Search

Background: Prehospital stroke triage scales help with the decision to transport patients with suspected stroke to suitable hospitals., Objective: To explore the effect of the region-wide use of the Japan Urgent Stroke Triage (JUST) score, which can predict several types of stroke: large vessel occlusion (LVO), intracranial hemorrhage (ICH), subarachnoid hemorrhage (SAH), and cerebral infarction other than LVO (CI)., Methods: We implemented the JUST score and conducted a retrospective and prospective multicenter cohort study at 13 centers in Hiroshima from April 1, 2018, to March 31, 2020. We investigated the success rate of the first request to the hospital, on-scene time, and transport time to hospital. We evaluated the door-to-puncture time, puncture-to-reperfusion time, and 90-day outcome among patients with final diagnoses of LVO., Results: The cohort included 5141 patients (2735 before and 2406 after JUST score implementation). Before JUST score implementation, 1269 strokes (46.4%) occurred, including 140 LVO (5.1%), 394 ICH (14.4%), 120 SAH (4.4%), and 615 CI (22.5%). The JUST score was used in 1484 (61.7%) of the 2406 patients after implementation, which included 1267 (52.7%) cases of stroke (186 LVO (7.7%), 405 ICH (16.8%), 109 SAH (4.5%), and 567 CI (23.6%)). Success rate of the first request to the hospital significantly increased after JUST score implementation (76.3% vs 79.7%, p=0.004). JUST score implementation significantly shortened the door-to-puncture time (84 vs 73 min, p=0.03), but the prognosis remained unaltered among patients with acute LVO., Conclusions: Use of prehospital stroke triage scales improved prehospital management and preparation time of intervention among patients with acute stroke., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To determine associations between cerebral microbleed (CMB) burden with recurrent ischemic stroke (IS) and intracerebral hemorrhage (ICH) risk after IS or TIA., Methods: We identified prospective studies of patients with IS or TIA that investigated CMBs and stroke (ICH and IS) risk during ≥3 months follow-up. Authors provided aggregate summary-level data on stroke outcomes, with CMBs categorized according to burden (single, 2-4, and ≥5 CMBs) and distribution. We calculated absolute event rates and pooled risk ratios (RR) using random-effects meta-analysis., Results: We included 5,068 patients from 15 studies. There were 115/1,284 (9.6%) recurrent IS events in patients with CMBs vs 212/3,781 (5.6%) in patients without CMBs (pooled RR 1.8 for CMBs vs no CMBs; 95% confidence interval [CI] 1.4-2.5). There were 49/1,142 (4.3%) ICH events in those with CMBs vs 17/2,912 (0.58%) in those without CMBs (pooled RR 6.3 for CMBs vs no CMBs; 95% CI 3.5-11.4). Increasing CMB burden increased the risk of IS (pooled RR [95% CI] 1.8 [1.0-3.1], 2.4 [1.3-4.4], and 2.7 [1.5-4.9] for 1 CMB, 2-4 CMBs, and ≥5 CMBs, respectively) and ICH (pooled RR [95% CI] 4.6 [1.9-10.7], 5.6 [2.4-13.3], and 14.1 [6.9-29.0] for 1 CMB, 2-4 CMBs, and ≥5 CMBs, respectively)., Conclusions: CMBs are associated with increased stroke risk after IS or TIA. With increasing CMB burden (compared to no CMBs), the risk of ICH increases more steeply than that of IS. However, IS absolute event rates remain higher than ICH absolute event rates in all CMB burden categories., (© 2016 American Academy of Neurology.)

Background: Few studies have examined the prevalence of peripheral arterial disease (PAD) with the use of computed tomography angiography (CTA) in patients with acute ischemic stroke (AIS), although several reports have examined its prevalence using an ankle brachial index (ABI). We aimed to determine the prevalence of PAD indicated by CTA in patients with AIS and to clarify the prevalence of PAD in each clinical ischemic stroke subtype., Methods: We included 199 consecutive patients with AIS admitted to our hospital and divided them into PAD and non-PAD groups according to the CTA findings., Results: Of the 199 patients, 40 (20.1%) had PAD; 27 (67.5%) of the PAD patients were asymptomatic. The prevalence of abnormal ABI (≤.9) was 12.2%. Patients with PAD were older (78.3 ± 10.2 versus 71.5 ± 10.9, P <.001) and had a significantly lower ABI value (.89 ± .24 versus 1.15 ± .09, P <.001) and higher prevalence of diabetes mellitus (50.0% versus 31.4%, P = .028), atrial fibrillation (40.0% versus 16.4%, P = .001), coronary artery disease (32.5% versus 8.2%, P <.001), and intracranial arterial stenosis (47.5% versus 28.9%, P = .025) than patients without PAD. The prevalence of cerebral microbleeds was not different between patients with PAD and those without PAD (25.6% versus 25.4%, P = .985). The prevalence of PAD among ischemic stroke subtypes was highest in patients with cardioembolic infarction (40.5%)., Conclusions: Almost one fourth of the AIS patients examined had PAD on CTA. Cardioembolic infarction patients showed the highest prevalence of PAD among the clinical ischemic subtypes, suggesting the coexistence of atheromatous diseases and atrial fibrillation., (Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Antiplatelet therapy (APT) plays an important role in the prevention of ischaemic stroke (IS). Our aim was to assess the influence of short-term single APT (SAPT) and dual APT (DAPT) on the prognosis of patients with acute IS with and without cerebral microbleeds (CMBs). We conducted a single-centre, retrospective, observational cohort study of patients with acute IS who underwent susceptibility-weighted imaging (SWI) to determine the presence of CMBs between January 2015 and December 2020. The patients were treated with either DAPT or SAPT and followed up for at least 2 years. The primary endpoint was a composite of recurrent IS and intracerebral haemorrhage (ICH), while either recurrent IS or ICH was considered as other endpoints. We computed weighted Kaplan-Meier curves and identified risk factors using the Cox proportional hazards model. Among the 581 enrolled patients, those with CMBs (n = 225; P = 0.004) had a higher risk of the primary endpoint than those without CMBs (n = 356), especially higher risk of recurrent IS (P = 0.029). In the SAPT group, the presence of CMBs increased the risk of the primary endpoint (P = 0.013), especially that of recurrent IS (P = 0.019). In the DAPT group, the occurrence of ICH was higher in patients with CMBs (P = 0.031). The CMB distribution did not influence the risk of recurrent IS or ICH. In patients with acute IS and CMBs, DAPT may offset the risk of recurrent IS due to CMBs but increase the risk of ICH., (© 2023 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Background: The hyperintense vessel sign (HVS) on fluid-attenuated inversion recovery images can frequently be detected in patients with acute cerebral infarction attributable to large artery stenosis or occlusion. The prognostic values and clinical characteristics of HVS remain to be elucidated. The aim of this study was to evaluate the association of HVS with ischemic lesions and severity of neurologic deficit., Methods: A total of 96 consecutive acute ischemic stroke patients (54 women, median age 76.5 [range 39-97] years), who had symptomatic severe stenosis or occlusion in the proximal middle cerebral artery that was detected with magnetic resonance angiography within 24 hours of onset, were enrolled. The extent of HVS was graded by a systematic quantitative scoring system (the HVS distribution score) based on Alberta Stroke Program Early Computed Tomographic Score., Results: An HVS was detected in 89 patients (93%) at admission, and the patients who displayed wider HVS distribution scores exhibited more severe neurologic deficits at admission (P<.05). The follow-up magnetic resonance imaging, which was obtained in 79 patients (82%), was performed an average of 13 days. The association between HVS distribution score and final ischemic lesions was strongly observed (n=67, P<.05) but not in the patients with intravenous thrombolysis (n=12, P=.06)., Conclusions: Although the distribution of HVS reflected final ischemic lesion, this association might not apply to the patients with the thrombolysis treatment. The interpretation of HVS distribution score with acute ischemic stroke patients should be discussed dependent on thrombolysis., (Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

We herein report two cases of acute ischemic stroke associated with iron deficiency anemia (IDA) due to bleeding from uterine fibroids. Anemia is not generally recognized as a risk factor for stroke. The physiological mechanisms that may factor in the development of ischemic stroke in patients with IDA include thrombocytosis, hypercoagulable state, and anemic hypoxia. In our two cases, IDA was considered to be the cause of ischemic stroke because all other known causes of stroke were ruled out. In patients with ischemic stroke due to anemia, early treatment of the anemia is important to prevent stroke recurrence.

