Location Of Cerebral Microbleeds Research Articles

Location of Cerebral Microbleeds May Predict Subsequent Stroke after Transient Ischemic Attack

Location of Cerebral Microbleeds May Predict Subsequent Stroke after Transient Ischemic Attack

Cerebral microbleeds are associated with physical frailty: a community-based study

The present study aimed to evaluate whether cerebral microbleeds (CMBs), as a presentation of cerebral small vessel diseases (CSVDs), are associated with physical frailty. This is a cross-sectional evaluation in participants from a community-based study, the I-Lan Longitudinal Aging Study. The physical frail status was evaluated using the Cardiovascular Health Study score, which includes components of weakness, low physical activity, slowness, exhaustion, and weight loss. The CMBs were assessed with magnetic resonance imaging using susceptibility-weighted imaging. Of the 962 subjects (62.5 [8.6] years, 44.2% men) included, 33.2% had physical prefrail and 3.3% had frail status. Compared with the robust subjects, prefrail and/or frail subjects presented with more overall CMB numbers and a higher number and/or incidence of CMB in the deep and/or infratentorial regions. Multivariate analysis with adjustment for age, sex, and vascular risk factors revealed that the CMB numbers were significantly associated with physical frailty. The brainstem was the only CMB location significantly associated with physical frailty (odds ratio, 95% CI, 13.50, 1.23–147.79) and the weakness component (5.04, 1.47–17.2), independent of age, sex, vascular risk factors, and the other presentations of CSVDs. Our results suggest that CSVD is involved in the pathophysiology of physical frailty.

Increased Number and Distribution of Cerebral Microbleeds Is a Risk Factor for Cognitive Dysfunction in Hemodialysis Patients: A Longitudinal Study.

The aim of this study was to explore the risk factors associated with longitudinal changes in hemodialysis patients including the correlation between number and distribution of cerebral microbleeds (CMBs).Sixty-one hemodialysis patients were enrolled in this prospective study. Twenty-eight patients had follow-up examinations with a mean interval of 24.79 ± 5.17 months. The number of CMBs was manually counted on susceptibility-weighted imaging. Subjects were divided into 2 groups with and without CMBs. In the CMB group, 8 of 33 patients did not have a mini-mental state examination (MMSE) because of blurred vision. Multiple logistic regression was used to investigate the risk factors for CMBs. Partial correlation was used to explore the correlation between the increased number of CMBs and the change of MMSE scores.CMBs were seen in 33 (54%) hemodialysis patients. Both age and pre/postdialysis systolic blood pressure (SBP) positively correlated with CMBs. Serum iron (SI), and high-density lipoprotein cholesterol (HDL-c) negatively correlated with CMBs (all P < 0.05). Among 25 patients with CMBs and MMSE, 9 patients had scores <27, which was considered as subnormal and most CMBs in these patients were located in the brainstem and basal ganglia. Considering age and follow-up time as the co-confounding factors, the number of new CMBs over the 2 imaging time points negatively correlated with the change of MMSE scores (r = −0.673, P = 0.023).The presence of new CMBs was a risk factor for cognitive dysfunction and the location of CMBs may be correlated with cognitive impairment. Both SI and HDL-c were protective factors for the CMBs. The risk factors for CMBs included age, pre- and postdialysis SBP.

Abstract 45: Cerebral Microbleeds and Cognitive Function in a Community-based Study

Introduction and Objective: Cerebral microbleeds (CMBs) have been acknowledged as a manifestation of age-related cerebral small vessel diseases. The prevalence of CMBs has been reported around 4.5%-15.3% in the general population, and could reach as high as 35.7% in people &gt;80 years old. Studies have evaluated the effects of CMBs on cognitive functions, however, the results about the influence of CMB location (e.g. deep/infratentorial or lobar) are inconsistent. Besides, there are scanty CMB studies of the Asian community-based population and even fewer have investigated in the impacts of CMBs on different cognitive domains. The present study aimed to evaluate the correlations between the CMBs and cognitive functions in a Taiwan community-based population. We determined whether the number and location of CMB had impacts on a variety of cognitive functions. Methods: Study subjects were from the community-based I-Lan Longitudinal Aging Study. Subjects with dementia and stroke were excluded. The cognitive domains including verbal memory, language, visuospatial executive, and verbal executive functions were evaluated. The number and location of CMBs were revealed by the 3T susceptibility weighted imaging MRI. Results: There were 401 subjects [63.87(8.82) years, 193(48.1%) men] included. CMBs were found in 11.7% of population. The results showed that lobar CMBs were significantly associated with poorer visuospatial instead of verbal executive function independent of age, gender, education, hypertension and the other markers of cerebral small vessel diseases. The presence of CMBs in the temporal and frontal lobes determined worse neuropsychological tests involving the visuospatial executive functions, the complex figure test [temporal CMBs: regression coefficient (95% confidence interval) = -4.59 (-9.46 - -0.35), p = 0.035; frontal CMBs: -2.13 (-6.91 - 2.65), 0.381] and clock drawing test [temporal CMBs: -1.55 (-3.17 - 0.10), p = 0.063; frontal CMBs: -1.48 (-3.15 - 0.18), 0.082]. Conclusion: The location is more important than amounts regarding the CMB effects on cognitive functions in non-demented non-stroke healthy subjects. Lobar CMBs, particular in the temporal and frontal lobe, are associated with poorer visuospatial executive function.

