Prevalence Of Silent Cerebral Infarction Research Articles

Silent cerebral infarction during immune TTP remission: prevalence, predictors, and impact on cognition

AbstractImmune thrombotic thrombocytopenic purpura (iTTP) survivors have increased risk of cardiovascular disease, including strokes, and report persistent cognitive difficulties during remission. We conducted this prospective study involving iTTP survivors during clinical remission to determine the prevalence of silent cerebral infarction (SCI), defined as magnetic resonance imaging (MRI) evidence of brain infarction without corresponding overt neurodeficits. We also tested the hypothesis that SCI is associated with cognitive impairment, assessed using the National Institutes of Health ToolBox Cognition Battery. For cognitive assessments, we used fully corrected T scores adjusted for age, sex, race, and education. Based on the diagnostic and statistical manual 5 criteria, we defined mild and major cognitive impairment as T scores with a 1 or 2 standard deviation (SD) and >2 SD below the mean on at least 1 test, respectively. Forty-two patients were enrolled, with 36 completing MRIs. SCI was present in 50% of the patients (18), of which 8 (44.4%) had prior overt stroke including during acute iTTP. Patients with SCI had higher rates of cognitive impairment (66.7% vs 27.7%; P = .026), including major cognitive impairment (50% vs 5.6%; P = .010). In separate logistic regression models, SCI was associated with any (mild or major) cognitive impairment (odds ratio [OR] 10.5 [95% confidence interval (95% CI), 1.45-76.63]; P = .020) and major cognitive impairment (OR 7.98 [95% CI, 1.11-57.27]; P = .039) after adjusting for history of stroke and Beck depression inventory scores. MRI evidence of brain infarction is common in iTTP survivors; the strong association of SCI with impaired cognition suggests that these silent infarcts are neither silent nor innocuous.

Silent Cerebral Infarction during Immune TTP Remission - Prevalence, Predictors and Impact on Cognition

BACKGROUND: Immune thrombotic thrombocytopenic purpura (iTTP) survivors are at increased risk cardiovascular events including stroke, which is associated with low remission ADAMTS13 activity. In the prospective Neurologic Sequelae of TTP (NeST) study, we evaluated the prevalence of silent cerebral infarction (SCI, ischemic lesions on brain MRI without overt neurodeficits that are a risk factor for future stroke), identified risk factors for SCI, and examined the association of SCI with cognitive impairment, which is prevalent in iTTP survivors. METHODS: We prospectively enrolled adult (age ≥ 18 years) patients with iTTP based on ADAMTS13 activity <10% during an acute episode. All study assessments were performed after achieving hematological remission. Participants undergo annual study visits that include: 1) Brain MRI: SCI is defined as a infarct like lesion (punctate T2 and FLAIR hyperintensity) ≥3 mm in size without corresponding neurodeficits., 2) NIH ToolBox Cognition battery, an extensively-validated tool that tests multiple cognitive domains including executive function (dimensional change card sort test, flanker inhibitory control and attention test), processing speed (pattern comparison test), episodic memory (picture sequence memory test), working memory (list sorting working memory test), language (oral reading recognition, picture vocabulary test). Fully-corrected T scores (normative mean 50, SD 10) adjusted for age, sex, race and educational attainment are computed for individual tests as well as composite scores for fluid cognition, crystallized cognition and total cognition. Mild and major cognitive impairment are defined as a T scores that are 1-2 SD below mean and > 2 SD below mean for any domain, respectively; 3) the Beck depression inventory was also completed since depression is a potential confounder that is common in iTTP and may contribute to impaired cognition. RESULTS: Between September 2020 and July 2022, 39 iTTP patients were enrolled; 32 patients completed MRI (2 excluded due to metal implant/shrapnel, 4 stopped for anxiety/claustrophobia). Median age was 48 years, 71% were female, and 23% had previous stroke (including during acute iTTP). Prevalence and predictors of SCI: MRI showed SCI in 53.1% (Figure 1). Only 47% (8/17) patients with SCI had prior overt stroke. Age [OR 1.07 (95% CI 1.01-1.15, P=0.025) and history of stroke [OR 12.8 (95% CI 1.07-152.9), P=0.044] were associated with SCI in a logistic regression model adjusted for number of iTTP episodes [OR 1.14 (95% CI 0.71-1.86), P=0.570], hypertension [OR 0.77 (95% CI 0.14 - 4.25), P=0.768], and Black race [OR 2.10 (95% CI 0.16-28.20], P=0.574]. SCI is associated with cognitive impairment: Mild and major cognitive impairment were present in 23.1% and 30.8%, respectively. Deficits most commonly involved executive function (flanker inhibitory control and attention test, dimensional change card sort test) and processing speed (pattern comparison test). Compared to patients without SCI, those with SCI had higher rates of cognitive impairment (70.5% vs. 26.7%) including major impairment (52.9% vs. 6.7%) (P=0.014) (Figure 2). In logistic regression models adjusted for age and prior stroke, SCI was associated with major cognitive impairment [OR 18.13 (95% CI 1.3-259.1), P=0.033] as well as mild cognitive impairment [OR 7.76 (95% CI 1.03-58.29]. Patient with SCI had lower composite scores on the NIH ToolBox cognition battery [fluid cognition composite 41 vs. 55, P=0.009, crystallized composite 50 vs. 60, P=0.033, total composite 46 vs, 59, P=0.004), as well as lower scores on tests of executive function (flanker inhibitory control and attention, P=0.020) and processing speed (pattern comparison test, P=0.004), which are most commonly affected in iTTP. Patients with SCI did not have higher mean Beck Depression inventory scores (12.0 ± 7.8 vs. 11.67 ± 11.5, P = 0.659) than those without SCI suggesting that the association with cognitive performance is not due to higher rates of depression in this group. CONCLUSIONS: MRI evidence of brain infarction is common in patients with iTTP with or without a clinical history of stroke. Ongoing follow up with serial MRI continues and will inform whether SCI are progressive in remission and whether low remission ADAMTS13 is a targetable risk factor. The strong association of SCI with impaired cognition suggests that these 'silent infarcts' are neither silent nor innocuous. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Cerebral Infarcts and Vasculopathy in Tanzanian Children With Sickle Cell Anemia

