Association between intracranial vessel calcifications, structural brain damage, and cognitive impairment after minor strokes: a prospective study

BackgroundVascular calcifications are a hallmark of atherosclerosis, and in the coronary arteries are routinely used as a prognostic marker. Calcifications of intracranial vessels (ICC) are frequently observed on non-contrast CT (NCCT) and their effect on post-stroke cognitive impairment (PSCI) remains unclear. Our aim was to explore the association of ICC with prospective long-term cognitive function and advanced MRI-measures in a large prospective cohort of cognitively intact mild stroke survivors.MethodsData from the Tel-Aviv brain acute stroke cohort (TABASCO) study [ClinicalTrials.gov #NCT01926691] were analyzed. This prospective cohort study (n = 575) aimed to identify predictors of PSCI, in cognitively intact mild stroke survivors. A quantitative assessment of the intracranial calcium content – The ICC score (ICCS) was calculated semi-automatically on NCCT using a validated calcium quantification application. Participants underwent a 3 T-MRI and prospective comprehensive cognitive clinical and laboratory assessments at enrollment, 6, 12, and 24-months.ResultsData were available for 531 participants (67.4 years, 59.5% males). The incidence of PSCI at two-years doubled in the high ICCS group (26% vs. 13.7%, p < 0.001). The high ICCS group had significantly greater small-vessel-disease (SVD) tissue changes and reduced microstructural-integrity assessed by Diffusion-Tensor-Imaging (DTI) maps (p < 0.05 for all). In multivariate analysis, a higher ICCS was independently associated with brain atrophy manifested by lower normalized white and gray matter, hippocampal and thalamic volumes (β = −0.178, β = −0.2, β = −0.137, β = −0.157; p < 0.05) and independently predicted PSCI (OR 1.83, 95%CI 1.01–3.35).ConclusionOur findings suggest that the ICCS, which is a simple and readily available imaging marker on NCCT, is associated with brain atrophy, microstructural damage, the extent of SVD, and may predict PSCI. This finding has implications for identifying individuals at risk for PSCI and implementing targeted interventions to mitigate this risk

Impact of Cerebral Microbleeds in Stroke Patients with Atrial Fibrillation

OBJECTIVES: Cerebral microbleeds are associated with the risks of ischemic stroke and intracranial hemorrhage, causing clinical dilemmas for antithrombotic treatment decisions. We aimed to evaluate the risks of intracranial hemorrhage and ischemic stroke associated with microbleeds in patients with atrial fibrillation treated with Vitamin K antagonists, direct oral anticoagulants, antiplatelets, and combination therapy (i.e. concurrent oral anticoagulant and antiplatelet) METHODS: We included patients with documented atrial fibrillation from the pooled individual patient data analysis by the Microbleeds International Collaborative Network. Risks of subsequent intracranial hemorrhage and ischemic stroke were compared between patients with and without microbleeds, stratified by antithrombotic use. RESULTS: A total of 7,839 patients were included. The presence of microbleeds was associated with an increased relative risk of intracranial hemorrhage (aHR 2.74, 95% confidence interval 1.76 - 4.26) and ischemic stroke (aHR 1.29, 95% confidence interval 1.04 - 1.59). For the entire cohort, the absolute incidence of ischemic stroke was higher than intracranial hemorrhage regardless of microbleeds burden. However, for the subgroup of patients taking combination of anticoagulant and antiplatelet therapy, the absolute risk of intracranial hemorrhage exceeded that of ischemic stroke in those with 2-4 microbleeds (25 vs 12 per 1,000 patient-years) and ≥11 microbleeds (94 vs 48 per 1,000 patient-years). INTERPRETATION: Patients with atrial fibrillation and high burden of microbleeds receiving combination therapy have a tendency of higher rate of intracranial hemorrhage than ischemic stroke, with potential for net harm. Further studies are needed to help optimize stroke preventive strategies in this high-risk group. This article is protected by copyright. All rights reserved

Walking and Sitting Time after a Stroke: A Comparison of Shifts and Changes over Time within an Acute Care Setting

