Multiple Cerebral Microbleeds Research Articles

Tumefactive cerebral amyloid angiopathy - related inflammation.

Cerebral amyloid angiopathy-related inflammation (CAA-ri) derives from inflammatory response to β-amyloid (Aβ) protein deposition within the cerebral blood vessel walls. We report a case that accentuates those clinical and imaging features that can contribute to raise suspicion for the condition and lead to early treatment initiation. A 72-year-old man was referred with one-month history of cognitive decline along with behavioral alterations. Brain MRI showed fluid attenuated inversion recovery (FLAIR) asymmetrical multifocal white matter hyperintensities (WMHs) along with multiple cerebral microbleeds (CMBs) and cortical superficial siderosis (cSS) on T2*-weighted gradient-recalled echo (T2*-GRE) images. Metabolic, infectious, and neoplastic causes were excluded, and subsequently corticosteroids were administered to the patient resulting in clinical recovery. Imaging on follow-up disclosed remission of WMHs, while CMBs load increased significantly. Clinical neurologists' acquaintance with the clinical and imaging features of CAA-ri allows prompt diagnosis and medication initiation, that is essential for a conceivably treatable condition.

Prevalence and Risk Factors of Cerebral Microbleeds in Community-Dwelling Adults in Urban Delhi.

Several observational studies have reported the prevalence of cerebral microbleeds (CMBs) and their risk factors in an elderly population. Any information in this regard is currently lacking from India. Aim of this study was to estimate the prevalence, risk factors of CMBs, and association with cognition in an Indian urban population aged 50 years and above. Household surveys were conducted as part of ongoing Longitudinal Cognition and Aging Research on Population of the National Capital Region (LoCARPoN) study in areas of urban Delhi. Magnetic resonance imaging of the brain was performed in 2599 participants. Using standard neuropsychological battery, mean Z-scores for each domain (memory, executive, information) were derived. Binary and stepwise logistic regression models were used to determine associated risk factors for the presence of CMB and its association with cognitive domains. The prevalence of CMBs was 14.42% (95% confidence interval [CI]: 13.06-15.73). Of these, 203 (7.81%) participants had single CMBs and 172 (6.61%) had multiple microbleeds (≥2). Higher prevalence was observed in older age (60-70 years: odds ratio [OR]: 1.25 [95% CI: 0.93-1.67]; 70-80 years: OR: 2.05 [95% CI: 1.48-2.84]; ≥80 years: OR: 3.27 [95% CI: 1.97-5.44]) compared to individuals in the age group 50-60 years. History of stroke (OR: 2.97 [95% CI: 1.56-5.66]), hypertension (OR: 1.36 [95% CI: 1.05-1.75]), and smoking (OR: 1.43 [95% CI: 1.11-1.85]) was associated with at least one CMB. Multiple CMBs were associated with worse scores in memory and executive domains. Older age, hypertension, history of stroke, and history of smoking emerged as important risk factors for the presence of multiple CMBs. Follow-up study is required to determine implications of CMBs.

Pro-Hemorrhagic Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy Associated with NOTCH3 p.R75P Mutation with Low Vascular NOTCH3 Aggregation Property.