BackgroundCerebral infarcts and vasculopathy in neurologically asymptomatic children with sickle cell anemia (SCA) have received little attention in African settings. This study aimed to establish the prevalence of silent cerebral infarcts (SCI) and vasculopathy and determine associations with exposure to chronic hemolysis, anemia, and hypoxia. MethodsWe prospectively studied 224 children with SCA with transcranial Doppler (TCD), and magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA). Regressions were undertaken with contemporaneous hemoglobin, reticulocyte count, mean prior hemoglobin, oxygen content, reticulocyte count, and indirect bilirubin. ResultsPrevalence of SCI was 27% (61 of 224); cerebral blood flow velocity was abnormal (>200 cm/s) in three and conditional (>170<200 cm/s) in one. Vasculopathy grades 2 (stenosis) and 3 (occlusion) occurred in 16 (7%) and two (1%), respectively; none had grade 4 (moyamoya). SCI was associated with vasculopathy on MRA (odds ratio 2.68; 95% confidence intervals [95% CI] 1.32 to 5.46; P = 0.007) and mean prior indirect bilirubin (odds ratio 1.02, 95% CI 1.00 to 1.03, P = 0.024; n = 83) but not age, sex, non-normal TCD, or contemporaneous hemoglobin. Vasculopathy was associated with mean prior values for hemoglobin (odds ratio 0.33, 95% CI 0.16 to 0.69, P = 0.003; n = 87), oxygen content (odds ratio 0.43, 95% CI 0.25 to 0.74, P = 0.003), reticulocytes (odds ratio 1.20, 95% CI 1.01-1.42, P = 0.041; n = 77), and indirect bilirubin (odds ratio 1.02, 95% CI 1.01 to 1.04, P = 0.009). ConclusionsSCI and vasculopathy on MRA are common in neurologically asymptomatic children with SCA living in Africa, even when TCD is normal. Children with vasculopathy on MRA are at increased risk of SCI. Longitudinal exposure to anemia, hypoxia, and hemolysis appear to be risk factors for vasculopathy.

PF742 CEREBRAL OXYGEN METABOLISM MEASUREMENTS WITH MRI IN ADULTS WITH SICKLE CELL DISEASE

Background:MRI studies have demonstrated a high prevalence of silent cerebral infarcts (SCI) in both children and adults with sickle cell disease (SCD). SCI are associated with cognitive impairment and lesion progression in adults with SCD. Disrupted oxygen transport can contribute to cerebral ischemic lesions, despite the compensatory elevation in cerebral blood flow (CBF) in SCD. Investigating the cerebral metabolic rate of oxygen (CMRO2) may therefore give insight into the hemodynamic etiology of SCI in SCD patients. We hypothesized that CMRO2 is reduced in adult patients with SCD as a result of chronic anemia and that vasodilation can improve CMRO2 by generating an increase in blood and oxygen flow.Aims:The purpose of this study was to measure CBF and OEF to compute CMRO2 and to measure the response to vasodilation with acetazolamide.Methods:We included adults with SCD (HbSS or HbSb0‐thalassaemia), and age‐, sex‐, and race‐matched controls. Exclusion criteria were contraindications to MRI and acetazolamide, and a clinical history of a cerebrovascular event or neurologic disease affecting cerebral autoregulation.The MRI protocol comprised fluid‐attenuated inversion recovery (FLAIR) for anatomy and lesions, T2‐prepared tissue relaxation with inversion recovery (T2‐TRIR) for oxygenation and T1 of blood, and pseudo continuous arterial spin labelling (pCASL) for cerebral blood flow. Paired tests were used to assess statistical significance of changes from baseline to post‐acetazolamide conditions. P &lt; .05 was considered significant. Variables were summarized by means and standard deviations.Results:Hb was lower in patients compared to controls (8.8 ± 1.4 vs 13.7 ± 1.3 g/dL, P &lt; .001). Oxygen delivery was similar in patients compared to controls (371 ± 70 vs 368 ± 39 μmol O2/100 g/min, P = .832), due to compensatory elevated CBF in patients versus controls (73 ± 16 vs 46 ± 4 mL/100 g/min, P &lt; .001). OEF was lower in patients compared to controls (27.1 ± 4.4 vs 35.3 ± 3.6 %, P = .001). SCD patients had lower CMRO2 compared to controls (99.7 ± 24.2 vs 126.6 ± 18.9 μmol O2/100 g/min, P = .003) (Figure 2). Cerebrovascular reserve was lower in patients versus controls (43.1 ± 12.5 vs 67.0 ± 20.0%, P = .003). After acetazolamide, CMRO2 did not change significantly in the healthy controls (P = .844), but declined in SCD patients (P = .036), showing that the ACZ challenge was indeed isometabolic in controls but not in patients. Finally, we found that increased CBF after ACZ was accompanied by a drop in OEF in patients with SCD (P &lt; .001) as well as in controls (P = .003).Summary/Conclusion:Our findings support our hypothesis that SCD patients have reduced CMRO2. This indicates that in this chronic condition, CMRO2, and therefore likely also neuronal function, have adapted to chronic low oxygen availability. Heterogeneous flow distribution could be the reason for the reduced CMRO2 we observed in patients with SCD, whereby oxygen shunted to the venous side without delivering oxygen to the brain tissue, and this was exacerbated by acetazolamide. We conclude that CMRO2 does not adjust quickly to transient changes in oxygen availability at the microvascular level despite the increase in CBFimage

