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 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 < 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

Does Malignancy Status Effect Outcomes in Patients With Large Vessel Occlusion Stroke and Cancer Who Underwent Endovascular Thrombectomy?

Background Cancer is associated with an increased risk of acute ischemic stroke, including large vessel occlusions. Whether cancer status affects outcomes in patients with large vessel occlusions that undergo endovascular thrombectomy remains unknown. Methods and Results All consecutive patients undergoing endovascular thrombectomy for large vessel occlusions were recruited into a prospective ongoing multicenter database, and the data were retrospectively analyzed. Patients with active cancer were compared with patients with cancer in remission. Association of cancer status with 90‐day functional outcome and mortality were calculated in multivariable analyses. We identified 154 patients with cancer and large vessel occlusions that underwent endovascular thrombectomy (mean age, 74±11; 43% men; median National Institutes of Health Stroke Scale 15). Of the included patients, 70 (46%) had a remote history of cancer or cancer in remission, and 84 (54%) had active disease. Outcome data at 90 days poststroke were available for 138 patients (90%) and was classified as favorable in 53 (38%). Patients with active cancer were younger and more often smoked but did not significantly differ from those without malignancy in other risk factors, stroke severity, stroke subtype, or procedural variables. Favorable outcome rates among patients with active cancer did not significantly differ compared with those seen in patients without active cancer, but mortality rates were significantly higher among patients with active cancer on univariate and multivariable analyses. Conclusions Our study suggests that endovascular thrombectomy is safe and efficacious in patients with history of malignancy as well as in those with active cancer at the time of stroke onset, although mortality rates are higher among patients with active cancer

Preventing post-stroke dementia. The MARCH Trial. Protocol and statistical analysis plan of a randomized clinical trial testing the safety and efficacy of Maraviroc in post-stroke cognitive impairment

BackgroundCurrent evidence suggest that 25%-33% of stroke-survivors develop post-stroke cognitive impairment (PSCI). The licensed drug Maraviroc, a CCR5-antagonist, is postulated to act via a neuroprotective mechanism that may offer the potential of preventing progression to vascular dementia. Our hypothesis: Maraviroc may have the potential to augment learning skills and cognitive performance by affecting synaptic plasticity, along with neuro-inflammatory modulation in patients with cerebral small vessel disease (SVD) and PSCI.DesignMARCH is a multi-center, double-blind randomized-control Phase-II trial of Maraviroc 150 or 600 mg/day versus placebo for 12-months in five stroke centers in Israel. Included are patients diagnosed with recent (1-24 months) subcortical stroke who experience mild PSCI and have evidence of white matter lesions and SVD on neuroimaging.OutcomesPrimary outcomes: 1. Change in cognitive scores. 2. Drug related adverse events. Secondary outcomes: change in functional and affective scores, MRI-derived measures, inflammatory markers, carotid atherosclerosis, cerebrospinal-fluid biomarkers in a sub-study. A sample size of 60 in each treatment group and 30 in the placebo group (total - 150 participants) provides 80% power between the treatment and the placebo groups.ConclusionsThe results of this work could lead to a novel, readily available, therapeutic avenue to reduce PSCI, and possibly other pathologies. This study will test safety and effectiveness of Maraviroc in limiting cognitive deterioration and/or post stroke cognitive impairment in patients with cerebral small vessel disease.ScheduleFirst-patient first-visit was May 2021. Recruitment to complete in 2023, follow-up to complete in 2024

Stroke Risk and Antithrombotic Treatment During Follow-up of Patients With Ischemic Stroke and Cortical Superficial Siderosis.

BACKGROUND AND OBJECTIVES In patients with ischemic stroke (IS) or TIA and cortical superficial siderosis (cSS), there are few data regarding the risk of future cerebrovascular events and also about the benefits and safety of antithrombotic drugs for secondary prevention. We investigated the associations of cSS and stroke risk in patients with recent IS or TIA. METHODS We retrospectively analyzed the Microbleeds International Collaborative Network (MICON) database. We selected patients with IS or TIA from cohorts who had MRI-assessed cSS, available data on antithrombotic treatments, recurrent cerebrovascular events [Intracranial hemorrhage -ICrH-, IS, or any stroke (ICrH or IS)], and mortality. We calculated incidence rates (IR) and performed univariable and multivariable Cox regression analyses. RESULTS Of 12.669 patients (mean age 70.4±12.3 years, 57.3% men), cSS was detected in 273 (2.2%) patients. During a mean follow-up of 24±17 months, IS was more frequent than ICrH in both cSS (IR 57.1 versus 14.6 per 1000 patient-years) and non-cSS groups (33.7 versus 6.3 per 1000 patient years). Compared to the non-CSS group, cSS was associated with any stroke on multivariable analysis [IR 83 versus 42 per 1000 patient-years, adjusted HR for cSS 1.62 (95%CI: 1.14-2.28; p=0.006)]. This association was not significant in subgroups of patients treated with antiplatelet drugs (n=6.554) or with anticoagulants (n=4.044). Patients with cSS who were treated with both antiplatelet drugs and anticoagulants (n=1.569) had a higher incidence of ICrH (IR 107.5 vs 4.9 per 1000 patient-years, adjusted HR 13.26; 95%CI: 2.90-60.63; p=0.001) and of any stroke (IR 198.8 vs 34.7 per 1000 patient-years, adjusted HR 5.03; 95%CI: 2.03-12.44; p<0.001) compared to the non-CSS group. DISCUSSION Patients with IS or TIA with cSS are at increased risk of stroke (ICrH or IS) during follow-up; the risk of IS exceeds that of ICrH for patients receiving antiplatelet or anticoagulant treatment alone, but the risk of ICrH exceeds that of IS in patients receiving both treatments. The findings suggest that either antiplatelet or anticoagulant treatment alone should not be avoided in patients with cSS, but combined antithrombotic therapy might be hazardous. Our findings need to be confirmed by randomized clinical trials

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