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Background: Cerebral small vessel disease is characterized by white matter hyperintensities (WMH) and acute small vessel occlusion (SVO) stroke. We investigated the effect of prior antiplatelet use (APU) on stroke outcome in 1151 patients with acute SVO stroke patients and moderate to severe WMH., Methods: Using a multicenter database, this retrospective study used quantitative WMH volume measurements and propensity score matching (PSM) for comparisons between patients with prior APU and without APU. Primary outcomes were stroke progression and poor functional outcome (modified Rankin Scale>2) at 3 months. Logistic regression analyses assessed associations between prior APU, WMH burden, and stroke outcomes., Results: Stroke progression was lower in the prior APU group in both the total cohort (14.8% vs. 6.9%, p < 0.001) and the PSM cohort (16.3% vs. 6.9%, p < 0.001). The proportion of poor functional outcomes at 3 months was not significantly different in the total cohort, but the PSM cohort showed a lower proportion in the prior APU group (30.8% vs. 20.2%, p = 0.002). Logistic regression analysis confirmed that prior APU was associated with a reduced risk of stroke progression (OR, 0.39; 95% CI, 0.22-0.70; p = 0.001) and poor functional outcome at 3 months (OR, 0.37; 95% CI, 0.23-0.59; p < 0.001)., Conclusion: Prior APU is associated with reduced stroke progression and improved functional outcome at 3 months in acute SVO stroke patients with moderate to severe WMH. Early treatment of WMH and acute SVO stroke may have potential benefits in improving stroke outcomes., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Optimal antithrombotic regimens to prevent recurrent stroke in patients with ischemic stroke due to atrial fibrillation (AF) and atherosclerotic large-vessel stenosis remain unknown., Aims: This study aimed to evaluate the effect of multiple antithrombotic therapies on outcomes at 1 year after ischemic stroke due to two or more causes., Methods: We identified 862 patients with ischemic stroke due to AF and large artery atherosclerosis from the linked data. These patients were categorized into three groups according to antithrombotic therapies at discharge: (1) antiplatelets, (2) oral anticoagulants (OAC), and (3) antiplatelets plus OAC. The study outcomes were recurrent ischemic stroke, composite outcomes for cardiovascular events, and major bleeding after 1 year. Inverse probability of treatment weighting (IPTW) was used to balance the three groups using propensity scores., Results: Among 862 patients, 169 (19.6%) were treated with antiplatelets, 405 (47.0%) were treated with OAC, and 288 (33.4%) were treated with antiplatelets and OAC. After applying IPTW, only OAC had a significant beneficial effect on the 1-year composite outcome (hazard ratio (HR): 0.37, 95% confidence interval (CI): 0.23-0.60, p < 0.001) and death (HR: 0.35, 95% CI: (0.19-0.63), p < 0.001). The combination of antiplatelet agents and OAC group had an increased risk of major bleeding complications (HR: 5.27, 95% CI: (1.31-21.16), p = 0.019). However, there was no significant difference in 1-year recurrent stroke events among the three groups., Conclusion: This study demonstrated that OAC monotherapy was associated with lower risks of composite outcome and death in patients at 1 year after ischemic stroke due to AF and atherosclerotic stenosis. In addition, the combination of an antiplatelet and OAC had a high risk of major bleeding.

Background: A high and low estimated glomerular filtration rate (eGFR) could affect outcomes after reperfusion therapy for ischemic stroke. This study aimed to determine whether renal function based on eGFR affects mortality risk in patients with ischemic stroke within 6 months following reperfusion therapy., Methods: This prospective registry-based cohort study included 2266 patients who received reperfusion therapy between January 2000 and September 2019 and were registered in the SECRET (Selection Criteria in Endovascular Thrombectomy and Thrombolytic Therapy) study or the Yonsei Stroke Cohort. A high and low eGFR were based on the Chronic Kidney Disease Epidemiology Collaboration equation and defined, respectively, as the 5th and 95th percentiles of age- and sex-specific eGFR. Occurrence of death within 6 months was compared among the groups according to their eGFR such as low, normal, or high eGFR., Results: Of the 2266 patients, 2051 (90.5%) had a normal eGFR, 110 (4.9%) a low eGFR, and 105 (4.6%) a high eGFR. Patients with high eGFR were younger or less likely to have hypertension, diabetes, or atrial fibrillation than the other groups. Active cancer was more prevalent in the high-eGFR group. During the 6-month follow-up, there were 24 deaths (22.9%) in the high-eGFR group, 37 (33.6%) in the low-eGFR group, and 237 (11.6%) in the normal-eGFR group. After adjusting for variables with P <0.10 in the univariable analysis, 6-month mortality was independently associated with high eGFR (hazard ratio, 2.22 [95% CI, 1.36-3.62]; P =0.001) and low eGFR (HR, 2.29 [95% CI, 1.41-3.72]; P =0.001). These associations persisted regardless of treatment modality or various baseline characteristics., Conclusions: High eGFR as well as low eGFR were independently associated with 6-month mortality after reperfusion therapy. Kidney function could be considered a prognostic factor in patients with ischemic stroke after reperfusion therapy.

