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Background: Intracardiac thrombosis is common in transthyretin amyloid cardiomyopathy (ATTR-CM), and patients are at risk for thromboembolic events. However, silent cerebral infarcts and the extent of cerebral small vessel disease in patients with cardiac amyloidosis are unknown. Methods: Thirty-two consecutively selected ATTR-CM patients were prospectively studied by cerebral magnetic resonance imaging (cMRI) and compared with 43 CHA2DS2-VASc-matched controls (Co). Structural clinical standard cMRI sequences and features of cerebral vessel involvement were included and quantified by two board certified neuroradiologists in consensus blinded to clinical status. Group differences were estimated using generalized (logistic) linear regression models adjusting for vascular risk factors based on the CHA2DS2-VASc score. Results: The median CHA2DS2-VASc score was 4 for ATTR-CM and Co (p = 0.905). There were no differences between groups in the frequency of current or former smokers (p = 0.755), body-mass-index > 30 (p = 0.106), and hyperlipidemia (p = 0.869). The number of territorial infarcts (4 vs. 0, p = 0.018) was higher in ATTR-CM compared to Co, as was the mean number of cerebral microbleeds (1.4 vs. 0.3, p ≤ 0.001) and the number of Virchow–Robin spaces (43.8 vs. 20.6, p ≤ 0.001). Lacunar lesion presence was higher in ATTR-CM (6 vs. 2, p = 0.054). CHA2DS2-VASc score, atrial fibrillation, anticoagulation, and the interaction term of CHA2DS2-VASc score and atrial fibrillation did not affect the probability of a territorial ischemic lesion or lacunar lesion in logistic regression modeling. Conclusions: In patients with ATTR-CM free from clinically apparent neurological symptoms, cMRI revealed unreported significant small cerebral vessel disease and territorial ischemia. Our findings may support low thresholds for anticoagulation and cMRI in patients with ATTR-CM. [ABSTRACT FROM AUTHOR]

Background: The predictive value of carotid plaque characteristics for silent stroke (SS) after carotid endarterectomy (CEA) is unclear. Objective: To investigate the associations between carotid plaque characteristics and postoperative SS in patients undergoing CEA. Study Type: Prospective. Population: One hundred fifty‐three patients (mean age: 65.4 ± 7.9 years; 126 males) with unilateral moderate‐to‐severe carotid stenosis (evaluated by CT angiography) referred for CEA. Field Strength/Sequence: 3 T, brain‐MRI:T2‐PROPELLER, T1‐/T2‐FLAIR, diffusion weighted imaging (DWI) and T2*, carotid‐MRI:black‐blood T1‐/T2W, 3D TOF, Simultaneous Non‐contrast Angiography intraplaque hemorrhage. Assessment: Patients underwent carotid‐MRI within 1‐week before CEA, and brain‐MRI within 48‐hours pre‐/post‐CEA. The presence and size (volume, maximum‐area‐percentage) of carotid lipid‐rich necrotic core (LRNC), intraplaque hemorrhage (Type‐I/Type‐II IPH) and calcification were evaluated on carotid‐MR images. Postoperative SS was assessed from pre‐/post‐CEA brain DWI. Patients were divided into moderate‐carotid‐stenosis (50%–69%) and severe‐carotid‐stenosis (70%–99%) groups and the associations between carotid plaque characteristics and SS were analyzed. Statistical Tests: Independent t test, Mann–Whitney U‐test, chi‐square test and logistic regressions (OR: odds ratio, CI: confidence interval). P value <0.05 was considered statistically significant. Results: SS was found in 8 (16.3%) of the 49 patients with moderate‐carotid‐stenosis and 21 (20.2%) of the 104 patients with severe‐carotid‐stenosis. In patients with severe‐carotid‐stenosis, those with SS had significantly higher IPH (66.7% vs. 39.8%) and Type‐I IPH (66.7% vs. 38.6%) than those without. The presence of IPH (OR 3.030, 95% CI 1.106–8.305) and Type‐I IPH (OR 3.187, 95% CI 1.162–8.745) was significantly associated with SS. After adjustment, the associations of SS with presence of IPH (OR 3.294, 95% CI 1.122–9.669) and Type‐I IPH (OR 3.633, 95% CI 1.216–10.859) remained significant. Moreover, the volume of Type‐II IPH (OR 1.014, 95% CI 1.001–1.028), and maximum‐area‐percentage of Type‐II IPH (OR 1.070, 95% CI 1.002–1.142) and LRNC (OR 1.030, 95% CI 1.000–1.061) were significantly associated with SS after adjustment. No significant (P range: 0.203–0.980) associations were found between carotid plaque characteristics and SS in patients with moderate‐carotid‐stenosis. Data Conclusions: In patients with unilateral severe‐carotid‐stenosis, carotid vulnerable plaque MR features, particularly presence and size of IPH, might be effective predictors for SS after CEA. Evidence Level: 2 Technical Efficacy: Stage 2 [ABSTRACT FROM AUTHOR]