We hypothesized that leukocytes have 2 opposing effects on patients with ischemic stroke treated with recombinant tissue plasminogen activator (rtPA). Patients with ischemic stroke treated with rtPA were divided into 2 groups using the peripheral leukocyte count: high leukocyte group (HLG) and low leukocyte group (LLG) and were evaluated with the National Institutes of Health stroke scale (NIHSS) during the first 24 hours. We defined significant improvement (SI) as NIHSS improving by more than 50% from the baseline, and deterioration following improvement (DFI) as the achievement of SI within 24 hours but its subsequent loss at 24 hours. Fifty-three patients were enrolled, and the rate of SI within 24 hours was higher in HLG than in LLG (85.2% vs 42.3%, P = .0011). However, the rate of DFI was significantly higher in HLG than in LLG (29.6% vs 7.7%, P = .0413). We found that leukocytes might have not only deleterious but also beneficial effects in intravenous rtPA treatment.

Background: Although brain microbleed has been reported to be a risk factor for antiplatelet-associated intracerebral hemorrhage, data on the use of specific antiplatelet agents are lacking. In this study, we examined the associations between specific antiplatelets and brain microbleeds in order to help select antiplatelet agents in patients with microbleeds., Methods: We evaluated 1914 consecutive acute stroke patients, including 412 patients with intracerebral hemorrhage and 1502 patients with ischemic stroke. The associations between the presence of microbleeds and antiplatelet use were evaluated, including specific antiplatelet agents (aspirin, clopidogrel, cilostazol, and ticlopidine)., Results: Antiplatelet use was associated with the presence of microbleeds in patients with intracerebral hemorrhage (odds ratio [OR] 2.418; 95% confidence interval [CI] 1.236-4.730; P = .0099), but not in patients with ischemic stroke. The use of a single antiplatelet medication was not associated with the presence of microbleeds. In patients with intracerebral hemorrhage, aspirin (OR 2.160; 95% CI 1.050-4.443; P = .0364) but not clopidogrel, cilostazol, or ticlopidine was associated with microbleeds. In these patients, dividing brain microbleeds into deep microbleeds and lobar microbleeds revealed an association only between antiplatelet use and the presence of deep microbleeds (OR 2.397; 95% CI 1.258-4.567; P = .0079). None of the antiplatelet agents were associated with the presence of deep microbleeds, although aspirin had a trend of association (OR 1.986; 95% CI 1.000-3.946; P = .0501)., Conclusions: Attention to microbleed-positive patients is necessary for the safe use of aspirin in order to avoid antiplatelet-associated hemorrhages, but prospective studies are needed to verify our results., (Copyright © 2013 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Background and Purpose: Although accumulating evidence suggests the presence of microbleeds as a risk factor for intracerebral hemorrhage (ICH), little is known about its significance in anticoagulated patients. The aim of this study was to determine whether the presence of microbleeds is associated with recurrent hemorrhagic stroke in patients who had received warfarin following atrial fibrillation-associated cardioembolic infarction., Materials and Methods: A total of 87 consecutive patients with acute recurrent stroke, including 15 patients with ICH and 72 patients with cerebral infarction, were enrolled in this study. International normalized ratios (INRs), vascular risk factors, and imaging characteristics, including microbleeds on T2*-weighted MR images and white matter hyperintensity (WMH) on T2-weighted MR images, were compared in the 2 groups., Results: Microbleeds were noted more frequently in patients with ICH than in patients with cerebral infarction (86.7% versus 38.9%, P = .0007). The number of microbleeds was larger in patients with ICH than in patients with cerebral infarction (mean, 8.4 versus 2.1; P = .0001). INR was higher in patients with ICH than in patients with cerebral infarction (mean, 2.2 versus 1.4; P < .0001). The frequency of hypertension was higher in patients with ICH than in patients with cerebral infarction (86.7% versus 45.8%, P = .0039). Multivariate analysis revealed that the presence of cerebral microbleeds (odds ratio, 7.383; 95% confidence interval, 1.052-51.830) was associated with ICH independent of increased INR and hypertension., Conclusion: The presence of cerebral microbleeds may be an independent risk factor for warfarin-related ICH, but more study is needed because of strong confounding associations with elevated INR and hypertension.

Background and Purpose: Previous studies have shown microbleeds to be a risk factor for intracerebral hemorrhage and white matter hyperintensity (WMH) to be a risk factor for ischemic stroke. This study was performed to determine whether combinations of the presence or absence of microbleeds and advanced WMH are risk factors for subsequent recurrent stroke types., Methods: In 266 patients with stroke, microbleeds on T2*-weighted MR images were counted, and WMH on T2-weighted images was graded. Patients were divided into 4 groups by the combinations of the presence or absence of microbleeds and advanced WMH and were followed up for stroke recurrence., Results: During a mean follow-up period of 564.8 +/- 220.5 days, 26 patients developed recurrent strokes, including 10 intracerebral hemorrhages and 16 ischemic strokes. Patients with microbleeds without advanced WMH (n = 42) developed only intracerebral hemorrhages (n = 8), and the recurrence rate of intracerebral hemorrhage in those patients estimated by the Kaplan-Meier method was the highest in the 4 groups (14.3% in 1 year and 21.2% in 2 years). In contrast, patients with advanced WMH without microbleeds (n = 39) developed only ischemic strokes (n = 6), and the estimated recurrent rate of ischemic stroke in those patients was the highest in the 4 groups (10.5% in 1 year and 17.4% in 2 years). Cox proportional hazards regression analysis revealed that microbleeds were associated with intracerebral hemorrhage (hazard ratio [HR], 85.626; 95% confidence interval [CI], 6.344-1155.649) and that advanced WMH was negatively associated with intracerebral hemorrhage (HR, 0.016; 95% CI, 0.001-0.258). Advanced WMH was associated with ischemic stroke (HR, 10.659; 95% CI, 2.601-43.678)., Conclusion: It appears that patients at high risk of subsequent intracerebral hemorrhage or ischemic stroke can be identified by combinations of the presence or absence of microbleeds and advanced WMH.

Both leukoaraiosis and asymptomatic microbleeds are associated with small-artery diseases. Although an association between hyperhomocysteinemia and leukoaraiosis has been reported, no studies have evaluated the association between total homocysteine (tHcy) level and presence of microbleeds in stroke patients. We evaluated the association between tHcy level and leukoaraiosis or microbleeds in stroke patients. In 102 patients with stroke (69.5 +/- 10.3 years old, 54 men and 48 women), microbleeds on T2*-weighted MR images were counted, leukoaraiosis on T2-weighted images was graded and fasting plasma tHcy concentrations were measured. Plasma tHcy level was significantly higher in patients with advanced leukoaraiosis than in those without advanced leukoaraiosis (13.9 +/- 4.6 micromol/l vs. 10.2 +/- 3.4 micromol/l, P < 0.0001). Plasma tHcy level was not significantly different in patients with microbleeds and those without microbleeds (11.3 +/- 4.1 micromol/l vs. 11.4 +/- 4.3 micromol/l, P = 0.9441). Elevated tHcy level is significantly and independently associated with advanced leukoaraiosis [odds ratio (OR), 1.330; 95% CI, 1.130-1.565] but not with the presence of microbleeds. Elevated tHcy level appears to be associated with ischemic small-artery disease rather than with bleeding-prone small-artery disease.

Background and Purpose: Asymptomatic microbleeds shown by T2*-weighted MR imaging are associated with small-artery diseases, especially with intracerebral hemorrhage. Few studies have focused on the prevalence of microbleeds in patients with recurrent stroke. We investigated frequency of microbleeds in patients with recurrent stroke and association of presence of microbleeds with a combination of stroke subtypes and severity of leukoaraiosis., Methods: The study population consisted of 102 patients with primary stroke and 54 patients with recurrent stroke. Microbleeds were counted and classified by using T2*-weighted MR imaging with a 1.0-T system., Results: Patients with recurrent stroke showed a significantly higher prevalence of microbleeds (68.5%) than did patients with primary stroke (28.4%) (P <.0001). Among patients with recurrent stroke, the highest frequency of microbleeds occurred in those with intracerebral hemorrhage alone (92.3%), with the next highest frequency occurring in those with a combination of intracerebral hemorrhage and ischemic stroke (76.5%) and then those with ischemic stroke alone (50.0%) (P <.05). Leukoaraiosis was more severe in patients with recurrent stroke than in patients with primary stroke, and correlations between grade of microbleeds and severity of leukoaraiosis were found in patients with primary stroke (r = 0.367, P <.001) and in patients with recurrent stroke (r = 0.553, P <.0001). Logistic regression analysis identified recurrent stroke (odds ratio, 4.487; 95% confidence interval, 1.989-10.120) and leukoaraiosis (odds ratio, 5.079; 95% confidence interval, 2.125-12.143) as being significantly and independently associated with microbleeds., Conclusion: Asymptomatic microbleeds are observed to occur frequently in patients with recurrent stroke, either hemorrhagic or ischemic stroke, and are closely associated with the severity of leukoaraiosis.

