Presence Of Cerebral Microbleeds Research Articles

Association of serum vascular endothelial growth factor levels and cerebral microbleeds in patients with Alzheimer's disease.

The association between the presence of cerebral microbleeds (CMBs) and serum vascular endothelial growth factor (VEGF) levels in patients with Alzheimer's disease (AD) was investigated. Consecutive AD patients who underwent magnetic resonance examination with susceptibility-weighted imaging (SWI) were prospectively examined. The presence of CMBs on SWI was independently interpreted. The number and location of microbleeds were assessed. Demographics including age, sex and risk factors were obtained. Serum VEGF levels were measured with an enzyme-linked immunosorbent assay. Of the 146 AD patients included, 47 (32.2%) patients had CMBs on SWI. The CMBs were most commonly located in strictly lobar locations (29/47, 61.7%). The mean VEGF levels were higher in the patients with CMBs than in those without (336.72 ± 15.18 vs. 192.37 ± 11.34 pg/ml). Multivariate logistic regression analyses showed that, for each 10 pg/ml increase of VEGF levels, there was a significant increase in the presence of CMBs after adjusting for age and sex, and after additional adjustment for cardiovascular risk factors, silent lacunar infarction and white matter hyperintensity in patients with AD (odds ratio 2.37; 95% confidence interval 1.53-4.02, P = 0.004). Serum VEGF levels are associated with the presence of CMBs in patients with AD.

Visceral Fat Is an Independent Predictor of Cerebral Microbleeds in Neurologically Healthy People

Background: Obesity has a significant contribution to the risk of intracerebral hemorrhage (ICH). However, little is known about the association between central obesity and the presence of cerebral microbleeds (CMBs), a precursor of ICH. We sought to assess whether visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) are associated with the presence of CMB. Methods: We conducted a cross-sectional study of 1,737 neurologically healthy people (mean age 55.9 ± 9.1; 790 men), who underwent brain MRI and abdominal CT. Risk factors, anthropometric parameters and clinical information were obtained. CMBs were evaluated through T2*-weighted gradient-recalled echo MRI. The cross-sectional surface areas of the abdominal fat compartments were calculated. Study subjects were stratified into quartiles according to the distribution of VAT/SAT ratio. Results: A total of 75 (4.3%) subjects were found to have CMBs. Subjects with a greater quartile of VAT/SAT ratio were more likely to have higher numbers of CMBs (0 to ≥2; p = 0.001). In multivariable analysis, age and history of hypertension were associated with the presence of CMB (OR 1.09, 95% CI 1.06-1.13, p < 0.001; OR 1.70, 95% CI 1.01-2.84, p = 0.046, respectively). A dose-response relationship was observed between the extent of VAT/SAT quartile and CMB: compared to the lowest VAT/SAT quartile, OR 2.14 (95% CI 0.86-5.35) for second VAT/SAT quartile; OR 2.26 (95% CI 0.86-5.92) for third VAT/SAT quartile; and OR 2.91 (95% CI 1.04-8.12) for the highest VAT/SAT quartile (p for trend 0.03). Conclusion: In our study, higher VAT/SAT ratios were found to be independent predictors of CMBs in neurologically healthy people. This finding strengthens previous data, suggesting that visceral fat distribution is an important contributor to cerebral small vessel disease.

Predictors of New Cerebral Microbleeds in Patients with Antiplatelet Drug Therapy

Cerebral microbleeds (CMB) are associated with an increased risk for ischemic and especially hemorrhagic stroke. The aim of the present study is to identify patients at high risk for the development of new CMB after initiation of an antiplatelet drug therapy. Patients received magnetic resonance imaging (MRI) within 1 week after initiation of an antiplatelet drug treatment due to a first ischemic stroke (n = 58) and after a follow-up period of 6 months (n = 40). We documented the presence and the number of CMB at baseline and follow-up and analyzed the influence of possible risk factors including vascular risk factors, stroke etiology, and number of CMB at baseline using stepwise logistic regression and Spearman's correlation coefficient. We compared progression rates of CMB in relation to each risk factor using the Mann-Whitney U-test. The logistic regression model could correctly predict the presence of CMB in 70.7% of patients at baseline and 80% at follow-up. The model correctly identified 85% of patients with new CMB. We observed progression of CMB in 40% of the patients. The overall progression rate was .8 CMB per patient. The progression rate was significantly influenced by age more than 70 years and atherothrombotic stroke. The number of new CMB correlated significantly with the number of CMB at baseline. We found several predictors of CMB after initiation of antiplatelet drug therapy. The results help to identify patients who need closer monitoring and thorough control of risk factors in order to lower the risk of new CMB and associated complications.

