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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.

Introduction: Suboptimal sleep duration and poor sleep quality have been proposed to increase stroke risk. However, their significance in young ischemic stroke is unclear. We aimed to investigate the importance of sleep duration and quality on young ischemic stroke patients., Methods: A multicenter matched case-control study was performed to evaluate under-recognized risk factors in young (&lt;45 years) ischemic stroke patients in 8 tertiary hospitals in Korea. A total of 225 patients and 225 age- and sex-matched controls were enrolled in the same period. Detailed information about patients' demographics, socioeconomic state, and traditional and nontraditional risk factors including sleep-related factors were obtained using structured questionnaires. Risk of ischemic stroke was estimated using conditional logistic regression analysis., Results: Although average sleep duration was similar in patients and controls, patients were more likely to have long (≥9 h) or extremely short (&lt;5 h) sleep durations. In addition, the proportion of subjects with dissatisfaction with sleep quality was higher in patients than controls (66.2 vs. 49.3%, p &lt; 0.001). In multivariable conditional logistic regression analysis, long sleep duration (OR: 11.076, 95% CI: 1.819-67.446, p = 0.009) and dissatisfaction with sleep quality (OR: 2.116, 95% CI: 1.168-3.833, p = 0.013) were independently associated with risk of ischemic stroke., Conclusions: Long sleep duration and dissatisfaction with sleep quality may be associated with increased risk of ischemic stroke in young adults. Improving sleep habit or quality could be important for reducing the risk of ischemic stroke., (© 2023 S. Karger AG, Basel.)

Purpose: The aim of this study is to investigate the effect of gradual dipyridamole titration and the incidence of dipyridamole-induced headache in patients with ischemic stroke or transient ischemic attack (TIA)., Methods: A randomized, double-blind, double-placebo, parallel group, phase 4 clinical trial (KCT0005457) was conducted between July 1, 2019, and February 25, 2020, at 15 medical centers in South Korea. The study included patients aged >19 years diagnosed with a noncardioembolic ischemic stroke or TIA within the previous 3 weeks. The participants were randomized 1:1:1 to receive Adinox® (aspirin 25 mg/dipyridamole 200 mg) and aspirin (100 mg) once daily for the first 2 weeks followed by Adinox® twice daily for 2 weeks (titration group), Adinox® twice daily for 4 weeks (standard group), and aspirin 100 mg once daily for 4 weeks (control group). The primary endpoint was incidence of headache over 4 weeks. The key secondary endpoint was mean cumulative headache., Results: Ninety-six patients were randomized into the titration (n = 31), standard (n = 32), and control (n = 33) groups. The titration and standard groups (74.1% vs. 74.2%, respectively) showed no difference in the primary endpoint. However, the mean cumulated headache was significantly lower in the titration group than in the standard group (0.31 ± 0.46 vs. 0.58 ± 0.51, p = 0.023). Further, adverse drug reactions were more common in the standard group than in the titration group (28.1% vs. 9.7%, respectively, p = 0.054), although not significantly different., Conclusion: The titration strategy was effective in lowering the incidence of cumulative dipyridamole-induced headache., (© 2022 S. Karger AG, Basel.)

Background and Purpose: Antiphospholipid syndrome (APS) is one of the uncommon causes of ischemic stroke, and is associated with young and female patients. However, the significance of antiphospholipid antibody (aPL) in older ischemic stroke patients is uncertain. We aimed to examine the significance of aPLs in ischemic stroke in these older patients., Materials and Methods: A total of 739 patients with acute ischemic stroke within 7 days of initial symptoms were collected consecutively. Clinical and laboratory data were obtained from medical records. aPLs (lupus anticoagulant, anti-cardiolipin antibody, anti-β2glycoprotein-I antibody) were measured the day after admission and the presence of at least one antibody was regarded as positive aPL. Patients with positive aPL were rechecked after at least 12 weeks for confirmation of APS., Result: Of the 739 patients, 103 (13.9%) had at least one aPL initially. These patients were older, had more atrial fibrillation and higher levels of inflammatory markers. Among the 103 aPL positive patients, 41 remained positive at 3 months, 23 showed negative conversion, and 39 were not available for follow-up. Patients diagnosed with APS had higher numbers of aPL and had specifically anti-β2glycoprotein-I IgG antibody. The patients with aPLs did not differ significantly from the others in terms of stroke subtype., Conclusion: aPL was rather common in ischemic stroke patients regardless of age. Although the influence of transient positive aPL on ischemic stroke remains uncertain, two or more aPLs and the presence of anti-β2glycoprotein-I IgG may predict a diagnosis of APS.