Early activity post-stroke reduces secondary complications and improves rehabilitation outcomes. This study aimed to describe the physical activities of stroke patients in an acute hospital setting, compare activity patterns between working shifts, and assess associations between activity and clinical status. Twenty-one patients (mean age 69.4 ± 33.4 years,13 men) admitted due to acute ischemic stroke wore activity monitors for two weeks or until discharge. During the morning and evening shifts, the activity monitor collected daily data on walking and body position. The study discovered that patients’ overall activity levels were low and that activity was higher during morning shifts than evening shifts (sitting time: 185.31 ± 109.31 min and 91.8 ± 98.46 min, p = 0.002; number of steps: 58.3 ± 32.73 and 30.4 ± 17.6 steps, p < 0.001). Upright and sitting time increased in morning shifts (p = 0.002), while the number of steps increased in both morning and evening shifts (p = 0.002). In the evening shift, there was a fair (r = 0.28, p = 0.02) positive correlation between grip strength and the number of steps, such that patients with higher grip strength took more steps. In addition, there were poor (r = −0.2, p = 0.02) correlations between motor function (Trunk Control Test and Functional Ambulation Category) and time in an upright position, such that patients with lower functional ability sat longer. Clinical characteristics and level of activity did not show any other correlations. To conclude, the main out-of-bed activity of patients was sitting during morning shifts. The findings highlight the temporal differences in activity throughout the day, as well as the disconnect between clinical characteristics and activity levels

Walking and Sitting Time after a Stroke: A Comparison of Shifts and Changes over Time within an Acute Care Setting

Early activity post-stroke reduces secondary complications and improves rehabilitation outcomes. This study aimed to describe the physical activities of stroke patients in an acute hospital setting, compare activity patterns between working shifts, and assess associations between activity and clinical status. Twenty-one patients (mean age 69.4 ± 33.4 years,13 men) admitted due to acute ischemic stroke wore activity monitors for two weeks or until discharge. During the morning and evening shifts, the activity monitor collected daily data on walking and body position. The study discovered that patients’ overall activity levels were low and that activity was higher during morning shifts than evening shifts (sitting time: 185.31 ± 109.31 min and 91.8 ± 98.46 min, p = 0.002; number of steps: 58.3 ± 32.73 and 30.4 ± 17.6 steps, p p = 0.002), while the number of steps increased in both morning and evening shifts (p = 0.002). In the evening shift, there was a fair (r = 0.28, p = 0.02) positive correlation between grip strength and the number of steps, such that patients with higher grip strength took more steps. In addition, there were poor (r = −0.2, p = 0.02) correlations between motor function (Trunk Control Test and Functional Ambulation Category) and time in an upright position, such that patients with lower functional ability sat longer. Clinical characteristics and level of activity did not show any other correlations. To conclude, the main out-of-bed activity of patients was sitting during morning shifts. The findings highlight the temporal differences in activity throughout the day, as well as the disconnect between clinical characteristics and activity levels

Increased rate of missense/in-frame mutations in individuals with NF1-related pulmonary stenosis: A novel genotype-phenotype correlation

Neurofibromatosis type 1 (NF1) and its related disorders (NF1-Noonan syndrome (NFNS) and Watson syndrome (WS)) are caused by heterozygous mutations in the NF1 gene. Pulmonary stenosis (PS) occurs more commonly in NF1 and its related disorders than in the general population. This study investigated whether PS is associated with specific types of NF1 gene mutations in NF1, NFNS and WS. The frequency of different NF1 mutation types in a cohort of published and unpublished cases with NF1/NFNS/WS and PS was examined. Compared with NF1 in general, NFNS patients had higher rates of PS (9/35 26% vs 25/2322 1.1%, P valueo0.001). Stratification according to mutation type showed that the increased PS rate appears to be driven by the NFNS group with non-truncating mutations. Eight of twelve (66.7%) NFNS cases with non-truncating mutations had PS compared with a 1.1% PS frequency in NF1 in general (Po0.001); there was no increase in the frequency of PS in NFNS patients with truncating mutations. Eight out of eleven (73%) individuals with NF1 and PS, were found to have non-truncating mutations, a much higher frequency than the 19% reported in NF1 cohorts (Po0.015). Only three cases of WS have been published with intragenic mutations, two of three had non-truncating mutations. Therefore, PS in NF1 and its related disorders is clearly associated with non-truncating mutations in the NF1 gene providing a new genotype-phenotype correlation. The data indicate a specific role of non-truncating mutations on the NF1 cardiac phenotype