischemic stroke subtypes. This study identified a possible link between sedentary behaviors and longitudinal cognitive decline among older patients with minor AIS, suggesting that reducing sedentary time might be helpful for preventing poststroke dementia.

Aging-related genes revealed Neuroinflammatory mechanisms in ischemic stroke by bioinformatics

Ischemic stroke (IS) is a leading cause of disability, morbidity, and mortality globally. Aging affects immune function and contributes to poor outcomes of IS in elderly individuals. However, little is known about how aging-related genes (ARGs) are involved in IS. In this study, the relationship between ARGs and IS immune microenvironment biomarkers was explored by bioinformatics. Two IS microarray datasets (GSE22255, GSE16561) from human blood samples were analyzed and 502 ARGs were identified, from which 29 differentially expressed ARGs were selected. Functional analysis revealed that 7 of these ARGs (IL1B, FOS, JUN, CXCL5, PTGS2, TNFAIP3 and TLR4) were involved in five top enriched pathways (IL-17 signaling pathway, TNF signaling pathway, Rheumatoid arthritis, NF-kappa B signaling pathway and Pertussis) related to immune responses and inflammation. Five hub DE-ARGs (IL2RB, FOS, IL7R, ALDH2 and BIRC2) were identified using machine learning algorithms, and their association with immune-related characteristics was confirmed by additional tests. Single-cell sequencing dataset GSE129788 was retrieved to analyze aging molecular-related features, which was in accordance with microarray datasets. Clustering analysis revealed two subtypes of IS, which were distinguished by their differential expression of genes related to the NF-kappa B signaling pathway. These findings highlight the importance of ARGs in regulating immune responses in IS and suggest potential prevention and treatment strategies as well as guidelines for future research.

Targeting inflammation to reduce recurrent stroke.

Approximately one in four stroke patients suffer from recurrent vascular events, underlying the necessity to improve secondary stroke prevention strategies. Immune mechanisms are causally associated with coronary atherosclerosis. However, stroke is a heterogeneous disease and the relative contribution of inflammation across stroke mechanisms is not well understood. The optimal design of future randomized control trials (RCTs) of anti-inflammatory therapies to prevent recurrence after stroke must be informed by a clear understanding of the prognostic role of inflammation according to stroke subtype and individual patient factors. In this narrative review, we discuss (1) inflammatory pathways in the etiology of ischemic stroke subtypes; (2) the evidence on inflammatory markers and vascular recurrence after stroke; and (3) review RCT evidence of anti-inflammatory agents for vascular prevention. Experimental work, genetic epidemiological data, and plaque-imaging studies all implicate inflammation in atherosclerotic stroke. However, emerging evidence also suggests that inflammatory mechanisms are also important in other stroke mechanisms. Advanced neuroimaging techniques support the role of neuroinflammation in blood-brain barrier dysfunction in cerebral small vessel disease (cSVD). Systemic inflammatory processes also promote atrial cardiopathy, incident and recurrent atrial fibrillation (AF). Although several inflammatory markers have been associated with recurrence after stroke, interleukin-6 (IL-6) and high-sensitivity C-reactive protein (hsCRP) are presently the most promising markers to identify patients at increased vascular risk. Several RCTs have shown that anti-inflammatory therapies reduce vascular risk, including stroke, in coronary artery disease (CAD). Some, but not all of these trials, selected patients on the basis of elevated hsCRP. Although unproven after stroke, targeting inflammation to reduce recurrence is a compelling strategy and several RCTs are ongoing. Evidence points toward the importance of inflammation across multiple stroke etiologies and potential benefit of anti-inflammatory targets in secondary stroke prevention. Taking the heterogeneous stroke etiologies into account, the use of serum biomarkers could be useful to identify patients with residual inflammatory risk and perform biomarker-led patient selection for future RCTs.

Carotid Dolichoarteriopathy (Elongation) of the Carotid Arteries in Patients with Ischemic Stroke Anamnesis.

Carotid artery elongation (ECA) is widespread in the asymptomatic population and among people with a history of ischemic stroke (IS). There are different points of view on the ways these changes contribute to brain ischemic damage pathogenesis. Materials and Methods: From 2019 to 2021, we included 1171 people who had suffered from IS less than one year before the investigation in the study, 404 (34.5%) women aged 27 to 95 years (64 ± 13 years) and 767 men (21-90; 60 ± 11 years). All patients involved in the study underwent multimodal radiological investigation in addition to assessments of their clinical and neurological data. Results: In this study, we were unable to detect a relationship between ECA localization and acute ischemic lesions. The frequency of ECA detection in patients with IS was the same as that in carotid and vertebral-basilar arterial systems. The prevalence of ECA was the same in patients with different IS subtypes (TOAST). There was no association between the localization of ECA and ischemic lesions; moreover, there were no differences in the IS frequency between anterior and posterior circulation. There were statistically significant decreases in linear peak systolic and end diastolic velocities in the internal carotid and vertebral arteries, as well as in the intracranial arteries in patients with ECA.