Abstract 178: Cerebral Microbleeds and Risk of Intracerebral Hemorrhage Post Intravenous Thrombolysis (IVT)

Background: Symptomatic intracranial hemorrhage (sICH) is the most feared complication of IVT for ischemic stroke, and patients who have cerebral microbleeds (CMBs) can potentially be at greater risk. This study aims to assess the association between the number and location of CMBs on MRI and the incidence of sICH post IVT. Subjects &amp; Methods: We analyzed consecutive IVT-treated patients during a 5-year period (2010-2014) at a tertiary care stroke center. Patients without pre or within 24-hour post-treatment MRI were excluded from the study. All neuroimaging studies were examined by two independent readers and a third reader as a tie-breaker. CMBs were defined according to recent consensus recommendations for MRI studies as round or oval, hypointense lesions with associated blooming on T2*-weighted MRI and can be up to 10 mm in diameter. Outcome measures in our study were occurrences of sICH and were defined according to European Cooperative Acute Stroke Study (ECASS)-III criteria combined with clinical deterioration of ≥4 points on NIHSS, or death. Results: Of 589 IVT patients (mean age 61±15 years, 51% men, median admission NIHSS: 6 points [IQR 3-11]), 97 patients had CMBs on T2*-MRI. Ten patients had more than 10, while the remaining 87 patients had 1-10 CMBs on T2*-MRI. The rates of sICH did not differ between patients with and without CMBs (4.1% vs. 3.5%; p=0.75). However, sICH occurred more frequently (p=0.0031) in patients with &gt;10MBs (30 %, 95%CI by the adjusted Wald method: 10%-61%) than in patients with 1-10 CMBs (1 %, 95%CI: 0%-7%). After adjusting for potential confounders, the presence of &gt;10 CMBs on T2*-MRI was independently (p=0.0004) associated with a higher likelihood for sICH [OR: 13.4, 95% CI: 3.2-55.9] in multivariate logistic regression analyses. Among patients with sICH in &gt;10 CMBs group, one patient developed multiple ICHs in different regions and one developed a large thalamic ICH remote from the infarcted area. In both these patients the location of ICHs corresponded to the location of CMBs on T2*-MRI. The third patient developed sub-arachnoid hemorrhage. Conclusions: Our findings indicate a higher risk of sICH after IVT when more than 10 CMBs are present. However, it does not demonstrate an increased risk of sICH among patients who have ≤ 10 CMBs.

Abstract 92: Cerebral Microbleeds in Transient Ischemic Attack and Minor Cerebrovascular Events

Background: Transient focal neurological episodes (TFNE) can occur in cerebral amyloid angiopathy (CAA) and can mimic transient ischemic attack (TIA). Hypothesis: Risk factors and outcomes of patients with minor stroke or TIA would differ in patients with and without cerebral microbleeds (CMB), including in patients with lobar microbleeds potentially consistent with CAA. Methods: 431 of 510 patients with high-risk TIA (motor or speech deficits &gt; 5 minutes) or minor stroke in the previously reported CATCH (CT and MRI in the triage of TIA and minor cerebrovascular events to identify high risk patients) study underwent baseline MRI. 416 scans with sufficient quality were analyzed for presence and location of CMB and cortical superficial siderosis. Clinical symptoms, baseline characteristics, recurrent TIA or stroke and 90 day modified Rankin scale (mRs) were prospectively collected. Results: CMB were detected in 65/416 (15.6 %), with a predominantly lobar pattern (75.4 %), and superficial siderosis in 11/416 (2.6 %). In a multivariable logistic regression model adjusted for number of risk factors age was associated with presence of CMB (odds ratio (OR) 1.04; 95 % confidence interval (CI) 1.02 - 1.06, P = 0.001). Presence of CMB was not associated with recurrent stroke or TIA (9.2 % vs. 11.1 %, P=0.65) or unfavorable mRS (&gt; 1) at 90 days (20 % vs. 16 %, P =0.42). Superficial siderosis was present in 11/416 (2.6%). 42 patients (10.1 %) fulfilled modified Boston criteria for possible or probable CAA. Presenting symptoms were not different between patients with vs. without possible/probable CAA, when considering either all patients or just those with TIA. Possible/probable CAA was not associated with recurrent stroke or TIA (7.1 % vs. 11.2 %, P = 0.42) or unfavorable mRs (&gt; 1) at 90 days (23.8 % vs. 15.8 %, P = 0.18). Conclusions: CMB in TIA and minor stroke patients are moderately common but do not strongly predict clinical recurrence and or 90-day functional outcome. Clinical presentations for CAA-related TFNE and TIA might be overlapping, suggesting that MRI may be needed to differentiate them.