Cerebral Infarcts and Cerebrovascular Disease in Neurologically Intact Tanzanian Children with Sickle Cell Anaemia

Introduction:Children and adolescents with sickle cell anemia (SCA) without history of neurological manifestations remain at risk of stroke and require cost effective screening as evidence-based stroke prevention interventions are developed. Although there are data on the prevalence of Transcranial Doppler (TCD) abnormality, there are relatively few studies on the prevalence of silent cerebral infarction (SCI) on magnetic resonance imaging (MRI) and vasculopathy on MR angiography (MRA), paricularly in Africa, where the burden of disease is greatest. In this study in Africa, we determined the prevalence of SCI on MRI and cerebral vasculopathy on MRA, and explored associations with age, sex, internal carotid/middle cerebral artery (ICA/MCA) and basilar cerebral blood flow velocities (CBFV) on TCD, and hematological variables.Patients and methods:We prospectively studied children with homozygous SCA (HbSS) without prior clinically overt stroke or TIA or seizures. Clinical information and blood for full blood count was collected for all patients. All were offered TCD using non-imaging equipment (Compumedics) and MRI and MRA of intracranial arteries on a Philips 1.5 Tesla scanner. MRA was graded as 1 Turbulence, 2 Stenosis, 3 Occlusion, 4 Occlusion with collaterals (moyamoya). Imaging was reviewed by 2 neuroradiologists (MJ and DS) and consensus was reached.Results:Within a period of 12 months, 395 children with SCA were recruited. Mean age was 12.7+/-4 (range 5-19 years); 199 (50.4%) were male. Mean hemoglobin was 7.6±1.1 (range 4.1-13.5) g/dl. 381 had TCD, of whom 227 (57%) have had brain MRI and MRA so far.Only 14/395 (3.5%) of patients had abnormal CBFV, 8 (2%) with maximum CBFV <50 cm/sec, 3 with CBFV 150-169 cm/sec, 1 with conditional (170-199 cm/sec) and 2 (0.5%) with abnormal CBFV (>200cm/sec).Prevalence of silent cerebral infarction was 29% (65/227) and was similar in males (30%; 34/114) and females (28%; 31/110) but was lower in children aged <9 years (20%; 10/51) than in those aged 10-14 years (33%; 27/83) or those aged 15-19 years (32%; 28/89); this was not significant (p=0.2).The prevalence of cerebral vasculopathy on MRA, defined as stenosis (Grade 2), occlusion (Grade 3) or occlusion with collaterals (moyamoya; Grade 4), was 9% (20/227). The internal carotid and/or middle cerebral artery was affected in all 20 and the anterior cerebral artery was affected in 7 patients. Vasculopathy was not observed on MRA in the posterior cerebral artery and no patients had moyamoya. An additional 9 (4%) patients had turbulence (Grade 1) in at least one artery on MRA.SCI were more common in those with MRA vasculopathy Grades 2-3 (12/64; 19%) and in those with Grade 1 Turbulence (2/9; 22%) than in those with normal MRA (8/165; 5%) (p<0.05). Patients with Grade 1 Turbulence had higher ICA/MCA CBFv (mean 122+/-36 cm/sec) than those with normal MRA (mean 101+/-25 cm/sec) or Grades 2-3 (mean 109+/-21 cm/sec) vasculopathy. The difference in those with Grade 1 turbulence compared with those with normal MRA was significant (mean difference 20 cm/sec, 95% confidence intervals 1, 39 cm/sec; p=0.037). Basilar velocity was also significantly higher in those with Grade 1 turbulence (87+/-21 cm/sec) than in those with normal MRA (76+/-14 cm/sec) and those with Grade 2-3 vasculopathy (80+/-11 cm/sec)(mean difference 11.5 cm/sec, 95% confidence intervals 0.3, 22.6 cm/sec; p=0.043). Basilar velocity weakly correlated with hemoglobin (r=-0.18) but the relationships between hemoglobin and ICA/MCA CBFV or either presence of SCI or MRA abnormality were not significant.Conclusions:The prevalence of SCI on MRI is high in children with SCA without neurological history living in Africa even when TCD CBFV is normal. Children and adolescents with all grades of vasculopathy on MRA are at higher risk of brain parenchymal injury. The lack of association between SCI and hemoglobin may be related to the relatively severe anemia in our African study. As MRA contrast depends on velocity of blood flowing in vessels, it is not surprising that Grade 1 turbulence on MRA appears to reflect high CBFV on TCD. Importantly, high TCD velocity and Grade 1 turbulence may reflect the potentially reversible early stages in the development of SCA vasculopathy when cerebral blood flow is high before stenosis and occlusion supervene. TCD is operator dependent and there may be a case for MRI and MRA screening if follow-up shows that these measures predict stroke. DisclosuresNo relevant conflicts of interest to declare.

