Location Of Cerebral Microbleeds Research Articles

Cerebral Microbleeds: Relationship to Antithrombotic Medications.

Cerebral microbleeds (CMBs) are represented by small areas of hemosiderin deposition, detected on brain magnetic resonance imaging (MRI), and found in ≈23% of the cognitively normal population over age of 60 years. CMBs predict risk of hemorrhagic and ischemic stroke. They correlate with increased cardiovascular mortality. In this article, we sought to determine in a population-based study whether antithrombotic medications correlate with CMBs and, if present, whether the association was direct or mediated by another variable. The study consisted of 1253 participants from the population-based Mayo Clinic Study of Aging who underwent T2* gradient-recalled echo magnetic resonance imaging. We tested the relationship between antithrombotic medications and CMB presence and location, using multivariable logistic-regression models. Ordinal logistic models tested the relationship between antithrombotics and CMB frequency. Using structural equation models, we assessed the effect of antithrombotic medications on presence/absence of CMBs and count of CMBs in the CMB-positive group, after considering the effects of age, sex, vascular risk factors, amyloid load by positron emission tomography, and apoE. Two hundred ninety-five participants (26.3%) had CMBs. Among 678 participants taking only antiplatelet medications, 185 (27.3%) had CMBs. Among 95 participants taking only an anticoagulant, 43 (45.3%) had CMBs. Among 44 participants taking an anticoagulant and antiplatelet therapy, 21 (48.8%) had CMBs. Anticoagulants correlated with the presence and frequency of CMBs, whereas antiplatelet agents were not. Structural equation models showed that predictors for presence/absence of CMBs included older age at magnetic resonance imaging, male sex, and anticoagulant use. Predictors of CMB count in the CMB-positive group were male sex and amyloid load. Anticoagulant use correlated with presence of CMBs in the general population. Amyloid positron emission tomography correlated with the count of CMBs in the CMB-positive group.

Cerebral Microbleeds and White Matter Hyperintensities are Associated with Cognitive Decline in an Asian Memory Clinic Study.

Cerebral Small Vessel Disease (SVD); lacunes, Cerebral Microbleeds (CMBs), and White Matter Hyperintensities (WMH) have a vital role in cognitive impairment and dementia. SVD in lobar location is related to cerebral amyloid angiopathy, whereas SVD in a deep location with hypertensive arteriopathy. It remains unclear how different locations of SVD affect long-term cognitive decline. The present study aimed to analyse the association between different locations and severity of SVD with global and domain-specific cognitive decline over the follow-up interval of 3 years. We studied 428 participants who had performed MRI scans at baseline and at least 3 neuropsychological assessments. Locations of lacunes and CMBs were categorized into strictly lobar, strictly deep and mixed-location, WMH volume into anterior and posterior. The National Institute of Neurological Disorders and Stroke-Canadian Stroke Network Harmonization Neuropsychological Battery was used to assess cognitive function. To analyse the association between baseline location and severity of SVD with cognitive decline, linear regression models with generalized estimated equations were constructed to calculate the mean difference, 95% confidence interval and two-way interaction factor between time and SVD. Increased numbers of baseline CMBs were associated with a decline in global cognition as well as a decline in executive function and memory domains. Location-specific analysis showed similar results with strictly lobar CMBs. There was no association with strictly deep and mixed-location CMBs with cognitive decline. Baseline WMH volume was associated with a decline in global cognition, executive function and memory. Similar results were obtained with anterior and posterior WMH volumes. Lacunes and their locations were not associated with cognitive decline. Strictly lobar CMBs, as well as WMH volume in anterior and posterior regions, were associated with cognitive decline. Future research focuses are warranted to evaluate interventions that may prevent cognitive decline related to SVD.

Number and location of cerebral microbleeds (CMBs) are associated with global and domain-specific cognitive impairment (4439)

Number and location of cerebral microbleeds (CMBs) are associated with global and domain-specific cognitive impairment (4439)

Classification differentiates clinical and neuroanatomic features of cerebral small vessel disease.

