Background
Cerebral microbleeds can confer a high risk of intracerebral hemorrhage, ischemic stroke, death and dementia, but estimated risks remain imprecise and often conflicting. We investigated ...the association between cerebral microbleeds presence and these outcomes in a large meta-analysis of all published cohorts including: ischemic stroke/TIA, memory clinic, “high risk” elderly populations, and healthy individuals in population-based studies.
Methods
Cohorts (with > 100 participants) that assessed cerebral microbleeds presence on MRI, with subsequent follow-up (≥3 months) were identified. The association between cerebral microbleeds and each of the outcomes (ischemic stroke, intracerebral hemorrhage, death, and dementia) was quantified using random effects models of (a) unadjusted crude odds ratios and (b) covariate-adjusted hazard rations.
Results
We identified 31 cohorts (n = 20,368): 19 ischemic stroke/TIA (n = 7672), 4 memory clinic (n = 1957), 3 high risk elderly (n = 1458) and 5 population-based cohorts (n = 11,722). Cerebral microbleeds were associated with an increased risk of ischemic stroke (OR: 2.14; 95% CI: 1.58–2.89 and adj-HR: 2.09; 95% CI: 1.71–2.57), but the relative increase in future intracerebral hemorrhage risk was greater (OR: 4.65; 95% CI: 2.68–8.08 and adj-HR: 3.93; 95% CI: 2.71–5.69). Cerebral microbleeds were an independent predictor of all-cause mortality (adj-HR: 1.36; 95% CI: 1.24–1.48). In three population-based studies, cerebral microbleeds were independently associated with incident dementia (adj-HR: 1.35; 95% CI: 1.00–1.82). Results were overall consistent in analyses stratified by different populations, but with different degrees of heterogeneity.
Conclusions
Our meta-analysis shows that cerebral microbleeds predict an increased risk of stroke, death, and dementia and provides up-to-date effect sizes across different clinical settings. These pooled estimates can inform clinical decisions and trials, further supporting cerebral microbleeds role as biomarkers of underlying subclinical brain pathology in research and clinical settings.
Cerebral amyloid angiopathy (CAA) is a common cause of cognitive impairment in older individuals. This study aimed to investigate predictors of dementia in CAA patients without intracerebral ...hemorrhage (ICH). A total of 158 non-demented patients from the Stroke Service or the Memory Clinic who met the modified Boston Criteria for probable CAA were included. At baseline, neuroimaging markers, including lobar microbleeds (cerebral microbleeds (CMBs)), white matter hyperintensities (WMH), cortical superficial siderosis (cSS), magnetic resonance imaging (MRI)-visible centrum semiovale perivascular spaces (CSO-PVS), lacunes, and medial temporal atrophy (MTA) were assessed. The overall burden of small vessel disease (SVD) for CAA was calculated by a cumulative score based on CMB number, WMH severity, cSS presence and extent and CSO-PVS severity. The estimated cumulative dementia incidence at 1 year was 14% (95% confidence interval (CI): 5%–23%), and 5 years 73% (95% CI: 55%, 84%). Age (hazard ratio (HR) 1.05 per year, 95% CI: 1.01–1.08, p = 0.007), presence of MCI status (HR 3.40, 95% CI: 1.97–6.92, p < 0.001), MTA (HR 1.71 per point, 95% CI: 1.26–2.32, p = 0.001), and SVD score (HR 1.23 per point, 95% CI: 1.20–1.48, p = 0.030) at baseline were independent predictors for dementia conversion in these patients. Cognitive deterioration of CAA patients appears attributable to cumulative changes, from both vasculopathic and neurodegenerative lesions.
Background
We aimed to investigate cortical superficial siderosis as an MRI predictor of lobar intracerebral hemorrhage (ICH) recurrence risk in cerebral amyloid angiopathy (CAA), in a large ...prospective MRI cohort and a systematic review.
Methods
We analyzed a single-center MRI prospective cohort of consecutive CAA-related ICH survivors. Using Kaplan–Meier and Cox regression analyses, we investigated cortical superficial siderosis and ICH risk, adjusting for known confounders. We pooled data with eligible published cohorts in a two-stage meta-analysis using random effects models. Covariate-adjusted hazard rations (adj-HR) from pre-specified multivariable Cox proportional hazard models were used.