Cognitive dysfunction in atrial fibrillation.

Atrial fibrillation (AF) is the most common arrhythmia in adults, and its incidence and prevalence increase with age. The risk of cognitive impairment and dementia also increases with age, and both AF and cognitive impairment or dementia share important risk factors. In meta-analyses of published studies, AF is associated with a 2.4-fold and 1.4-fold increase in the risk of dementia in patients with or without a history of stroke, respectively. This association is independent of shared risk factors such as hypertension and diabetes mellitus. Neuroimaging has illustrated several potential mechanisms of cognitive decline in patients with AF. AF is associated with increased prevalence of silent cerebral infarcts, and more recent data also suggest an increased prevalence of cerebral microbleeds with AF. AF is also associated with a pro-inflammatory state, and the relationship between AF-induced systemic inflammation and dementia remains to be investigated. Preliminary reports indicate that anticoagulation medication including warfarin can reduce the risk of cognitive impairment in patients with AF. Catheter ablation, increasingly used to maintain sinus rhythm in patients with AF, is associated with the formation of new silent cerebral lesions. The majority of these lesions are not detectable after 1 year, and insufficient data are available to evaluate their effect on cognition. Large prospective studies are urgently needed to confirm the association between AF and dementia, to elucidate the associated mechanisms, and to investigate the effect of anticoagulation and rhythm control on cognition.

Silent infarct is a risk factor for infarct recurrence in adults with sickle cell anemia.

Because of the high prevalence of silent cerebral infarcts (SCIs) in adults with sickle cell anemia (SCA) and lack of information to guide treatment strategies, we evaluated the risk of recurrent SCIs and overt stroke in adults with SCA with preexisting SCI. This observational study included adults with SCA (HbSS or Sβ0 thalassemia) aged 18 to 40 years. Participants received 3-tesla brain MRI and a detailed neurologic examination. Time-to-event analysis assessed those with or without baseline SCI and with new or progressive infarcts. The incidence rate of new events was compared by log-rank test. Univariable Cox regression assessed the association of SCI with infarct progression. Among adults with SCA with 2 MRIs and at least 6 months between MRIs (n = 54, mean interval = 2.5 years), 43% had SCI at baseline. Of participants with baseline SCI, 30% had new or progressive SCI over 2.5 years compared to 6% with no SCI at baseline; no participant had an overt stroke. New SCIs at follow-up were present in 12.9 per 100 patient-years with existing SCI compared with 2.4 per 100 patient-years without prior SCI (log-rank test, p = 0.021). No statistically significant differences were seen among those with or without baseline SCI in use of hydroxyurea therapy, hydroxyurea dose, or other stroke risk factors. The presence of SCI was associated with increased hazard of a new or progressive infarct (hazard ratio 5.27, 95% confidence interval 1.09-25.51, p = 0.039). Silent infarcts in adults with SCA are common and are a significant risk factor for future silent infarcts.

Silent Cerebral Infarctions with Reduced, Mid-Range and Preserved Ejection Fraction in Patients with Heart Failure.

Heart failure predisposes to an increased risk of silent cerebral infarction, and data related to left ventricular ejection fraction are still limited. Our objective was to describe the clinical and echocardiographic characteristics and factors associated with silent cerebral infarction in patients with heart failure, according to the left ventricular ejection fraction groups. A prospective cohort was performed at a referral hospital in Cardiology between December 2015 and July 2017. The left ventricular ejection fraction groups were: reduced (≤ 40%), mid-range (41-49%) and preserved (≥ 50%). All patients underwent cranial tomography, transthoracic and transesophageal echocardiography. Seventy-five patients were studied. Silent cerebral infarction was observed in 14.7% of the study population (45.5% lacunar and 54.5% territorial) and was more frequent in patients in the reduced left ventricular ejection fraction group (29%) compared with the mid-range one (15.4%, p = 0.005). There were no cases of silent cerebral infarction in the group of preserved left ventricular ejection fraction. In the univariate analysis, an association was identified between silent cerebral infarction and reduced (OR = 8.59; 95%CI: 1.71 - 43.27; p = 0.009) and preserved (OR = 0.05; 95%CI: 0.003-0.817, p = 0.003) left ventricular ejection fraction and diabetes mellitus (OR = 4.28, 95%CI: 1.14-16.15, p = 0.031). In patients with heart failure and without a clinical diagnosis of stroke, reduced and mid-range left ventricular ejection fractions contributed to the occurrence of territorial and lacunar silent cerebral infarction, respectively. The lower the left ventricular ejection fraction, the higher the prevalence of silent cerebral infarction.

Association of Exhaled Carbon Monoxide With Stroke Incidence and Subclinical Vascular Brain Injury: Framingham Heart Study.