Intracerebral hemorrhage (ICH) and cerebral microbleeds (CMB) in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy are more common in East Asian populations than in people of white European ancestry. We hypothesized that the ethnic difference is explained by the East Asian-specific NOTCH3 p.R75P mutation. This retrospective observational study included 118 patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy in Japanese and Korean cohorts. We investigated whether the p.R75P mutation is associated with symptomatic ICH and multiple CMB (>5) using quasi-Poisson regression models. We predicted the NOTCH3 extracellular domain protein structures in silico and graded NOTCH3 extracellular domain immunostaining in skin vessels of some patients, with subsequent comparisons between p.R75P and other conventional mutations. Among 63 Japanese patients (median age 55 years; 56% men), 15 had a p.R75P mutation, significantly associated with symptomatic ICH (adjusted relative risk 9.56, 95% CI 2.45-37.31), multiple CMB (3.00, 1.34-6.71), and absence of temporopolar lesions (4.91, 2.29-10.52) after adjustment for age, sex, hypertension, and antithrombotics. In the Korean cohort (n = 55; median age 55 years; 51% men), the p.R75P mutation (n = 13) was also associated with symptomatic ICH (8.11, 1.83-35.89), multiple CMB (1.90, 1.01-3.56), and absence of temporopolar lesions (2.32, 1.08-4.97). Structural analysis revealed solvent-exposed free cysteine thiols in conventional mutations, directly causing aggregation, whereas a stereochemically incompatible proline residue structure in p.R75P lowers correct disulfide bond formation probability, indirectly causing aggregation. Pathologically, the p.R75P mutation resulted in less vascular NOTCH3 extracellular domain accumulation than the other conventional mutations. NOTCH3 p.R75P mutation is associated with hemorrhagic presentations, milder temporopolar lesions, and distinct mutant protein structure properties. ANN NEUROL 2024;95:1040-1054.

Total Body Irradiation Is Associated with Higher Prevalence of Cerebral Microbleeds in Haematopoietic Stem Cell Transplant Survivors

Introduction Myeloablative conditioning (MAC) for haematopoietic stem cell transplant (HSCT) is associated with a wide range of toxicities. Cognitive impairment (CI) is a common late effect occurring in over 50% of HSCT survivors. We previously reported an increased incidence of cerebral microbleeds (CMBs) - haemosiderin deposits, appearing as hypointense lesions on magnetic resonance imaging (MRI) - in patients with ITP. No healthy controls in this cohort had CMBs (Cooper, 2020). CMBs can be caused by a range of factors, including cranial irradiation with 18 Gy or higher. Studies in patients receiving cranial irradiation for cerebral tumours have correlated CMBs with cognitive impairment. The presence of multiple CMBs has also been independently linked to an increased risk of dementia, stroke and intracerebral haemorrhage. TBI doses used in HSCT rarely exceed 15 Gy. Although this dose is smaller than reported in previous studies linking irradiation to CMBs, it is delivered at a time of considerable physiological stress. To date, there are no studies investigating the effect of TBI on the prevalence of CMBs. Aims Given the established association of CMBs with cranial radiotherapy, this study aims to assess the impact of TBI-based MAC on the prevalence of CMBs, as well as their association with cognitive impairment. Method We recruited HSCT survivors, at least 3 years post-HSCT. Patients who received TBI as part of their MAC (TBI group) and those who received purely chemotherapeutic MAC (control group) were included. We excluded patients with a known history of cranial irradiation, uncontrolled hypertension or insulin-dependent diabetes. All participants underwent a Susceptibility Weighted Imaging (SWI) MRI and CANTAB Insight cognitive testing. The number of CMBs was reported by a neuro-radiologist blinded to the patient data. Mann-Whitney U test was used to assess the location shift in CMB numbers between groups and Fisher's exact test was used to compare the prevalence of at least one or at least three CMBs. We used Spearman's rank correlation to assess the association between CMB number and CI. Results A total of 15 patients were recruited: 9 in the TBI group and 6 in control. The median patient age was 42 years: 41 years in the TBI group (range: 32-59 years) and 43.5 years in control (range: 27-62 years) with the median time since transplant being 66 months: 81 months in TBI group (range: 41-149 years) and 43.5 years in control (range: 40-72 years). All patients had a primary diagnosis of either AML (TBI: 5, control: 4), ALL (TBI: 2, control: 1) or CML (TBI: 2, control: 1). 8 patients received conditioning with cyclophosphamide-TBI and 1 with etoposide-TBI (median TBI dose 13.2 Gy; range: 12-14.4 Gy). 4 patients in the control group received thiotepa-busulfan-fludarabine and 2 received busulfan-cyclophosphamide. The median time to platelet engraftment was 18 days: 18 days in the TBI group (range: 13-73 days) and 21.5 days in control (range: 16-44 days). 5 patients in the TBI group and 4 in the control group had a history of chronic GVHD. None had disease relapse or more than one transplant. 9 of 15 patients had at least one CMB; 7 in TBI group (78%) compared to 2 in control (33%) (p=0.119). Although this was not significantly different, patients following TBI were more likely to have a higher number of CMBs: 4 patients (44%) in the TBI group had 3 or more CMBs, compared to none in the control (p=0.092). Median number of CMBs was 2 in TBI group (range: 0-9) and 0 in control (range: 0-2) (p=0.05) (Fig.1). Older age at HSCT was positively correlated with CMB number (ρ=0.5, p=0.06) with the correlation reaching statistical significance in an analysis of the TBI group only (ρ=0.78, p=0.01) (Fig.2). 7 patients (47%) showed impairment in processing speed and 6 (40%) in executive function. However, CMB number was not significantly correlated with the number of cognitively impaired domains on CANTAB insight testing (p=0.535). Conclusions The study provides the first evidence that low radiation doses, delivered through TBI, may increase CMB burden in HSCT survivors. The clinical significance of CMBs in this population remains unclear and our study did not demonstrate an association with impaired cognitive function. Given the complexity of peri-transplant physiology, further studies with larger cohorts would benefit from robust case-control matching and a longer follow-up with baseline cognitive assessment. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Association Between Plasma Biomarkers of Amyloid, Tau, and Neurodegeneration with Cerebral Microbleeds.