Aims Atrial fibrillation (AF) is a risk factor for brain infarction, which can lead to epilepsy. We aimed to investigate whether treatment of AF with direct oral anticoagulants (DOACs) affects the risk of epilepsy in comparison to treatment with the vitamin K antagonist phenprocoumon (PPC). Methods and results We performed an active comparator, nested case-control study based on the German Pharmacoepidemiological Research Database that includes claims data from statutory health insurance providers of about 25 million persons since 2004. In 2011–17, 227 707 AF patients initiated treatment with a DOAC or PPC, of which 1828 cases developed epilepsy on current treatment with an oral anticoagulant. They were matched to 19 084 controls without epilepsy. Patients with DOAC treatment for AF had an overall higher risk of epilepsy with an odds ratio of 1.39, 95% CI (1.24; 1.55) compared to current PPC treatment. Cases had higher baseline CHA2DS2-VASc scores and more frequently a history of stroke than controls. After excluding patients with ischaemic stroke prior to the diagnosis of epilepsy, the risk of epilepsy was still higher on DOACs than on PPC. In contrast, within a cohort of patients with venous thromboembolism, the risk of epilepsy on treatment with DOACs was less elevated [adjusted odds ratio 1.15, 95% CI (0.98; 1.34)]. Conclusion In patients with AF initiating oral anticoagulation, treatment with a DOAC was associated with an increased risk of epilepsy compared to the vitamin K antagonist PPC. Covert brain infarction may explain the observed elevated risk of epilepsy. [ABSTRACT FROM AUTHOR]

The main idea of this article is based on the uncertainty of the current recommendations, according to which a temporary shunt (TS) during carotid endarterectomy (CEE) can be used selectively, routinely, and even completely abandon its use. This statement is supported by the low level of evidence (class B) of the conclusion that indications for the use of TS are established only on the basis of a decrease in retrograde pressure in the internal carotid artery (ICA) and/or indicators of cerebral oximetry. Thus, the low efficiency of these procedures makes it possible not to use them at all.

IntroductionHeart failure (HF) is associated with ischemic stroke (IS). However, there are limited studies on the prevalence of IS, white matter hyperintensities (WMHs), and silent brain infarcts (SBIs). Furthermore, interaction with ejection fraction (EF) is unclear.MethodsWe searched three databases (viz., PubMed, Embase, and Cochrane) for studies reporting the incidence or prevalence of IS, WMHs, and SBIs in HF. A total of two authors independently selected included studies. We used random-effects models, and heterogeneity was evaluated with I2 statistic. Meta-regression was used for subgroup analysis.ResultsIn total, 41 articles involving 870,002 patients were retrieved from 15,267 records. Among patients with HF, the pooled proportion of IS was 4.06% (95% CI: 2.94–5.59), and that of WMHs and SBIs was higher at 15.67% (95% CI: 4.11–44.63) and 23.45% (95% CI: 14.53–35.58), respectively. Subgroup analysis of HFpEF and HFrEF revealed a pooled prevalence of 2.97% (95% CI: 2.01–4.39) and 3.69% (95% CI: 2.34–5.77), respectively. Subgroup analysis of WMH Fazekas scores 1, 2, and 3 revealed a decreasing trend from 60.57 % (95% CI: 35.13–81.33) to 11.57% (95% CI: 10.40–12.85) to 3.07% (95% CI: 0.95–9.47). The relative risk and hazard ratio of patients with HF developing IS were 2.29 (95% CI: 1.43–3.68) and 1.63 (95% CI: 1.22–2.18), respectively. Meta-regression showed IS prevalence was positively correlated with decreasing anticoagulant usage.ConclusionWe obtained estimates for the prevalence of IS, WMH, and SBI in HF from systematic review of the literature.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=255126, PROSPERO [CRD42021255126].

Abstract Background Studies indicate that uninterrupted anticoagulation (UA) is superior to interrupted anticoagulation (IA) in the periprocedural period during catheter ablation of atrial fibrillation. Still IA is followed in many centers considering the bleeding risk. This meta‐analysis compares interrupted and uninterrupted direct oral anticoagulation during catheter ablation of atrial fibrillation. Methods A systematic search into PubMed, EMBASE, and the Cochrane databases was performed and five studies were selected that directly compared IA vs UA before ablation and reported procedural outcomes, embolic, and bleeding events. The primary outcome of the study was major adverse cerebro‐cardiovascular events. Results The meta‐analysis included 840 patients with UA and 938 patients with IA. Median follow‐up was 30 days. Activated clotting time (ACT) before first heparin bolus was significantly longer with UA (P = .006), whereas mean ACT was similar between the two groups (P = .19). Total heparin dose needed was significantly higher with IA (mean, ‒1.61; 95% CI, ‒2.67 to ‒0.55; P = .003). Mean procedure time did not vary between groups (P = .81). Overall complication rates were low, with similar major adverse cerebro‐cardiovascular event (P = .40) and total bleeding (P = .55) rates between groups. Silent cerebral events (SCEs) were significantly more frequent with IA (log odds ratio, ‒0.90; 95% CI, ‒1.59 to ‒0.22; P