Age-related cerebral small vessel disease involves heterogeneous pathogenesis, such as arteriosclerosis/lipohyalinosis and cerebral amyloid angiopathy. MRI can visualize the brain lesions attributable to small vessel disease pathologies, including white-matter hyperintensities, lacune and cerebral microbleeds. However, these MRI markers usually coexist in small vessel disease of different aetiologies. Currently, there is no available classification integrating these neuroimaging markers for differentiating clinical and neuroanatomic features of small vessel disease yet. In this study, we tested whether our proposed stratification scheme could characterize specific clinical, neuroanatomic and potentially pathogenesis/aetiologies in classified small vessel disease subtypes. Cross-sectional analyses from a community-based non-demented non-stroke cohort consisting of ≥50 years old individuals were conducted. All participants were scanned 3T brain MRI for small vessel disease detection and neuroanatomic measurements and underwent physical and cognitive assessments. Study population were classified into robust and four small vessel disease groups based on imaging markers indicating (i) bleeding or non-bleeding; (ii) specific location of cerebral microbleeds; and (iii) the severity and combination of white-matter hyperintensities and lacune. We used whole-brain voxel-based morphometry analyses and tract-based spatial statistics to evaluate the regional grey-matter volume and white-matter microstructure integrity for comparisons among groups. Among the 735 participants with eligible brain MRI images, quality screening qualified 670 for grey-matter volume analyses and 617 for white-matter microstructural analyses. Common and distinct patterns of the clinical and neuroimaging manifestations were found in the stratified four small vessel disease subgroups. Hierarchical clustering analysis revealed that small vessel disease type 4 had features distinct from the small vessel disease types 1, 2 and 3. Abnormal white-matter microstructures and cognitive function but preserved physical function and grey-matter volume were found in small vessel disease type 4. Among small vessel disease types 1, 2 and 3, there were similar characteristics but different severity; the clinical features showed both physical frail and cognitive impairment and the neuroanatomic features revealed frontal–subcortical white-matter microstructures and remote, diffuse cortical abnormalities. This novel stratification scheme highlights the distinct clinical and neuroanatomic features of small vessel disease and the possible underlying pathogenesis. It could have potential application in research and clinical settings.

Abstract P49: Pattern of Cerebral Microbleeds and Cerebral Amyloid: The ARIC-PET Study

Background: Cerebral microbleeds (CMBs) are associated with cognitive decline, but their importance outside of clinical cerebral amyloid angiopathy is less well understood, as are the mechanisms of their impact on cognition. In a community-based dementia-free cohort, we evaluate cross-sectional associations between CMB patterns and cerebral amyloid β (Aβ) deposition, measured by florbetapir PET. Methods: ARIC-PET recruited nondemented individuals from 3 US sites. Participants completed 3T brain MRI with T2*GRE (with CMBs read for presence, frequency, location (lobar vs subcortical), and pattern, as well as florbetapir (Aβ) PET (global cortical standardized uptake value ratio >1.2 as a positive scan). Multivariable (see Table) logistic regression models of Aβ+ scans evaluated CMB presence, frequency, location, and pattern, in separate models. Effect modification by sex, race, APOE status, and cognition (normal vs mild cognitive impairment) was evaluated. Results: Nearly 25% of the 322 individuals included had CMBs. No significant associations were found between CMBs (presence or number) and Aβ positivity, but a pattern of isolated lobar CMBs or superficial siderosis was associated with over a 4-fold higher odds of elevated Aβ vs having no CMBs, without a similar elevated risk in those with isolated subcortical CMBs or mixed subcortical + either lobar CMBs or superficial siderosis. Although no significant interactions were found, a mixed pattern was nonsignificantly protective (OR estimates 0.4-0.6) and lobar only CMBs had a (nonsignificantly) higher risk (OR up to 6.4) of Aβ for three subgroups: women (vs men); Blacks (vs whites), APOE ε4 noncarriers (vs carriers), and cognitively normal (vs MCI). Conclusions: A lobar-only pattern of CMBs is most strongly associated with brain Aβ, with no elevated risk for a mixed CMB pattern. Further study is needed to understand differences in these CMB patterns and their meaning across distinct demographic subgroups.