Background and Purpose: The aim was to investigate whether cerebral small vessel disease (CSVD) markers and the total CSVD burden are associated with functional outcome, mortality, stroke recurrence and haematoma expansion in patients with spontaneous intracerebral haemorrhage (ICH)., Methods: Following a previously registered protocol (PROSPERO protocol: CRD42021287743), PubMed, Web of Science and Embase were systematically searched to identify relevant literature up to November 2021. Cohort studies that examined the association between CSVD markers (white matter hyperintensity [WMH], lacune, enlarged perivascular space [EPVS], cerebral microbleed [CMB] and brain atrophy) or CSVD burden and prognosis in patients with ICH were included. The pooled estimates were calculated using random effects models., Results: Forty-one studies with 19,752 ICH patients were pooled in the meta-analysis. WMH (odds ratio [OR] 1.50, 95% confidence interval [CI] 1.32-1.70), lacune (OR = 1.32, 95% CI 1.18-1.49), CMB (OR = 2.60, 95% CI 1.13-5.97) and brain atrophy (OR = 2.22, 95% CI 1.48-3.31) were associated with worse functional outcome. CSVD markers concerning increased risk of mortality were WMH (OR = 1.57, 95% CI 1.38-1.79) and brain atrophy (OR = 1.84, 95% CI 1.11-3.04), and markers concerning increased risk of stroke recurrence were WMH (OR = 1.62, 95% CI 1.28-2.04) and lacune (OR = 3.00, 95% CI 1.68-5.37). Enlarged perivascular space was not related to prognosis. There was a lack of association between CSVD markers and haematoma expansion. CSVD burden increased the risk of worse functional outcome, mortality and stroke recurrence by 57%, 150% and 44%, respectively., Conclusions: In patients with spontaneous ICH, WMH, lacune, CMB, brain atrophy and the total CSVD burden are associated with substantially increased risk of worse functional outcome, mortality or stroke recurrence., (© 2022 European Academy of Neurology.)

White matter lesions have been implicated in the setting of stroke, dementia, intracerebral haemorrhage, several other cerebrovascular conditions, migraine, various neuroimmunological diseases like multiple sclerosis, disorders of metabolism, mitochondrial diseases and others. While much is understood vis a vis neuroimmunological conditions, our knowledge of the pathophysiology of these lesions, and their role in, and implications to, management of cerebrovascular diseases or stroke, especially in the elderly, are limited. Several clinical assessment tools are available for delineating white matter lesions in clinical practice. However, their incorporation into clinical decision-making and specifically prognosis and management of patients is suboptimal for use in standards of care. This article sought to provide an overview of the current knowledge and recent advances on pathophysiology, as well as clinical and radiological assessment, of white matter lesions with a focus on its development, progression and clinical implications in cerebrovascular diseases. Key indications for clinical practice and recommendations on future areas of research are also discussed. Finally, a conceptual proposal on putative mechanisms underlying pathogenesis of white matter lesions in cerebrovascular disease has been presented. Understanding of pathophysiology of white matter lesions and how they mediate outcomes is important to develop therapeutic strategies., (© 2021 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Background: Anticoagulant therapy increases the risk that cerebral microbleeds (CMBs) progress to intracerebral hemorrhage, but whether the therapy increases risk of CMB occurrence is unclear. We performed a systematic review and meta-analysis to investigate the potential association between anticoagulant use and CMB occurrence in stroke and stroke-free individuals., Methods: We searched observational studies in PubMed, Ovid EMBASE, and Cochrane Library from their inception until September 2019. We calculated the pooled odds ratio (OR) and 95% confidence interval (CI) for the prevalence and incidence of CMBs in anticoagulant users relative to non-anticoagulant users., Results: Forty-seven studies with 25,245 participants were included. The pooled analysis showed that anticoagulant use was associated with CMB prevalence (OR 1.54, 95% CI 1.26-1.88). The association was observed in subgroups stratified by type of participants: stroke-free, OR 1.86, 95% CI 1.25-2.77; ischemic stroke/transient ischemic attack, OR 1.33, 95% CI 1.06-1.67; and intracerebral hemorrhage, OR 2.26, 95% CI 1.06-4.83. Anticoagulant use was associated with increased prevalence of strictly lobar CMBs (OR 1.68, 95% CI 1.22-2.32) but not deep/infratentorial CMBs. Warfarin was associated with increased CMB prevalence (OR 1.64, 95% CI 1.23-2.18), but novel oral anticoagulants were not. Anticoagulant users showed higher incidence of CMBs during long-term follow-up (OR 1.72, 95% CI 1.22-2.44)., Conclusion: Anticoagulant use is associated with higher prevalence and incidence of CMBs. This association appears to depend on location of CMBs and type of anticoagulants. More longitudinal investigations with adjustment for confounders are required to establish the causality.

Abstract: For patients with nonvalvular atrial fibrillation (NVAF) following hemorrhagic infarction (HI)/hemorrhage transformation (HT) and complicated with venous thrombosis, the management of anticoagulation is controversial. Our study intends to explore the safety and effectiveness of using low-dose of low molecular weight heparin (LMWH) to treat NVAF patients with HI (or HT) and complicated with venous thrombosis.Between January 2018 and January 2019, NVAF related acute ischemic stroke patients with HT/HI, hospitalized in the department of neurology or rehabilitation in our hospital, are enrolled retrospectively. Among them, those who were found to have venous thrombosis and undergo anticoagulation (LMWH) during the treatment were extracted. We investigate the efficacy and safety in those patients who have been treated with anticoagulant of LMWH.Five cases accepted LMWH within 3 weeks attributed to the appearance of venous thrombosis, and all of them did not display new symptomatic bleeding or recurrent stroke. However, based on the results of a head computed tomography scan, there were 2 cases of slightly increased intracranial hemorrhage, and then we reduced the dose of anticoagulant. In addition, color ultrasound showed that venous thrombosis disappeared or became stable.Patients with NVAF following HI/HT have a higher risk of thromboembolism. Early acceptance of low-dose LMWH as an anticoagulant is relatively safe and may gain benefit. However, in the process of anticoagulant therapy, we should follow-up head computed tomography/magnetic resonance imaging frequently, as well as D-dimer values, limb vascular ultrasound. Besides, the changes of symptoms and signs should be focused to judge the symptomatic bleeding or recurrent stroke. Furthermore, it is better to adjust anticoagulant drug dosage according to specific conditions., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: Although cerebral microbleeds predict the occurrence and recurrence of cerebrovascular events in stroke patients, their clinical impacts are unclear in coronary artery disease patients. We aimed to investigate the clinical effect of the presence of cerebral microbleeds in patients with coronary artery disease receiving antithrombotic treatment., Methods: We included 447 coronary artery disease patients taking at least one thrombotic agent who underwent brain MRI. The association between the presence of cerebral microbleeds and incidence of major adverse cardiac and cerebrovascular events was investigated., Results: Cerebral microbleeds were identified in 18.7% of patients. Median follow-up duration was 1055 (interquartile range, 781-1172) days. Kaplan-Meier survival analysis demonstrated that patients with cerebral microbleeds had a higher incidence of major adverse cardiac and cerebrovascular events than those without (log-rank P = 0.003). A multivariate Cox regression analysis revealed that the presence of cerebral microbleeds was independently correlated with the occurrence of major adverse cardiac and cerebrovascular events after adjusting for other classical risk factors of coronary artery disease (hazard ratio 1.965, 95% confidence interval 1.086-3.556, P = 0.026). Hypertension was associated with the presence of cerebral microbleeds. The cut-off values to maximize the predictive power of SBP and DBP were 132 and 74 mmHg, respectively (P < 0.001)., Conclusion: The presence of cerebral microbleeds predicts major adverse cardiac and cerebrovascular events in coronary artery disease patients receiving antithrombotic treatment. Evaluation of cerebral microbleeds and hypertension treatment complying with the established guidelines may be beneficial in the management of coronary artery disease patients., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Aim: This study aimed to evaluate the associations of blood pressure (BP) variability in patients with ischemic stroke during the subacute phase using ambulatory blood pressure monitoring and the ankle-brachial index (ABI)., Methods: We retrospectively examined 831 consecutive patients (women 44.8%, mean age 76 ± 12 years) with acute ischemic stroke who underwent 24-h ambulatory blood pressure monitoring during the subacute phase of stroke (median 9 days from onset) and an ABI examination. BP variability was evaluated by assessing the standard deviation and coefficient of variation of systolic BP and diastolic BP. A low ABI was defined as an ABI <0.9., Results: Of the 831 patients, 201 (24.2%) had a low ABI. Older age, lower body mass index, diabetes mellitus, chronic kidney disease, atrial fibrillation and a higher National Institutes of Health Stroke Scale score at admission were independently associated with a low ABI. The patients with a low ABI had a higher mean 24-h diastolic BP, higher standard deviation of both BP measurements (systolic BP and diastolic BP) and a higher coefficient of variation in both BP measurements than those with a higher ABI. According to the multivariable linear regression analysis, a low ABI was independently associated with increased BP variability (a high standard deviation or coefficient of variation of both BP measurements) after adjusting for baseline confounders., Conclusions: A low ABI was associated with increased BP variability during the subacute ischemic phase. Geriatr Gerontol Int 2020; 20: 448-454., (© 2020 Japan Geriatrics Society.)