Exhaled carbon monoxide (CO) is associated with cardiometabolic traits, subclinical atherosclerosis, and cardiovascular disease, but its specific relations with stroke are unexplored. We related exhaled CO to magnetic resonance imaging measures of subclinical cerebrovascular disease cross-sectionally and to incident stroke/transient ischemic attack prospectively in the Framingham Offspring study. We measured exhaled CO in 3313 participants (age 59±10 years; 53% women), and brain magnetic resonance imaging was available in 1982 individuals (age 58±10 years; 54% women). Participants were analyzed according to tertiles of exhaled CO concentration. In age- and sex-adjusted models, the highest tertile of exhaled CO was associated with lower total cerebral brain volumes, higher white-matter hyperintensity volumes, and greater prevalence of silent cerebral infarcts (P<0.05 for all). The results for total cerebral brain volume and white-matter hyperintensity volume were consistent after removing smokers from the sample, and the association with white-matter hyperintensity volume persisted after multivariable adjustment (P=0.04). In prospective analyses (mean follow-up 12.9 years), higher exhaled CO was associated with 67% (second tertile) and 97% (top tertile) increased incidence of stroke/transient ischemic attack relative to the first tertile that served as referent (P<0.01 for both). These results were consistent in nonsmokers and were partially attenuated upon adjustment for vascular risk factors. In this large, community-based sample of individuals without clinical stroke/transient ischemic attack at baseline, higher exhaled CO was associated with a greater burden of subclinical cerebrovascular disease cross-sectionally and with increased risk of stroke/transient ischemic attack prospectively. Further investigation is necessary to explore the biological mechanisms linking elevated CO with stroke.

Abstract 16816: Association of Exhaled Carbon Monoxide With Stroke Incidence and Subclinical Vascular Brain Injury: The Framingham Study

Introduction: Exhaled carbon monoxide (CO) is associated with cardiometabolic traits, subclinical atherosclerosis, and cardiovascular disease, but its specific relations with stroke have not been explored. Hypothesis: We hypothesized that exhaled CO is related to MRI measures of subclinical cerebrovascular disease cross-sectionally, and to incident stroke/ transient ischemic attack (TIA) prospectively in the Framingham Offspring Study. Methods: We measured exhaled CO in 3313 participants (age 59±10 years, 53% women) and Brain MRI imaging was available in 1982 individuals (age 58±10, 54% women). Participants were analyzed according to tertiles of exhaled CO concentration. Results: In age- and sex-adjusted models, the highest tertile of exhaled CO was associated with lower total cerebral brain volumes (TCBV), higher white matter hyperintensity volumes (WMHV), and greater prevalence of silent cerebral infarcts (p &lt;0.05 for all). The results for TCBV and WMHV were consistent after removing smokers from the sample, and the association with WMHV persisted after multivariable adjustment (p=0.04). In prospective analyses (mean follow-up 12.9 years), higher exhaled CO was associated with 67% (second tertile) and 97% (top tertile) increased incidence of stroke/TIA relative to the first tertile that served as referent (p &lt;0.01 for both), Table. These results were consistent in nonsmokers, and were partially attenuated upon adjustment for vascular risk factors, but were maintained after adjusting for circulating biomarkers B-type natriuretic peptide and C-reactive protein, Table. Conclusion: In this large, community-based sample of individuals free of clinical stroke/TIA at baseline, higher exhaled CO was associated with a greater burden of subclinical cerebrovascular disease cross-sectionally, and with increased risk of stroke/TIA prospectively. Further investigation is necessary to explore the biological mechanisms linking CO with stroke.

Clinical and echocardiographic predictors of silent cerebral infarctions in patients with persistent atrial fibrillation

Summary Aim. The aims of the study were to evaluate prevalence of silent cerebral infarctions (SCI) and determine their clinical and echocardiographic predictors in patients with atrial fibrillation (AF). Patients and methods. In prospective cross sectional study we examined 134 patients with non-valvular AF. Clinical examination, laboratory tests, transoesophageal, transthoracic echocardiography and multislice computed tomography of the brain were performed for all patients. According to current guidelines, SCI was defined as imaging (≥3 mm) or neuropathological evidence of central nervous system infarction, without a history of acute neurological dysfunction attributable to the lesion. Results. Silent cerebral infarctions were detected in 34.3% (n = 46) of patients, and infarctions ≥ 15 mm (mean diameter 31.3 mm) were detected in 11.2% (n = 15) of patients. Superficial SCIwere found in 12.7%and basal SCI in 21.6% of cases. In multivariate analysis low creatinine clearance &lt; 90 ml/min was independently associated with small basal SCI (p = 0.04). In univariate analysis age ≥ 65 years was significantly associated with basal SCI, p = 0.004, but not with SCI ≥ 15 mm or superficial SCI. The results of multivariate analysis showed that CHA2DS2VASc score was an independent predictor of superficial SCI; low left atrial appendage velocity (LAAV) &lt; 30 cm/s was independently associated both with SCI ≥ 15 mm (p = 0.03) and superficial SCI (p = 0.02). Conclusions. Large and superficial SCI were significantly and independently associated with low LAAV &lt; 30 cm/s and other echocardiographic embolic risk factors and in case of absence of significant large arteries atherosclerosis may be considered as those of cardiac origin. Small basal SCI were associated with age and low creatinine clearance &lt; 90 ml/min which was their independent predictor. CHA2DS2VASc score is useful for assessment of risk of cerebral infarctions even those without history of acute symptoms

Parent education and biologic factors influence on cognition in sickle cell anemia