Intracerebral Hemorrhage in Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy: Prevalence, Clinical and Neuroimaging Features and Risk Factors.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a monogenic cerebral small vessel disease. The role of intracerebral hemorrhage (ICH) in CADASIL remains elusive. The present study aims to investigate the prevalence, characteristics, and risk factors for ICH in CADASIL. This retrospective cross-sectional study investigated ICH and cerebral microbleeds (CMBs) in brain susceptibility-weighted imaging or T2*-weighted gradient-recalled echo images of 127 Taiwanese patients with genetically confirmed CADASIL. We analyzed CMBs, lacunes, white matter hyperintensity, and perivascular space. The total small vessel disease score (range, 0-4) was calculated to estimate the overall magnetic resonance imaging burden of small vessel disease. Multivariate regression analysis was performed to identify factors related to ICH lesions in CADASIL. Thirty-seven ICH lesions, including 15 symptomatic and 22 asymptomatic lesions, were found in 27 (21.3% [95% CI, 14.0%-30.9%]) of the 127 patients with CADASIL. The thalamus and lobar regions were the most common ICH locations, and 72.7% of the lobar hemorrhages occurred silently. Patients with CADASIL with ICH lesions more often had hypertension and a higher total small vessel disease score than those without ICH (odds ratio [95% CI]: 3.22 [1.25-8.30] and 3.79 [1.51-9.51]). The presence of CMBs in the brain stem and a total CMB count >10 were independently associated with ICH lesions in patients with CADASIL, with odds ratio (95% CI) of 5.82 (1.80-18.80) and 3.83 (1.08-13.67), respectively. ICH is an underestimated but important manifestation of CADASIL. The location and number of CMBs are associated with the presence of ICH lesions in patients with CADASIL.

Microbleeds, Cerebral Hemorrhage, and Functional Outcome After Endovascular Thrombectomy.

To determine whether pretreatment cerebral microbleeds (CMBs) presence and burden are correlated with an increased risk of intracranial hemorrhage (ICH) or poor functional outcome following endovascular thrombectomy (EVT) for acute ischemic stroke (AIS). Consecutive patients treated by EVT for anterior circulation AIS were retrospectively analyzed. Experienced neuroradiologists blinded to functional outcomes rated CMBs on T2*-MRI using a validated scale. We investigated associations of CMB presence and burden with ICH and poor clinical outcome at 3 months (modified Rankin Scale score >2). Among 513 patients, 281 (54.8%) had a poor outcome and 89 (17.3%) had ≥1 CMBs. A total of 190 (37%) patients experienced ICH; 66 (12.9%) were symptomatic. CMB burden was associated with poor outcome in a univariable analysis (odds ratio [OR], 1.18; 95% confidence interval [CI], 1.03-1.36 per 1-CMB increase; p = 0.02), but significance was lost after adjustment for sex, age, stroke severity, hypertension, diabetes mellitus, atrial fibrillation, prior antithrombotic medication, IV thrombolysis, and reperfusion status (OR, 1.05; 95% CI, 0.92-1.20 per 1-CMB increase; p = 0.50). Results remained nonsignificant when taking into account CMB location or presumed underlying pathogenesis. CMB presence, burden, location, or presumed pathogenesis were not independently correlated with ICH. Poor functional outcome or ICH were not correlated with CMB presence or burden on pre-EVT MRI after adjustment for confounding factors. Excluding such patients from reperfusion therapies is unwarranted. This study provides Class II evidence that in patients with AIS undergoing EVT, after adjustment for confounding factors, the presence of CMBs is not significantly associated with clinical outcome or the risk of ICH.

Cerebral Microbleeds in Patients with Parkinson's Disease and Dementia with Lewy Bodies: Comparison Using Magnetic Resonance Imaging and 99mTc-ECD SPECT Subtraction Imaging.

Cerebral microbleeds (CMBs) in patients with Parkinson's disease (PD) or dementia with Lewy bodies (DLB) have not been adequately studied. This study aims to find a difference in the total number, prevalence, and common locations of CMBs between PD and DLB and evaluate 99mTc-ECD SPECT subtraction images of these two diseases. We examined 112 patients with PD (53 males and 59 females; age: 77.4±3.6 years) and 28 age-matched patients with DLB (15 males and 13 females; age: 77.1±6.7 years) using brain magnetic resonance imaging (MRI) and 99mTc-ECD SPECT subtraction imaging. The total number of CMBs was higher in patients with DLB (41.2%) than in those with PD (11.5%), and the prevalence was significantly higher in the former (0.7±1.1) than the latter (0.2±0.5, p < 0.05). The odds ratio was 5.4 (95% confidence interval [CI]: 1.7-17.4). Furthermore, CMBs were commonly located in the basal ganglia of patients with PD (6 out of 87 patients) but in the occipital lobe of patients with DLB (8 out of 17 patients). 99mTc-ECD SPECT subtraction imaging indicated lower cerebral blood flow in the posterior cingulate gyrus among the patients with CMB-positive DLB than among those with CMB-positive PD; additionally, the cerebral blood flow was lower in the bilateral basal ganglia and midbrain among patients with CMB-positive DLB compared to those with CMB-negative DLB. A reduction in occipital glucose metabolism may be related to CMBs in the occipital lobe of patients with DLB.