Cerebral microbleeds (CMBs) are a common vascular pathology associated with future intracerebral hemorrhage. Plasma biomarkers of amyloid, tau, and neurodegeneration may provide a screening avenue to identify those with CMBs, but evidence is conflicting. To determine the association between plasma biomarkers (Aβ40, Aβ42, t-tau, p-tau181, p-tau217, neurofilament light chain (NfL)) and CMBs in a population-based study of aging and whether these biomarkers predict higher signal on Aβ-PET imaging in patients with multiple CMBs. 712 participants from the Mayo Clinic Study of Aging with T2* GRE MRI and plasma biomarkers were included. Biomarkers were analyzed utilizing Simoa (Aβ40, Aβ42, t-tau, NfL) or Meso Scale Discovery (p-tau181, p-tau217) platforms. Cross-sectional associations between CMBs, plasma biomarkers and Aβ-PET were evaluated using hurdle models and multivariable regression models. Among the 188 (26%) individuals with≥1 CMB, a lower plasma Aβ42/Aβ40 ratio was associated with more CMBs after adjusting for covariables (IRR 568.5 95% CI 2.8-116,127). No other biomarkers were associated with risk or number CMBs. In 81 individuals with≥2 CMBs, higher plasma t-tau, p-tau181, and p-tau217 all were associated with higher Aβ-PET signal, with plasma p-tau217 having the strongest predictive value (r2 0.603, AIC -53.0). Lower plasma Aβ42/Aβ40 ratio and higher plasma p-tau217 were associated with brain amyloidosis in individuals with CMBs from the general population. Our results suggest that in individuals with multiple CMBs and/or lobar intracranial hemorrhage that a lower plasma Aβ42/Aβ40 ratio or elevated p-tau217 may indicate underlying cerebral amyloid angiopathy.

