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Background: Thrombi retrieved from patients with acute ischemic stroke may contain prognostic information., Objective: To investigate the relationship between the immunologic phenotype of thrombi and future vascular events in patients with a stroke., Methods: This study included patients with acute ischemic stroke who underwent endovascular thrombectomy at Chung-Ang University Hospital in Seoul, Korea, between February 2017 and January 2020. Laboratory and histological variables were compared between patients with and without recurrent vascular events (RVEs). Kaplan-Meier analysis followed by the Cox proportional hazards model was used to identify factors related to RVE. Receiver operating characteristic (ROC) analysis was conducted to evaluate the performance of the immunologic score by combining immunohistochemical phenotypes to predict RVE., Results: A total of 46 patients were included in the study with 13 RVEs (mean±SD age, 72.8±11.3 years; 26 (56.5%) men). Thrombi with a lower percentage of programmed death ligand-1 expression (HR=11.64; 95% CI 1.60 to 84.82) and a higher number of citrullinated histone H3 positive cells (HR=4.19; 95% CI 0.81 to 21.75) were associated with RVE. The presence of high-mobility group box 1 positive cell was associated with reduced risk of RVE, but the association was lost after adjustment for stroke severity. The immunologic score, which consists of the three immunohistochemical phenotypes, showed good performance in predicting RVE (area under the ROC curve, 0.858; 95% CI 0.758 to 0.958)., Conclusions: The immunological phenotype of thrombi could provide prognostic information after stroke., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Rationale: The optimal duration of dual antiplatelet therapy (DAPT) with clopidogrel-aspirin for the large artery atherosclerotic (LAA) stroke subtype has been debated., Aims: To determine whether the 1-year risk of recurrent vascular events could be reduced by a longer duration of DAPT in patients with the LAA stroke subtype., Methods and Study Design: A total of 4806 participants will be recruited to detect a statistically significant relative risk reduction of 22% with 80% power and a two-sided alpha error of 0.05, including a 10% loss to follow-up. This is a registry-based, multicenter, prospective, randomized, open-label, blinded end point study designed to evaluate the efficacy and safety of a 12-month duration of DAPT compared with a 3-month duration of DAPT in the LAA stroke subtype. Patients will be randomized (1:1) to either DAPT for 12 months or DAPT for 3 months, followed by monotherapy (either aspirin or clopidogrel) for the remaining 9 months., Study Outcomes: The primary efficacy outcome of the study is a composite of stroke (ischemic or hemorrhagic), myocardial infarction, and all-cause mortality for 1 year after the index stroke. The secondary efficacy outcomes are (1) stroke, (2) ischemic stroke or transient ischemic attack, (3) hemorrhagic stroke, and (4) all-cause mortality. The primary safety outcome is major bleeding., Discussion: This study will help stroke physicians determine the appropriate duration of dual therapy with clopidogrel-aspirin for patients with the LAA stroke subtype., Trial Registration: URL: https://cris.nih.go.kr/cris. CRIS Registration Number: KCT0004407.

Background: Elevated metabolic activity of amygdala is known to be related to atherosclerotic cardiovascular event by increasing inflammatory cell production from bone marrow. We tried to identify the factors of metabolic activity in the amygdala, vertebrae, liver, spleen, and internal carotid artery related to the future vascular events after stroke., Methods: A total of 110 patients with acute stroke were included (72±10 years of age, 39% women) and underwent whole-body 18 F-fluorodeoxyglucose (FDG) positron emission tomography between August 1, 2015 and February 28, 2020. We compared the FDG uptake in the amygdala, vertebrae, liver, spleen, and internal carotid artery between patients with and without recurrent vascular event. Cox proportional hazards model was used to identify factors related to recurrent stroke and vascular event., Results: During the median follow-up period of 18 months, 22 patients experienced vascular events, including 15 stroke recurrence. Patients with recurred vascular event had a significantly higher FDG uptake in the amygdala and vertebrae than those without. The Cox proportional hazard model including diabetes, renal function, and carotid stenosis showed that a higher FDG uptake in the amygdala was independently associated with total vascular events (hazard ratio, 3.11 [95% CI, 1.11-8.70]) and higher FDG uptake in the vertebrae with stroke recurrence (hazard ratio, 4.94 [95% CI, 1.29-18.9])., Conclusions: The increased metabolic activities of the vertebrae and amygdala are related to future vascular event among stroke survivors.