Jose-Luis Clua-Espuny,1 Eulalia Muria-Subirats,2 Juan Ballesta-Ors,3 Blanca Lorman-Carbo,4 Josep Clua-Queralt,5 Elena Palà,6 Iñigo Lechuga-Duran,7 Delicia Gentille-Lorente,7 Alejandro Bustamante,8 Miguel Ángel Muñoz,9 Joan Montaner6 On Behalf of the AFRICAT Research Group1EAP Tortosa 1-Est, Institut Català Salut, Servei Atenció Primària, UUDD Terres De l’Ebre. Universidad Rovira I Virgili, Programa Doctorat, Tortosa, Spain; 2EAP Tortosa 1-Est, Institut Català Salut, SAP Terres De l’Ebre, España Universidad Rovira I Virgili. Programa Doctorat, Tortosa, Tarragona, Spain; 3EAP Tortosa 1-Est, Institut Català Salut, SAP Terres De l’Ebre, Universidad Rovira I Virgili. Programa Doctorat. Tortosa, Tarragona, Spain; 4EAP Tortosa 1-Est, Institut Català Salut, SAP Terres De l’Ebre, España Universidad Rovira I Virgili. Programa Doctorat. Tortosa, Tarragona, Spain; 5Universitat De Lleida, Lérida, Spain; 6Neurovascular Research Laboratory, Vall d’Hebron Institute of Research (VHIR)-Universitat Autónoma De Barcelona, Barcelona, Spain; 7Servicio Cardiología, Hospital Virgen De La Cinta, Institut Català Salut Tortosa, Tarragona, Spain; 8Department of Neurology, Hospital Universitari Vall d’Hebron, Barcelona, Spain; 9Institut d’Investigació En Atenció Primària IDIAP Jordi Gol, Unitat De Suport a La Recerca De Barcelona, Barcelona, SpainCorrespondence: Jose-Luis Clua-EspunyEAP Tortosa 1-Est, Institut Català Salut, Servei Atenció Primària, UUDD Terres De l’Ebre. Universidad Rovira I Virgili, Programa Doctorat, CAP Temple, Carrilet Square s/Num. Tortosa, 43500, SpainTel +34 977 510018Fax +34 977 44 57 28Email jlclua@telefonica.netPurpose: To evaluate a model for calculating the risk of AF and its relationship with the incidence of ischemic stroke and prevalence of cognitive decline.Materials and Methods: It was a multicenter, observational, retrospective, community-based study of a cohort of general population ≥ 6ct 35 years, between 01/01/2016 and 31/12/2018. Setting: Primary Care. Participants: 46,706 people ≥ 65 years with an active medical history in any of the primary care teams of the territory, information accessible through shared history and without previous known AF. Interventions: The model to stratify the risk of AF (PI) has been previously published and included the variables sex, age, mean heart rate, mean weight and CHA2DS2VASc score. Main measurements: For each risk group, the incidence density/1000 person/years of AF and stroke, number of cases required to detect a new AF, the prevalence of cognitive decline, Kendall correlation, and ROC curve were calculated.Results: The prognostic index was obtained in 37,731 cases (80.8%) from lowest (Q1) to highest risk (Q4). A total of 1244 new AFs and 234 stroke episodes were diagnosed. Q3-4 included 53.8% of all AF and 69.5% of strokes in men; 84.2% of all AF and 85.4% of strokes in women; and 77.4% of cases of cognitive impairment. There was a significant linear correlation between the risk-AF score and the Rankin score (p < 0.001), the Pfeiffer score (p < 0.001), but not NIHSS score (p 0.150). The overall NNS was 1/19.Conclusion: Risk stratification allows identifying high-risk individuals in whom to intervene on modifiable risk factors, prioritizing the diagnosis of AF and investigating cognitive status.Keywords: vascular risk score, atrial arrhythmia, cerebrovascular disease, silent stroke, cognitive decline

Aim. To analyze inhospital outcomes of carotid endarterectomy (CE) in the acute period (within 3 days from the onset) of ischemic stroke.Material and methods. This retrospective multicenter study for the period from January 2008 to August 2020 included 357 patients who underwent CE in the acute period of stroke. An interdisciplinary commission defined the revascularization timing. There were following inclusion criteria: 1. Mild neurological disorders: NIHSS stroke of 3-8; modified Rankin Scale score 61; 2. Indications for CE according to the current national guidelines; 3. Brain ischemic focus 3b bleeding, internal carotid artery thrombosis, composite endpoint (death + all strokes/TIA + MI). Silent strokes were those strokes, established according to control multi-slice computed tomography angiography, without symptoms.Results. During the in-hospital follow-up period, 8 deaths (2,24%), 5 MIs (1,4%), 6 strokes/TIAs (1,7%), 15 silent ischemic strokes (4,2%), 13 hemorrhagic transformations (3,6%), 26 silent hemorrhagic transformations (7,3%), and 6 BARC type >3b bleeding (1,7%) were recorded. Thus, the combined endpoint was 20,4% (n=73).Conclusion. Due to the high incidence of cardiovascular events, CE is not a safe operation for patients in the acute period of ischemic stroke. The stroke + mortality rate exceeding 3% demonstrates the ineffectiveness of this method of treatment.

Abstract Background Incidentally discovered silent brain infarcts (id-SBIs) are an understudied condition with probable clinical significance, but it is not known how patients respond to or prioritize this condition. We sought to assess reporting of id-SBIs and how patients approach their diagnosis. Methods Patients with id-SBIs were identified from sequential scans between 12/2015–5/2016, were referred by treating clinicians, or self-referred for the study. This study used qualitative semi-structured interviews. Purposeful sampling was used to achieve diversity in acuity, setting, and recruitment strategy. Interviews were audio-recorded and transcribed. A constant comparative method was used to develop a coding schema, find consensus, and iteratively explore emergent themes until thematic saturation was achieved. Results Only 10 of 102 patients prospectively identified by neuroimaging were informed of the imaging findings. Twelve participants in total were interviewed. Among the study participants, the primary themes were cognitive, emotional, and behavioral responses to diagnostic, prognostic, and therapeutic uncertainty regarding id-SBIs. Clinicians described id-SBIs to participants as an ambiguous condition. Participants feared potential consequences of id-SBIs, including symptomatic stroke, dementia, and disability. Participants attempted to reduce uncertainty with strategies including equating id-SBIs with symptomatic stroke, self-education about stroke, and seeking second opinions. Conclusion Participants considered id-SBIs to be a serious medical condition. Ambiguous counseling by clinicians on id-SBIs provoked or failed to attenuate fear, leading to participants adopting strategies aimed at reducing uncertainty.