Association of HbA1c with functional outcome by ischemic stroke subtypes and age.

To determine whether high HbA1c levels are related to short-and long-term functional outcomes in patients with ischemic stroke (IS) and whether this association differs according to the IS subtype and the patient's age. The data of 7,380 IS patients admitted to 16 hospitals or regional stroke centers in South-Korea, between May 2017 and December 2019, were obtained from the Clinical Research Collaboration for Stroke-Korea-National Institute of Health database and retrospectively analyzed. Among these patients, 4,598 were followed-up for one-year. The HbA1c levels were classified into three groups (<5.7, 5.7 to <6.5%, ≥6.5%). Short-and long-term poor functional outcomes were defined using the modified Rankin Scale score of 2 to 6 at three-months and one-year, respectively. IS subtypes were categorized according to the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) classification. There was an association between higher HbA1c (≥6.5%) and poor functional outcomes at three-months in all patients (three-months; OR, 1.299, 95% CI 1.098, 1.535, one-year; OR, 1.181, 95% CI 0.952, 1.465). When grouped by age, the associations after both 3 months and 1 year observed in younger adult group (<65 years), but not in group aged 65 years and older (three-months; <65 years OR, 1.467, 95% CI 1.112, 1.936, ≥65 years OR, 1.220, 95% CI 0.987, 1.507, p for interaction = 0.038, one-year; <65 years OR, 1.622, 95% CI 1.101, 2.388, ≥65 years OR, 1.010, 95% CI 0.778, 1.312, p for interaction = 0.018). Among younger adult group, the higher HbA1c level was related to short-and long-term functional loss in patients with the small vessel occlusion subtype (three-months; OR, 2.337, 95%CI 1.334, 4.095, one-year; OR, 3.004, 95% CI 1.301, 6.938). However, in patients with other TOAST subtypes, a high HbA1c level did not increase the risk of poor outcomes, regardless of the age of onset. High HbA1c levels increase the risk of short-and long-term poor functional outcomes after IS onset. However, this association differs according to stroke subtype and age. Thus, pre-stroke hyperglycemia, reflected by HbA1c, may be a significant predictor for a poor prognosis after ischemic stroke, particular in young- and middle-aged adults.

Hemorrhagic transformation in patients with large-artery atherosclerotic stroke is associated with the gut microbiota and lipopolysaccharide.

Abstract JOURNAL/nrgr/04.03/01300535-202407000-00032/figure1/v/2023-11-20T171125Z/r/image-tiff Hemorrhagic transformation is a major complication of large-artery atherosclerotic stroke (a major ischemic stroke subtype) that worsens outcomes and increases mortality. Disruption of the gut microbiota is an important feature of stroke, and some specific bacteria and bacterial metabolites may contribute to hemorrhagic transformation pathogenesis. We aimed to investigate the relationship between the gut microbiota and hemorrhagic transformation in large-artery atherosclerotic stroke. An observational retrospective study was conducted. From May 2020 to September 2021, blood and fecal samples were obtained upon admission from 32 patients with first-ever acute ischemic stroke and not undergoing intravenous thrombolysis or endovascular thrombectomy, as well as 16 healthy controls. Patients with stroke who developed hemorrhagic transformation (n = 15) were compared to those who did not develop hemorrhagic transformation (n = 17) and with healthy controls. The gut microbiota was assessed through 16S ribosomal ribonucleic acid sequencing. We also examined key components of the lipopolysaccharide pathway: lipopolysaccharide, lipopolysaccharide-binding protein, and soluble CD14. We observed that bacterial diversity was decreased in both the hemorrhagic transformation and non-hemorrhagic transformation group compared with the healthy controls. The patients with ischemic stroke who developed hemorrhagic transformation exhibited altered gut microbiota composition, in particular an increase in the relative abundance and diversity of members belonging to the Enterobacteriaceae family. Plasma lipopolysaccharide and lipopolysaccharide-binding protein levels were higher in the hemorrhagic transformation group compared with the non-hemorrhagic transformation group. lipopolysaccharide, lipopolysaccharide-binding protein, and soluble CD14 concentrations were associated with increased abundance of Enterobacteriaceae. Next, the role of the gut microbiota in hemorrhagic transformation was evaluated using an experimental stroke rat model. In this model, transplantation of the gut microbiota from hemorrhagic transformation rats into the recipient rats triggered higher plasma levels of lipopolysaccharide, lipopolysaccharide-binding protein, and soluble CD14. Taken together, our findings demonstrate a noticeable change in the gut microbiota and lipopolysaccharide-related inflammatory response in stroke patients with hemorrhagic transformation. This suggests that maintaining a balanced gut microbiota may be an important factor in preventing hemorrhagic transformation after stroke.