Incidental DWI Lesions in Patients with Recent Small Subcortical Infarctions

ObjectivesIncidental acute ischemic lesions distinct from the primary neurological insult are identified on diffusion-weighted imaging (DWI) in a number of conditions where cerebral microvascular pathology plays a central role. Another major manifestation of cerebral small vessel disease (CSVD) is ischemic stroke named as recent small subcortical infarction (RSSI). In this study, we sought to identify the prevalence and predictors of incidental DWI lesions in patients with RSSI. Materials and MethodsWe retrospectively analyzed a consecutive series of acute ischemic stroke patients with DWI evidence of acute lesions solely localized to perforator artery territories. Images were evaluated for the presence of additional acute or subacute subcortical DWI lesions, apart from the symptomatic lesion. Clinical features including vascular risk factor burden, together with imaging markers of chronic CSVD, were compared among patients with and without incidental acute or subacute lesions. ResultsAmong 396 patients with no alternate stroke etiology additional incidental subcortical DWI bright lesions were identified in 74 (19%) cases. These lesions were primarily localized in the corona radiata, or centrum semiovale. Patients with incidental DWI lesions were more likely to have a history of hypertension, a higher white matter hyperintensities burden in the periventricular and subcortical region, higher perivascular spaces burden in the basal ganglia, multiple cerebral microbleeds, and multiple chronic lacunes. Presence of multiple chronic lacunes (OR 5.98, 95% CI 3.18-11.24) and ≥2 vascular risk factors (OR 2.03, 95% CI 1.05-3.91) stood out as features significantly associated with incidental DWI lesions in multivariate analysis. ConclusionsOur study shows that acute or subacute ischemic lesions can be incidentally detected in approximately one-fifth of patients with RSSI. This observation suggests that the course of CSVD might be more active, temporally and spatially, in a distinct subgroup of RSSI patients, specifically those with a higher chronic lacune and vascular risk factor burden.

Abstract 10971: Prevalence and Risk Factors of Silent Brain Microbleeds in Patients with Severe Valvular Heart Disease

Introduction: The presence of cerebral microbleeds (CMBs) has been described using MRI in patients with cardiovascular risk factors or prior stroke and could predict future cognitive dysfunction or cardiovascular mortality. CMBs are highly frequent (> 50%) in patients with infective endocarditis (IE). However, the association of CMBs and clinical factors in patients' valvular disease without IE remains unclear. Hypothesis: Valvular heart disease without IE confers a risk factor for microbleeds. Methods: We retrospectively examined data from the consecutive 96 patients ( 72 ± 9 years, 49 men) with severe valvular disease who underwent T2*-weighted brain MRI before cardiac surgery. The patients with neurological abnormalities or IE were excluded. Conventional echocardiography was performed to evaluate the left ventricular volume and valvular abnormalities. CMBs were coded by researchers blind to clinical details, who independently assessed the presence and location of CMBs using a standardized form. The study population consisted of 59 patients with severe aortic stenosis (AS) (group A) and 40 patients with severe aortic or mitral regurgitation (group B). Results: CMBs were found in 26 patients (27%), 14 (15%) had multiple CMBs. CMBs were most frequently seen in the lobar locations (69%), followed by deep or infratentorial locations (62%). No significant relationship was found between CMBs in dyslipidemia, diabetes mellitus, smoking status, anticoagulant, and antiplatelet therapy in both groups. In group A, the HAS-BLED score was higher in patients with CMBs, and the presence of CMBs was associated with hypertension (P<0.05); however, no significant differences were observed in the left ventricular mass index (LVMI), LV end-diastolic volume (LVEDV), any aortic valve severity parameters. In group B, there were significant differences in LVMI and LVEDV between patients with CMBs and those without (154 ± 40 g/m 2 vs 125 ± 32 g/m 2 , P < 0.01 ; 150 ± 39 ml vs 111 ± 38 ml, P<0.01). Conclusion: CMBs were frequently observed in severe valvular heart disease without IE. The presence of CMBs was independent of antiplatelet or anticoagulant therapy. In aortic or mitral regurgitation patients, LV remodeling may contribute to the development of CMBs.

Imaging Markers of Subcortical Vascular Dementia in Patients With Multiple-Lobar Cerebral Microbleeds.