Abstract 90: Cerebral Microbleeds in CADASIL: Influence of APOE Genotype and Hypertension

Introduction: CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) is a genetic disorder with an important predisposition for development of cerebral microbleeds (CMB). However, the relative impact of the two most common risk factors for CMB, hypertension and cerebral amyloid angiopathy, in CADASIL is uncertain. Hypothesis: We hypothesized that APOE (apolipoprotein E, an important predictor and correlate of cerebral amyloid angiopathy) genotype and hypertension influenced the presence and distribution of CMB in patients with CADASIL. Methods: CMB were identified as small (up to 10 mm) areas of signal void seen on 3.0T MRI susceptibility-weighted images. The locations of CMB were characterized as lobar, deep, and infra-tentorial. Results: In 83 patients with CADASIL (mean age 62.5 years), CMB were observed in 69.9% (58/83) of the total patient population. The most common areas of CMB were deep (57.8%, 48/83), lobar (50.6%, 42/83), and infra-tentorial location (38.4%, 33/83). Hypertension was found in 59% (49/83) of patients. APOE genotype frequencies were: ε2/ε3 9.6% (8/83); ε2/ε4 2.4% (2/83); ε3/ε3 57.8% (48/83); ε3/ε4 30.1% (25/83). Hypertension was associated with presence of CMB in lobar (p&lt;0.001), deep (p=0.035), and infra-tentorial locations (p=0.012). However, no significant associations were found between APOE genotype and presence of CMB in any location. Conclusions: In this cohort of CADASIL patients, hypertension but not APOE genotype predicted presence of CMB in all locations. These findings suggest that hypertension may amplify the arteriopathy of CADASIL in the development of CMB.

Abstract WMP58: Burden and Distribution of Cerebral Microbleeds Predict Long-Term Mortality in Lacunar Stroke Patients

Background and Purpose: Cerebral microbleeds (CMBs) are frequently observed in patients with lacunar infarction. CMBs are associated with an increased risk of mortality in stroke patients with nonvalvular atrial fibrillation and in the elderly population. We investigated the association of CMBs with long-term mortality in patients with lacunar infarction according to characteristics of CMBs. Methods: This was a retrospective hospital-based observational study. This study included 315 patients with first-ever lacunar infarction who underwent brain gradient-recalled echo imaging. The mortality data were obtained from the Korean National Statistical Office. By using a Cox regression analysis, we investigated the relationship between CMB characteristics and all-cause, ischemic stroke, and hemorrhagic stroke mortality. Results: CMBs were noted in 17.5% of patients (55/315). During a follow-up of 4.8 median years (interquartile range, 3.4-6.2 years), 43 patients (13.7%) died (ischemic stroke, 8; hemorrhagic stroke, 3). In multivariate analysis (age, sex p &lt; 0.1 in univariate), the presence of multiple (≥4) CMBs was an independent predictor for all-cause (hazard ratio [HR], 6.02), ischemic stroke (HR, 15.44), and hemorrhagic stroke (HR, 16.56) mortality. Considering CMB location, strictly lobar CMBs were independently related to hemorrhagic stroke mortality (HR, 101.22)(Tables and Figures). Conclusions: The presence, multiplicity, and distribution of CMBs were predictive of long-term mortality in acute lacunar infarction. The detection and evaluation of CMBs are of value in predicting long-term prognosis in patients with lacunar infarction.