Background: Studies indicate that uninterrupted anticoagulation (UA) is superior to interrupted anticoagulation (IA) in the periprocedural period during catheter ablation of atrial fibrillation. Still IA is followed in many centers considering the bleeding risk. This meta‐analysis compares interrupted and uninterrupted direct oral anticoagulation during catheter ablation of atrial fibrillation. Methods: A systematic search into PubMed, EMBASE, and the Cochrane databases was performed and five studies were selected that directly compared IA vs UA before ablation and reported procedural outcomes, embolic, and bleeding events. The primary outcome of the study was major adverse cerebro‐cardiovascular events. Results: The meta‐analysis included 840 patients with UA and 938 patients with IA. Median follow‐up was 30 days. Activated clotting time (ACT) before first heparin bolus was significantly longer with UA (P =.006), whereas mean ACT was similar between the two groups (P =.19). Total heparin dose needed was significantly higher with IA (mean, ‒1.61; 95% CI, ‒2.67 to ‒0.55; P =.003). Mean procedure time did not vary between groups (P =.81). Overall complication rates were low, with similar major adverse cerebro‐cardiovascular event (P =.40) and total bleeding (P =.55) rates between groups. Silent cerebral events (SCEs) were significantly more frequent with IA (log odds ratio, ‒0.90; 95% CI, ‒1.59 to ‒0.22; P <.01; I2, 33%). Rates of major bleeding, minor bleeding, pericardial effusion, cardiac tamponade, and puncture complications were similar between groups. Conclusions: UA during atrial fibrillation ablation has similar bleeding event rates, procedural times, and mean ACTs as IA, with fewer SCEs. [ABSTRACT FROM AUTHOR]

Background: The difference in coagulation state during the periprocedural period of atrial fibrillation (AF) ablation among patients with uninterrupted anticoagulation has not been fully elucidated.Objective: The purpose of this study was to compare periprocedural trends in coagulation markers among patients on uninterrupted anticoagulation for AF ablation.Methods: In total, 275 consecutive patients who underwent AF ablation were evaluated. These patients were divided according to the anticoagulant they received into the dabigatran group (DG) (n = 64); rivaroxaban group (RG) (n = 62); apixaban group (AG) (n = 60); edoxaban group (EG) (n = 59); and warfarin group (WG) (n = 30). The trends in coagulation markers and the rate of silent stroke (SS) confirmed by postoperative magnetic resonance imaging were evaluated.Results: The fibrin monomer complex (FMC) level on postoperative day 1 and the prothrombin fragment 1+2 (PF1+2) levels on the operative day and postoperative day 1 were higher in DG than in the other groups (P <.05, <.001, and <.001, respectively). The incidence of SS in DG (17%) was significantly higher than in RG (6%), AG (3%, EG (7%), or WG (4%) (P <.05). Dabigatran use independently predicted the occurrence of SS (odds ratio 4.12; 95% confidence interval 1.37-12.7; P <.05).Conclusion: FMC and PF1+2 levels during the periprocedural period of AF ablation were higher in DG than in the other groups. Dabigatran use independently predicted the occurrence of SS. [ABSTRACT FROM AUTHOR]

Aim: Older patients with bipolar disorder (BD) are at a high risk of stroke. Silent stroke could be neglected in BD patients after middle age, particularly in those with illness onset at the young age. Therefore, we investigated the morbidity and related factors for stroke in older BD patients with typical‐onset age. Methods: Older patients with bipolar I disorder (age > 50 years) and their illness onset prior to the age of 40 years were recruited. After whole‐brain magnetic resonance imaging was conducted, the patients were divided into stroke and non‐stroke groups. Clinical data were obtained by reviewing all available medical records and directly interviewing the patients along with their reliable family members. Results: We recruited 62 patients with a mean age of 60.4 years and illness onset at the mean age of 28.4 years. Cerebral infarction or old stroke was observed in 24 (38.7%) patients, including 22 without any reported clinical history of stroke. That is, silent stroke (n = 22) was detected in 36.7% of 60 patients without clinical history of stroke. The stroke group had significantly higher mean numbers of lifetime mood episodes (P = 0.006) than the non‐stroke one. Logistic regression analysis showed that 10 or more prior mood episodes (odds ratio = 3.43, 95% confidence interval = 1.12–10.47, P < 0·04) was significantly associated with the occurrence of stroke. The two study groups did not exhibit any other differences in demographic and clinical variables, such as age, laboratory or physical measurements during the last acute psychiatric hospitalisation, body mass index, and substance use problems and concurrent medical diseases. Conclusions: High morbidity of stroke, particularly silent stroke, could be found in older bipolar patients with typical‐onset age. In addition to traditional risk factors, the number of recurrent mood episodes in a lifetime may increase the risk of stroke in older BD patients. [ABSTRACT FROM AUTHOR]