Microbleeds and Outcome in Patients With Acute Ischemic Stroke and Atrial Fibrillation Taking Anticoagulants.

We investigated the impact of the presence, burden, and location of cerebral microbleeds (CMBs) on the risk of major adverse cerebrovascular and cardiovascular events (MACCE) in patients with acute ischemic stroke and atrial fibrillation treated with oral anticoagulants (OACs). We also examined whether the clinical effect of CMBs differs according to the type of OACs. A total of 1742 patients with acute ischemic stroke and atrial fibrillation treated with OACs were enrolled in this cohort study. The primary composite outcome was the occurrence of MACCE (a composite of stroke, acute myocardial infarction, or vascular death) over a 2-year period according to CMB status. CMB presence was significantly associated with the risk of future MACCE (hazard ratio, 1.89 [95% CI, 1.23-2.88]; P=0.003) after adjustment for confounders in patients with acute ischemic stroke and atrial fibrillation taking OACs. Patients with exactly 1 CMB had a similar rate of MACCE compared with those without CMBs (P=0.461). However, patients with multiple CMBs (≥2), particularly high burden CMBs (≥5), had a significantly higher proportion of MACCE. Both CMB-positive groups with lobar and deep CMB had more frequent MACCE than the CMB-negative group, and the rate of MACCE was not different according to CMB location. In patients treated with warfarin, CMB was significantly associated with a risk of MACCE (P=0.002), but not in patients treated with direct OACs (P=0.517). The study results indicate that the risk of future MACCE increased with increasing CMB burden in patients with AIS and atrial fibrillation taking OACs, while the anatomic location of CMBs did not influence the risk of future MACCE. This risk seemed to be more apparent in patients taking warfarin.

Hemorrhagic risk after intravenous thrombolysis for ischemic stroke in patients with cerebral microbleeds and white matter disease

ObjectivesAim of this study was to evaluate the association between cerebral microbleeds (CMBs) and white matter disease (WMD) with intracerebral hemorrhage (ICH) after intravenous thrombolysis (IVT) with rt-PA. We also evaluated whether CMBs characteristics and WMD burden correlate with symptomatic ICH and outcome.MethodsWe included acute ischemic stroke (AIS) patients treated with IVT. The number and location of CMBs as well as severity of WMD were rated analyzing pre- or post-treatment MRI. Multivariable regression analysis was used to determine the impact of CMB and WMD on ICH subgroups and outcome measures.Results434 patients were included. CMBs were detected in 23.3% of them. ICH occurred in 34.7% of patients with CMBs. Independent predictors of parenchymal hemorrhage were the presence of CMBs (OR 2.724, 95% CI 1.360–5.464, p = 0.005) as well as cortical-subcortical stroke (OR 3.629, 95% CI 1.841–7.151, p < 0.001) and atherothrombotic stroke subtype (OR 3.381, 95% CI 1.335–8.566, p = 0.010). Either the presence, or number, and location of CMBs, as well as WMD, was not independently associated with the development of SICH. No independent association between the presence, number, or location of CMBs or WMD and outcome measures was observed.ConclusionsThe results of our study suggest that the exclusion of eligible candidates to administration of IV rt-PA only on the basis of CMBs presence is not justified. The clinical decision should be weighed with a case-by-case approach. Additional data are needed to evaluate the benefit-risk profile of rt-PA in patients carrying numerous microbleeds.

Oral anticoagulant use and the development of new cerebral microbleeds in cardioembolic stroke patients with atrial fibrillation.