Background and Purpose: Cerebral microbleeds (CMBs) are extravasations of blood from lipohyalinized or amyloid angiopathic cerebral arterioles, and the presence and numbers of CMBs are significantly associated with the development of oral anticoagulation (OA)-related intracranial haemorrhage (ICH). The aim of this study was to investigate whether there is a difference in CMBs burden according to CHADS(2) scores or CHA(2) DS(2) -VASc scores in non-valvular atrial fibrillation (NVAF) patients., Methods: We included 550 ischaemic stroke patients who had NVAF and who had undergone brain magnetic resonance imaging (MRI) with gradient-recalled echo (GRE) T2 sequences from our prospective stroke registry between January 2005 and November 2011. We calculated CHADS(2) scores and CHA(2) DS(2) -VASc scores for all patients based on their underlying cardiovascular diseases. The presence, location and number of CMBs were assessed in each patient. We also investigated whether the CMBs were actually associated with the development of ICH during follow-up., Results: The mean patient age was 70.4 ± 10.5 years, and 324 (58.9%) patients were men. One-hundred and seventy-three patients (31.5%) had CMBs detected on GRE MRI. Higher CHADS(2) scores or CHA(2) DS(2) -VASc scores were strongly associated with the presence and number of CMBs. During follow-up of median 3.1 ± 1.6 years, the presence of CMBs was independently associated with the development of ICH, whilst the CHADS(2) scores or CHA(2) DS(2) -VASc scores were not., Conclusions: Considering the positive association between the presence of CMBs and OA-related ICH, our results suggest that the increase in ICH in high-risk groups during OA may be related to an increased burden of CMBs., (© 2012 The Author(s) European Journal of Neurology © 2012 EFNS.)

Background: Cerebral microbleeds (CMBs), a notable neuroimaging finding often associated with cerebral microangiopathy, demonstrate a heightened prevalence in patients diagnosed with acute ischemic stroke (AIS), which is in turn linked to less favourable clinical prognoses. Nevertheless, the exact prevalence of CMBs and their influence on post-reperfusion therapy outcomes remain inadequately elucidated. Materials and Methods: Through systematic searches of PubMed, Embase and Cochrane databases, studies were identified adhering to specific inclusion criteria: (a) AIS patients, (b) age ≥ 18 years, (c) CMBs at baseline, (d) availability of comparative data between CMB-positive and CMB-negative groups, along with relevant post-reperfusion therapy outcomes. The data extracted were analysed using forest plots of odds ratios, and random-effects modelling was applied to investigate the association between CMBs and symptomatic intracerebral haemorrhage (sICH), haemorrhagic transformation (HT), 90-day functional outcomes, and 90-day mortality post-reperfusion therapy. Results: In a total cohort of 9776 AIS patients who underwent reperfusion therapy, 1709 had CMBs, with a pooled prevalence of 19% (ES 0.19; 95% CI: 0.16, 0.23, p < 0.001). CMBs significantly increased the odds of sICH (OR 2.57; 95% CI: 1.72; 3.83; p < 0.0001), HT (OR 1.53; 95% CI: 1.25; 1.88; p < 0.0001), as well as poor functional outcomes at 90 days (OR 1.59; 95% CI: 1.34; 1.89; p < 0.0001) and 90-day mortality (OR 1.65; 95% CI: 1.27; 2.16; p < 0.0001), relative to those without CMBs, in AIS patients undergoing reperfusion therapy (encompassing intravenous thrombolysis [IVT], endovascular thrombectomy [EVT], either IVT or EVT, and bridging therapy). Variations in the level of association can be observed among different subgroups of reperfusion therapy. Conclusions: This meta-analysis underscores a significant association between CMBs and adverse postprocedural safety outcomes encompassing sICH, HT, poor functional outcome, and increased mortality in AIS patients undergoing reperfusion therapy. The notable prevalence of CMBs in both the overall AIS population and those undergoing reperfusion therapy emphasizes their importance in post-stroke prognostication. [ABSTRACT FROM AUTHOR]

Background: Stroke is a common neurological disorder that disproportionately affects middle-aged and elderly individuals, leading to significant disability and mortality. Recently, human blood metabolites have been discovered to be useful in unraveling the underlying biological mechanisms of neurological disorders. Therefore, we aimed to evaluate the causal relationship between human blood metabolites and susceptibility to stroke. Methods: Summary data from genome-wide association studies (GWASs) of serum metabolites and stroke and its subtypes were obtained separately. A total of 486 serum metabolites were used as the exposure. Simultaneously, 11 different stroke phenotypes were set as the outcomes, including any stroke (AS), any ischemic stroke (AIS), large artery stroke (LAS), cardioembolic stroke (CES), small vessel stroke (SVS), lacunar stroke (LS), white matter hyperintensities (WMH), intracerebral hemorrhage (ICH), subarachnoid hemorrhage (SAH), transient ischemic attack (TIA), and brain microbleeds (BMB). A two‐sample Mendelian randomization (MR) study was conducted to investigate the causal effects of serum metabolites on stroke and its subtypes. The inverse variance-weighted MR analyses were conducted as causal estimates, accompanied by a series of sensitivity analyses to evaluate the robustness of the results. Furthermore, a reverse MR analysis was conducted to assess the potential for reverse causation. Additionally, metabolic pathway analysis was performed using the web-based MetOrigin. Results: After correcting for the false discovery rate (FDR), MR analysis results revealed remarkable causative associations with 25 metabolites. Further sensitivity analyses confirmed that only four causative associations involving three specific metabolites passed all sensitivity tests, namely ADpSGEGDFXAEGGGVR* for AS (OR: 1.599, 95% CI 1.283–1.993, p = 2.92 × 10−5) and AIS (OR: 1.776, 95% CI 1.380–2.285, p = 8.05 × 10−6), 1-linoleoylglycerophosph-oethanolamine* for LAS (OR: 0.198, 95% CI 0.091–0.428, p = 3.92 × 10−5), and gamma-glutamylmethionine* for SAH (OR: 3.251, 95% CI 1.876–5.635, p = 2.66 × 10−5), thereby demonstrating a high degree of stability. Moreover, eight causative associations involving seven other metabolites passed both sensitivity tests and were considered robust. The association result of one metabolite (glutamate for LAS) was considered non-robust. As for the remaining metabolites, we speculate that they may potentially possess underlying causal relationships. Notably, no common metabolites emerged from the reverse MR analysis. Moreover, after FDR correction, metabolic pathway analysis identified 40 significant pathways across 11 stroke phenotypes. Conclusions: The identified metabolites and their associated metabolic pathways are promising circulating metabolic biomarkers, holding potential for their application in stroke screening and preventive strategies within clinical settings. [ABSTRACT FROM AUTHOR]

Over 30 million people suffer from the consequences of ischemic stroke. The precise molecular mechanism of neuronal damage during ischemic stroke remains unclear; therefore, the effective treatment of post‐ischemic stroke remains a critical challenge. Recently, iron has emerged as a crucial factor in post‐reperfusion injuries, participating in cell peroxidation, excitotoxicity, and a distinctive cell death pathway, namely, ferroptosis. Since iron is tightly regulated in the brain and important for brain functions, the imbalance of its metabolism, including its overload and deficiency, has been shown to impact ischemic stroke outcomes. This review summarizes the current understanding of pathological events associated with iron in ischemic stroke and discusses relevant drug development. [ABSTRACT FROM AUTHOR]

Cerebral small vessel disease (CSVD) is a group of pathological processes affecting small arteries, arterioles, capillaries, and small veins of the brain. It is one of the most common subtypes of cerebrovascular diseases, especially highly prevalent in elderly populations, and is associated with stroke occurrence and recurrence, cognitive impairment, gait disorders, psychological disturbance, and dysuria. Its diagnosis mainly depends on MRI, characterized by recent small subcortical infarcts, lacunes, white matter hyperintensities (WMHs), enlarged perivascular spaces (EPVS), cerebral microbleeds (CMBs), and brain atrophy. While the pathophysiological processes of CSVD are not fully understood at present, inflammation is noticed as playing an important role. Herein, we aimed to review the relationship between plasma inflammatory biomarkers and the MRI features of CSVD, to provide background for further research. [ABSTRACT FROM AUTHOR]