Introduction: Clopidogrel is an antiplatelet agent that is widely used for the secondary prevention of cardiovascular and cerebrovascular events. The genotype of cytochrome P450 2C19 ( CYP2C19 ) differentially affects the liver's metabolism of clopidogrel, which may influence the drug's response and efficacy for cardiovascular event prevention. In contrast to prior studies of patients with coronary artery diseases, little is known about whether the CYP2C19 genotype influences the preventive efficacy of clopidogrel in patients who had a stroke. We hypothesise that, among patients who had an acute ischaemic stroke who are prescribed clopidogrel, the patients with a loss-of-function CYP2C19 genotype (poor and intermediate metabolisers) may be at a higher risk of composite cardiovascular events than those who are non-carriers (extensive metabolisers)., Methods and Analysis: This prospective observational multicentre study was designed to determine whether composite cardiovascular events would differ among patients who had an ischaemic stroke prescribed clopidogrel according to CYP2C19 genotype (poor or intermediate vs extensive metabolisers). Inclusion criteria were patients who had an acute ischaemic stroke who underwent CYP2C19 genotype evaluation and received clopidogrel within 72 hours of stroke onset. The primary outcome is composite cardiovascular events (stroke, myocardial infarction, or cardiovascular death) within 6 months after acute ischaemic stroke between patients categorised as poor or intermediate metabolisers and those categorised as extensive metabolisers according to their CYP2C19 genotype., Ethics and Dissemination: The Institutional Review Board of Severance Hospital, Yonsei University College of Medicine approved this study (3-2019-0195). We received study approval from the institutional review board of each participating hospital. We plan to disseminate our findings at relevant conferences and meetings and through peer-reviewed journals., Trial Registration Number: NCT04072705., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Diabetes mellitus (DM) predisposes individuals to vascular injury, leading to poor outcomes after ischemic stroke and symptomatic hemorrhagic transformation (SHT) after thrombolytic and endovascular treatment (EVT). Metformin (MET), an oral antidiabetic drug, has shown potential neuroprotective effects, but its impact on stroke prognosis in DM patients undergoing EVT remains unclear. In a multicenter study, 231 patients with DM undergoing EVT for acute ischemic stroke were enrolled. Prior MET use was identified, and patients were stratified into MET+ and MET− groups. Demographics, clinical data, and outcomes were compared between groups. Multivariate analysis was used to assess the effect of MET on stroke prognosis. Of the enrolled patients, 59.3% were previously on MET. MET+ patients had lower initial infarct volumes and NIHSS scores compared to MET-taking patients. Multivariate analysis showed that MET+ was associated with a lower risk of stroke progression and SHT (with stroke progression as follows: odd ratio [OR] 0.24, 95% confidence interval [CI] [0.12–0.48], p < 0.001; SHT: OR 0.33, 95% CI [0.14–0.75], p = 0.01) and was also associated with better 3-month functional outcomes (mRS 0–2) after EVT. Prestroke MET use in DM patients undergoing EVT is associated with improved stroke prognosis, including reduced risk of stroke progression and SHT and better functional outcomes. These findings suggest the potential neuroprotective role of MET in this population and highlight its clinical utility as an adjunctive therapy in the management of ischemic stroke. Further research is warranted to elucidate the underlying mechanisms and to optimize MET therapy in this setting. [ABSTRACT FROM AUTHOR]