ObjectiveCerebral microbleeds (CMBs) are a magnetic resonance imaging (MRI) marker for cerebral small vessel disease. Existing CMBs and those that newly develop are associated with the risks of stroke incidence and recurrence. The purpose of the present study was to investigate the association of oral anticoagulant (OAC) use and the development of new CMBs in cardioembolic stroke patients with atrial fibrillation.Subjects and methodsWe prospectively followed cardioembolic stroke patients with atrial fibrillation who had been hospitalized in the stroke center of our hospital, had been prescribed anticoagulants at discharge, and underwent repeated brain MRI with an interval of at least one year from the baseline MRI. Assessing the presence, number and location of CMBs using T2*-weighted gradient-recalled echo MRI, we used logistic regression models to investigate the associations between OAC use and the incidence of new CMBs. We also examined associations of subsequent stroke with OACs and CMBs during the follow-up.ResultsA total of 81 patients, consisting of 45 patients receiving direct oral anticoagulants (DOACs) and 36 patients receiving warfarin (WF), were analyzed in the present study. Baseline CMBs were observed in 19/81 patients (23.5%) and new CMBs in 18/81 patients (22.2%) on follow-up MRI (median interval, 34 months). Of the 31 new CMBs, 25 (80.6%) developed in the lobar location and 6 (19.4%) in the deep or infratentorial location. New CMBs occurred in 4 patients (10.0%) taking DOACs alone, in 10 patients (35.7%) taking WF alone, in 3 patients (37.5%) taking WF plus antiplatelet agents and in 1 patient (20.0%) taking DOAC plus antiplatelet agent. Regarding location, the new CMBs were the lobar type in 7 of the 10 patients taking WF alone, as well as in 3 of the 4 patients taking DOACs alone. In multivariate analysis, the presence of CMBs at baseline and WF use (vs. DOAC use) were associated with new CMBs (CMB presence at baseline: OR 4.16, 95% CI 1.19–14.44; WF use: OR 3.38, 95% CI 1.02–11.42). The presence of ≥ 2 CMBs at baseline was related to a higher risk of subsequent stroke (OR 7.25, 95% CI 1.01–52.35, P = 0.048).ConclusionOur findings suggest that DOAC compared with WF use at discharge is associated with a lower incidence of new CMBs in cardioembolic stroke patients with atrial fibrillation. Further prospective studies in the clinical setting are needed to confirm our exploratory data.

Association of Cerebral Microbleeds with Cognitive Decline: A Longitudinal Study.

The role of cerebral microbleeds (CMBs) in cognitive impairment remains controversial. To investigate the possible links between the presence, progression, number, and location of CMBs and cognition. We assessed 792 subjects from the Alzheimer's Disease Neuroimaging Initiative who underwent both brain 3 Tesla MRI scans and cognitive testing. The association between CMBs and cognitive change was explored using linear mixed-effects models (LME). Presence and number of CMBs were associated with memory (β= -0.03, p = 0.015; β= -0.01, p = 0.003), executive function (β= -0.04, p = 0.010; β= -0.01, p = 0.014), and global cognitive function (β= -0.06, p = 0.025; β= -0.03, p < 0.001). Progression of CMBs showed significant negative associations with executive function (β= -0.05, p = 0.025) and global cognitive function (β= -0.12, p = 0.015). The relations with cognitive performance (memory, executive function and global cognitive function) were mainly driven by lobar CMBs (β= -0.03, p = 0.041; β= -0.04, p = 0.010; β= -0.07, p = 0.029, respectively), especially those located in temporal lobe (β= -0.08, p = 0.027; β= -0.13, p = 0.001; β= -0.26, p < 0.001, respectively). Furthermore, white matter hyperintensities may mediate the association between CMBs and cognition. The presence, progression, number, and location of CMBs, especially those located in temporal lobe, are associated with cognitive decline. These findings suggest CMBs play a role in cognitive impairment.

Role of susceptibility-weighted imaging in patients with idiopathic intracranial hypertension.

To evaluate the role of susceptibility-weighted imaging (SWI) in patients with idiopathic intracranial hypertension (IIH). A prospective study was done on 55 patients with IIH who underwent SWI of the brain. The images were evaluated by two independent readers for cerebral microbleeds (CMBs) and the interobserver agreement between both readers was calculated. The graphic rating scale (GRS) for headache was calculated. CMBs were found in 16 (29%) of patients with IIH for both readers with excellent interobserver agreement (K = 0.8, p = 0.001). There was excellent interobserver agreement for location (K = 0.8, p = 0.001) and side of CMBs (K = 0.8, p = 0.001). There was good interobserver agreement for size of CMBs (K = 0.75, p = 0.002) and number (K = 0.6, p = 0.006). The mean GRS for headache in patients with CMBs (5.61 ± 1.3) was significantly higher (p = 0.02) than that of patients without CMBs (4.9 ± 0.8). We concluded that SWI can detect CMBs in patients with IIH especially in patients with higher GRS for headache.