Background and Purpose: Small vessel disease (SVD) imaging markers are related to ischemic and hemorrhage stroke and to cognitive dysfunction. This study aimed to clarify the relationship between SVD imaging markers and subcortical vascular dementia in severe SVD burden.Methods: A total of 57 subjects with multiple lobar cerebral microbleeds (CMBs) and four established SVD imaging markers were enrolled from the dementia and stroke registries of a single center. Visual rating scales that are used to semi-quantify SVD imaging changes were analyzed individually and compositely to make correlations with cognitive domains and subcortical vascular dementia.Results: Dementia group had higher subcortical and total white matter hyperintensities (WMHs) and SVD composite scores than non-dementia group. Individual imaging markers correlated differently with one another and had distinct cognitive correlations. After adjusting for demographic factors, multivariate logistic regression indicated associations of subcortical WMHs (odds ratio [OR] 2.03, CI 1.24–3.32), total WMHs (OR 1.43, CI 1.09–1.89), lacunes (OR 1.18, CI 1.02–1.35), cerebral amyloid angiopathy-SVD scores (OR 2.33, CI 1.01–5.40), C1 scores (imaging composite scores of CMB and WMH) (OR 1.41, CI 1.09–1.83), and C2 scores (imaging composite scores of CMB, WMH, perivascular space, and lacune) (OR 1.38, CI 1.08–1.76) with dementia.Conclusions: SVD imaging markers might have differing associations with cognitive domains and dementia. They may provide valuable complementary information in support of personalized treatment planning against cognitive impairment, particularly in patients with a heavy SVD load.

Dural Arteriovenous Fistula with Retrograde Drainage into the Cortical Veins (Case Report)

We present clinical case of a patient who was referred for brain MRI to clarify the cause of a first-time seizure. MRI examination showed cortical and medullary veins ectasia in the left cerebral hemisphere with multiple cerebral microbleeds around the medullary veins. The revealed changes were considered as a manifestation of regional venous hypertension, however, its cause remained unclear. We decided to perform non-contrast 3D-TOF angiography that revealed a dural arteriovenous fistula between the left occipital artery and the sigmoid venous sinus with retrograde drainage into cortical veins (Borden type II, Cognard type IIb). Early diagnosis and treatment of «aggressive» dural arteriovenous fistulas avoids the development of lifethreatening complications (an annual hemorrhage rate of 8,1%).

Abstract P623: Lipid-Lowering Therapy and Intracerebral Hemorrhage Risk: Comparative Meta-Analysis of Statins and PCSK9 Inhibitors

Background: Statins were shown to increase intracerebral hemorrhage rates in patients with a first cerebrovascular event in 2006 (SPARCL), likely due to off-target antithrombotic effects, but continued to sometimes be used in elevated ICH risk patients due to absence of alternative agents. Recently, the PCSK9 inhibitors (PCK9is) have become available as potent lipid-lowering class that may not share the hemorrhagic propensity of statins. Methods: Systematic comparative meta-analysis assessing ICH rates across all completed statin and PCSK9i RCTs, following PRISMA guidelines. In addition to ICH rates across all trials, causal relation was probed by evaluating for dose-response relationships by agent (low vs high agent dose) and by degree of brain injury at inception (none vs ischemic stroke vs ICH). Results: The systematic review identified 33 statin RCTs (203,305 patients) and 4 PCSK9i RCTs (53,253 patients). Across all patient types and all agent doses, statins were associated with increased ICH: relative risk (RR) 1.15, p=0.04; PCSK9is were not (p=0.59). In the agent dose analysis (Table), higher dose statins (7 trials, 62,204 patients) were associated with magnified ICH risk: RR 1.53, p=0.002; higher dose PCSK9is (2 trials, 31,153 patients) were not (p=0.99). In the brain injury dose analysis (Table), for statins, h/o ischemic stroke was associated with a magnified risk of ICH: RR 1.40, p=0.03; and h/o initial ICH was associated with an extremely high effect estimate of risk of recurrent ICH: RR 4.06. For PCSK9is, h/o ischemic stroke was not associated with ICH (p=0.97). Conclusion: Statins increase the risk of intracerebral hemorrhage, and the risk is magnified in an agent dose- and brain injury dose-dependent manner; PCSK9is do not ICH risk. PCSK9is may be a preferred lipid-lowering agent class in patients with elevated ICH risk, including patients with intracerebral hemorrhage or multiple covert cerebral microbleeds.