• Microglia are activated after ischemic stroke and sTREM2 levels are considered to reflect the activation of microglia. • Early increment of sTREM2 and late decrement of sTREM2 were more common in patients with poor outcome after ischemic stroke. • Early increment of sTREM2 were independently associated with poor outcome after ischemic stroke. Soluble triggering receptor expressed on myeloid cells 2 (sTREM2) is derived from cleavage of TREM2, which is expressed on the cell surface of microlgia and other tissue-specific macrophages. In the present study, the changes in the sTREM2 levels after ischemic stroke (IS) and their association with clinical outcomes were evaluated. A total of 43 patients diagnosed with non-cardioembolic IS between June 2011 and May 2014 were consecutively included in this study. Patients treated with intravenous thrombolysis or intra-arterial thrombectomy were excluded. Plasma samples were collected three times (days 1, 7, and 90) after ictus. The sTREM2 level was measured in the samples using the highly sensitive solid-phase proximity ligation assay (SP-PLA). Among the 43 subjects, higher initial NIH stroke scale (NIHSS) score (P = 0.005), early increment of sTREM2 (P < 0.001), and late decrement of sTREM2 (P = 0.002), were more common in patients with poor outcome. Based on multivariate analysis, initial NIHSS score (P = 0.015) and early increment of sTREM2 (P = 0.032) were independently associated with poor outcome. The results from the present study indicate that increment of sTREM2 level at the early phase was a predictor of poor outcome. Serial follow-up of sTREM2 may aid prognosis after stroke. [ABSTRACT FROM AUTHOR]

Ischemic stroke during nocturnal sleep, known as wake-up stroke (WUS), has been reported to have more severe symptoms and worse outcomes than non-WUS. However, studies on risk factors for WUS are scarce and the association between nocturnal blood pressure (BP) and WUS is unclear. In this study, we used ambulatory blood pressure monitoring (ABPM) to examine the association between WUS and variation in nocturnal BP. A total of 369 patients with ischemic stroke within one week were consecutively enrolled. ABPM was applied 1–2 weeks after the ictus because of possible reactive increments of BP; antihypertensive medications were delayed until ABPM. Patients were classified into two groups: WUS and non-WUS. Clinical characteristics, including ABPM parameters, were compared. Sixty-seven (18%) patients had WUS. In univariate analysis, patients with WUS had more severe stroke symptoms than patients with non-WUS. There were no differences in clinical characteristics. In addition, ABPM parameters, including nocturnal BP dipping and morning BP surge, were not associated with occurrence of WUS. Patients with WUS had more severe stroke symptoms and worse outcomes than those with non-WUS. Variation in nocturnal BP may not associated with the occurrence of WUS. [ABSTRACT FROM AUTHOR]