Underlying embolic and pathologic differentiation by cerebral microbleeds in cryptogenic stroke.

Cryptogenic stroke encompasses diverse emboligenic mechanisms and pathogeneses. Cerebral microbleeds (CMBs) occur differently among stroke subtypes. The association of CMBs with cryptogenic stroke is essentially unknown. CHALLENGE ESUS/CS (Mechanisms of Embolic Stroke Clarified by Transesophageal Echocardiography for ESUS/CS) is a multicenter registry with comprehensive data including gradient-echo T2*-weighted magnetic resonance imaging of cryptogenic stroke patients who underwent transesophageal echocardiography. Patients' clinical characteristics were compared according to the presence and location of CMBs. A total of 661 patients (68.7 ± 12.7years; 445 males) were enrolled, and 209 (32%) had CMBs. Age (odds ratio [OR] 1.02, 95% confidence interval [CI] 1.00-1.04, p = 0.020), male sex (OR 1.85, 95% CI 1.18-2.91, p = 0.007), hypertension (OR 1.71, 95% CI 1.03-2.86, p = 0.039), chronic kidney disease (OR 1.64, 95% CI 1.11-2.43, p = 0.013), deep and subcortical white matter hyperintensity (OR 1.82, 95% CI 1.16-2.85, p = 0.009), and periventricular hyperintensity (OR 2.18, 95% CI 1.37-3.46, p = 0.001) were independently associated with the presence of CMBs. Aortic complicated lesions (OR 1.78, 95% CI 1.12-2.84, p = 0.015) were associated with deep and diffuse CMBs, whereas prior anticoagulant therapy (OR 7.88, 95% CI, 1.83-33.9, p = 0.006) was related to lobar CMBs. CMBs were common, and age, male sex, hypertension, chronic kidney disease, and cerebral white matter diseases were related to CMBs in cryptogenic stroke. Aortic complicated lesions were associated with deep and diffuse CMBs, while prior anticoagulant therapy was related to lobar CMBs.

Cerebral microbleeds and their influence on cognitive impairment in Dialysis patients.

Cerebral microbleeds (CMBs) in dialysis patients have recently attracted much attention, and the different locations of CMBs indicate different pathological processes. Previous studies on the relationship between CMBs and cognitive impairment (CI) in the general population and in dialysis patients have reported controversial results. A total of 180 chronic dialysis patients were enrolled in our study. Based on brain magnetic resonance imaging (MRI) analysis of CMBs, the patients were divided into 4 groups (without-CMBs group, strictly lobar group, strictly deep group, and mixed group). A wide range of cognitive tests was administered to evaluate cognitive function. The risk factors for CMBs were explored, and the correlation between CMB distribution and CI was investigated by regression analysis. The prevalence of CMBs was 32.8% in the total study population, 36.1% in the haemodialysis (HD) subgroup and 26.2% in the peritoneal dialysis (PD) PD subgroup. Sixteen subjects (8.9%) were classified as the lobar group, 12 subjects (6.7%) as the mixed group, and 31 subjects (17.2%) as the deep group. A significant association was shown between deep CMBs and impaired cognitive function, involving overall cognitive function, memory, language ability and executive function. Deep CMBs were significantly associated with dialysis vintage, mean arterial pressure (MAP) and lacunar infarcts number, while deep CMBs showed no correlation with dialysis modality and current heparin medication. Deep CMBs are closely associated with global and specific CI in dialysis patients. Blood pressure control may prevent deep CMBs and their associated CI.

Magnetic Resonance Imaging Evaluation of Cerebral Microbleeds: A Comparative Analysis of Susceptibility Weighted Imaging and T2 Gradient Recalled Echo Sequences