Children with sickle cell anemia have a high prevalence of silent cerebral infarcts (SCIs) that are associated with decreased full-scale intelligence quotient (FSIQ). While the educational attainment of parents is a known strong predictor of the cognitive development of children in general, the role of parental education in sickle cell anemia along with other factors that adversely affect cognitive function (anemia, cerebral infarcts) is not known. We tested the hypothesis that both the presence of SCI and parental education would impact FSIQ in children with sickle cell anemia. A multicenter, cross-sectional study was conducted in 19 US sites of the Silent Infarct Transfusion Trial among children with sickle cell anemia, age 5-15 years. All were screened for SCIs. Participants with and without SCI were administered the Wechsler Abbreviated Scale of Intelligence. A total of 150 participants (107 with and 43 without SCIs) were included in the analysis. In a multivariable linear regression model for FSIQ, the absence of college education for the head of household was associated with a decrease of 6.2 points (P = 0.005); presence of SCI with a 5.2 point decrease (P = 0.017); each $1000 of family income per capita with a 0.33 point increase (P = 0.023); each increase of 1 year in age with a 0.96 point decrease (P = 0.023); and each 1% (absolute) decrease in hemoglobin oxygen saturation with 0.75 point decrease (P = 0.030). In conclusion, FSIQ in children with sickle cell anemia is best accounted for by a multivariate model that includes both biologic and socioenvironmental factors.

Silent Cerebral Infarctions in Type II Diabetes Mellitus Patients; Could Brain MRI Be a Routine Investigation?

Objective: To study the prevalence of silent cerebral infarction in Type II diabetes mellitus. Patients and Methods: The study was a prospective on 80 patients recruited from neurology, endocrine outpatient clinics. Patients were type II diabetics as described by the American Diabetes Association, 2011 criteria. All patients underwent full metabolic profiles to diagnose diabetes mellitus and MRI brain scans to detect cerebral infarction. Results: Silent cerebral infarctions were detected in 60% of patients (48/80 patients) predominately along periventricular white matter area and subcortical areas (Basal ganglia, Thalamus). Conclusion: Asymptomatic Type II diabetes mellitus patients could have vascular cerebral changes without neurological symptoms. MRI brain scans could be recommended as routine diagnosis (if possible) for early cerebral infarct detection in type II diabetic patients.

Subtle Post-Procedural Cognitive Dysfunction After Atrial Fibrillation Ablation

This study sought to determine whether post-operative neurocognitive dysfunction (POCD) occurs after ablation for atrial fibrillation (AF). Ablation for AF is a highly effective strategy; however, the risk of transient ischemic attack and stroke is approximately 0.5% to 1%. In addition, magnetic resonance imaging studies report a 7% to 14% prevalence of silent cerebral infarction. Whether cerebral ischemia results in POCD after ablation for AF is not well established. The study included 150 patients; 60 patients undergoing ablation for paroxysmal atrial fibrillation (PAF), 30 patients undergoing ablation for persistent atrial fibrillation (PeAF), and 30 patients undergoing ablation for supraventricular tachycardia (SVT) were compared witha matched nonoperative control group of patients with AF awaiting radiofrequency ablation (n= 30). Eight neuropsychological tests were administered at baseline and at 2 days and 90 days post-operatively. The tests were administered at the sametimepoints to the nonoperative control group. The reliable change index was used to calculate POCD. The prevalences of POCD at day 2 post-procedure were 28% in patients with PAF, 27% in patients with PeAF, 13% in patients with SVT, and 0% in control patients with AF (p= 0.007). At day 90, the prevalences of POCD were 13% in patients with PAF, 20% in patients with PeAF, 3% in patients with SVT, and 0% in control patients with AF (p= 0.03). When analyzing the 3 procedural groups together, 29 of 120 patients (24%) manifested POCD at day 2 and 15 of 120 patients (13%) at day 90 post-procedure (p= 0.029). On univariate analysis, increasing left atrial access time was associated with POCD at day 2 (p= 0.04) and day 90 (p= 0.03). Ablation for AF is associated with a 13% to 20% prevalence of POCD in patients with AF at long-term follow-up. These results were seen in a patient population with predominant CHADS2 (Congestive heart failure, Hypertension, Age≥75 years, Diabetes mellitus, previous Stroke/transient ischemic attack) scores of 0 to 1, representing the majority of patients undergoing ablation for AF. The long-term implications of these subtle changes require further study.

Silent Cerebral Infarctions in Children and Adolescents with Hemoglobin SC Disease