Quantity of Cerebral Microbleeds, Antiplatelet Therapy, and Intracerebral Hemorrhage Outcomes: A Systematic Review and Meta-analysis

Cerebral microbleeds (CMBs) increase future intracerebral hemorrhage (ICH) risk after ischemic stroke (IS) or transient ischemic attack (TIA). However, whether CMB-related ICH risk depends on CMB quantity, CMB location, or antithrombotic agents is unclear. We performed a systematic review and meta-analysis to investigate CMB-related ICH risk, stratifying patients according to the quantity of CMB, the location of CMB, and the type of antithrombotic therapy used. Literature databases were searched for prospective cohorts reporting ICH outcomes in patients with IS or TIA with baseline CMB evaluation. We calculated pooled relative ratios (RRs) for ICH among patients with and without CMBs. Pooled RRs of CMB-related ICH were further calculated in subgroups stratified by CMB quantity, CMB location, and antithrombotic therapy. Among the 10 included studies, the pooled RR of future ICH was 7.73 (95% confidence interval [CI], 4.07-14.70; P < .001) in CMB versus non-CMB patients. Subgroup analysis revealed that compared with non-CMB patients, multiple-CMB patients were at an increased risk for future ICH (RR = 8.02; 95% CI, 3.21-20.01; P < .001), whereas single-CMB patients did not incur this risk (RR = 2.33; 95% CI, .63-8.63; P = .205). A strong association was found between CMB presence and subsequent ICH in antiplatelet users (RR = 16.56; 95% CI, 3.68-74.42; P < .001). Studies on CMB-related ICH according to CMB locations and in anticoagulant users are lacking for subgroup analysis. Our study revealed that patients with IS or TIA with multiple CMBs may incur a higher risk of future ICH, and the presence of CMBs in patients with IS or TIA using antiplatelet agents may significantly increase the subsequent ICH risk.

Incidental Cerebral Microbleeds and Cerebral Blood Flow in Elderly Individuals.

Cerebral microbleeds (CMBs) are collections of blood breakdown products that are a common incidental finding in magnetic resonance imaging of elderly individuals. Cerebral microbleeds are associated with cognitive deficits, but the mechanism is unclear. Studies show that individuals with CMBs related to symptomatic cerebral amyloid angiopathy have abnormal vascular reactivity and cerebral blood flow (CBF), but, to our knowledge, abnormalities in cerebral blood flow have not been reported for healthy individuals with incidental CMBs. To evaluate the association of incidental CMBs with resting-state CBF, cerebral metabolism, cerebrovascular disease, β-amyloid (Aβ), and cognition. A cross-sectional study of 55 cognitively normal individuals with a mean (SD) age of 86.8 (2.7) years was conducted from May 1, 2010, to May 1, 2013, in an academic medical center in Pittsburgh; data analysis was performed between June 10, 2013, and April 9, 2015. 3-Tesla magnetic resonance imaging was performed with susceptibility-weighted imaging or gradient-recalled echo to assess CMBs, arterial spin labeling for CBF, and T1- and T2-weighted imaging for atrophy, white matter hyperintensities, and infarcts. Positron emission tomography was conducted with fluorodeoxyglucose to measure cerebral metabolism and Pittsburgh compound B for fibrillar Aβ. Neuropsychological evaluation, including the Clinical Dementia Rating scale, was performed. Magnetic resonance images were rated for the presence and location of CMBs. Lobar CMBs were subclassified as cortical or subcortical. Measurements of CBF, metabolism, and Aβ were compared with the presence and number of CMBs with voxelwise and region-of-interest analyses. The presence of cortical CMBs was associated with significantly reduced CBF in multiple regions on voxelwise and region-of-interest analyses (percentage difference in global CBF, -25.3%; P = .0003), with the largest reductions in the parietal cortex (-37.6%; P < .0001) and precuneus (-31.8%; P = .0006). Participants with any CMBs showed a nonsignificant trend toward reduced CBF. Participants with cortical CMBs had a significant association with greater prevalence of infarcts (24% vs 6%; P = .047) and demonstrated a trend to greater prevalence of deficits demonstrated on the Clinical Dementia Rating scale (45% vs 19%; P = .12). There was no difference in cortical amyloid (measured by Pittsburgh compound B positron emission tomography) between participants with and without CMBs (P = .60). In cognitively normal elderly individuals, incidental CMBs in cortical locations are associated with widespread reductions in resting-state CBF. Chronic hypoperfusion may put these people at risk for neuronal injury and neurodegeneration. Our results suggest that resting-state CBF is a marker of CMB-related small-vessel disease.