Although clinical studies have demonstrated that prior use of antiplatelets was associated with decreased blood viscosity (BV) in patients with acute ischemic stroke, the impact of previous anticoagulant use on blood viscosity in cardioembolic stroke with non-valvular AF (NVAF) has not yet been clearly studied. This single-center retrospective observational study aimed to determine the impact of prior antithrombotic (antiplatelet and anticoagulant) use on BV in patients with cardioembolic stroke (CES) due to NVAF. Patients with CES and NVAF were analyzed with the following inclusion criteria: (1) patients over 20 years of age admitted within five days of stroke onset; (2) ischemic stroke presumably due to an NVAF-derived embolus; (3) compatible cortical/subcortical lesion on brain computed tomography or magnetic resonance imaging; (4) hemoglobin level of 10–18 mg/dL; and (5) receiving antiplatelets within five days or anticoagulants within two days if previously medicated. From the screening of 195 patients (22% of the total stroke population during the study period) who had experienced ischemic stroke with AF, 160 were included for the final analysis. Eighty-nine patients (56%) were taking antithrombotics (antiplatelet, 57%; warfarin, 13%; NOACs, 30%) regularly. Compared to patients without previous antithrombotic use, those with previous antithrombotic use (antiplatelets, warfarin, and NOACs) were significantly associated with decreased systolic BV (SBV) and diastolic BV (DBV) (p < 0.036). In multiple linear regression analysis, hematocrit (Hct) level and prior antithrombotic use were significantly associated with decreased SBV and DBV. Hct was positively correlated with increased SBV and DBV. In Hct-adjusted partial correlation analysis, prior uses of any antithrombotic agents were associated with decreased SBV (r < −0.270, p < 0.015) and DBV (r < −0.183, p < 0.044). In conclusion, this study showed that prior antithrombotic use (antiplatelets, VKAs, and NOACs) was associated with decreased SBV and DBV in patients presenting with acute CES secondary to NVAF. Our results indicated that previous use of NOACs may be a useful hemorheological parameter in patients with acute CES due to NVAF. Accumulation of clinical data from a large number of patients with the risk of stroke occurrence, initial stroke severity, and functional outcome is necessary to assess the usefulness of BV. [ABSTRACT FROM AUTHOR]

Stroke is a leading cause of disability worldwide, with a growing need for effective rehabilitation strategies. Forest therapy, involving structured activities in natural environments, has shown significant beneficial effects in various health-related outcomes but no studies have assessed its direct effect on functional recovery after acute ischemic stroke. We assessed whether forest therapy is effective in recovering functional outcome of acute ischemic stroke compared to conventional rehabilitation therapy. This prospective cohort study included patients with acute ischemic stroke admitted within 24 hours of symptom onset. Participants were randomized into forest therapy (n=15) and control (n=27) groups. The forest therapy group underwent five sessions of guided activities in a national forest center, while the control group received standard outpatient rehabilitation. Primary outcome was changes in the modified Rankin Scale (mRS) scores, with secondary outcomes including grip strength, body composition, and psychological well-being assessed using the Worker's Stress Response Inventory and the Positive and Negative Affect Schedule from the time of hospital discharge to 3 months after stroke onset. Change of mRS were analyzed using the generalized estimating equation to compare changes over time between the two groups. At three-month follow-up, the forest therapy group demonstrated a significant improvement in mRS scores compared to the control group (p=0.034). Although no significant differences were found in grip strength or body composition, reductions in somatization and job-related stress were observed in the forest therapy group. No significant changes in positive or negative affect were detected. Forest therapy can contribute to functional recovery and reduce stress-related indicators in acute ischemic stroke patients. These findings support that the integration of forest therapy into stroke rehabilitation protocols to address both physical and psychological aspects of recovery, highlighting the potential for multidisciplinary approaches in post-stroke care. • Forest therapy improves functional outcomes in acute ischemic stroke patients. • Stress-related indicators was also improved after forest treatment. • Forest therapy can help restore physical and mental health. [ABSTRACT FROM AUTHOR]

Background: Atrial fibrillation (AF) is the most common cardiac arrhythmia among adults. Despite the proven advantages in primary and secondary stroke prevention in patients with AF, oral anticoagulation (OAC) therapy is still underused in many countries. In this study, we investigated the incidence of AF-related ischemic stroke over the past decade in South Korea and trends of preventive antithrombotic therapy use before stroke in a nationwide cohort. Methods and findings: The data source for this study was a nationwide sample cohort comprising 1,025,340 individuals that was established by the nationwide health insurance system in 2002. A total of 10,215 patients with acute ischemic stroke (AIS) were selected from the cohort between 2004 and 2013. AF was identified in 1,662 patients, and 979 patients had preexisting AF before AIS. The annual proportion of patients with AIS with AF gradually increased from 13.4% to 22.6% over the study period (p for trends <0.001). Only 14.0% of patients with high risk AF were receiving OAC before the stroke, and this proportion remained relatively constant during the study period. However, the proportion of patients treated with antiplatelet agents had increased from 18.8% in 2004 to 45.3% in 2013, while that of patients receiving no antithrombotic agent decreased from 64.6% in 2004 to 43.9% in 2013. As a limitation, no information was available about non-vitamin K antagonist oral anticoagulants, because they were widely used since late 2014 in Korea. Conclusions: The number of patients with AIS and AF has steadily increased over the last 10 years in Korea. However, a small portion of patients with AF were receiving OAC therapy before the stroke and about half of the patients did not receive any antithrombotic medication. Our study demonstrates that there is huge gap between clinical practice and treatment guidelines for patients with AF in Korea. [ABSTRACT FROM AUTHOR]