AbstractAbstract 1011▪▪This icon denotes a clinically relevant abstract BackgroundChildren with sickle cell disease (SCD), especially sickle cell anemia, are at high risk of overt and silent cerebral infarctions, leading to physical and cognitive deficits. Less is known about the risks of cerebral infarction in children with Hemoglobin SC (Hb SC). Prior studies have found a prevalence of silent cerebral infarction of 5.8%1 to 46%2 in children with Hb SC disease. We sought to define the prevalence of cerebral infarctions in a population of children and adolescents with Hb SC disease, and to identify medical risk factors for cerebral infarctions. MethodsSince 2006, screening brain magnetic resonance imaging (MRI) exams have been performed on all children with SCD followed at St. Louis Children's Hospital at approximately age 6 years. Furthermore, brain MRI is performed if patients present with possible stroke symptoms, such as severe headache, visual changes, weakness, or seizures. Cerebral infarctions were defined as T2- or FLAIR-weighted hyperintensities visible in at least 2 planes; silent infarcts were diagnosed when the patient had no neurological symptoms that correlated with the infarct lesions. Human Studies Committee approval and waiver of consent was obtained prior to reviewing all brain MRIs from children with Hb SC disease. SPSS version 20 was used for statistical analysis. ResultsBetween January 2004 and May 2012, 95 children and adolescents with Hb SC disease underwent brain MRI; 54% were male. Forty-nine children (51.6%) had no neurological symptoms at the time of the initial MRI; of the 46 children with neurological symptoms, poor school performance (16 children, 16.8%) and headaches (15 children, 15.8%) were cited most commonly. Neurological symptoms provoking MRI included unilateral hearing loss (2 children) and Bell's palsy (3 children).Prevalence of silent infarctions was 14.7% (14/95 children). Seven (50%) of subjects with silent infarctions were male. The mean age at identification of cerebral infarction was 11.9 years (range, 6.2–19.3 years). Five of the infarctions were identified by screening asymptomatic children. Nine children were found to have infarctions while experiencing neurological symptoms; in all cases, the infarct lesions did not explain the presenting neurological symptoms. Among 84 children with initial MRIs that were free of infarctions, 3 developed silent cerebral infarctions subsequently. There was no association between silent cerebral infarctions and a history of asthma, headaches, school difficulties, or school failure.In all cases, the silent cerebral infarctions were located in periventricular, frontal, or parietal white matter; there were no lobar strokes identified. Infarcts ranged in size from 1 mm to 1 cm. All children with silent cerebral infarctions were referred for neurocognitive testing and evaluation for an individualized educational plan. Ten of the 14 children with silent infarctions have had followup MRIs, ranging from 0.1 to 6.4 years following the initial MRI. None have had progressive silent infarct lesions or overt strokes.Magnetic resonance angiography (MRA) was performed in 83 subjects. None of the children had arterial stenosis or occlusion, moyamoya, or aneurysms. Five subjects had subtle irregularities of cerebral arteries noted on MRA, but none progressed to more severe abnormalities. ConclusionApproximately 15% of children and adolescents with Hb SC disease in this retrospective cohort have silent cerebral infarctions, a much higher prevalence than was found in the Cooperative Study of Sickle Cell Disease.1 The prevalence is lower than that of Steen et al's cohort,2 perhaps due to the fact that our center screens all school-aged children. Clinically significant angiographic abnormalities were not identified in this cohort. Children with silent cerebral infarctions should be referred for neurocognitive testing. Further work is needed to define risk factors and treatments for children with silent cerebral infarctions in Hb SC disease. Disclosures:No relevant conflicts of interest to declare.

Non-linear association between ankle-brachial pressure index and prevalence of silent cerebral infarction in Japanese patients with type 2 diabetes

ObjectivePatients with peripheral artery disease (PAD), defined as having low ankle-brachial pressure index (ABI), have increased risk for incident stroke compared with those without PAD. We aimed to reveal whether ABI abnormality, especially high ABI is associated with prevalent silent cerebral infarction (SCI) in type 2 diabetic patients. MethodsWe studied 538 Japanese type 2 diabetic patients, 227 women and 311 men, with a mean [±SD] age of 64±11 years. All patients underwent cranial magnetic resonance imaging (MRI). Values of ABI were classified as low (<0.9), normal (0.9≤ and <1.3), and high (1.3≤). Logistic regression model was used to calculate odds ratio and 95% confidence interval (95% CI) for prevalent SCI. ResultsThe mean ABI among the overall 538 patients was 1.09±0.16. Low and high ABI values were found in 52 (9.7%) and 33 (6.1%) patients, respectively. SCI was detected in 297 (55.2%) patients. The prevalence in patients with low, normal, and high ABI values were 88.5%, 49.7%, and 78.8 (p<0.001), respectively. In the multivariate logistic regression analysis, both patients with high and low ABI were significantly increased risk of prevalent SCI (odds ratio 4.53, 95% CI 1.67–12.34, p=0.003 and odds ratio 3.50, 95% CI 1.50–10.29, p=0.005), independently of other traditional cardiovascular risk factors, than those with normal ABI. ConclusionsBoth high and low ABI may be strongly associated with prevalent SCI in Japanese patients with type 2 diabetes.

Carotid Artery Atherosclerosis, MRI Indices of Brain Ischemia, Aging, and Cognitive Impairment