Aims: Data on the comparison between uninterrupted and interrupted by one dose strategies for direct oral anticoagulant (DOAC) use during the periprocedural period of atrial fibrillation (AF) ablation are scarce. The purpose of this study is to investigate the feasibility of uninterrupted DOAC strategy by evaluating the incidence of silent stroke (SS) and perioperative trends in coagulation markers compared with the interrupted strategy.Methods and Results: We randomly divided 200 consecutive patients receiving DOACs, who underwent AF ablation into uninterrupted group (UG = 100) and interrupted by one dose group (IG = 100). The rate of SS confirmed by post-operative magnetic resonance imaging and periprocedural trends in coagulation markers was investigated. A significant difference in SS incidence was found between the UG and IG (UG 4%, IG 17%, P < 0.005), although there were no differences in the rate of complications including bleeding and symptomatic thrombo-embolic events between the two groups. Intraoperative cardioversion [odds ratio (OR) 7.27, 95% confidence interval (CI) 1.76-30.0; P < 0.01] and the length of procedure time (OR 1.03, 95% CI 1.01-1.05; P < 0.05) independently predicted the occurrence of SS in the IG. A significant increase in prothrombin fragment 1 + 2 (PF1 + 2) values was observed in the IG compared with the UG on the operative and first post-operative days.Conclusion: Silent stroke incidence in the IG was significantly higher than that in the UG; this seems to be supported by the difference in PF1 + 2 values between the UG and IG. Intraoperative cardioversion and procedure time predicted the occurrence of SS in the IG. [ABSTRACT FROM AUTHOR]

Background: Although several studies have reported an association between parity and increased risk of stroke, this relationship remains controversial.Aims: The present study aimed to determine whether parity is associated with silent brain infarction (SBI), independent of other confounders.Methods: We analyzed the brain magnetic resonance imaging findings in 576 of community-dwelling older adults with a mean age of 72.1 years. All female participants were asked to provide information regarding the total number of live births, their age at the last parity, and their age at menopause.Results: The prevalence of SBI and the number of infarcts per participant were higher in men than in women. Although all women who had given birth (0, 1-2, 3-4, or 5+ times) exhibited lower age-adjusted odds ratios (ORs) for SBI than men, a significant difference was observed between women with ≧5 births and men after adjustment for common vascular risk factors (OR: .348, 95% confidence interval [95% CI]: .123-.986). Among women who had given birth, the relationship between fertility and SBI was attenuated, but was enhanced after adjustment for age at the last parity (OR: .300, 95% CI: .102-.886).Conclusions: Our findings indicate that fertile women may be protected against SBI or cerebral small vessel disease via the biological effects associated with reproductive activity, and that high fertility may be a marker of protection against SBI. However, late childbearing may blunt protective effects of fertility against SBI. [ABSTRACT FROM AUTHOR]

Background: Atrial fibrillation (AF) ablation is associated with a substantial risk of silent cerebral events/lesions (SCEs/SCLs) detected on magnetic resonance imaging (MRI).Objective: The purpose of this study was to investigate the factors associated with the incidence of SCEs/SCLs during second-generation cryoballoon ablation.Methods: Two hundred fifty-six AF patients underwent brain MRI 1 day after pulmonary vein (PV) isolation using second-generation cryoballoons with a single 28-mm balloon and short freeze strategy.Results: Overall, 991 of 1016 PVs (97.5%) were successfully isolated by 4.9 ± 1.3 cryoballoon applications per patient, and 25 PVs required touch-up radiofrequency ablation. The total procedure time was 72.7 ± 26.1 minutes. SCEs and SCLs were detected in 68 (26.5%) and 27 (10.5%) patients, respectively. None of the patients reported any neurologic symptoms. Reinsertion of once withdrawn cryoballoons and subsequent applications significantly increased the incidence of SCEs (odds ratio [OR] 2.057; 95% confidential interval [CI] 1.051-4.028; P = .035), and additional left atrial mapping with a multielectrode catheter significantly increased the incidence of SCLs (OR 3.317; 95% CI 1.365-8.056; P = .008). Transient coronary air embolisms were significantly associated with the incidence of SCLs (OR 3.447; 95% CI 1.015-11.702; P = 0.047). On the contrary, an uninterrupted anticoagulation regimen, use of radiofrequency deliveries for transseptal access, cryoballoon air removal with extracorporeal balloon inflations, strength of the MRI magnet, internal electrical cardioversion, and touch-up ablation were not associated with the incidence of SCEs/SCLs.Conclusion: A significant number of SCE/SCL occurrences was observed after second-generation cryoballoon ablation procedures. These results suggest that air embolisms are the main mechanism of SCEs/SCLs, and the injected air volume might determine the lesion type. [ABSTRACT FROM AUTHOR]

Although in the last few years emerging conventional and unconventional radiological and laboratory techniques have shed light on different pathophysiologic causes of stroke, nowadays almost 25% of ischemic strokes results of undetermined etiology. Different diagnostic criteria have been developed to define cryptogenic stroke and to establish its prevalence in stroke units. Different studies tried to unravel mechanisms of cryptogenic stroke and to evaluate adequate primary and secondary preventive measures, but standardized diagnostic and therapeutic strategies are still missing. In this review we report the most relevant updated notions in cryptogenic stroke providing an overview of the definition, the recommendations for diagnostic evaluation and the updated treatment strategies for secondary prevention.

Low-grade inflammation is implicated in the pathogenesis of atherosclerosis, metabolic syndrome, and apathy as a form of vascular depression. We analyzed the brain magnetic resonance imaging findings in 259 community-dwelling older adults (122 men and 137 women, with a mean age of 68.4 years). The serum concentrations of high-sensitivity C-reactive protein (hsCRP) were measured by a quantitative enzyme-linked immunosorbent assay. Logistic regression analysis revealed that the log10 hsCRP value and the presence of a metabolic syndrome were independently associated with confluent but not punctate deep white matter lesions (DWMLs). Path analysis based on structural equation modeling (SEM) indicated that the direct path from the log10 hsCRP to the DWMLs was significant (β = 0.119, p = 0.039). The direct paths from the metabolic syndrome to the log10 hsCRP and to the DWMLs were also significant. The direct path from the DWMLs to apathy (β = −0.165, p = 0.007) was significant, but the direct path from the log10 hsCRP to apathy was not significant. Inflammation (i.e., elevated serum hsCRP levels) was associated with DWMLs independent of common vascular risk factors, while DWMLs were associated with apathy. The present analysis with SEM revealed the more realistic scheme that low-grade inflammation was associated with apathy indirectly via DWMLs in community-dwelling older adults.