Presence of Cerebral Microbleeds Is Unrelated to the Body Mass Index in Amerindians. A Population Study in Rural Ecuador (The Atahualpa Project)

Background: Information on the relationship between the presence of cerebral microbleeds (CMB) and the body weight is inconsistent. Moreover, studies have been limited to Asian and White populations. We aimed at assessing the association between CMB and the body mass index (BMI) in an indigenous South American population. Methods: CMB were identified by gradient-echo MRI and the BMI was calculated in community dwellers aged ≥60 enrolled in the Atahualpa Project. The association between CMB and the BMI was examined in logistic regression models adjusted for relevant confounders. Results: CMB were recognized in 41 (13%) out of 311 participants. These individuals were older, more often hypertensive, had a worse diet, had more severe white matter hyperintensities and strokes than those without CMB. Anthropometric measurements were 148 ± 9 cm for height, 58 ± 12 kg for weight, and 26.7 ± 5 kg/m² for the BMI. Multivariate models showed no association between the presence of CMB and the BMI (OR 0.97; 95% CI 0.89-1.05; p = 0.508). Analyses with CMB categorized according to their location did not show associations between strictly lobar or deep CMB and the BMI. Conclusion: The presence of CMB is unrelated to abnormal BMI determinations in Ecuadorian natives/mestizos.

Cerebral Microbleeds and Lacunar Infarcts Are Associated with Walking Speed Independent of Cognitive Performance in Middle-Aged to Older Adults

Background: The positive relationship between cognitive and physical performance has been widely established. The influence of brain structure on both domains has been shown as well. Objective: We studied whether the relationship between brain structure and physical performance is independent of cognitive performance. Methods: This was a cross-sectional analysis of 297 middle-aged to older adults (mean age ± SD 65.4 ± 6.8 years). Memory function, executive function and physical performance measured by the Tandem Stance Test, Chair Stand Test, 4-meter walk and 25-meter walk were assessed. Magnetic resonance imaging was available in 237 participants and used to determine the (sub)cortical gray matter, white matter, hippocampal and basal ganglia volumes and the presence of cerebral small-vessel disease, i.e. white matter hyperintensities, cerebral microbleeds (CMBs) and lacunar infarcts (LIs). Regression analysis was used adjusting for age, gender, education and whole-brain volume. A Bonferroni correction was applied considering p values <0.017 as statistically significant. Results: Poor memory function was associated with a slower 4-meter walking speed (p < 0.01). No association was found between brain structure and cognitive performance. The presence of CMBs and LIs was associated with a slower 25-meter walking speed (p < 0.001). This result did not change after additional adjustment for cognitive performance. Conclusions: In middle-aged to older adults, CMBs and LIs are associated with walking speed independent of cognitive performance. This emphasizes the clinical relevance of identifying each of the possible underlying mechanisms of physical performance, which is required for the development of timely and targeted therapies.

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.

Impaired renal function is related to deep and mixed, but not strictly lobar cerebral microbleeds in patients with ischaemic stroke and TIA.

The vasculature of the brain and kidneys are similarly vulnerable to hypertension, so their microvascular damage may be correlated. We investigated the relationship of renal function to the anatomical distribution of cerebral microbleeds (CMBs), a marker of underlying cerebral small vessel disease (hypertensive arteriopathy or cerebral amyloid angiopathy), in a Western patient cohort. This was a retrospective study of referrals to a hospital stroke service. All patients with clinical data and a T2*-weighted gradient-recalled echo (T2*-GRE) MRI were included. MRI scans were rated for CMBs using the Microbleed Anatomical Rating Scale. Renal function was assessed by estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease formula. We included 202 patients, 39 with CMBs (19.3 %); 15 had "strictly lobar", 12 had "strictly deep" and 12 had "mixed" CMBs. Patients without CMBs had a higher eGFR than those with CMBs (mean difference 6.50 ml/min/1.73 m(2), 95 % CI -14.73 to 1.72 ml/min/1.73 m(2), p = 0.121). Multivariable analysis found that those with deep and mixed CMBs had a lower eGFR than those without CMBs (mean difference -10.70 ml/min/1.73 m(2), 95 % CI -20.35 to -1.06 ml/min/1.73 m(2), p = 0.030). There was no difference in eGFR found between those with strictly lobar CMBs and those without CMBs (mean difference -1.59 ml/min/1.73 m(2), 95 % CI -13.08 to 9.89 ml/min/1.73 m(2), p = 0.79). In a Western patient cohort, there appears to be an association between eGFR and the presence of deep and mixed CMBs, but not strictly lobar CMBs. This suggests a shared vulnerability of renal afferent and cerebral deep and superficial perforating arterioles to systemic hypertension. The arteriopathy underlying strictly lobar CMBs (i.e. cerebral amyloid angiopathy), appears to be less related to renal impairment.