Deep Cerebral Microbleeds and Renal Dysfunction in Patients with Acute Lacunar Infarcts

Cerebral small-vessel disease (SVD) is associated with renal dysfunction such as chronic kidney disease. Although cerebral microbleeds (CMBs) are common in patients with acute lacunar infarcts (ALI), the association between renal dysfunction and CMBs in such patients remains unclear. Between April 2007 and March 2013, we evaluated consecutive first-ever ALI patients, who were admitted to our hospital within 24 hours of stroke onset. CMBs were defined as focal areas of signal loss in brain parenchyma less than 5 mm on T2(∗)-weighted gradient-echo imaging. Renal dysfunction was defined as an estimated glomerular filtration rate less than 60 mL/minute/1.73 m(2) on admission. Correlations between renal dysfunction and the presence (model 1) and location of CMBs (model 2; any deep or infratentorial CMBs) were determined by multivariable logistic regression analyses. Among 152 patients (33.6% men; mean age, 67.6 years), 53 had CMBs. Patients with CMBs were older (69.9 versus 66.3 years, P = .03) and had a higher frequency of white matter hyperintensity (WMH; 62.3% versus 25.3%, P < .001), silent lacunar infarcts (SLI; 75.5% versus 43.3%, P < .001), and renal dysfunction (41.5% versus 22.2%, P = .015) than those without CMBs. On multivariable analyses, renal dysfunction (odds ratio, 95% confidence interval; model 1: 2.38, 1.02-5.66; model 2: 2.78, 1.16-6.81), WMH (3.87, 1.76-8.80; 3.72, 1.64-8.71), SLI (3.85, 1.71-9.14; 4.20, 1.77-10.8), and diabetes mellitus (.26, .09-.63; .24, .08-.63) were independently associated with CMBs. In patients with ALI, renal dysfunction was positively associated with CMBs independent of cerebral SVD.

Cerebral microbleeds and postthrombolysis intracerebral hemorrhage risk Updated meta-analysis.

We performed a systematic review and meta-analysis to assess whether the presence of cerebral microbleeds (CMBs) on pretreatment MRI scans of patients with acute ischemic stroke treated with thrombolysis is associated with an increased risk of symptomatic intracerebral hemorrhage (ICH). We searched PubMed for relevant studies and calculated pooled odds ratios (ORs) for symptomatic ICH, using the Mantel–Haenszel fixed-effects method, among individuals with vs without CMBs on pretreatment MRI scans. To minimize potential bias, sensitivity analysis was performed including studies providing data on patients treated only with IV thrombolysis. Ten eligible studies including 2,028 patients were pooled in meta-analysis. The overall prevalence of CMBs was 23.3%. Among patients with CMBs, 40 of 472 (8.5%; 95%confidence interval [CI]: 6.1%–11.4%) experienced a symptomatic ICH after thrombolysis compared with 61 of 1,556 patients (3.9%; 95% CI: 3%–5%) without CMBs. The pooled OR of ICH across all studies was 2.26 (95%CI: 1.46–3.49; p , 0.0001). Eight studies, including 1,704 patients (n 5 401 with CMBs), provided data on patients treated with IV thrombolysis only; OR for the presence of CMBs and the development of symptomatic ICH was 2.87 (95%CI: 1.76–4.69; p , 0.0001). Our meta-analysis of the available published data demonstrates an increased risk of symptomatic ICH after thrombolysis for acute ischemic stroke in patients with CMBs. However, we cannot fully exclude bias or confounding, so our results should be considered hypothesis generating. Detecting CMBs should not prevent thrombolytic treatment based on present evidence. Further analyses, taking into account CMB number and location, as well as measures of functional outcome, are needed.

Carotid arterial stiffness and risk of incident cerebral microbleeds in older people: the Age, Gene/Environment Susceptibility (AGES)-Reykjavik study.

Age and high blood pressure are major risk factors for cerebral microbleeds (CMBs). However, the underlying mechanisms remain unclear and arterial stiffness may be important. We investigated whether carotid arterial stiffness is associated with incidence and location of CMBs. In the prospective, population-based Age, Gene/Environment Susceptibility (AGES)-Reykjavik study, 2512 participants aged 66 to 93 years underwent a baseline brain MRI examination and carotid ultrasound in 2002 to 2006 and returned for a repeat brain MRI in 2007 to 2011. Common carotid arterial stiffness was assessed using a standardized protocol and expressed as carotid arterial strain, distensibility coefficient, and Young elastic modulus. Modified Poisson regression was applied to relate carotid arterial stiffness parameters to CMB incidence. During a mean follow-up of 5.2 years, 463 people (18.4%) developed new CMBs, of whom 292 had CMBs restricted to lobar regions and 171 had CMBs in a deep or infratentorial region. After adjusting for age, sex, and follow-up interval, arterial stiffness measures were associated with incident CMBs (risk ratio per SD decrease in carotid arterial strain, 1.11 [95% confidence interval, 1.01-1.21]; per SD decrease in natural log-transformed distensibility coefficient, 1.14 [1.05-1.24]; and per SD increase in natural log-transformed Young elastic modulus, 1.13 [1.04-1.23]). These measures were also significantly associated with incident deep CMBs (1.18 [1.02-1.37]; 1.24 [1.08-1.42]; and 1.23 [1.07-1.42]) but not with lobar CMBs. When further adjusted for blood pressure and other baseline vascular risk factors, carotid plaque, prevalent CMBs, subcortical infarcts, and white matter hyperintensities, the associations persisted. Our findings support the hypothesis that localized increases in carotid arterial stiffness may contribute to the development of CMBs, especially in a deep location attributable to hypertension.