Background and Purpose: The purpose of this study was to determine the complex associations among chronic kidney disease (CKD), subclinical brain infarction (SBI), and cognitive impairment.Methods: We used structural equation modeling (SEM) to examine the complex relationships among CKD, SBI, and cognitive function with Mini-Mental State Examination (MMSE; global function) and modified Stroop test (executive function) in a population-based cohort of 560 non-demented elderly subjects.Results: Path analysis based on SEM revealed that the direct paths from estimated glomerular filtration rate (eGFR) to SBI and from SBI to executive function were significant (β = -.10, P = .027, and β = .16, P < .001, respectively). Furthermore, the direct path from eGFR to executive function was also significant (β = -.12, P = .006), indicating that the effects of CKD on executive function are independent of SBI. The direct paths from age and education to global cognitive function were highly significant (β = -.17 and .22, respectively, P < .001), whereas the direct path from eGFR to MMSE was not significant.Conclusions: Our findings indicate that CKD confers a risk of vascular cognitive impairment or executive dysfunction through mechanisms dependent and independent of SBI. Treating CKD may be a potential strategy to protect against vascular cognitive impairment or executive dysfunction in healthy elderly subjects. [ABSTRACT FROM AUTHOR]

Background and Objective: The silent brain infarctions are common in first-ever stroke. Some recent studies show the possible role of silent brain infarction in ischemic stroke. The aim of this study was to evaluate the frequency of silent brain infarction in acute first-ever ischemic stroke and its association with stroke risk factors. Materials and Methods: This descriptive - analytical study was carried out on 203 (94 males, 109 females) patients with acute first-ever ischemic stroke in Shafa hospital in Kerman, Iran during 2010. The diagnosis of ischemic stroke was made by physical examination and was confirmed by MRI and CT Scan. A questionnaire containing demographic information and risk factors including hypertension, diabetes, hyperlipidemia, cigarette smoking, ischemic and non-ischemic heart disease for stroke as well as presence of silent stroke was completed for each patient. Data were analyzed using SPSS-16 and logistic regression test. Results: The mean age of patients was 62.56±17.35 years. Among our patients history of hypertension, hyperlipidemia, cigarette smoking, diabetes, history of ischemic heart disease, history of other cardiac disease and silent stroke were observed in 66 (32.5%), 26 (12.8%), 16 (7.9%), 40 (19.7%), 27 (13.3%), 16 (7.9%) and 31 (15.3%), respectively. The probability of silent stroke among patient with hyperlipidemia, was 3.7 times more than those without hyperlipidemia (95%CI: 1.556-12.780, P

Aims: Atrial fibrillation (AF) is a risk factor for brain infarction, which can lead to epilepsy. We aimed to investigate whether treatment of AF with direct oral anticoagulants (DOACs) affects the risk of epilepsy in comparison to treatment with the vitamin K antagonist phenprocoumon (PPC)., Methods and Results: We performed an active comparator, nested case-control study based on the German Pharmacoepidemiological Research Database that includes claims data from statutory health insurance providers of about 25 million persons since 2004. In 2011-17, 227 707 AF patients initiated treatment with a DOAC or PPC, of which 1828 cases developed epilepsy on current treatment with an oral anticoagulant. They were matched to 19 084 controls without epilepsy. Patients with DOAC treatment for AF had an overall higher risk of epilepsy with an odds ratio of 1.39, 95% CI (1.24; 1.55) compared to current PPC treatment. Cases had higher baseline CHA2DS2-VASc scores and more frequently a history of stroke than controls. After excluding patients with ischaemic stroke prior to the diagnosis of epilepsy, the risk of epilepsy was still higher on DOACs than on PPC. In contrast, within a cohort of patients with venous thromboembolism, the risk of epilepsy on treatment with DOACs was less elevated [adjusted odds ratio 1.15, 95% CI (0.98; 1.34)]., Conclusion: In patients with AF initiating oral anticoagulation, treatment with a DOAC was associated with an increased risk of epilepsy compared to the vitamin K antagonist PPC. Covert brain infarction may explain the observed elevated risk of epilepsy., Competing Interests: Conflict of interest: The funder of the study, Federal Joint Committee in Germany, had no influence on the design and conduct of the study, the interpretation of the data, or the decision to publish. K.P., R.F., A.V., I.P., and T.S. are working at an independent, non-profit research institute, the Leibniz Institute for Prevention Research and Epidemiology—BIPS. Unrelated to this study, BIPS occasionally conducts studies financed by the pharmaceutical industry. Almost exclusively, these are post-authorization safety studies requested by health authorities. The design and conduct of these studies as well as the interpretation and publication are not influenced by the pharmaceutical industry. No financial relationships with any organizations that might have an interest in the submitted work in the previous three years; No other relationships or activities that could appear to have influenced the submitted work., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Although in the last few years emerging conventional and unconventional radiological and laboratory techniques have shed light on different pathophysiologic causes of stroke, nowadays almost 25% of ischemic strokes results of undetermined etiology. Different diagnostic criteria have been developed to define cryptogenic stroke and to establish its prevalence in stroke units. Different studies tried to unravel mechanisms of cryptogenic stroke and to evaluate adequate primary and secondary preventive measures, but standardized diagnostic and therapeutic strategies are still missing. In this review we report the most relevant updated notions in cryptogenic stroke providing an overview of the definition, the recommendations for diagnostic evaluation and the updated treatment strategies for secondary prevention. [ABSTRACT FROM AUTHOR]

The article discusses a study focusing on the role of silent cerebral infarcts (SCI) in causing morbidity in children with sickle cell anaemia (SCA). Topics discussed include intracranial vasculopathy and infarct recurrence in children with SCA; the magnetic resonance angiography (MRA) performed on the children under study; and the increased risk of SCI in children with intracranial vasculopathy.