Background: Stroke is the second leading cause of death worldwide, causing a considerable disease burden. Ischemic stroke is more frequent, but haemorrhagic stroke is responsible for more deaths. The clinical management and treatment are different, and it is advantageous to classify their risk as early as possible for disease prevention. Furthermore, retinal characteristics have been associated with stroke and can be used for stroke risk estimation. This study investigated machine learning approaches to retinal images for risk estimation and classification of ischemic and haemorrhagic stroke. Study design: A case-control study was conducted in the Shenzhen Traditional Chinese Medicine Hospital. According to the computerized tomography scan (CT) or magnetic resonance imaging (MRI) results, stroke patients were classified as either ischemic or hemorrhage stroke. In addition, a control group was formed using non-stroke patients fromthe hospital and healthy individuals from the community. Baseline demographic and medical information was collected from participants' hospital medical records. Retinal images of both eyes of each participant were taken within 2 weeks of admission. Classification models using a machine-learning approach were developed. A 10-fold cross-validation method was used to validate the results. Results: 711 patients were included, with 145 ischemic stroke patients, 86 haemorrhagic stroke patients, and 480 controls. Based on 10-fold cross-validation, the ischemic stroke risk estimation has a sensitivity and a specificity of 91.0% and 94.8%, respectively. The area under the ROC curve for ischemic stroke is 0.929 (95% CI 0.900 to 0.958). The haemorrhagic stroke risk estimation has a sensitivity and a specificity of 93.0% and 97.1%, respectively. The area under the ROC curve is 0.951 (95% CI 0.918 to 0.983). Conclusion: A fast and fully automaticmethod can be used for stroke subtype risk assessment and classification based on fundus photographs alone. [ABSTRACT FROM AUTHOR]

BACKGROUND: Cerebral microbleeds (CMBs) may increase the risk of future intracerebral hemorrhage and ischemic stroke. However, It is unclear whether antiplatelet medication is associated with CMBs. This study aimed to investigate the association between antiplatelet medication and CMBs in a community-based stroke-free population. METHODS: In this cross-sectional study, stroke-free participants aged 18-85 years were recruited from a community in Beijing, China. Demographic, clinical, and antiplatelet medication data were collected through a questionnaire, and all participants underwent blood tests and brain magnetic resonance imaging at 3.0T. The presence, count, and location of CMBs were evaluated using susceptibility-weighted imaging. The association between antiplatelet medication and the presence of CMBs was analyzed using multivariable logistic regression. The associations between antiplatelet medication and CMBs by location (lobar, deep brain or infratentorial, and mixed regions) were also analyzed using multinomial logistic regression. A linear regression analysis was conducted to determine the association between antiplatelet medication and the log-transformed number of CMBs. RESULTS: Of the 544 participants (mean age: 58.65 ± 13.66 years, 217 males), 119 participants (21.88%) had CMBs, and 64 participants (11.76%) used antiplatelet medication. Antiplatelet medication was found to be associated with CMBs at any location [odds ratio (OR) = 2.39, 95% CI: 1.24-4.58] and lobar region (OR = 2.83, 95% CI: 1.36-5.86), but not with the number of CMBs (β = 0.14, 95% CI: -0.21-0.48). Among antiplatelet medications, aspirin use was found to be associated with any CMB (OR = 3.17, 95% CI: 1.49-6.72) and lobar CMBs (OR = 3.61, 95% CI: 1.57-8.26). CONCLUSIONS: Antiplatelet medication was associated with CMBs in stroke-free participants, particularly lobar CMBs. Among antiplatelet medications, aspirin use was associated with any CMB and lobar CMBs. Our findings suggest that it might be essential to optimize the management of antiplatelet medication in the stroke-free population with a higher burden of vascular risk factors to reduce the potential risk of CMBs. [ABSTRACT FROM AUTHOR]

Background: Hyperintense Acute Reperfusion Marker (HARM) is a hyperintense subarachnoid signal on FLAIR MRI sequence caused by gadolinium contrast leakage into the subpial space. While, on FLAIR, HARM may mimic subarachnoid hemorrhage, it is differentiated from it on computed tomography (CT) and SWAN MRI sequences. Cerebral microbleeds are black, rounded spots on SWAN caused by blood-products deposition following red blood cell leakage from small cerebral vessels brain. Both microbleeds and HARM carry important prognostic implication as they are associated with blood-brain barrier disruption and an increased risk of intracerebral hemorrhage.Case Presentation: A 79-year-old man presented with aphasia and right hemiparesis due to ischemic stroke with left middle cerebral artery occlusion. Admission NIHSS score was 7, and he was successfully treated by intravenous thrombolysis and mechanical thrombectomy. On day 1, his clinical condition worsened, and he had an urgent gadolinium-enhanced MRI. There was no evidence of early recurrence, nor of hemorrhage on SWAN or on FLAIR. Left middle cerebral artery was permeable. The patient was anticoagulated for newly diagnosed atrial fibrillation, and a second MRI following a generalized tonic-clonic seizure showed multiple left hemispheric diffusion-weighted imaging (DWI) hyperintense spots and a left hemispheric sub-arachnoid hyperintensity on FLAIR, compatible with a subarachnoid hemorrhage. This diagnosis was excluded by SWAN MRI sequence and a normal cerebral CT the same day. The diagnosis of HARM was retained. At day 9, patient's condition improved, and a control MRI did not show evidence of HARM. However, numerous microbleeds were detected in the left hemisphere only (ipsilateral with HARM and stroke).Conclusions: This case highlights first of all the importance of differentiating HARM and subarachnoid hemorrhage, especially in an anticoagulated patient with clinical aggravation. Secondly, it is crucial to identify microbleeds and understand their pathophysiology, as they are associated with higher risk of hemorrhage and stroke recurrence in ischemic stroke patients. Finally, the mono-hemispheric appearance of microbleeds in this case suggests for the first time that, in some acute ischemic stroke patients, a relationship between HARM and cerebral microbleeds may exist. [ABSTRACT FROM AUTHOR]

Cerebral microbleeds (CMBs) are associated with an increased risk of ischemic and particularly hemorrhagic stroke and are considered a marker of cerebrovascular disease in cranial magnetic resonance imaging (MRI). Rivaroxaban is a new-generation oral anticoagulant and a direct inhibitor of Factor Xa. In this study, we aimed to evaluate the frequency of CMBs in patients using rivaroxaban to prevent cardiac embolism in non-valvular atrial fibrillation. Seventy-four patients using rivaroxaban and 64 controls were included in the study. The group using rivaroxaban had been using medication for at least 6 months. Susceptibility Weighted Angiography (SWAN) sequence was taken from all participants in a 1.5 Tesla MR device to detect CMBs. In the rivaroxaban group, the frequency of CMBs was significantly higher than the control group (p= 0.028), and it increased with the increasing duration of rivaroxaban use (p=0.005). Also, in the rivaroxaban group, there was the frequency of CMBs in specific areas such as the frontal lobe, basal ganglia, and thalamus compared with the control group participants. Since it is known that presence of CMBs increase the risk of stroke, we conclude that caution should be taken in patients who are on rivaroxaban for prophylaxis of cardiac thromboembolism. However, we also believe that this finding needs to be confirmed in studies including larger patient series. [ABSTRACT FROM AUTHOR]

Intracerebral hemorrhage (ICH) remains a common and debilitating form of stroke. This neurological emergency must be diagnosed and treated rapidly yet effectively. In this article, we review the medical, surgical, repair, and regenerative treatment options for managing ICH. Topics of focus include the management of blood pressure, intracranial pressure, coagulopathy, and intraventricular hemorrhage, as well as the role of surgery, regeneration, rehabilitation, and secondary prevention. Results of various phase II and III trials are incorporated. In summary, ICH patients should undergo rapid evaluation with neuroimaging, and early interventions should include systolic blood pressure control in the range of 140 mmHg, correction of coagulopathy if indicated, and assessment for surgical intervention. ICH patients should be managed in dedicated neurosurgical intensive care or stroke units where continuous monitoring of neurological status and evaluation for neurological deterioration is rapidly possible. Extravasation of hematoma may be helpful in patients with intraventricular extension of ICH. The goal of care is to reduce mortality and enable multimodal rehabilitative therapy. [ABSTRACT FROM AUTHOR]

Objective: This investigation aimed at studying the prevalence of cerebral microbleeds (CMBs), including risk factors and the correlation of CMBs to ischemic stroke (IS) patient end results. Methods: Four hundred and fifty-nine acute IS cases were recruited between April 2014 and December 2016. Cerebral microbleeds were analyzed using susceptibility-weighted imaging (SWI) brain MRI scan. The enrolled patients with acute IS were followed up for 12–24 months, with a median follow-up time of 19 months. The follow-up endpoint events including recurrent ischemic stroke (RIS), intracranial hemorrhage (ICH), transient ischemic attack (TIA), mortality, and cardiovascular events. The associations between vascular risk factors and CMBs in IS patients were analyzed using univariate and multivariate logistic regression analysis. Cox regression model was employed for evaluating CMB impact on clinical outcome. Results: Among 459 enrolled patients, 187 (40.7%) had CMBs and 272 (59.2%) had no CMB. In comparison with patients with no CMBs, age was higher and hypertension was more frequent in patients with CMBs. Multivariate logistic regression analyses revealed age and hypertension were independently associated with the presence of CMBs. Among the patient cohort, 450 cases completed the follow-up. During the follow-up period, 22 (4.9%) of patients developed ICH, 12 (2.7%) developed TIA, 68 (15.1%) developed RIS, cardiovascular events occurred in 20 (4.44%), and 13 (2.89%) cases were mortalities. Compared with patients without CMBs, IS patients with CMBs have an increased prevalence of ICH (p < 0.05). However, no statistically valid variations regarding other outcome incidences between both groups was identified (p > 0.05). The incidence of ICH was elevated in tandem with elevations in number of CMBs. Following adjusting for age, multivariate Cox proportional-hazards regression analysis revealed that CMBs ≥10 were independent predictors of ICH in acute IS patients. Conclusion: Age and hypertension are independently associated with the presence of CMBs. Intracranial hemorrhage incidence rate was increased with the number of CMBs, and the number of CMBs ≥10 were independent predictors of ICH in acute stroke patients. [ABSTRACT FROM AUTHOR]