Introduction: Cerebral Microbleeds (CMBs) are increasingly recognised as an important predictor of small vessel disease and cannot be detected on routine Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) sequences. Aim: CMBs on MRI and to compare the sensitivity of Susceptibility Weighted Imaging (SWI) and T2* Gradient Recalled Echo (GRE) sequences in detection of these microbleeds. Also, to evaluate association between topography (size, number and location) of CMBs and various risk factors. Materials and Methods: This Prospective Observational analytical study comprised of 67 patients with CMBs who were evaluated with Siemens 1.5 Tesla MRI machine. T2*-weighted GRE sequence and SWI were taken in all the patients in addition to routine MRI sequences. Two observers blinded to clinical information, independently interpreted the T2*GRE and SWI sequences. Both observers recorded the topographical details of CMBs which included presence, number, size and location and their association with various risk factors (hypertension, diabetes, smoking and hyperlipidemia). Inter-rater agreement for the number of CMBs on SWI and T2*GRE was calculated using Cohen’s Kappa (κ) as measure of agreement. Intra-Class Correlation Coefficient (ICC) for reliability index in test-retest, intra-rater and inter-rater reliability was also analysed. The intra-rater reliabilities of each rater were compared. The correlations between CMBs and risk factors was performed with Pearson’s correlation Coefficient (r). The p-value &lt;0.05 was considered statistically significant. Results: The SWI with its Reverse Phase (RP) detected more number of CMBs as compared to T2*GRE. Majority of the subjects (71.6%) had more than five CMBs. CMBs ≥5 mm had a strong correlation with both hypertension and diabetes as compared to CMBs &lt;5 mm. There was a higher frequency of patients with lobar CMBs (89.6%) followed by the deep location (70.1%). An almost perfect agreement was found between both observers for number of CMBs on RP SWI with ‘κ’ value of 0.97a (0.96-0.98) in contrast to a weak agreement on RP T2*GRE with κ=0.52a (0.40-0.64). For SWI, an almost perfect reliability was found (ICC=0.998) as compared to a moderate reliability on T2*GRE (ICC=0.6826). An excellent reliability was seen for size of CMBs &lt;5 mm on RP SWI (ICC 0.998). Conclusion: SWI offered greater reliability and sensitivity for CMB detection as compared to the T2*GRE sequence and is presently the gold standard sequence of MRI for quantifying CMBs. The burden of CMBs may further indicate inappropriately treated hypertension and diabetes.

Coexistence of Cerebral Microbleeds and Amyloid Pathology in Patients with Cognitive Complaints.

Background and PurposeWe investigated the prevalence of amyloid positivity and cerebral microbleeds (CMBs) in subjects with cognitive complaints with the aim of identifying differences in clinical parameters and cognitive function according to the pattern of coexistence.MethodsWe retrospectively enrolled 200 subjects with memory impairment and applied both standardized 18F-florbetaben PET and brain MRI, including susceptibility-weighted imaging. The amyloid burden was visually classified as positive or negative, and the number and location of CMBs were also analyzed visually. Descriptive analysis was performed for the prevalence of amyloid positivity and CMBs. The relationship between the coexisting pattern of those two findings and clinical parameters including the results of neuropsychiatric tests was analyzed.ResultsPositive amyloid PET scans were exhibited by 102 (51.5%) of the 200 patients, and 51 (25.5%) of them had CMBs, which were mostly located in lobar areas in the patients with positive amyloid scans. The patients with CMBs were older and had a higher burden of white-matter hyperintensities than the patients without CMBs. The patients with CMBs also performed worse in confrontation naming and frontal/executive function. When classified by topographical region, parietal CMBs (odds ratio=3.739, p=0.024) were significantly associated with amyloid positivity.ConclusionsThe prevalence of CMBs was higher in patients with cognitive decline than in the general population. CMBs play distinctive roles in affecting clinical parameters and neuropsychological profiles according to the coexistence of amyloid pathology.

Prevalence of and Risk Factors for Cerebral Microbleeds in Moyamoya Disease and Syndrome in the American Population