Microbleed Status and 3-Month Outcome After Intravenous Thrombolysis in 717 Patients With Acute Ischemic Stroke.

Whether cerebral microbleeds (CMBs) detected on pretreatment magnetic resonance imaging increase the risks of symptomatic intracranial hemorrhage (sICH) and, most importantly, poor outcome in patients treated by intravenous thrombolysis for acute ischemic stroke is still debated. We assessed the effect of CMB presence and burden on 3-month modified Rankin Scale and sICH in a multicentric cohort. We analyzed prospectively collected data of consecutive patients solely treated by intravenous thrombolysis for acute ischemic stroke, in 2 centers where magnetic resonance imaging is the first-line pretreatment imaging. Neuroradiologists blinded to clinical data rated CMBs on T2* sequence using a validated scale. Logistic regressions were used to assess relationships between CMBs and 3-month modified Rankin Scale or sICH. Among 717 patients, 150 (20.9%) had ≥1 CMBs. CMB burden was associated with worse modified Rankin Scale in univariable shift analysis (odds ratio, 1.07; 95% confidence interval, 1.00-1.15 per 1-CMB increase; P=0.049), but significance was lost after adjustment for age, hypertension, and atrial fibrillation (odds ratio, 1.03; 95% confidence interval, 0.96-1.11 per 1-CMB increase; P=0.37). Results remained nonsignificant when taking into account CMB location or presumed underlying vasculopathy. The incidence of sICH ranged from 3.8% to 9.1%, depending on the definition. Neither CMB presence, burden, location, nor presumed underlying vasculopathy was independently associated with sICH. Poor outcome or sICH was not associated with CMB presence or burden on pre-intravenous thrombolysis magnetic resonance imaging after adjustment for confounding factors. An individual patient data meta-analysis is needed to determine whether a subgroup of patients with CMBs carries an independent risk of poor outcome that might outweigh the expected benefit of intravenous thrombolysis.

Renal dysfunction is associated with deep cerebral microbleeds but not white matter hyperintensities in patients with acute intracerebral hemorrhage.

Kidney disease is a risk factor for cerebral microangiopathy and spontaneous intracerebral hemorrhage (ICH). We aimed to determine the association of renal dysfunction (RD) with MRI correlates of different patterns of cerebral microangiopathies including cerebral microbleeds (CMB) and white matter lesions (WML) in patients with ICH. In a prospectively collected, single-center cohort of ICH patients, glomerular filtration rate (eGFR) was estimated using the Modification of Diet in Renal Disease equation. We classified the renal function in five categories: category 1 (eGFR ≥ 90 mL/min/1.73 m(2)), category 2 (eGFR 60-89), category 3 (eGFR 30-59), category 4 (eGFR 15-29), and category 5 (eGFR <15) and dichotomized at an eGFR of 60. Number, location, and extent of CMB and WML were measured on MRI. ICH and CMB locations were classified as lobar or deep. 97 ICH patients with MRI (mean age 65.9 ± 13.9 years) were included. Intracerebral hemorrhage was lobar in 52.6 %. Median eGFR was 85.8 mL/min/1.73 m(2) (IQR 34.3). Renal dysfunction was present in 12.4 % of the patients. At least one CMB was present in 57.7 % of patients, WML were even more frequent (97.7 %). Age and impaired renal function were factors independently associated with the presence of CMB. The presence of CMB was independently associated with the number and extent of WML. RD is a frequent comorbidity in patients with ICH. Associations of RD with hypertension and with CMB in deep location suggest a predominant impact of RD on deep rather than on lobar microangiopathy.