ABSTRACT BACKGROUND AND PURPOSE We investigated the relationship between transcranial Doppler (TCD) pulsatility index (PI) and central aortic pressure by measurement of the aortic augmentation index (AIx). METHODS We enrolled 148 consecutive patients with a diagnosis of acute ischemic stroke. Patients were eligible for the study if they experienced their first ischemic stroke within the preceding 7 days and were 45 years of age or older. At Day 7 (±2) after stroke onset, TCD studies were performed and AIx was measured by applanation tonometry on the same days. RESULTS The mean age was 66.3 (47-90) years and 37.8% were women. The mean middle cerebral artery (MCA) PI was significantly related with age ( r =.361), hypertension ( r = .184), peripheral systolic blood pressure (SBP; r = .211), peripheral pulse pressure (PP; r = .396), aortic SBP ( r = .184), aortic DBP ( r = -.181), and aortic PP ( r = .371). The basilar artery (BA) PI was significantly related with age ( r = .311), peripheral DBP ( r = -.267), peripheral PP ( r = .358), aortic DBP ( r = -.266), and aortic PP ( r = .347). CONCLUSIONS TCD PI was significantly related with central aortic pressure, especially PP. The PI in the MCA and BA is closely associated with the pulsatile component of BP in the systemic circulation. [ABSTRACT FROM AUTHOR]

Abstract: The aim of the present study was to explore the relationship between augmentation index (AIx) and vascular risk factors according to stroke subtypes. Patients were eligible for this study if they experienced their first ischemic stroke within the preceding 7days and were 45years of age or older. AIx was measured by applanation tonometry (SphygmoCor, AtCor Medical, Sydney, Australia) and ischemic stroke was classified according to the Trial of Org 10172 in the Acute Stroke Treatment (TOAST) classification system. A total of 189 patients were enrolled. The most frequent stroke subtype was lacune (76, 40.2%), followed by stroke of undetermined etiology, negative work-up (SUDn) (59, 31.2%), large artery atherosclerosis (LAA) (31, 16.4%), and cardioembolism (23, 12.2%). While there were no significant differences among the groups for hemodynamic indices, AIx at 75beats per minute (AIx@75) was higher in lacune subtype (29.6%) than SUDn (28.4%), LAA (26.6%), and cardioembolism (24.8%) (p =0.064). The AIx@75 was significantly related to age (r=0.189), sex (r=0.252), peripheral systolic blood pressure (SBP) (r=0.189), peripheral diastolic blood pressure (DBP) (r=0.191), and peripheral mean arterial pressure (MAP) (r=0.327). Multiple linear regression analysis revealed that age, sex, peripheral SBP, peripheral DBP and peripheral MAP were significant (p <0.002). This study showed that arterial stiffness is increased in acute lacunar infarction. Considering the pathogenesis of lacunar infarction and the potential interconnected causes of arterial stiffness, our findings indicate that increased arterial stiffness in acute lacunar infarction may be related to the pathogenesis of lacunar infarction. [Copyright &y& Elsevier]

Abstract: Background: We investigated a method for assessing early improvement and predictive factors of early and late outcomes in patients receiving thrombolytic therapy. Methods: A total of 160 consecutive patients who received thrombolytic therapy were included in the study. Using National Institutes of Health Stroke Scale (NIHSS) scores, percent improvement [(baseline NIHSS score−24-hour NIHSS score)/baseline NIHSS score×100] was calculated and compared with delta (baseline NIHSS score−24-hour NIHSS score) and with major neurological improvement (MNI, NIHSS score of 0–1 or ≥8 point improvement at 24 h) by receiver operating characteristic (ROC) curve analysis. Finally, we investigated the independent predictors of improvement at 24 h after the thrombolytic therapy and of favorable 3-month outcome (modified Rankin scale score 0–2). Results: By pairwise comparison of ROC curves, percent improvement was stronger than delta (p =0.004) and MNI (p <0.001) in predicting long-term outcome. First day improvement (FDI), defined as greater than 20% improvement, was a strong predictor of favorable 3-month outcome (OR 12.55, 95% CI 5.41–29.10). Recanalization (OR 3.30, 95% CI 1.28–8.45), absence of carotid T occlusion (OR 0.09, 95% CI 0.02–0.42) and hemorrhagic transformation (OR 0.25, 95% CI 0.09–0.73) were independent predictors of FDI. Independent predictors of favorable 3-month outcome were FDI, current smoking, absence of carotid T occlusion and hemorrhagic transformation. Conclusions: Percent improvement at 24 h after thrombolytic therapy is a useful surrogate marker for predicting the long-term outcome. Our findings highlight the importance of early stroke management. [Copyright &y& Elsevier]