The value of fluid-attenuated inversion recovery vascular hyperintensity (FVH)-diffusion-weighted imaging (DWI)mismatch in predicting outcome with acute stroke is unclear. We assessed the association between FVH-DWI mismatch and functional outcome in patients with acute stroke patients receiving endovascular therapy. FVH-DWI mismatch, DWI volume, the functional outcome at 3 months (modified Rankin scale; mRS) and other clinical data were collected for 59 acute stroke patients receiving MRI within 6 h before endovascular therapy. Statistical analysis was performed to predict functional outcome after stroke. Patients with FVH-DWI mismatch (n = 39) had a higher FVH score (p = 0.038), smaller DWI volume (p = 0.007), higher American Society of Interventional and Therapeutic Neuroradiology (ASITN) (p = 0.043), higher interval time of ASITN (p = 0.038), and better functional outcome (p = 0.010) than patients with no FVH-DWI mismatch (n = 20). The good functional outcome group (n = 32) had a higher FVH score (p = 0.028), smaller DWI volume (p = 0.003) and higher ASITN grade (p = 0.043) than the poor functional outcome group (n = 27). Multivariable logistic analysis demonstrated that DWI volume (OR, 1.031; 95% CI, 1.005–1.058; P = 0.021) and FVH-DWI mismatch (OR, 14.311; 95% CI, 2.670–76.703; P = 0.002) were independently associated with functional outcome. Assessing DWI volume and FVH-DWI mismatch in acute stroke patients might be useful for predicting functional outcome after stroke. [ABSTRACT FROM AUTHOR]

Cerebral microbleeds (CMBs) are very frequent diagnoses with MRI imaging in the elderly or in patients with cerebral infarction, intracranial hemorrhage (ICH), and dementia. The mechanisms for CMBs are not fully understood but may be secondary to injury to the vascular wall from long-standing hypertension or amyloid deposition in the tissue. The presence of CMB increases the risk for stroke, dementia, and death. The increasing number of CMBs is also associated with a higher risk of hemorrhagic complications with the long-term use of anticoagulants in atrial fibrillation and in patients requiring thrombolysis for acute stroke. The presence of CMBs is however not a contraindication for anticoagulation or thrombolysis as was recently shown from the results of the CROMIS-2 study. This review will summarize our current understanding of the natural history of CMBs and offer suggestions on the best management in common clinical settings. [ABSTRACT FROM AUTHOR]

Purpose: Fluid-attenuated inversion recovery vascular hyperintensity (FVH) is frequently found in stroke patients after intracranial arterial occlusion, but the prognostic value of FVH findings is unclear. We assessed whether FVH is associated with cerebral collateral status and functional outcome in patients with acute stroke patients receiving endovascular therapy.Methods: FVH score, American Society of Interventional and Therapeutic Neuroradiology (ASITN) grade, the functional outcome at 3 months (modified Rankin Scale (mRS)), and other clinical data were collected for 37 acute stroke patients with large vessel occlusion (LVO) receiving MRI before and after endovascular therapy. Statistical analysis was performed to predict functional outcome after stroke.Results: The good functional outcome group (n = 16) had a higher FVH1 (FVH before therapy) score (4.63 ± 1.20 vs 3.14 ± 1.15; p = 0.001) and ASITN grade (3.31 ± 0.48 vs 2.00 ± 1.22; p < 0.001) and a lower FVH2 (FVH after therapy) score than the poor functional outcome group (n = 21; 0.125 ± 0.50 vs 1.44 ± 2.16; p = 0.030). mRS at 3 months was negatively correlated with FVH1 (r = - 0.525, p = 0.001) and the ASITN grade (r = - 0.478, p = 0.003) and positively correlated with FVH2 (r = 0.376, p = 0.034). FVH1 (OR, 0.085; 95% CI, 0.013-0.577; p = 0.012) and FVH2 (OR, 2.724; 95% CI, 1.061-6.996; p = 0.037) were independently associated with functional outcome in multivariable logistic regression analysis.Conclusions: Assessing FVH before and after therapy in acute stroke patients with LVO might be useful for predicting functional outcome after stroke.Key Points: • Fluid-attenuated inversion recovery vascular hyperintensity is a circular or serpentine brightening in the brain parenchyma or cortical surface bordering the subarachnoid space on MR imaging. • A prospective study showed that fluid-attenuated inversion recovery vascular hyperintensity is associated with cerebral collateral circulation and prognosis. • Fluid-attenuated inversion recovery vascular hyperintensity helps clinicians to predict the prognosis of patients with acute stroke. [ABSTRACT FROM AUTHOR]

Aim: We investigated the long‐term risk of dementia for up to 10 years in patients with stroke and broadened the correlates. Methods: We carried out a case–control study using the Taiwan National Health Insurance Research database in 2000 with a sampled population of 1 million. The study cohort comprised 8236 patients with stroke and no dementia history. We carried out a 1:1 case–control matched analysis on estimated propensity scores. Cox proportional hazards regressions were carried out to estimate the risk of dementia during the 5‐ and 10‐year follow‐up periods. The risk factors were also investigated. Results: The stroke cohort was significantly at more risk of dementia during the 5‐ and 10‐year follow‐up periods, with adjusted hazard ratios 1.87 and 1.53, respectively. The patients with ischemic stroke, transient ischemic attack and intracerebral hemorrhage had a significantly higher risk of dementia after 5 and 10 years, with adjusted hazard ratios of 1.81 and 1.49, 1.92 and 1.61, and 2.14 and 1.61, respectively. The significant risk factors of dementia were age ≥60 years, resident in southern and eastern regions, having low insurance range, and antiplatelet use. Conclusions: Stroke and the subtypes, including ischemic stroke, transient ischemic attack and intracerebral hemorrhage, increase the long‐term risk of dementia. The incidence of post‐stroke dementia increases yearly, but the relative risk decreases gradually. Older adults, residents in southern and eastern regions, having low insurance range and antiplatelet use were prominent risk factors of post‐stroke dementia in Taiwan. Careful management of stroke and risk factors of post‐stroke dementia with long‐term follow up of cognition should be reinforced. Geriatr Gerontol Int 2019; 19: 815–822. [ABSTRACT FROM AUTHOR]

Background: Although subcortical infarction patients sometimes show larger infarction size than the definition of small vessel occlusion (SVO), there are no specific predictors of larger size. The aim of this study was to identify the factors, including magnetic resonance imaging (MRI) and ultrasonographic parameters, to predict larger subcortical infarction. Methods: Consecutive patients with acute supratentorial subcortical infarction were studied. Patients were classified into 2 groups (L: larger group, ≥15 mm and ≥3 slices; S: smaller group, SVO based on the TOAST classification). Clinical information, MRI findings including the presence of microbleeds, and ultrasonography findings were evaluated and compared between the 2 groups. Results: A total of 120 patients (81 male, mean 67 years old) were enrolled. The L group included 22 patients (18%), and the S group had 98 patients (82%). On neuroimaging, microbleeds were seen less frequently in the L group than in the S group (23 vs. 53%, p = 0.017), and peak systolic velocity (PSV) by transcranial color-coded sonography was faster in the L group than in the S group (121 ± 39.8 vs. 83.4 ± 25.4 cm/s, p = 0.002). On multivariate logistic regression analysis, no evidence of microbleeds (OR 4.4, 95% CI 1.41–13.68, p = 0.011) and PSV over 92 cm/s (OR 3.1, 95% CI 1.007–9.719, p = 0.049) were found to be independently associated with larger size. Conclusion: Microbleeds is related to smaller size and middle cerebral artery PSV > 92 cm/s indicate larger size in supratentorial subcortical infarcts. [ABSTRACT FROM AUTHOR]