Cerebral Microbleeds and Cognitive Function in Ischemic Stroke or Transient Ischemic Attack Patients

Background: We explored the association between cerebral microbleeds (CMBs) and cognitive impairment in patients with ischemic stroke/transient ischemic attack (TIA). Methods: A total of 488 ischemic stroke/TIA patients received magnetic resonance imaging. Montreal Cognitive Assessment (MoCA) was used to evaluate global cognitive function and cognitive domains. The association of CMB quantity with cognitive function and the impact of CMB locations (strictly lobar, strictly deep, and mixed regions) on cognitive impairment were examined in regression models with adjustments for confounders. Results: A total of 113 subjects (23.2%) had ≥1 CMB. Strictly lobar, strictly deep, and mixed CMBs were identified in 36, 40, and 37 patients, respectively. The presence of ≥5 CMBs or strictly deep CMBs was associated with the MoCA total score (p = 0.007 and 0.020, respectively). Of all MoCA domains tested, a lower score in the attention domain was related to the presence of ≥5 CMBs (p = 0.014) and strictly deep CMBs (p = 0.028). Conclusion: CMBs were associated with cognitive dysfunction in stroke/TIA patients, especially in the attention domain. This association was mainly driven by CMBs in the deep region, underlining the role of hypertensive microangiopathy in stroke-related cognitive impairment.

Quantitative assessment and correlation analysis of cerebral microbleed distribution and leukoaraiosis in stroke outpatients

Objective:Cerebral microbleeds (CMBs) are bleeding events associated with cerebral small vessel disease (SVD). Strictly lobar CMBs and strictly deep CMBs are likely caused by cerebral amyloid angiopathy (CAA) and hypertensive arteriopathy, respectively. Leukoaraiosis (LA) reflects an ischaemic change in SVD, and LA severity has been correlated with CMBs. However, whether different locations (aetiologies) of CMBs correlate with LA is unknown.Methods:Patients receiving brain MRI and tbl2*-weighted gradient-recalled echo scans in a stroke outpatient department were screened for CMBs. The MRI results of the patients with CMBs were sent to investigators for further review and were evaluated using the Microbleed Anatomical Rating Scale. Cerebral microbleed severity was graded using a numerical scale. Leukoaraiosis severity was assessed using the Fazekas scale.Results:Cerebral microbleeds were observed in 14.6% of the 1289 screened patients. The CMB incidence increased with age (in years, < 50: 1.3%; 50–59: 10.7%; 60–69: 17.6% and ≥ 70: 23.6%; P = 0.000). The CMB locations were distributed as follows: 23.4% strictly lobar, 12.2% strictly deep, 6.4% strictly infratentorial and 58.0% mixed. Cerebral microbleed severity correlated with the total Fazekas scale score. The numbers of lobar, deep and infratentorial CMBs correlated with the total Fazekas scale score. The mixed CMB group displayed a significantly higher Fazekas scale score than the strictly lobar CMB group (P = 0.000).Discussion:Cerebral microbleed incidence increased with age. Mixed CMB type displayed the highest incidence. The severity and number of CMBs at any location correlated with LA severity. These results suggested interactions between hypertension and CAA during LA progression.

Clinical significance of cerebral microbleeds locations in CADASIL with R544C NOTCH3 mutation.

Background and PurposeAlthough cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common single-gene disorder of cerebral small blood vessels caused by NOTCH3 mutations, little has been described about the variation in the clinical findings between its underlying types of mutations. In particular, the presence of cerebral microbleeds (CMBs) has been an increasingly recognized magnetic resonance imaging finding in CADASIL, but their clinical significance is not clear. The purpose of this study is to assess whether CMBs are associated with symptomatic stroke in the CADASIL patients with R544C mutation and to compare the cerebral distribution of CMBs between CADASIL patients with and without symptomatic stroke.MethodsThis is a cohort study of patients who were diagnosed with genotype-confirmed R544C-mutation CADASIL. Primary neurologic symptoms were recorded. Symptomatic strokes were defined as transient ischemic attack, ischemic strokes and hemorrhagic strokes. CMBs were defined as focal areas of round signal loss on T2*-weighted gradient echo planar images with a diameter of less than 10 mm. The locations of CMBs were divided into lobar, basal ganglia, thalamus, brain stem and cerebellum. Multiple logistic regressions were performed to identify the epidemiologic or vascular risk factors associated with symptomatic stroke in patients with CADASIL.ResultsAmong total of 51 subjects in this cohort, CMBs were present in 20 of 32 patients (64.5%) in the symptomatic stroke-group and in 8 of 19 patients (42.1%) in the non-stroke group (p = 0.16). CMBs were observed more frequently in the basal ganglia (p<0.001) and the cerebellum (p<0.018) in the symptomatic stoke group compared to the non-stroke group. The mean number of CMBs was significantly higher in the symptomatic stroke group (15.4±18.0 lesions per patients with CMBs) versus those without symptomatic stroke (3.3±3.0 lesions per patients with CMBs) (p = 0.003). Hypertension was an independent risk factor for symptomatic stroke in CADASIL (p = 0.014). It was independently associated with CMBs locations as basal ganglia (p = 0.016), thalamus (p = 0.010), brainstem (p = 0.044), and cerebellum (p = 0.049). However, It was not independently associated with CMBs on lobar lesion (p = 0.152).ConclusionsIn this study hypertension was an independent predictor of CMBs presence in specific brain locations, as well as symptomatic stroke in the CADASIL patients. The distribution and burden of CMBs might be a clinically useful marker for the risk of symptomatic stroke. However, further prospective studies on the relationship between CMBs distribution and symptomatic stroke are required in order to support these preliminary findings.