Carotid atherosclerosis has been associated with increased risk of stroke and poorer cognitive performance in older adults. The relation of carotid atherosclerosis to cognitive impairment and MRI indices of ischemia and aging in midlife is less clear. We studied 1975 Framingham Offspring Study participants free of stroke and dementia with available carotid ultrasound, brain MRI, and neuropsychological testing. We related common and internal carotid artery intima-media thickness and internal carotid stenosis to large white matter hyperintensity (>1 SD above age-specific mean), total brain volume, hippocampal volume, silent cerebral infarcts, and neuropsychological measures of verbal memory, executive function, and nonverbal memory measures. We observed that internal carotid artery intima-media thickness, but not common carotid artery intima-media thickness, was associated with higher prevalence of silent cerebral infarcts (OR, 1.21; 95% CI, 1.03-1.43; P<0.05), large white matter hyperintensity (OR, 1.19; 95% CI, 1.03-1.38; P<0.05), lower total brain volume (-0.05 per SD; P<0.05), and poorer performance in verbal memory (-0.06 per SD; P<0.05) and nonverbal memory measures (-0.08 per SD; P<0.01), but not with hippocampal volume. Internal carotid stenosis >or=25% was associated with a higher prevalence of large white matter hyperintensity (adjusted OR, 1.77; 95% CI, 1.25-2.53) and lower total brain volume (-0.11 per SD; P=0.042) but not with silent cerebral infarcts or hippocampal volume. Internal carotid stenosis >or=50% was associated with higher prevalence of silent cerebral infarcts (OR, 2.53; 95% CI, 1.17-5.44), large white matter hyperintensity (OR, 2.35; 95% CI, 1.08-5.13), and poorer performance on executive function (-0.39 per SD; P<0.05), but not with total brain volume or hippocampal volume. Carotid atherosclerosis markers were associated with MRI indices of brain ischemia and aging and with cognitive impairment in a community-based sample of middle-aged adults. Our data suggest that internal carotid artery intima-media thickness may be a better marker for cognitive impairment than common carotid artery intima-media thickness.

Prevalence and Correlates of Silent Cerebral Infarcts in the Framingham Offspring Study

Previous estimates of the prevalence of silent cerebral infarction (SCI) on MRI in community-based samples have varied between 5.8% and 17.7% depending on age, ethnicity, presence of comorbidities, and imaging techniques. We document the prevalence and risk factors associated with SCI at midlife in the community-based Framingham sample. Our study sample comprised 2040 Framingham Offspring (53% female; mean age, 62+/-9 years) who attended the sixth examination (1996-1998), underwent volumetric brain MRI (1999-2005,) and were free of clinical stroke at MRI. We examined the age- and sex-specific prevalences and the clinical correlates of SCI using multivariable logistic regression models. At least 1 SCI was present in 10.7% of participants; 84% had a single lesion. SCI was largely located in the basal ganglia (52%), other subcortical (35%) areas, and cortical areas (11%). Prevalent SCI was associated with the Framingham Stroke Risk Profile score (OR, 1.27; 95% CI, 1.10-1.46); stage I hypertension was determined by JNC-7 criteria (OR,1.56; CI,1.15-2.11), an elevated plasma homocysteine in the highest quartile (OR, 2.23; CI, 1.42-3.51), atrial fibrillation (OR, 2.16; CI, 1.07-4.40), carotid stenosis >25% (OR, 1.62; 1.13-2.34), and increased carotid intimal-medial thickness above the lowest quintile (OR, 1.65; CI, 1.22-2.24). The prevalence and distribution of SCI in the Framingham Offspring are comparable to previous estimates. Risk factors previously associated with clinical stroke were also found to be associated with midlife SCI. Our results support current guidelines emphasizing early detection and treatment of stroke risk factors.

Masked Hypertension in Diabetes Mellitus: A Potential Risk

The prevalence and clinical significance of masked hypertension (MHT) in diabetics have infrequently been described. The authors assessed the association of MHT (defined using a clinic blood pressure [BP] <140/90 mm Hg and daytime ambulatory BP > or = 135/85 mm Hg) with microvascular and macrovascular end organ damage in 81 clinically normotensive Japanese diabetic persons. The prevalence of silent cerebral infarcts (SCIs), increased left ventricular mass, and albuminuria were evaluated. Of 81 patients, 38 (46.9%) were classified as having MHT and showed significantly more SCIs (mean +/- SE: 2.5+/-0.5 vs 1.1+/-0.2; P=.017), and more albuminuria (39% vs 16%; P=.025), but no increase in left ventricular mass index, than the normotensive persons in office and on ambulatory BP monitoring group. The prevalence of MHT in this diabetic population was high (47%). Diabetic patients with MHT showed evidence of brain and kidney damage. Hence, out-of-office monitoring of BP may be indicated in diabetics whose BP is normal in the clinic.

Impact of Blood Pressure vs. Glycemic Factors on Target Organ Damage in Patients With Type 2 Diabetes Mellitus

The hypothesis that three measures of target organ damage in type 2 diabetics would be more closely related to blood pressure (BP) than to glycemic factors was tested by recording 24-hour ambulatory BP and glycosylated hemoglobin. The prevalence of silent cerebral infarcts with brain magnetic resonance imaging, left ventricular mass index with cardiac ultrasonography, and albuminuria in 244 asymptomatic diabetics (mean age, 65.4+/-9 years; 122 men and 122 women; hypertension, 73%) were evaluated. Multivariate analysis showed that age (standard partial regression coefficient: b=0.299; p<0.001), duration of hypertension (b=0.176; p=0.007), and 24-hour systolic BP (b=0.195; p=0.004) were significantly associated with the number of silent cerebral infarcts, but glycosylated hemoglobin (b=0.104; p=0.109) and duration of diabetes were not. Left ventricular mass index was associated with 24-hour systolic BP (b=0.377; p<0.001) and male sex (b=0.172; p=0.019). Presence of albuminuria was significantly associated with 24-hour systolic BP (b=0.209; p=0.003), duration of diabetes (b=0.154; p=0.022), cholesterol (b=0.132; p=0.042), and insulin use (b=0.150; p=0.026). In conclusion, all three measures of target organ damage were related to 24-hour BP, but only albuminuria was related to glycosylated hemoglobin in type 2 diabetics. BP may be more important than glycemic factors for predicting future cardiovascular complications.