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 TMP13: The Prevalence of Microbleeds in Moyamoya Disease and Moyamoya Syndrome in the United States

Introduction: Silent cerebral microbleeds (CMB) are common in Moyamoya Disease (MMD) and Moyamoya syndrome (MMS) in Asia. The incidence was reported to be 30-40%. The presence of CMB was found to be a predictor for subsequent cerebral hemorrhage in MMD. The significance of CMB in MMD/MMS in non-Asian population has not been reported. We try to investigate the prevalence of CMB in MMD/MMS in United States and its predictive value for subsequent cerebral hemorrhage. Methods: Moyamoya Database was established in our institution after reviewing patients with ICD9 code of Moyamoya Disease or Moyamoya Syndrome or cerebrovascular occlusive disease from 2007 to 2015. Patients in the database were reviewed retrospectively and included in the study if there were MR images (including GRE, SWI or T2* sequences) at diagnosis or during follow up and available for review. Patients with poor image quality were excluded. Patients were noted to have microbleeds if it was found on initial or follow up MRI. Multivariate logistic regression analysis was used to identify clinical and imaging predictors of CMB. Results: Sixty-three females and fourteen males were included with average age of 39 ± 13 at the time of diagnosis. The majorities were MMD (79.2%) and presented with ischemic events (79.2%). Hemorrhagic stroke was found in 9 (11.7%) patients before diagnosis. Ethnicity included Caucasian (61%), Asian (10.4%), Black (11.7%), and Hispanic (16.9%). Of total 77 patients, 7 (9.1%) had CMB but none of them presented with hemorrhagic stroke. During follow up of average 36 ± 29 months in these 7 patients, no cerebral hemorrhage was reported while ischemic events occurred in 2 (28.6%) patients. Of 70 patients without CMB, 51 had follow up of average 47 ± 46 months. One (2%) had cerebral hemorrhage while 12 (23.5%) had ischemic events. No independent predictors for CMB were identified among age, gender, ethnicity, etiology, presenting stroke, and comorbidities. Conclusions: Silent CMB was less prevalent in MMD/MMS in United States than in Asia. No specific risk factors were identified to be associated with the presence of silent CMB. It was not associated with increased risk of subsequent cerebral hemorrhage in non-Asian population. Further studies are needed to confirm these findings.

Automated detection of cerebral microbleeds in patients with Traumatic Brain Injury.

In this paper a Computer Aided Detection (CAD) system is presented to automatically detect Cerebral Microbleeds (CMBs) in patients with Traumatic Brain Injury (TBI). It is believed that the presence of CMBs has clinical prognostic value in TBI patients. To study the contribution of CMBs in patient outcome, accurate detection of CMBs is required. Manual detection of CMBs in TBI patients is a time consuming task that is prone to errors, because CMBs are easily overlooked and are difficult to distinguish from blood vessels.This study included 33 TBI patients. Because of the laborious nature of manually annotating CMBs, only one trained expert manually annotated the CMBs in all 33 patients. A subset of ten TBI patients was annotated by six experts. Our CAD system makes use of both Susceptibility Weighted Imaging (SWI) and T1 weighted magnetic resonance images to detect CMBs. After pre-processing these images, a two-step approach was used for automated detection of CMBs. In the first step, each voxel was characterized by twelve features based on the dark and spherical nature of CMBs and a random forest classifier was used to identify CMB candidate locations. In the second step, segmentations were made from each identified candidate location. Subsequently an object-based classifier was used to remove false positive detections of the voxel classifier, by considering seven object-based features that discriminate between spherical objects (CMBs) and elongated objects (blood vessels). A guided user interface was designed for fast evaluation of the CAD system result. During this process, an expert checked each CMB detected by the CAD system.A Fleiss' kappa value of only 0.24 showed that the inter-observer variability for the TBI patients in this study was very large. An expert using the guided user interface reached an average sensitivity of 93%, which was significantly higher (p = 0.03) than the average sensitivity of 77% (sd 12.4%) that the six experts manually detected. Furthermore, with the use of this CAD system the reading time was substantially reduced from one hour to 13 minutes per patient, because the CAD system only detects on average 25.9 false positives per TBI patient, resulting in 0.29 false positives per definite CMB finding.