Positron emission tomography with 18 F-sodium fluoride (NaF) radioligand has been actively investigated in atherosclerosis research because it is known to detect microcalcification activity within atheroma. We studied whether NaF shows any uptake in the brain tissue of patients with acute ischemic stroke. This is a post-hoc analysis of previously reported cerebral atherosclerosis research with positron emission tomography which applied the two radioligands, 18 F-fluorodeoxyglucose and NaF for the detection of culprit atheroma among 20 acute cerebral infarction patients (mean age = 75.1 ± 9.0 years; 10 women). In this study, we measured the maximum and mean standardized uptake value (SUVmax and SUVmean) of NaF uptake level in the cerebral infarct region between lesions with and without diffusion weighted image (DWI) positivity, indicating acute ischemic cell death. Correlation analysis was performed between NaF uptake levels and imaging and clinical variables, including neurological severity. The NaF uptake levels were significantly higher in DWI positive lesions than in negative lesions (SUVmax: 2.0 [0.60-4.2] versus 0.20 [0.10-0.40], p = 0.021 by Mann-Whitney U test). The intensity of NaF uptake (SUVmax) was significantly correlated with the initial neurological severity (Spearman's ρ = 0.579, p= 0.007) and white blood cell count (Spearman's ρ = 0.626, p p 0.003). During ischemic stroke NaF was concentrated in brain tissue undergoing acute cell death and its uptake intensity was correlated with neurological severity, suggesting that NaF could reflect acute ischemic cell death after stroke., (© 2022. The Author(s).)

Background: We investigated the microRNA expression pattern from thrombus retrieved by mechanical thrombectomy in acute stroke patients to understand the stroke mechanism., Methods: This study included acute ischemic stroke patients who had undergone intra-arterial thrombectomy at Chung-Ang University Hospital in Seoul, Korea between February 2016 and March 2019. The thrombus was retrieved and stored at -70℃ after obtaining informed consent. MicroRNA microarray analysis was performed for the patients with identified stroke mechanisms including (1) large artery atherosclerosis, (2) cardioembolism with atrial fibrillation, and (3) cardioembolism with valvular heart disease. The microRNAs derived from microarray analysis were validated by quantitative real-time polymerase chain reaction (qRT-PCR) from different patient populations. The correlation analysis was performed between microRNA levels and laboratory data to understand the functional relevance of the altered microRNA., Results: In total, 55 thrombi were obtained from 74 patients, and the microRNAs were analyzed in 45 samples. Microarray analysis of 2578 microRNAs revealed that 50 microRNAs were significantly altered among the three groups. Validation using qRT-PCR showed that miR-378f and miR-450b-5p were significantly elevated among the cardioembolic thrombi; both microRNAs were inversely correlated with the ejection fraction from echocardiography. Thrombi from patients with early neurological deterioration exhibited higher levels of miR-93-5p and lower levels of miR-629-5p than those from neurologically stable patients., Conclusions: The microRNA expression pattern can provide information regarding the mechanism of stroke by reflecting the underlying pathological status of the organ from which the thrombus was derived., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Purpose: Renal dysfunction is known to affect vasculature and lead to systemic arterial stiffness. It also independently increases the risk of cerebral small vessel disease (cSVD) and stroke. We aimed to examine the effect of renal dysfunction on cerebral hemodynamics and the burden of cSVD., Methods: Of the 412 patients admitted to Seoul National University Hospital, between May 2015 and 2019, with lacunar infarction and no major intracranial arterial stenosis observed on magnetic resonance angiography, we included 283 patients who had undergone a transcranial Doppler (TCD) ultrasound after 72 h of stroke onset. The patients were divided into renal dysfunction (estimated glomerular filtration rate [eGFR] <60 mL/min/1.73 m2 at admission) and control (eGFR ≥60 mL/min/1.73 m2) groups. We investigated the correlations between renal function, the pulsatility index (PI), and the total MRI burden of cSVD. Furthermore, multivariate analysis was performed to assess the association between renal dysfunction and the PI of the middle cerebral artery (MCA) measured through TCD ultrasound., Results: Among the total patients, 74 (26.1%) had renal dysfunction (eGFR <60 mL/min/1.73 m2 at admission). Patients with renal dysfunction were significantly older, showed higher pulse pressure, and had a higher prevalence of hypertension, diabetes mellitus, and coronary artery disease. Renal dysfunction was significantly associated with higher distal cerebrovascular flow resistance (median PI 1.12, interquartile range [IQR]: 0.85-1.57 vs. controls 0.84, IQR: 0.54-1.22; p < 0.001). Also, patients with renal dysfunction had a significantly higher total MRI burden of cSVD (median cSVD score 2, IQR: 1-3 vs. controls median score 1, IQR: 0-2; p < 0.001). There was an inverse proportional relationship between the PI and eGFR. Finally, multivariate analysis showed renal dysfunction (adjusted odds ratio: 4.516, 95% confidence interval: 1.051-20.292) and older age (adjusted odds ratio: 1.076, 95% confidence interval: 1.038-1.114) as independent predictors of a high PI., Conclusions: Renal dysfunction is independently associated with a high PI of MCA. Renal dysfunction leads to systemic arterial stiffness including stiffness in cerebral arteries, thus increasing the burden of cSVD. Therefore, noninvasive screening for high PI by TCD in kidney failure patients might be helpful., (© 2021 The Author(s). Published by S. Karger AG, Basel.)