BACKGROUND White matter lesions (WMLs) are a common finding in stroke patients, and the most important risk factors are old age and hypertension. Although many studies have described the association between WMLs and ambulatory blood pressure monitoring (ABPM) parameters in healthy subjects and hypertensive patients, little is known about the association in hypertensive ischemic stroke patients. METHODS From July 2009 to June 2012, 169 consecutive hypertensive noncardioembolic ischemic stroke patients were recruited within 1 week of suffering a stroke, and ABPM was applied 1 or 2 weeks after stroke onset. The subjects were classified into 2 groups according to the presence of advanced WMLs, and their ABPM parameters were compared. Finally, multivariable logistic regression analyses were performed to investigate the independent relationships between WMLs and ABPM parameters. RESULTS Seventy (41%) patients had advanced WMLs. In univariable analysis, higher 24-hour, awake, and asleep systolic blood pressure (SBP)/diastolic blood pressure levels and 24-hour pulse pressure were associated with advanced WMLs. However, circadian blood pressure parameters such as 24-hour BP variability, morning surge, and nocturnal dipping pattern were not associated with advanced WMLs. After adjustments, old age (odds ratio (OR) = 1.063; 95% confidence interval (CI) = 1.024–1.104; P = 0.002), high 24-hour SBP levels (OR = 1.055; 95% CI = 1.028–1.082; P < 0.001), and high 24-hour heart rate (OR = 1.041; 95% CI = 1.006–1.078; P = 0.023) were independently associated with advanced WMLs. CONCLUSIONS In addition to old age and elevated 24-hour SBP, increased heart rate is associated with advanced WMLs in ischemic stroke patients. Heart rate deserves more attention in predicting advanced WMLs in those patients. [ABSTRACT FROM PUBLISHER]

Background: Stromal cell-derived factor-1α (SDF-1α) provides neurotrophic support to neurons. In this prospective study, we investigated the association between SDF-1α and long-term outcome in patients with acute ischemic stroke. Methods: This study included 104 patients with first-ever ischemic stroke, identified within 24 h of symptom onset. Serum samples were collected immediately after admission and 3 months thereafter, as well as from age- and sex-matched normal controls. The correlation between acute-stage serum SDF-1α and stroke severity were analyzed. Finally, the relationship between serum SDF-1α and long-term outcome was evaluated by multivariate analysis. Results: Serum SDF-1α levels were only higher in acute-stage stroke patients compared with the normal control group (p = 0.011). The serum SDF-1α level was increased in proportion to infarct volume (r = 0.220, p = 0.025) and initial National Institutes of Health Stroke Scale score (r = 0.275, p = 0.005). After adjustment for covariates, a high initial serum SDF-1α level (OR 1.167, p = 0.023) or second and third tertiles of SDF-1α level compared to first tertile (OR 4.644, p = 0.044 and OR 9.396, p = 0.025, respectively) were significantly associated with a favorable long-term outcome. Conclusions: This prospective study demonstrated a correlation between serum SDF-1α and favorable long-term outcome in patients with acute ischemic stroke. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background Regulatory T cells (Tregs) are thought to play a modulatory role in immune responses and to improve outcomes after ischemic stroke. Thus, various strategies for increasing Tregs in animal models of ischemic stroke have yielded successful results. The aim of this study was to examine the potential effect of poly (ADP-ribose) polymerase-1 (PARP-1) inhibitor on Treg proportion in stroke patients. Methods Peripheral blood samples were collected from 12 ischemic stroke patients (within 72 h of stroke onset) and 5 healthy control subjects. Flow cytometry analyses and quantitative reverse transcription polymerase chain reactions (qRT-PCR) were performed on peripheral blood mononuclear cells (PBMCs) before and after treating them with PARP-1 inhibitor (3-AB; JPI-289 1 μm, JPI-289 10 μm) for 24 h. Results Treg proportions were significantly higher in healthy controls (median 2.8%, IQR 2.6–5.0%) than ischemic stroke patients (median 1.6%, IQR 1.25–2.2%) ( p  < 0.001). In the latter, Treg proportions were positively correlated with age (r = 0.595, p  = 0.041), but not with infarct volume (r = 0.367, p  = 0.241). After PARP-1 inhibitor treatment, Treg proportions among PBMCs increased in response to high dose (10 μm) JPI-289 (median 2.3%, IQR 2.0–2.9%) as did Treg-associated transcription factors such as FoxP3 and CTLA-4 mRNA. PARP-1 inhibitor treatment also decreased pro-inflammatory cytokines (IFN-γ, TNF-α, and IL-17) and increased anti-inflammatory cytokines (IL-4, IL-10, and TGF-β1). Conclusion Treg proportions are reduced in ischemic stroke patients and increased by treatment with high-dose PARP-1 inhibitor JPI-289. The PARP-1 inhibitor also had a possible anti-inflammatory effect on cytokine levels, and may ameliorate the outcome of ischemic stroke by up-regulating Tregs. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Intracranial atherosclerosis (ICAS) is a major cause of ischemic stroke; however it is rather neglected. Vessel wall visualization by high resolution magnetic resonance imaging (HRMRI) might provide more accurate information. Methods: A total of 219 consecutive patients with acute ischemic stroke underwent MRI, MRA and proton-density weighted HRMRI. Using HRMRI, the patients were divided into 3 groups with respect to basilar plaques: no plaque (n = 85), minimal plaque (n = 72) and apparent plaque (n = 62). Demographics and characteristics were compared between the groups, and the extents of stenoses calculated from MRA versus HRMRI data were also compared. Factors potentially associated with basilar plaque were validated by multivariate analysis. Results: Patients with apparent plaque had higher frequencies of diabetes mellitus, lower high-density lipoprotein and higher hemoglobin A1c, erythrocyte sedimentation rate and homocysteine. Of the 62 cases of apparent plaque, severe stenosis (>50%) was observed in 10 (16%) by MRA and in 27 (43%) by HRMRI, which points to overestimation of plaques by HRMRI. In addition, no stenosis was evident on MRA in 13 patients with apparent plaque even though they had up to 72% stenosis on HRMRI. After adjusting for covariates, basilar artery apparent plaque was independently associated with old age, previous stroke, diabetes mellitus, low HDL and high levels of homocysteine. Conclusions: Basilar artery stenosis with plaque is more accurately detected using HRMRI than MRA. In addition, the associated risk factors differ somewhat. The use of HRMRI for evaluating ICAS deserves more attention. [Copyright &y& Elsevier]