Relationship between cerebral microbleeds, ventricular enlargement and white matter hyperintensities in Alzheimer’s disease

AbstractBackgroundTo investigate whether the number of cerebral microbleeds (CMB) could be a useful indicator to predict glymphatic system dysfunction in Alzheimer’s disease (AD) patients, by comparing the degree of cerebral spinal fluid (CSF) and interstitial fluid (ISF) stasis.MethodForty probable AD patients were included, with those exhibiting two or more CMB were included in the multiple CMB group (mCMB, n = 21, mean = 11.1), and none or one CMB included in the non‐multiple CMB group (nmCMB, n = 19, mean = 0.84). CMB were defined in axial gradient recalled echo (GRE) T2*‐weighted images. Evans index (EI) was calculated to measure lateral ventricle enlargement, Voxel‐based Specific Regional Analysis System for Alzheimer's Disease (VSRAD) software was used to determine the extent of gray and white matter atrophy, and Fazekas scale (FS) was used to determine white matter hyperintensities (WMH).ResultEI was significantly larger in mCMB than in nmCMB, while the gray and white matter volume was not different between groups. Thus, the difference in lateral ventricle enlargement between AD with and without multiple CMB reflects a combination of the degree of brain atrophy and the extent of CSF stasis. FS was higher in mCMB than in the nmCMB, suggesting the failure of ISF elimination was more severe in mCMB cases.ConclusionThe difference in lateral ventricle enlargement and WMH between AD with or without multiple CMB may reflect a difference in the degree of CSF/ISF stagnation.

Large and Small Cerebral Vessel Involvement in Severe COVID-19: Detailed Clinical Workup of a Case Series.

Case series indicating cerebrovascular disorders in coronavirus disease 2019 (COVID-19) have been published. Comprehensive workups, including clinical characteristics, laboratory, electroencephalography, neuroimaging, and cerebrospinal fluid findings, are needed to understand the mechanisms. We evaluated 32 consecutive critically ill patients with COVID-19 treated at a tertiary care center from March 9 to April 3, 2020, for concomitant severe central nervous system involvement. Patients identified underwent computed tomography, magnetic resonance imaging, electroencephalography, cerebrospinal fluid analysis, and autopsy in case of death. Of 32 critically ill patients with COVID-19, 8 (25%) had severe central nervous system involvement. Two presented with lacunar ischemic stroke in the early phase and 6 with prolonged impaired consciousness after termination of analgosedation. In all but one with delayed wake-up, neuroimaging or autopsy showed multiple cerebral microbleeds, in 3 with additional subarachnoid hemorrhage and in 2 with additional small ischemic lesions. In 3 patients, intracranial vessel wall sequence magnetic resonance imaging was performed for the first time to our knowledge. All showed contrast enhancement of vessel walls in large cerebral arteries, suggesting vascular wall pathologies with an inflammatory component. Reverse transcription-polymerase chain reactions for SARS-CoV-2 in cerebrospinal fluid were all negative. No intrathecal SARS-CoV-2-specific IgG synthesis was detectable. Different mechanisms of cerebrovascular disorders might be involved in COVID-19. Acute ischemic stroke might occur early. In a later phase, microinfarctions and vessel wall contrast enhancement occur, indicating small and large cerebral vessels involvement. Central nervous system disorders associated with COVID-19 may lead to long-term disabilities. Mechanisms should be urgently investigated to develop neuroprotective strategies.

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.

Cilostazol versus aspirin in ischemic stroke with cerebral microbleeds versus prior intracerebral hemorrhage.