The transcription factor (TF) Zbtb20 is important for the hippocampal specification and the regulation of neurogenesis of neocortical projection neurons. Herein, we show a critical involvement of the TF Zbtb20 in the neurogenesis of both projection neurons and interneurons of the olfactory bulb during embryonic stages. Our data indicate that the lack of Zbtb20 significantly diminishes the generation of a set of early-born Tbr2+ neurons during embryogenesis. Furthermore, we provide evidence that Zbtb20 regulates the transition between neurogenesis to gliogenesis in cortical radial glial progenitor cells at the perinatal (E18.5) stage. In the adult mammalian brain, Zbtb20 is expressed by GFAP+ neural progenitor cells (NPCs) located in the forebrain neurogenic niche, i.e., the subventricular zone (SVZ) of the lateral ventricles. Upon induction of cerebral ischemia, we found that Zbtb20 expression is upregulated in astrocytic-like cells, whereas diminishing the expression levels of Zbtb20 significantly reduces the ischemia-induced astrocytic reaction as observed in heterozygous Zbtb20 loss-of-function mice. Altogether, these results highlight the important role of the TF Zbtb20 as a temporal regulator of neurogenesis or gliogenesis, depending on the developmental context. [ABSTRACT FROM AUTHOR]

Stroke in young women is commonly cryptogenic or associated with an underlying hypercoagulable state (e.g., hormonal contraception). Paradoxical embolization has been postulated as a potential risk factor for stroke in young adults. Many sources of venous thrombosis leading to paradoxical embolization have been described. There have been few reported cases of uterine enlargement leading to iliac vein compression and paradoxical embolization. We present the case of a young adult woman who had a left middle cerebral artery infarction related to patent foramen ovale and right common iliac vein compression from an enlarged fibroid uterus. [ABSTRACT FROM AUTHOR]

Objectives: To identify differences in clinical characteristics and severity of cerebral small vessel disease (CSVD) including cerebral microbleeds (CMBs), between patients suffering ischemic stroke (IS) or intracerebral hemorrhage (ICH) while taking novel (non‐vitamin K antagonists) oral anticoagulants (NOACs). Methods: Multicenter, prospective, observational cohort study performed at 38 centers between 2012 and 2015. We compared demographics, comorbidity, and functional status (before and after stroke) between NOAC‐IS and NOAC‐ICH patients. Extent of white matter lesions (WML), and location and counts of CMBs were analyzed in a subgroup of patients for whom MRI including hemorrhage‐sensitive sequences was available. Results: A total of 351 patients were included (290 NOAC‐IS, 61 NOAC‐ICH). Functional status was worse in NOAC‐ICH patients before and after stroke. No significant differences were found for demographic variables and cardiovascular comorbidity. In the subgroup with available MRI (n = 116), the proportion of patients with at least one CMB was higher in NOAC‐ICH than in NOAC‐IS (15/19 [79%] vs 36/97 [37%], P < .001), as was the absolute number of CMBs (median 5 [IQR 1‐24] vs 0 [0‐1], P < .001). WML were more extensive in NOAC‐ICH than in NOAC‐IS patients. Adjusted for WML, logistic regression analysis showed higher odds of NOAC‐ICH in patients with CMB than without (OR 5.60 [1.64‐19.14], P = .006). Conclusions: Patients with NOAC‐ICH have similar clinical characteristics but a higher prevalent burden of CSVD compared to NOAC‐IS. The role of neuroimaging in selection of patients for anticoagulation with NOAC requires further investigation in longitudinal studies. [ABSTRACT FROM AUTHOR]

The increasing prevalence of multifocal cerebral microhemorrhages (CMHs, also known as "cerebral microbleeds") is a significant, newly recognized problem in the aging population of the Western world. CMHs are associated with rupture of small intracerebral vessels and are thought to progressively impair neuronal function, potentially contributing to cognitive decline, geriatric psychiatric syndromes, and gait disorders. Clinical studies show that aging and hypertension significantly increase prevalence of CMHs. CMHs are also now recognized by the National Institutes of Health as a major factor in Alzheimer's disease pathology. Moreover, the presence of CMHs is an independent risk factor for subsequent larger intracerebral hemorrhages. In this article, we review the epidemiology, detection, risk factors, clinical significance, and pathogenesis of CMHs. The potential age-related cellular mechanisms underlying the development of CMHs are discussed, with a focus on the structural determinants of microvascular fragility, age-related alterations in cerebrovascular adaptation to hypertension, the role of oxidative stress and matrix metalloproteinase activation, and the deleterious effects of arterial stiffening, increased pulse pressure, and impaired myogenic autoregulatory protection on the brain microvasculature. Finally, we examine potential treatments for the prevention of CMHs based on the proposed model of agingand hypertension-dependent activation of the reactive oxygen species-matrix metalloproteinases axis, and we discuss critical questions to be addressed by future studies. [ABSTRACT FROM AUTHOR]

Rationale: Cerebral microbleeds seen on brain magnetic resonance imaging are markers of small vessel disease, linked to cognitive dysfunction and increased ischemic and hemorrhagic stroke risk. Observational studies suggest that aspirin use may induce cerebral microbleeds, and associated overt intracranial hemorrhage, but this has not been definitively resolved. Aims: ASPREE-NEURO will determine the effect of aspirin on cerebral microbleed development over three years in healthy adults aged 70 years and over, participating in the larger 'ASPirin in Reducing Events in the Elderly (ASPREE)' primary prevention study of aspirin. Sample size: Five hundred and fifty-nine participants provide 75% power (two-sided p value of 0.05) to determine an average difference of 0.5 cerebral microbleed per person after three years. Methods and design: A multi-center, randomized placebo-controlled trial of 100 mg daily aspirin in participants who have brain magnetic resonance imaging at study entry, one and three years after randomization and who undergo cognitive testing at the same time points. Study outcomes: The primary outcome is the number of new cerebral microbleeds on magnetic resonance imaging after three years. Secondary outcomes are the number of new cerebral microbleeds after one year, change in volume of white matter hyperintensity, cognitive function, and stroke. Discussion: ASPREE-NEURO will resolve whether aspirin affects the presence and number of cerebral microbleeds, their relationship with cognitive performance, and indicate whether consideration of cerebral microbleeds alters the risk-benefit profile of aspirin in primary prevention for older people. [ABSTRACT FROM AUTHOR]

Purpose: Prominent hypointense cerebral vessels on susceptibility-weighted imaging (SWI) and the hyperintense vessel sign (HVS) on fluid-attenuated inversion recovery (FLAIR) imaging are considered as markers of compromised tissue perfusion in cerebral ischemia. In this study, we aimed to identify the correlation between HVS on FLAIR and hypointense vessels on SWI, and to determine whether these imaging features provide independent prognostic information in patients with ischemic stroke.Methods: We retrospectively analyzed consecutive ischemic stroke patients with proximal middle cerebral artery (MCA) occlusion who underwent SWI and FLAIR within 24 h of symptom onset. The presence of hypointense vessels on SWI and hyperintense vessels on FLAIR in >4 of 10 slices encompassing the MCA territory were considered to represent prominent hypoperfusion.Results: Among 50 patients, 62% had a prominent HVS on FLAIR and 68% had prominent hypointense vessels on SWI. There was a moderate but significant correlation between the number of slices with HVS on FLAIR and prominent hypointense vessels on SWI (r=0.425, P = 0.002). In multivariate analyses, the prominence of hypointense vessels on SWI, but not HVS on FLAIR, was significantly associated with a higher discharge NIHSS score (P = 0.027), mRS score (P = 0.021), and lesion growth (P = 0.050).Conclusion: The significant, albeit moderate, correlation between markers of compromised tissue perfusion on FLAIR and SWI suggests that these imaging features reflect different but interrelated aspects of cerebral hemodynamics during ischemic stroke. Our findings highlight that while HVS on FLAIR denotes the presence of leptomeningeal collaterals, hypointense vessels on SWI signify the sufficiency of cerebral blood flow at the tissue level and are therefore more critical in terms of prognosis. [ABSTRACT FROM AUTHOR]

Background and Purpose: Hyperintense vessels (HV) detected on fluid-attenuated inversion recovery (FLAIR) in patients with acute ischemic stroke (AIS) indicate cerebral hypoperfusion. However, the clinical meaning of changes in HV is yet to be clarified. Here, we investigated serial changes to HV in patients with AIS who received tissue plasminogen activator (t-PA) therapy. Methods: We studied t-PA patients presenting with HV on FLAIR in the middle cerebral artery territory. Patients underwent brain MRI 1 h before and after t-PA infusion. HV scores (range 1-7) were evaluated according to Alberta Stroke Program Early Computed Tomography Score territories, and then by subtracting HV scores at 1 h after t-PA infusion from those on admission, with a result of >1 defined as decrease in HV score (DHV). Patients were divided into 2 groups based on the presence or absence of DHV. Multivariate logistic regression analysis was conducted to identify variables independently associated with good outcome (modified Rankin Scale score at 90 days after stroke onset of 0-1). Results: A total of 118 consecutive patients were enrolled (73 men; mean age 76 ± 9.7; median initial National Institutes of Health Stroke Scale (NIHSS) 13; median initial HV score 5), of whom 52 (44%) had DHV. Patients with DHV showed a significantly lower NIHSS time course (p < 0.001) and significantly smaller infarct volume time course (p < 0.001) compared to those without DHV. Multivariate analysis showed that DHV was independently associated with good outcome (OR 3.89; 95% CI 1.55-9.77; p < 0.01). The sensitivity and specificity of DHV for good outcome were 70 and 68%, respectively. Conclusion: A DHV on FLAIR predicts good outcome in patients receiving t-PA. [ABSTRACT FROM AUTHOR]