Abstract TP67: Cerebral Microbleeds Are Associated With Hemorrhagic Infarction Among Acute Ischemic Stroke Patients With NVAF: The SAMURAI-NVAF Study

Background and purpose: Cerebral microbleeds (CMBs) are prevalent among stroke patients, and have shown to be the risk factor for the future ischemic or hemorrhagic stroke in several reports. However, the significance of CMBs among acute ischemic stroke patients, especially those with non-valvular arterial fibrillation (NVAF), remains unknown. Methods: Of 1,192 patients who participated in the SAMURAI-NVAF study (an ongoing prospective, multicenter, observational study), 1,099 patients (77.6±10.0 y.o, 620 men) underwent a T2* weighted image (T2*WI). Association of CMBs detected on T2*WI with the incidence of any hemorrhagic infarction (any HI and PH) and PH2 seven days after the index stroke and symptomatic hemorrhagic events and modified Rankin Scale (mRS) at discharge were assessed. Results: CMBs were detected in 256 patients (23.2%); single CMB in 96, 2-4 CMBs in 109, and ≥5 CMBs in 51. Hemorrhagic infarction was more frequent as the number of CMBs increased (21.5%, 21.9%, 26.6%, and 33.3% in patients with 0, 1, 2-4, and ≥5 CMBs, respectively: p=0.024, analyzed by Cochran-Armitage test for trend). PH2 was identified in 2.5%, 0%, 2.8% and 3.9%, respectively (p=0.824), symptomatic hemorrhagic event in 1.2%, 1.0%, 0%, and 0%, respectively (p=0.5910), and mRS 3-6 in 51.5%, 54.2%, 54.1%, and 62.7%, respectively (p=0.4370). Presence of CMBs was independently associated with any hemorrhagic infarction [odds ratio (OR) 1.72; 95% confidence interval (CI) 1.18-2.51; p=0.005] after adjustment for age, sex, premorbid mRS, infarct size, infarct number, and intravenous thrombolysis, but not with PH2 (p=0.639), symptomatic hemorrhagic events (p=0.633), or mRS 3-6 (p=0.212). Among 253 patients receiving intravenous thrombolysis or endvascular therapy, CMBs were also independently associated with hemorrhagic infarction (OR 2.75; 95%CI 1.27-6.04; p=0.010), but not with the other outcomes. Conclusions: CMBs were associated with any hemorrhagic infarction in acute ischemic stroke patients with NVAF regardless of receiving thrombolysis or not. However, they were not associated with PH2, symptomatic hemorrhagic events, or unfavorable vital or functional outcomes.

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 TP62: The Incidence of Post-treatment Cerebral Microbleeds After Combined Therapy of Endovascular Thrombectomy and tPA

Introduction: Cerebral microbleeds (CMBs) are considered as a risk factor for stroke. The incidence of post-tPA microbleeds have been reported in recent studies, however, it is not clear that whether hybrid procedure (the combination of tPA and endovascular thrombectomy) for ischemic stroke would increase risk of post-treatment CMBs more than treatment with tPA or endovascular thrombectomy alone. Objective of this study is to compare the incidence of post-treatment CMBs and symptomatic exraischemic hemorrhage by treatments: hybrid procedure, tPA alone, and endovascular thrombectomy alone. Hypothesis: Combined therapy of endovascular thrombectomy and tPA for ischemic stroke have higher incidence of post-treatment CMBs than tPA or endovascular thrombectomy alone. Methods: We retrospectively reviewed pre- and post-T2*-weighted MRI of ischemic stroke patients who received above treatments in our hospital during 2010 to 2014. The presence and number of CMBs were assessed according to the Brain Observer Microbleeds Scale. We compared the number of pre-treatment CMBs, incidence of newly-occurred post-treatment CMBs and symptomatic extraischemic hemorrhage within a year after treatments among hybrid procedure, tPA alone, and endovascular thrombectomy alone. Results: A total of 147 (hybrid procedure n=17, tPA alone n=90, endovascular thrombectomy alone n=40) patients’ pre- and post-treatment MRIs were reviewed. The average number of pre- treatment CMBs was 1.4±4.0 and there was no difference among treatments. The incidence of post-treatment CMBs was significantly higher in hybrid procedure (n=5, 29.4%) and tPA alone (n=18, 20.0%) than endovascular thrombectomy (n=1, 2.5%). However, there was no difference between hybrid procedure and tPA alone. Symptomatic extraischemic hemorrhage was found only one patient who received endovascular thrombectomy alone. Conclusion: The incidence of CMBs after treatments was increased in treatments using tPA. However, there was no difference in post-treatment incidence between hybrid procedure and tPA alone. This result suggests that additional thrombectomy after tPA would not increase the risk of CMBs.