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Silent focal ischemic mini infarcts in the brain are thought to cause no clinically overt symptoms. Some populations of hippocampal cells are particularly sensitive to ischemic events, however, rendering hippocampal functions especially vulnerable to ischemia-induced deficits. The present study investigated whether an otherwise silent ischemic mini infarct in the hippocampus (HPC) can produce impairments in spatial performance in rats. Spatial performance was assessed in the ziggurat task (ZT) using a 10-trial spatial learning protocol for four days prior to undergoing hippocampal ischemic lesion or sham surgery. Hippocampal silent ischemia was induced by infusion of endothelin-1 (ET-1), a potent vasoconstrictor, into either the dorsal or the ventral hippocampus (dHPC and vHPC). When tested postoperatively in the ZT using a standard testing protocol for eight days, rats with hippocampal lesions exhibited no spatial deficit. Although spatial learning and memory in the ZT were not affected by the ET-1-induced silent ischemia, rats with dHPC stroke showed more returns when navigating the ZT as opposed to the vHPC rats. Comparison of region-specific HPC lesions in the present study indicated that dorsal hippocampal function is critically required for topographic orientation in a complex environment. Topographic disorientation as reflected by enhanced return behaviours may represent one of the earliest predictors of cognitive decline after silent ischemic insult that may be potentially traced with sensitive clinical examination in humans.

Background: Although physical inactivity is a major public health problem, the causative factors for physical inactivity per se are poorly understood. To address this issue, we investigated the relationship between deep white matter lesions (DWMLs) on magnetic resonance imaging, apathy, and physical activities using structural equation modeling (SEM).Methods: We examined 317 community-dwelling elderly subjects (137 men and 180 women with a mean age of 64.5 years) without dementia or clinically apparent depression. Physical activity was assessed with a questionnaire consisting of 3 components (leisure-time, work, and sport activities).Results: The mean score from the apathy scale (a visual analogue version of Starkstein's apathy scale) of the Grades 2-3 DWML group was 420 (95% confidence interval [CI] 379-461), which was lower (more apathetic) than the Grade 0 DWML group score of 478 (95% CI 463-492) after adjustment for education as a covariate. SEM showed that the direct paths from DWMLs or education to apathy were significant, and the direct path from apathy to leisure-time activity was highly significant (β = .25, P < .001). The degree of apathetic behavior was negatively associated with sport activity in female subjects and positively associated with TV watching in male subjects.Conclusions: The results of the study show that DWMLs are one of the major factors that cause apathetic behavior and that apathy has significant negative effects on leisure-time physical activity in community-dwelling elderly subjects. Even a minor level of apathy without major depression would have a significant impact on activities of daily living and quality of life. [ABSTRACT FROM AUTHOR]

Background Cerebral small vessel disease is probably one of the most common pathogenetic mechanisms underlying stroke in Latin America. However, the importance of silent markers of small vessel disease, including white matter hyperintensities of presumed vascular origin, has not been assessed so far. Aim The study aims to evaluate prevalence and correlates of white matter hyperintensities in community-dwelling elders living in Atahualpa (rural Ecuador). Methods Atahualpa residents aged ≥60 years were identified during a door-to-door survey and invited to undergo brain magnetic resonance imaging for identification and grading white matter hyperintensities and other markers of small vessel disease. Using multivariate logistic regression models, we evaluated whether white matter hyperintensities is associated with demographics, cardiovascular health status, stroke, cerebral microbleeds, and cortical atrophy, after adjusting for the other variables. Results Out of 258 enrolled persons (mean age, 70 ± 8 years; 59% women), 172 (67%) had white matter hyperintensities, which were moderate to severe in 63. Analyses showed significant associations of white matter hyperintensities presence and severity with age and cardiovascular health status, as well as with overt and silent strokes, and a trend for association with cerebral microbleeds and cortical atrophy. Conclusions Prevalence and correlates of white matter hyperintensities in elders living in rural Ecuador is almost comparable with that reported from industrialized nations, reinforcing the concept that the burden of small vessel disease is on the rise in underserved Latin American populations. [ABSTRACT FROM AUTHOR]

Background/Objectives Evidence of a relationship between non-breathing-related sleep symptoms and silent markers of cerebral small vessel disease (SVD) is scarce. The present study aimed to evaluate this association in older people living in rural Ecuador, where the burden of stroke is on the rise. Methods A group of Atahualpa residents, aged ≥60 years, were interviewed with a validated Spanish version of the Pittsburgh Sleep Quality Index, and underwent magnetic resonance imaging (MRI) for identification of silent markers of SVD. Using multinomial logistic regression analysis, after adjusting for demographics and cardiovascular health status, it was evaluated whether sleep quality is associated with the severity of white matter hyperintensity (WMH), lacunar infarcts, and deep microbleeds. Results Out of 311 people aged ≥60 years, 237 (76%) were enrolled into the study. Mean age was 70 ± 8 years, 59% were women, 83% had primary school education only, and 73% had a poor cardiovascular health status. Seventy-eight (33%) had poor sleep quality. The MRI showed: WMH in 154 (65%) participants (moderate-to-severe in 52); silent lacunar infarcts in 28 (12%); and deep microbleeds in 17 (7%). Poor sleep quality was associated with WMH presence (OR 2.44, 95% CI 1.26 to 4.71, p  = 0.008) and severity (β coefficient 0.77, SE 0.37, p  = 0.037), but not with silent lacunar infarcts or deep microbleeds. Conclusions The present study showed an association between poor sleep quality and WMH severity. Further longitudinal studies would help to elucidate the cause and effect of this relationship. [ABSTRACT FROM AUTHOR]