Results
The cohort included 240 CAA-ICH survivors (cortical superficial siderosis prevalence: 36%). During a median follow-up of 2.6 years (IQR: 0.9–5.1 years) recurrent ICH occurred in 58 patients (24%). In prespecified multivariable Cox regression models, cortical superficial siderosis presence and disseminated cortical superficial siderosis were independent predictors of increased symptomatic ICH risk at follow-up (HR: 2.26; 95% CI: 1.31–3.87, p = 0.003 and HR: 3.59; 95% CI: 1.96–6.57, p < 0.0001, respectively). Three cohorts including 443 CAA-ICH patients in total were eligible for meta-analysis. During a mean follow-up of 2.5 years (range: 2–3 years) 92 patients experienced recurrent ICH (pooled risk ratio: 6.9% per year, 95% CI: 4.2%–9.7% per year). In adjusted pooled analysis, any cortical superficial siderosis and disseminated cortical superficial siderosis were the only independent predictors associated with increased lobar ICH recurrence risk (adj-HR: 2.4; 95% CI: 1.5–3.7; p < 0.0001, and adj-HR: 4.4; 95% CI: 2–9.9; p < 0.0001, respectively).
Conclusions
In CAA-ICH patients, cortical superficial siderosis presence and extent are the most important MRI prognostic risk factors for lobar ICH recurrence. These results can help guide clinical decision making in patients with CAA.
OBJECTIVE:We hypothesized that florbetapir, a Food and Drug Administration–approved PET tracer, could distinguish cerebral amyloid angiopathy (CAA)–related intracerebral hemorrhage (ICH) from ...hypertensive ICH (HTN-ICH).
METHODS:We prospectively enrolled survivors of primary ICH related to probable CAA (per Boston Criteria, n = 10) and HTN-ICH (n = 9) without dementia. All patients underwent florbetapir-PET and multimodal MRI, and patients with CAA had additional Pittsburgh compound B (PiB) PET. Amyloid burden was assessed quantitatively (standard uptake value ratio SUVR) and visually classified as positive or negative.
RESULTS:The CAA and HTN-ICH groups had similar age (66.9 vs 67.1), sex, and leukoaraiosis volumes (31 vs 30 mL, all p > 0.8). Florbetapir uptake and PiB retention strongly correlated in patients with CAA both globally within cerebral cortex (r = 0.96, p < 0.001) and regionally in lobar cortices (all r > 0.8, all p ≤ 0.01). Mean global cortical florbetapir uptake was substantially higher in CAA than HTN-ICH (SUVR1.41 ± 0.17 vs 1.15 ± 0.08, p = 0.001), as was mean occipital SUVR (1.44 ± 0.12 vs 1.17 ± 0.08, p < 0.001), even after correcting for global SUVR (p = 0.03). Visual rating for positive/negative florbetapir demonstrated perfect interrater agreement (k = 1) and was positive for all 10 patients with CAA vs 1 of 9 HTN-ICH patients (sensitivity 100%, specificity 89%).
CONCLUSIONS:Florbetapir appears to label vascular amyloid in patients with CAA-related ICH. The approved florbetapir binary visual reading method can have diagnostic value in appropriate clinical settings.
CLASSIFICATION OF EVIDENCE:This study provides Class II evidence that florbetapir-PET provides a sensitivity of 100% (95% confidence interval CI 66%–100%) and specificity of 89% (95% CI 51%–99%) for determination of probable CAA among cognitively normal patients.
Perivascular spaces are an emerging marker of small vessel disease. Perivascular spaces in the centrum semiovale have been associated with cerebral amyloid angiopathy. However, a direct topographical ...relationship between dilated perivascular spaces and cerebral amyloid angiopathy severity has not been established. We examined this association using post-mortem magnetic resonance imaging in five cases with evidence of cerebral amyloid angiopathy pathology. Juxtacortical perivascular spaces dilation was evaluated on T2 images and related to cerebral amyloid angiopathy severity in overlying cortical areas on 34 tissue sections stained for Amyloid β. Degree of perivascular spaces dilation was significantly associated with cerebral amyloid angiopathy severity (odds ratio = 3.3, 95% confidence interval 1.3–7.9, p = 0.011). Thus, dilated juxtacortical perivascular spaces are a promising neuroimaging marker of cerebral amyloid angiopathy severity.
BACKGROUND AND OBJECTIVESHematoma expansion (HE) is a major determinant of neurologic deterioration and poor outcome in intracerebral hemorrhage (ICH) and represents an appealing therapeutic target. ...We analyzed the prognostic effect of different degrees of HE.METHODSThis was a retrospective analysis of patients with ICH admitted at 8 academic institutions in Italy, Germany, Canada, China, and the United States. All patients underwent baseline and follow-up imaging for HE assessment. Relative HE (rHE) was classified as follows: none (<0%), mild (0%-33%), moderate (33.1%-66%), and severe (>66%). Absolute HE (aHE) was classified as none (<0 mL), mild (0-6.0 mL), moderate (6.1-12.5 mL), and severe (>12.5 mL). Predictors of poor functional outcome (90 days modified Rankin Scale 4-6) were explored with logistic regression.RESULTSWe included 2,163 patients, of whom 1,211 (56.0%) had poor outcome. The occurrence of severe aHE or rHE was more common in patients with unfavorable outcome (13.9% vs 6.5%, p < 0.001 and 18.3% vs 7.2%, p < 0.001 respectively). This association was confirmed in logistic regression (rHE odds ratio OR 1.98, 95% CI 1.38-2.82, p < 0.001; aHE OR 1.73, 95% CI 1.23-2.45, p = 0.002) while there was no association between mild or moderate HE and poor outcome. The association between severe HE and poor outcome was significant only in patients with baseline ICH volume below 30 mL.DISCUSSIONThe strongest association between HE and outcome was observed in patients with smaller initial volume experiencing severe HE. These findings may inform clinical trial design and guide clinicians in selecting patients for antiexpansion therapies.