Abstract: Evidence suggesting an association between n-3 polyunsaturated fatty acids (PUFA) and stroke risk has been inconsistent, possibly because previous studies have not differentiated between different stroke types. The present study investigated the hypothesis that tissue levels of n-3 PUFA are positively associated with hemorrhagic stroke and negatively associated with ischemic stroke. We recruited 120 subjects for this case-control study, with 40 cases each of hemorrhagic stroke, ischemic stroke, and unaffected controls. Patients with a family history of hemorrhagic stroke had a significantly increased risk for hemorrhagic stroke. Omega-3 Index (20:5n3 + 22:6n3 in erythrocytes) and 22:6n3 were negatively (P < .01) associated with the risk of both hemorrhagic and ischemic stroke in multivariate analyses. Saturated fatty acids 16:0 and 18:0 were positively associated, whereas 18:2n6 and 18:3n6 were negatively (P < .05) associated with risk of ischemic stroke. Monounsaturated fatty acid, 18:1n9, increased (P = .03) the odds of hemorrhagic stroke. Omega-3 Index and docosahexaenoic acid were significantly lower in patients with both subtypes of hemorrhagic stroke, subarachnoid and intracerebral hemorrhage, but only in one subtype of ischemic stroke, small-artery occlusion. Saturated fatty acids 16:0 and 18:0 were significantly higher, but 20:4n6 was significantly lower, in patients with small-artery occlusion. Linoleic acid was significantly lower in patients with small-artery occlusion and large-artery atherosclerosis, whereas 18:1n9 was higher in both subgroups of hemorrhagic stroke. In conclusion, the results of our case-control study suggest that erythrocyte n-3 PUFA may protect against hemorrhagic stroke and ischemic stroke, particularly in the case of small-artery occlusion. [Copyright &y& Elsevier]