Background and Purpose: Cerebral microbleeds (CMB) are reported to be frequent in moyamoya disease (MMD) and moyamoya syndrome (MMS) in the Asian population. It is associated with an increased risk of intracerebral hemorrhage. The significance of CMB in MMD/MMS in non-Asian populations has not been well established. Our study aimed to investigate the prevalence of CMB in MMD/MMS in a moymoya cohort with a majority of non-Asians and to identify risk factors for developing a CMB and its predictive value for subsequent vascular events. Methods: The moyamoya database was compiled by screening for MMD/MMS among patients admitted to the Zale-Lipshy University Hospital at the University of Texas Southwestern Medical Center. We identified and analyzed data of 67 patients with MMD or MMS. Patients were characterized as CMB+ or CMB– based on MRI findings. In CMB+ patients, the total number and location of CMB were identified. Univariate and multivariate logistic regression were used to identify risk factors for developing CMB and whether CMB are associated with the development of subsequent vascular events. Results: Out of a total of 67 patients, 11 (16%) had CMB. Males had significantly higher odds of having CMB as compared to females (OR 1.76; 95% CI 1.40–24.3, p = 0.021). The incidence of CMB was also associated with age at diagnosis (mean age of CMB+ patients vs. CMB– patients: 44 vs. 34 years, respectively, p = 0.024), smoking (p = 0.006), and hemorrhagic stroke at presentation (p = 0.034). Logistic regression with multivariate analysis found that gender and age at diagnosis remained statistically significant. New ischemic events occurred in 2 (20%) out of 10 CMB+ patients and 13 (23%) out of 55 CMB– patients, respectively (p = 0.79). While 2 (3%) CMB– patients had a new cerebral hemorrhage during follow-up, none of the CMB+ patients did. Conclusions: CMB are less prevalent in MMD/MMS in the USA than in Asia. An older age at diagnosis and male gender were associated with CMB. The presence of CMB was not associated with an increased risk of a subsequent ischemic or hemorrhagic stroke.

Use of anticoagulant therapy and cerebral microbleeds: a systematic review and meta-analysis.

Anticoagulant therapy increases the risk that cerebral microbleeds (CMBs) progress to intracerebral hemorrhage, but whether the therapy increases risk of CMB occurrence is unclear. We performed a systematic review and meta-analysis to investigate the potential association between anticoagulant use and CMB occurrence in stroke and stroke-free individuals. We searched observational studies in PubMed, Ovid EMBASE, and Cochrane Library from their inception until September 2019. We calculated the pooled odds ratio (OR) and 95% confidence interval (CI) for the prevalence and incidence of CMBs in anticoagulant users relative to non-anticoagulant users. Forty-seven studies with 25,245 participants were included. The pooled analysis showed that anticoagulant use was associated with CMB prevalence (OR 1.54, 95% CI 1.26-1.88). The association was observed in subgroups stratified by type of participants: stroke-free, OR 1.86, 95% CI 1.25-2.77; ischemic stroke/transient ischemic attack, OR 1.33, 95% CI 1.06-1.67; and intracerebral hemorrhage, OR 2.26, 95% CI 1.06-4.83. Anticoagulant use was associated with increased prevalence of strictly lobar CMBs (OR 1.68, 95% CI 1.22-2.32) but not deep/infratentorial CMBs. Warfarin was associated with increased CMB prevalence (OR 1.64, 95% CI 1.23-2.18), but novel oral anticoagulants were not. Anticoagulant users showed higher incidence of CMBs during long-term follow-up (OR 1.72, 95% CI 1.22-2.44). Anticoagulant use is associated with higher prevalence and incidence of CMBs. This association appears to depend on location of CMBs and type of anticoagulants. More longitudinal investigations with adjustment for confounders are required to establish the causality.

Distribution preponderance of cerebral microbleeds according to severity of leukoaraiosis in Alzheimer's disease

Cerebral microbleeds (CMBs) and leukoaraiosis (LA) are common findings in Alzheimer's disease (AD). But clinical or topographic relation of CMBs associated with LA in AD has been lacking. This study was performed to determine frequency and topographic preponderance of CMBs according to severity of LA in AD and compare the cognition and behavior of the AD patients according to severity of LA in AD, also. •101 AD patients were classified in three groups as patients with minimal LA (n=55), moderate LA (n=30) and with severe LA (n=16).•CMBs were counted using mainly 1.5 Tesla SWI (n=90) and gradient-echo (n=10) imaging•The Microbleed Anatomical Rating Scale (MARS) was used to localize each CMB location.•Leukoaraiosis was rated on T2-weighted MRI using the CREDOS white matter hyperintensity visual rating scale.•Numbers and location of CMBs in moderate to severe LA group were statistically compared with those of CMBs in minimal LA group.•Moreover, we compared neuropsychology between the two groups by Seoul Neuropsychological Battery-1 •Total CMBs in moderate to severe LA group (CMBs = 77) was significantly more than CMBs (CMBs=32) in minimal LA group (P=0.024*, t-test)•There is not distribution predominance of CMBs in AD according to leukoaraiosis (P=0.775, Chi-square test)•There is no statistically significant cognitive differences between two groups. •As LA progresses, total number of CMBs increases without affecting cognition and behavior in AD patients and these findings suggest there is no distribution predominance of CMBs in AD according to leukoaraiosis