Background/objective: Cerebral herniation due to brain edema is the major cause of neurological worsening in patients suffering large hemispheric strokes. In this study, we investigated whether quantitative pupillary response could help identify the neurological worsening due to brain swelling in patients with large hemispheric strokes., Methods: Quantitative pupillary assessment using an automated pupillometer (NPi-100) was performed between April 2017 and August 2019 for patients suffering large hemispheric strokes. Consecutive pupillary responses were measured every 2 or 4 h as a part of routine clinical care. We compared the mean neurological pupil index (NPi) values, NPi value at the time of neurological deterioration, and percentage change in NPi from the immediate previous value between patients with and without neurological worsening., Results: In this study, 2442 quantitative pupillary assessments were performed (n = 30; mean age, 67.9 years; males, 60.0%). Among the included patients, 10 (33.3%) experienced neurological worsening. Patients with neurological worsening had a significantly lower mean value of NPi and a sudden decrease in the NPi value as compared to those without neurological worsening during the whole monitoring period (3.88 ± 0.65 vs. 4.45 ± 0.46, P < 0.001; and 29.5% vs. 11.1%, P = 0.006, respectively). All patients with NPi values below 2.8 showed neurological deterioration., Conclusions: Quantitative monitoring of the pupillary response using an automated pupillometer could be a useful and noninvasive tool for detecting neurological deterioration due to cerebral edema in large hemispheric stroke patients.

Background: Inflammation plays an important role in atherosclerosis and its complications. Since a dysregulated inflammatory response is associated with early neurological deterioration (END), serum neutrophil-to-lymphocyte ratio (NLR) could be a marker of END as well., Aim: In this study, we evaluated the relationship between the serum NLR and END in patients with ischemic stroke due to large-artery atherosclerosis (LAA)., Methods: We evaluated consecutive patients with ischemic stroke due to LAA between January 2010 and December 2015. END was defined as an increase ≥ 2 on the total NIHSS score or ≥ 1 on the motor NIHSS score within the first 72 hours of admission. The NLR was calculated by dividing the absolute neutrophil count by the absolute lymphocyte count., Results: Of the 349 included patients, 18.1% (n = 63) had END events. In multivariate analysis, serum NLR was independently associated with END (adjusted odds ratio, 1.08; 95% confidence interval [1.00-1.16], P = 0.043). Time to admission, and in-situ thrombosis and artery-to-artery embolization mechanisms were also significantly associated with END events. In an analysis of the relationship between serum NLR and vascular lesion burden, serum NLR was positively correlated with both the degree of stenotic lesions (P for trend = 0.006) and the number of vessel stenosis (P for trend = 0.038) in a dose-response manner. We also compared serum NLR by the stroke mechanisms: patients with hypoperfusion or in-situ thrombosis had the highest levels of NLR: however, only those with in-situ thrombosis had significantly higher NLR in the END group compared to the non-END group (P = 0.005)., Conclusions: Serum NLR levels were associated with END events in patients with ischemic stroke due to LAA. Since NLR was also closely correlated with the underlying vascular lesions, our results indicated clues for mechanisms of END events., Competing Interests: The authors have declared that no competing interests exist.