The neurovascular unit, which consists of astrocytic end-feet, neurons, pericytes, and endothelial cells, plays a key role in maintaining brain homeostasis by forming the blood-brain barrier and carefully controlling local cerebral blood flow. When the blood-brain barrier is disrupted, blood components can leak into the brain, damage the surrounding tissue and lead to cognitive impairment. This disruption in the blood-brain barrier and subsequent impairment in cognition are common after stroke and during cerebral amyloid angiopathy and Alzheimer's disease. Matrix metalloproteinases are proteases that degrade the extracellular matrix as well as tight junctions between endothelial cells and have been implicated in blood-brain barrier breakdown in neurodegenerative diseases. This review will focus on the roles of MMP2 and MMP9 in dementia, primarily post-stroke events that lead to dementia, cerebral amyloid angiopathy, and Alzheimer's disease. [ABSTRACT FROM AUTHOR]

The clinical significance of cerebral microbleeds (CMB) in patients hospitalized with atrial fibrillation (AF) and cerebral ischemia is unclear. We aimed to determine the prevalence of CMB in this population and determine the future risk of intracerebral hemorrhage (ICH) and cerebral infarction (CI). The medical records and brain imaging of patients hospitalized with cerebral ischemia due to AF between 2008 and 2011 were reviewed. Followup was obtained through medical record review, mailed survey, and acquisition of death certificates. Prevalence was calculated from those patients with a hemosiderin-sensitive MRI sequence. Recurrent CI and ICH were calculated using Kaplan-Meier curves censored at 3 years. Among 426 patients hospitalized with cerebral ischemia due to AF, 134 had an MRI with hemosiderin-sensitive sequences. The prevalence of CMB was 27.6 %. At 3 years, 90.6 % of CMB-negative patients were overall stroke free (ICH and CI) compared to 78.6 % CMB-positive patients ( p = 0.0591). Only one patient in the CMB-positive group had an ICH distant to the CMB. There was a nonsignificant trend toward higher recurrent CI, recurrent overall stroke rate, and mortality in patients with 5 or more CMB compared to 0-4 CMB. The rate of prospective CI in patients with prior cerebral ischemia due to AF is higher than the rate of ICH in patients with CMB. Further study is warranted to assess larger numbers of patients to determine appropriate antithrombotic use in this high-risk population. [ABSTRACT FROM AUTHOR]

Objectives: To study whether Clopidogrel-Aspirin combined treatment for high risk transient ischaemic attack (TIA) or minor stroke results in increased number of lesions associated with anti-thrombotic cerebral haemorrhage or cerebral micro-bleeds (CMB) than aspirin alone treatment. Methods: The patients recruited in CHANCE test in our hospital participated in this study. We made a comparison between treatments Aspirin-Clopidogrel combined group and the Aspirin alone group in the numbers of CMB and subsequent cerebral haemorrhages. In addition, we analysed the association between the increased numbers of CMB and subsequent intracerebral haemorrhages. All 129 patients with high risk TIA with microbleeds or minor stroke within 24hours after the onset (average age 65.9±9.3, 48.7% were male patients) were divided randomly into two groups: (1) 67 patients were given combination therapy with clopidogrel and aspirin (clopidogrel at an initial dose of 300mg, then 75mg per day for 90days, plus aspirin at a dose of 75mg per day for the first 21days);(2) the rest patients were given aspirin treatment (75mg per day for 90days). All participants received open-label aspirin at a clinician-determined dose of 75-300mg on the first day. Results: The CMB were found in 52.7% of all patients in both groups. There was no siginificant difference between the Aspirin group and the Aspirin-clopidogrel treated group, though the latter showed some slight increase in CMB (Odds ratios (OR)=1.16, 95% confidence intervals (CI) =0.54-2.47, P=0.71). But the numbers of CMB were remarkably associated with the number of primary existing CMB (OR=6.46, 95%CI 2.57-16.23, P<0.001), especially that of primary existing CMB ≥3.In addition, the increasing numbers of CMB associated with primary CMB lesions, which located in corticosubcortical area (CSC) (OR=4.69, 95%CI 1.51-14.53, P=0.007). Conclusions: For the treatment of high-risk TIA or minor stroke patients, the clopidogrel-aspirin treatment did not increase the number of CMB than Aspirin alone. It appears that the extent of CMB was associated with the extent of existing CMB occurred in previous stroke, which was mostly located in cortical, subcortical zone. [ABSTRACT FROM AUTHOR]

Objective Cerebral hemorrhage has been shown to occur in animals experimentally infected with Streptococcus mutans carrying the collagen-binding Cnm gene. However, the relationship between cerebral microbleeds and oral hygiene, with a focus on Cnm gene-positive S. mutans infection, remains unclear. Material and Methods One hundred and thirty-nine subjects participated. The presence or absence of Cnm-positive S. mutans and its collagen-binding activity were investigated using saliva samples, and relationship with cerebral microbleeds detected on MRI investigated, including clinical information and oral parameters. Results Fifty-one subjects were identified as Cnm-positive S. mutans carriers (36.7%), with cerebral microbleeds being detected in 43 (30.9%). A significantly larger number of subjects carried Cnm-positive S. mutans in the cerebral microbleeds (+) group. S. mutans with Cnm collagen-binding ability was detected in 39 (28.1%) of all subjects, and the adjusted odds ratio for cerebral microbleeds in the Cnm-positive group was 14.4. Regarding the presence of cerebral microbleeds, no significant differences were noted in the number of remaining teeth, dental caries, or in classic arteriosclerosis risk factors. Conclusions The occurrence of cerebral microbleeds was higher in subjects carrying Cnm-positive S. mutans, indicating that the presence of Cnm-positive S. mutans increases cerebral microbleeds, and is an independent risk for the development of cerebrovascular disorders. [ABSTRACT FROM AUTHOR]

Background and rationale The increasing use of oral anticoagulants, mostly to prevent ischemic stroke due to atrial fibrillation in an ageing population, has been associated with a fivefold increased incidence of oral anticoagulant-associated intracerebral hemorrhage: a rare, serious, and unpredictable complication. We hypothesize that cerebral microbleeds and other markers of cerebral small vessel disease on magnetic resonance imaging, and genetic polymorphisms (e.g. influencing cerebral small vessel integrity or anticoagulation stability), are associated with an increased risk of oral anticoagulant-associated intracerebral hemorrhage, with potential to improve risk prediction. Aims (1) To determine the incidence, clinical, radiological, and genetic associations of oral anticoagulant-associated intracerebral hemorrhage in a prospective, multicentre cohort study of patients with atrial fibrillation-related ischemic stroke or transient ischemic attack started on oral anticoagulants; (2) To investigate characteristics of oral anticoagulant-associated intracerebral hemorrhage compared with non-oral anticoagulants related intracerebral hemorrhage in a prospective study. Design and methods Study 1: Prospective, multicentre, inception cohort study of 1425 adults started on oral anticoagulants (including vitamin K antagonists and the nonvitamin K oral anticoagulants) after recent ischemic stroke and concurrent atrial fibrillation. Participants will have standardized brain magnetic resonance imaging (including a T2*-weighted gradient-recalled echo sequence) and DNA sample collection at baseline, with two-year follow-up by postal questionnaire and medical records surveillance for symptomatic intracranial hemorrhage, other serious vascular events, and death. We will compare the rates of symptomatic intracranial hemorrhage (primary outcome; subclassified as intracerebral, subdural, extradural, intraventricular), other vascular events, and death (secondary outcomes) in participants with one or more cerebral microbleeds to the rates in those without cerebral microbleeds. Study : Prospective case-control study of oral anticoagulant-associated intracerebral hemorrhage compared with non-oral anticoagulant-associated intracerebral hemorrhage to investigate genetic, clinical, and radiological associations with oral anticoagulant-associated intracerebral hemorrhage. In participants with intracerebral hemorrhage (including at least 300 with oral anticoagulant-associated intracerebral hemorrhage), we will collect a DNA sample, standardized clinical data and routine brain imaging (magnetic resonance imaging or computed tomography), and information on functional outcome. Expected outcomes We will identify the factors associated with increased intracranial hemorrhage risk after oral anticoagulants for secondary prevention after ischemic stroke due to atrial fibrillation. We will determine clinical, radiological and genetic factors, and clinical outcomes associated with oral anticoagulant-associated intracerebral hemorrhage. [ABSTRACT FROM AUTHOR]