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.

Longitudinal relationship between chronic kidney disease and distribution of cerebral microbleeds in patients with ischemic stroke

Chronic kidney disease (CKD) has been reported to be independently associated with cerebral microbleeds (CMB). Since both glomerular afferent arterioles and cerebral perforating arteries are strain vessels, CKD and CMB may share similar dynamic changes. To clarify whether CKD and CKD progression are related to the distribution and evolution of CMB in patients with ischemic stroke. We retrospectively examined the data from the CASISP study. 500 patients with ischemic stroke were analyzed. The number and distribution of CMB were assessed using Microbleed Anatomical Rating Scale. Renal function was evaluated by the estimated glomerular filtration rate (eGFR) and proteinuria. 51 (10.2%) and 158 (31.6%) had decreased eGFR (<60ml/min/1.73m(2)) and CMB at baseline, respectively; 31 (6.6%) and 84 (16.8%) had CKD and CMB progression. Decreased eGFR at baseline (OR=1.533, 95% CI: 1.111-2.114; p=0.009), proteinuria (OR=1.778, 95% CI: 1.026-3.083; p=0.040), CKD progression (OR=2.004, 95% CI: 1.191-3.370; p=0.009) and history of hypertension (OR=2.084, 95% CI: 1.241-3.49; p=0.005) were independently associated with the presence of deep or infratentorial CMB at follow-up. CMB progression in deep or infratentorial area was more frequent in patients with CKD progression than those without (29.0% versus 13.1%, p=0.028). Logistic regression analyses showed that CKD progression (OR=2.577, 95% CI: 1.393-4.769; p=0.003) was independently associated with the progression of deep or infratentorial CMB. CKD and CKD progression are independently associated with presence and evolution of deep or infratentorial CMB, but not lobar CMB.

Interaction of incidental microbleeds and prior use of antithrombotics with early hemorrhagic transformation: Causative or protective?

Background:Gradient echo (GRE) sequence of magnetic resonance imaging (MRI) is a sensitive tool to detect hemorrhagic transformation (HT) and old cerebral microbleeds (CMBs). Presence of CMBs and prior use of antithrombotics pose a risk of HT in ischemic stroke. We evaluated the association of CMBs and antithrombotic use with resultant HT in acute ischemic stroke (AIS).Methods:This retrospective study included AIS patients admitted to our center between January 2009 and August 2010 who underwent GRE-weighted MRI within 48 h of admission. Demographic and clinical data including diabetes mellitus, hypertension, hyperlipidemia, prior intake of antiplatelets/anticoagulants/statins, and presence of CMBs at admission were collected and compared between patients who developed HT and those who did not. We did a multivariate analysis using logistic regression to assess the effect of CMBs and prior use of antithrombotic agents on the risk of development for early HT in ischemic stroke.Results:Of 529 AIS patients, 81 (15%) were found to have HT during the initial hospital course. CMBs were found in only 9 of 81 patients (11%) with HT and in 40 out of remaining 448 patients (9%) who did not develop HT. The presence of CMBs was not associated with increased risk of HT (P = 0.53). However, prior use of antiplatelets (33% vs. 47% in the patients without HT, P = 0.02) was associated with decreased risk of HT in ischemic stroke.Conclusion:Presence of incidental CMBs was not associated with increased risk for early HT of an ischemic stroke. Interestingly, the prior intake of antiplatelets was found to be protective against HT of ischemic stroke.

Cerebral microbleeds in idiopathic normal pressure hydrocephalus.