Outcomes in Patients With Poststroke Seizures

Published data about the impact of poststroke seizures (PSSs) on the outcomes of patients with stroke are inconsistent and have not been systematically evaluated, to the authors' knowledge. To investigate outcomes in people with PSS compared with people without PSS. MEDLINE, Embase, PsycInfo, Cochrane, LILACS, LIPECS, and Web of Science, with years searched from 1951 to January 30, 2023. Observational studies that reported PSS outcomes. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist was used for abstracting data, and the Joanna Briggs Institute tool was used for risk-of-bias assessment. Data were reported as odds ratio (OR) and standardized mean difference (SMD) with a 95% CI using a random-effects meta-analysis. Publication bias was assessed using funnel plots and the Egger test. Outlier and meta-regression analyses were performed to explore the source of heterogeneity. Data were analyzed from November 2022 to January 2023. Measured outcomes were mortality, poor functional outcome (modified Rankin scale [mRS] score 3-6), disability (mean mRS score), recurrent stroke, and dementia at patient follow-up. The search yielded 71 eligible articles, including 20 110 patients with PSS and 1 166 085 patients without PSS. Of the participants with PSS, 1967 (9.8%) had early seizures, and 10 605 (52.7%) had late seizures. The risk of bias was high in 5 studies (7.0%), moderate in 35 (49.3%), and low in 31 (43.7%). PSSs were associated with mortality risk (OR, 2.1; 95% CI, 1.8-2.4), poor functional outcome (OR, 2.2; 95% CI, 1.8-2.8), greater disability (SMD, 0.6; 95% CI, 0.4-0.7), and increased dementia risk (OR, 3.1; 95% CI, 1.3-7.7) compared with patients without PSS. In subgroup analyses, early seizures but not late seizures were associated with mortality (OR, 2.4; 95% CI, 1.9-2.9 vs OR, 1.2; 95% CI, 0.8-2.0) and both ischemic and hemorrhagic stroke subtypes were associated with mortality (OR, 2.2; 95% CI, 1.8-2.7 vs OR, 1.4; 95% CI, 1.0-1.8). In addition, early and late seizures (OR, 2.4; 95% CI, 1.6-3.4 vs OR, 2.7; 95% CI, 1.8-4.1) and stroke subtypes were associated with poor outcomes (OR, 2.6; 95% CI, 1.9-3.7 vs OR, 1.9; 95% CI, 1.0-3.6). Results of this systematic review and meta-analysis suggest that PSSs were associated with significantly increased mortality and severe disability in patients with history of stroke. Unraveling these associations is a high clinical and research priority. Trials of interventions to prevent seizures may be warranted.

Higher Habitual Dietary Intakes of Flavanols and Anthocyanins Differentially Associate with Lower Incidence of Ischemic Stroke Subtypes—A Follow-Up Analysis

BackgroundWe previously reported that habitual consumption of dietary flavanol oligomers + polymers and anthocyanins is associated with a lower risk of ischemic stroke. However, no studies have investigated their relationship with ischemic stroke subtypes. ObjectivesIn this follow-up analysis, we aimed to examine the association of flavanol oligomers + polymers and anthocyanin intake with ischemic stroke subtypes, including the following: 1) large-artery atherosclerosis, 2) cardioembolism, 3) small-vessel occlusion, 4) other determined etiology, and 5) undetermined etiology. MethodsParticipants (n = 55,094) from the Danish Diet, Cancer, and Health Study were followed up for <16 y for first-time ischemic stroke events, which were classified according to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria. Intakes of flavanol oligomers + polymers and anthocyanins were calculated from food frequency questionnaires using the Phenol-Explorer database, and their relationships with ischemic stroke subtypes were investigated using restricted cubic splines within Cox proportional hazards models. After multivariable adjustment, higher habitual intakes (quintile 5 compared with quintile 1) of flavanol oligomers + polymers and anthocyanins were associated with a lower risk of specific ischemic stroke subtypes, including large-artery atherosclerosis [flavanol oligomers + polymers, hazard ratio {HR} (95% confidence interval {CI}): 0.64 (0.47, 0.87)], cardioembolism [anthocyanins, HR (95% CI): 0.45 (0.25, 0.82)], and small-vessel occlusion [flavanol oligomers + polymers, HR (95% CI): 0.65 (0.54, 0.80); anthocyanins, HR (95% CI): 0.79 (0.64, 0.97)], but not stroke of other determined or undetermined etiology. ConclusionsHigher habitual intakes of flavanols and anthocyanins are differentially associated with a lower risk of ischemic stroke from atherosclerosis and/or cardioembolism but not with other subtypes.