Abstract T P320: Clinical Relevance of Cerebral Microbleeds in Patients with Atrial Fibrillation and Stroke

Background: Cerebral microbleeds (CMB) incidentally found during an MRI evaluation of ischemic stroke present a therapeutic dilemma. Case control studies suggest a relationship of cerebral microbleeds and intracerebral hemorrhage. Limited prospective studies of patients with ischemic stroke show variability in whether CMB hemorrhage rates are greater than recurrent ischemic stroke rates. Our aim was to determine the prevalence and characteristics of CMB in patients with atrial fibrillation presenting with stroke and secondly what the rate of prospective intracerebral hemorrhage (ICH) was in those same patients. Methods: Consecutive patients admitted with atrial fibrillation and stroke were identified in our institution’s Get with the Guideline database between 2008-2009. Data from the incident hospitalization included: demographic information, use of antithrombotic and/or anticoagulation, and cerebrovascular risk factors. Radiologic imaging was reviewed to determine if a GRE or SWI sequence was included and record the number and location of CMB. Follow up information was obtained by chart review and written survey or phone call. Death certificates were obtained where applicable. Results: 240 patients were identified, 128 of whom had a CT only and 112 who had an MRI. Of those with an MRI, 76 had GRE or SWI sequences. Twenty-one of 76 patients with a GRE or SWI sequence had a CMB (prevalence: 27.6%). One patient in the CMB (+) group had a prospective hemorrhage during an average follow up of 3 years (rate: 0.33 ICH per patient year of follow up). No patients in the CMB negative group had an ICH. Conclusions: Our study demonstrates the prevalence of cerebral microbleeds is much higher than the actual prospective hemorrhage rate. The prospective hemorrhage rate is low and consistent with findings from large, randomized anticoagulation studies in patients with atrial fibrillation.

Abstract W P164: Cerebral Microbleeds and Physical performance: The Framingham Heart Study

Objective: To study the association of cerebral microbleeds (CMB) on MRI and physical performance in a community based cohort free of stroke and dementia. Background: Impaired mobility and physical function are associated with increased morbidity and mortality. CMB are believed to be subclinical markers of hemorrhage-prone small vessel disease, but CMB-induced neuronal injury may promote physical impairment in individuals free of stroke and dementia by disrupting the complex cerebral pathways involved in gait control and balance. Methods: We evaluated 1710 Framingham Offspring Study participants (mean age 64.6 years, 54% women) attending a baseline examination (1998-2008), who had brain MRI allowing for CMB detection and available measurements of physical performance. Walking speed was available in all, while a subset (N≈500) had available standing balance, chair standing and short physical battery scores. Using multivariable logistic regression we related CMB presence overall and stratified by brain location (lobar or deep) to the physical performance measures. Results: CMB were observed in 7.7% of subjects. We observed an association of presence of any CMB with lower walking speed score (4 vs. &lt;4) after adjustment for age, sex, time between MRI and study exam, and MRI markers of ischemic small vessel disease (OR 0.53, 95% CI 0.30-0.93, p=0.03). The association was no longer significant after adjusting for vascular risk factors (hypertension, diabetes, smoking, prevalent cardiovascular disease) instead of MRI markers (OR 0.63, 95% CI 0.36-1.11, p=0.11). There were no significant associations by CMB location and CMB were not associated with the remaining physical performance measures in the smaller samples. Conclusions: CMB were associated with lower gait speed, a relation that was partly dependent on presence of vascular risk factors. Our findings are limited by the small sample in subgroups of CMB across physical performance measures other than gait speed, but if replicated in other studies, would suggest a negative impact of CMB on physical function in community dwelling persons without stroke or dementia. These findings are significant given longer life expectancy and increasing prevalence of CMB with age.