BackgroundA vascular disease could be involved in pathophysiology of normal pressure hydrocephalus (INPH). If so, there should be an association between INPH and cerebral microbleeds (CMB). This study aims to analyze if CMB are associated with INPH.MethodsIn this case-control study we included 14 patients with INPH (mean age 76 years, 60 % female) and 41 healthy controls (HeCo; mean age 71 years, 60 % female). All were investigated with magnetic resonance imaging (MRI) using a T2*-sequence. The MRI exams were reviewed by two neuroradiologists for the presence of CMBs; the prevalence of findings of two or more CMBs was compared between INPH group and control group. After investigation, INPH patients underwent shunt surgery.ResultsTwo or more CMB were detected more frequently in the INPH group compared to HeCo (n = 6, 43 % vs. n = 4, 10 %; p = 0.01). Among the participants where MRI revealed CMB, the number of CMB was higher among the INPH patients than the HeCo (median 8; IQR 2-34 vs. median 1; IQR 1–2; p = 0.005).ConclusionsThis study supports a vascular component to the pathophysiology of INPH.

New Cerebral Microbleeds After Mechanical Thrombectomy for Large-Vessel Occlusion Strokes.

The interval appearance of cerebral microbleeds (CMBs) after endovascular treatment has never been described. We investigated the frequency and predictors of new CMBs that developed shortly after mechanical thrombectomy for acute ischemic stroke, and its impact on clinical outcome.We retrospectively analyzed patients with large-vessel occlusion strokes treated with Merci Retriever, Penumbra System, or stent-retriever devices. Serial T2∗-weighted gradient-recall echo (GRE) magnetic resonance imaging (MRI) before and 48 h after endovascular thrombectomy were assessed to identify new CMBs. We examined independent factors associated with new CMBs after mechanical thrombectomy. We analyzed the association of the presence, burden, and distribution of new CMBs with clinical outcome.A total of 187 consecutive patients with serial GRE were enrolled in this study. CMBs were evident in 36 (19.3%) patients before mechanical thrombectomy. New CMBs occurred in 41 (21.9%) patients after mechanical thrombectomy. Of the 68 new CMBs, 45 appeared in the lobar location, 18 in the deep location and 5 in the infratentorial location. The presence of baseline CMBs was associated with new CMBs after mechanical thrombectomy (OR 5.38; 95% CI 2.13–13.59; P < 0.001), no matter whether the patients were treated primarily with mechanical thrombectomy or with intravenous thrombolysis followed by mechanical thrombectomy. Patients with new CMBs did not have increased rates of hemorrhagic transformation, in-hospital mortality, and modified Rankin Scale score 4 to 6 at discharge.New CMBs are common after mechanical thrombectomy in one-fifth of patients with acute ischemic stroke. Baseline CMBs before mechanical thrombectomy predicts the development of new CMBs. New CMBs after mechanical thrombectomy do not influence clinical outcome.

Oily fish consumption is inversely correlated with cerebral microbleeds in community-dwelling older adults: results from the Atahualpa Project.

Oily fish is a major dietary source of omega-3 polyunsaturated fatty acids (ω-3 PUFAs). These nutrients improve endothelial dysfunction, reduce β-amyloid induced damage of neurovascular units, and might prevent the occurrence of cerebral microbleeds. However, this relationship has not been investigated so far. To evaluate the association between oily fish intake and cerebral microbleeds in a population of frequent fish consumers living in coastal Ecuador. Cerebral microbleeds were identified by gradient-echo MRI and oily fish consumption was calculated in community-dwellers aged ≥60years enrolled in the Atahualpa Project. The association between cerebral microbleeds and fish servings was examined in regression models adjusted for relevant confounders. A predictive model was constructed using quintiles of fish servings to take into account the non-linearity in the relationship. Out of 311 eligible individuals, 293 (94%) were enrolled. Cerebral microbleeds were recognized in 37 (13%) individuals. Mean fish consumption was 8.8±5.4 servings per week (ω-3 PUFAs estimates: 10.2±7.1g). Multivariate analysis showed an inverse relationship between cerebral microbleeds and fish consumption (p<0.001). Predictive margins of CMB were higher for individuals in the lowest (≤4.3) than for those in the highest (≥13.1) quintile of fish servings (17.4 vs 2.3%, p<0.001). This study shows a lower cerebral microbleed presence among older adults eating large amounts of oily fish (13 servings per week, equivalent to about 15g of ω-3 PUFAs). These high requirements can be more readily accomplished in other populations by taking fish oil preparations. Longitudinal studies are warranted to assess whether these interventions reduce incident cerebral microbleeds in high-risk individuals.