Abstract Introduction The Boston criteria are the basis for a noninvasive diagnosis of cerebral amyloid angiopathy (CAA) in the setting of lobar intracerebral hemorrhage (ICH). We assessed the ...accuracy of these criteria in individuals with lobar microbleeds (MBs) without ICH. Methods We identified individuals aged >55 years having brain magnetic resonance imaging (MRI) and pathological assessment of CAA in a single academic hospital and a community-based population (Framingham Heart Study FHS). We determined the positive predictive value (PPV) of the Boston criteria for CAA in both cohorts, using lobar MBs as the only hemorrhagic lesion to fulfill the criteria. Results We included 102 individuals: 55 from the hospital-based cohort and 47 from FHS (mean age at MRI 74.7 ± 8.5 and 83.4 ± 10.9 years; CAA prevalence 60% and 46.8%; cases with any lobar MB 49% and 21.3%; and cases with ≥2 strictly lobar MBs 29.1% and 8.5%, respectively). PPV of “probable CAA” (≥2 strictly lobar MBs) was 87.5% (95% confidence interval CI, 60.4–97.8) and 25% (95% CI, 13.2–78) in hospital and general populations, respectively. Discussion Strictly lobar MBs strongly predict CAA in non-ICH individuals when found in a hospital context. However, their diagnostic accuracy in the general population appears limited.
Anticoagulation substantially reduces the risk of stroke in patients with atrial fibrillation (AF). However, recent studies have shown that up to 22%-36% of patients on anticoagulation will suffer an ...ischaemic stroke (IS). In this narrative review, we provide an overview of risk factors, mechanisms, management of acute IS and strategies for secondary prevention for patients with AF with stroke despite oral anticoagulation. For this paper, we reviewed available literature from important studies (randomised clinical trials, meta-analyses, reviews and case series) on patients with IS despite anticoagulation. We focused on recent studies that examined safety and efficacy of acute stroke treatments and evaluation and management strategies for secondary prevention. The literature review suggests that patients with AF with IS despite anticoagulation are a heterogeneous group with several possible mechanisms, which may include reduced or non-adherence to anticoagulation, competing non-cardioembolic stroke aetiologies or cardioembolic mechanisms separate from AF. The identification of one or more possible mechanisms of stroke despite anticoagulation may allow for a more targeted and individualised approach for secondary prevention. There are limited data to guide management in such patients, and strategies to prevent recurrent strokes include strict risk factor control and therapies targeting the most likely stroke mechanism. In cases where AF is suspected to be the culprit, clinical trials are needed to test the safety and efficacy of left atrial appendage occlusion plus anticoagulation versus continued anticoagulation alone.
OBJECTIVE:We sought to explore the mechanisms leading to cerebral amyloid angiopathy (CAA)-related cortical superficial siderosis (cSS) by examining its neuroimaging and genetic association with ...cerebral microbleeds (CMBs).
METHODS:MRI scans of 84 subjects with probable or definite CAA participating in a longitudinal research study were graded for cSS presence and severity (focal, restricted to ≤3 sulci vs disseminated, ≥4 sulci), and CMB count. APOE ε variants were directly genotyped. We performed cross-sectional analysis comparing CMB counts and APOE ε2 and ε4 allele frequency between subjects with no, focal, or disseminated cSS.
RESULTS:cSS was present in 48% (n = 40) of the population. APOE ε2 was overrepresented among participants with focal (odds ratio OR 7.0, 95% confidence interval CI 1.7–29.3, p = 0.008) and disseminated (OR 11.5, 95% CI 2.8–46.2, p = 0.001) cSS relative to individuals without cSS. CMB counts decreased with increasing severity of cSS (median41, 38, and 15 for no cSS, focal cSS, and disseminated cSS, respectively, p = 0.09). The highest CMB count tertile was associated with APOE ε4 (OR 3.0, 95% CI 1.4–6.6, p = 0.006) relative to the lowest tertile.
CONCLUSIONS:Among individuals with advanced CAA, cSS tends to occur in individuals with relatively lower CMB counts and with a distinct pattern of APOE genotypes. These results suggest that CAA-related cSS and CMBs may arise from distinct vasculopathic mechanisms.
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