Silent or asymptomatic lacunar infarcts (LACI) are common in elderly individuals, but it remains largely unclear how these often neglected silent brain infarcts lead to multiple domain cognitive deficits and even Alzheimer's disease (AD). In this study, we investigated the difference between patients with silent LACI in basal ganglia region and healthy controls for the structural and functional changes in the aspects of alterations of gray matter (GM) volume and intra-/inter-default mode network (DMN) and salience network (SN) connectivity. Thirty patients with silent LACI in the basal ganglia region and thirty healthy controls participated in the study. Voxel-based morphometry analysis was employed to measure the GM volume. We further investigated the intra/inter-network connectivity of DMN and SN using resting-state functional magnetic resonance imaging. Compared with healthy controls, patients performed worse in cognitive function in the aspects of general mental status, attention, and memory. The LACIs showed more severe GM atrophy in insula, anterior cingulate cortex, caudate, and superior temporal pole than controls. The connectivity within and between two networks was also reduced in patients. Importantly, the disrupted connectivity correlated with the patients' cognitive performance. Our findings support the hypothesis that silent lacunar infarcts result in cognitive decline, GM, and functional connectivity loss. [ABSTRACT FROM AUTHOR]

The aim of our study was to investigate the effects of subclinical brain lesions and cognitive function on gait performance with or without concurrent cognitive task in community-dwelling elderly subjects. Participants without dementia (92 men and 109 women with a mean age of 67.8 years) underwent brain magnetic resonance imaging, neuropsychologic tests, and gait measurements. Impaired gait velocity of the Timed Up and Go test was associated with deep white matter lesions (odds ratio [OR], 2.338; 95% confidence interval [CI], 1.120-4.880) and diabetes mellitus (OR, 2.725; 95% CI, 1.120-6.630) after adjusted for age, sex, education, and cognitive function tests. Impaired gait velocity of dual task walking was associated with age and the score of Rivermead Behavioral Memory Test (OR, .899/1 point higher; 95% CI, .813-.994), whereas deep white matter lesions were not significantly associated with dual task walking. The present study showed that gait represents not only physical functioning but also subclinical cognitive dysfunction particularly memory impairment in healthy elderly subjects. [ABSTRACT FROM AUTHOR]

Silent focal ischemic mini infarcts in the brain are thought to cause no clinically overt symptoms. Some populations of hippocampal cells are particularly sensitive to ischemic events, however, rendering hippocampal functions especially vulnerable to ischemiainduced deficits. The present study investigated whether an otherwise silent ischemic mini infarct in the hippocampus (HPC) can produce impairments in spatial performance in rats. Spatial performance was assessed in the ziggurat task (ZT) using a 10-trial spatial learning protocol for 4 days prior to undergoing hippocampal ischemic lesion or sham surgery. Hippocampal silent ischemia was induced by infusion of endothelin-1 (ET-1), a potent vasoconstrictor, into either the dorsal or the ventral hippocampus (dHPC and vHPC). When tested postoperatively in the ZT using a standard testing protocol for 8 days, rats with hippocampal lesions exhibited no spatial deficit. Although spatial learning and memory in the ZT were not affected by the ET-1-induced silent ischemia, rats with dHPC stroke showed more returns when navigating the ZT as opposed to the vHPC rats. Comparison of region-specific HPC lesions in the present study indicated that dorsal hippocampal function is critically required for topographic orientation in a complex environment. Topographic disorientation as reflected by enhanced return behaviors may represent one of the earliest predictors of cognitive decline after silent ischemic insult that may be potentially traced with sensitive clinical examination in humans. [ABSTRACT FROM AUTHOR]

Our previous study showed that the male predominance of silent brain infarction (SBI) was largely because of higher prevalence of alcohol habit and smoking in men than in women. In the present study, we further conducted an analysis of brain magnetic resonance imaging findings to examine whether early menopause contributes to SBI in community-dwelling subjects. Women were queried as to the age and cause of menopause, the total number of children, and the age at giving birth to her last child. Among 306 female subjects aged 60 years or older, univariate analysis showed that early menopause (total or natural) was significantly associated with SBI but age at natural menopause, number of children, and age at the last parity were not. In the total of 715 subjects (283 men and 432 women with a mean age of 67.2 years), the forward stepwise method of logistic analysis revealed that natural early menopause (odds ratio [OR] 4.28, 95% confidence interval [CI] 1.07-17.11), in addition to age, hypertension, alcohol intake, and smoking, was a significant factor concerning SBI. Also in the subgroup of female subjects aged 60 years or older, natural early menopause was a significant factor concerning SBI (OR 4.35, 95% CI 1.05-18.08) adjusted for covariates. Although the prevalence of natural early menopause was low (3.3% of 306 female subjects), natural menopause before the age of 40 years may be a risk for SBI or small-vessel disease of the brain. [Copyright &y& Elsevier]