In PreventIon of CArdiovascular Events in Ischaemic Stroke Patients with High Risk of Cerebral HaemOrrhage (PICASSO), cilostazol versus aspirin was comparable for the end points of cerebral hemorrhage and major vascular events. However, underlying hemorrhage-prone lesions could modify the treatment effect. We explored whether the safety and efficacy of cilostazol versus aspirin would differ between hemorrhage-prone lesions (multiple cerebral microbleeds vs. prior intracerebral hemorrhage). In this post hoc analysis of PICASSO, we divided patients into the cerebral microbleeds and prior intracerebral hemorrhage subgroups. The primary safety end point was the first occurrence of cerebral hemorrhage. The primary efficacy end point was the composite of stroke, myocardial infarction, or vascular death. Of 1512 patients, 903 (59.7%) had multiple cerebral microbleeds and 609 (40.3%) had prior intracerebral hemorrhage. The cerebral hemorrhage risk was lower with cilostazol versus aspirin (0.12%/year vs. 1.49%/year; hazard ratio, 0.08 [95% confidence interval 0.01-0.60]; p = 0.015) in the cerebral microbleeds subgroup, but was not different (1.26%/year vs. 0.79%/year; hazards ratio 1.60 [0.52-4.90]; p = 0.408) in the prior intracerebral hemorrhage subgroup. The interaction of treatment-by-subgroup was significant (pinteraction = 0.011). For the composite of major vascular events, there was a trend toward a lower risk with cilostazol versus aspirin (3.56%/year vs. 5.53%/year; hazards ratio 0.64 [0.41-1.01]; p = 0.056) in the cerebral microbleeds subgroup, but was comparable (5.21%/year vs. 5.05%/year; hazards ratio 1.03 [0.63-1.67]; p = 0.913) in the prior intracerebral hemorrhage subgroup without a significant treatment-by-subgroup interaction (pinteraction = 0.165). Cilostazol versus aspirin might be a better option in ischemic stroke with multiple cerebral microbleeds, but confirmatory trials are needed. URL:http://www.clinicaltrials.gov. NCT01013532.

Cerebral Microbleeds Are Associated with Cerebral Hypoperfusion in Patients with Alzheimer's Disease.

BACKGROUND Although cerebral microbleeds (CMBs) are commonly observed in patients with Alzheimer's disease (AD), their clinical relevance for AD remains unclear. OBJECTIVE We investigated the significance of CMBs in AD by examining the relationship between CMBs and cerebral blood flow (CBF) in patients with AD. METHODS Thirty-four patients (aged 77.9±7.6 years; 17 men) with probable AD and multiple (≥8) CMBs were selected from 394 consecutive patients. For each lobe of the brain, the correlation between the number of CMBs observed on susceptibility-weighted images and the decrease in CBF observed on single-photon emission computed tomography was assessed. RESULTS The number of microbleeds was significantly correlated with the severity of decrease in the occipital lobe (Spearman's r = 0.531, p < 0.001) and temporal lobe (r = 0.437, p < 0.001) but not in the frontal lobe (r = 0.201, p = 0.101) and parietal lobe (r = 0.178, p = 0.146). These results were unchanged in the partial correlational analysis after controlling the effect of other small vessel disease such as lacunars and white matter hyperintensities. CONCLUSION Multiple CMBs are associated with cerebral hypoperfusion in AD. The effects of CMBs on CBF differed according to brain location, possibly reflecting different distributions of the underlying cerebral amyloid angiopathy and AD-related histopathology, such as neurofibrillary tangles.

Cortical Superficial Siderosis: A Descriptive Analysis in a Memory Clinic Population.

Cortical superficial siderosis (cSS) is a hemorrhagic marker of blood-brain barrier disruption detected in brain MRI. Together with cerebral microbleeds (CMB), they are recognized as a small vessel disease marker associated with cerebral amyloid angiopathy. This study aims to determine the prevalence and the characteristics of cSS in a memory clinic population. Cross-sectional retrospective analysis of 613 patients from Geneva University Hospitals memory clinic. All patients underwent standardized brain MRI and neuropsychological assessment with diagnosis confirmed by an expert. The presence of cSS was visually assessed and classified as focal (restricted to 3 sulci) or disseminated within the correspondent topography. CMB were classified according to the Microbleed Anatomical Rating Scale. cSS was detected in 26/613 patients (4.2%), classified as disseminated in 5/26 cases (19%). Alzheimer's disease (AD) and AD associated with a significant vascular component were the diagnoses more frequently related to cSS (18/26; 69%). Patients with cSS had an increased prevalence of both hypertension (81% versus 57%; p = 0.015) and WMH burden (p = 0.012). The overall prevalence of cerebral microbleeds (69% versus 32%; p < 0.01), as well as their mean number (0.69±0.47 versus 0.32±0.46; p < 0.01) were both increased in patients with cSS. In the logistic regression model, the presence of 5 or more CMB (OR 11.35; 95% CI 4.68-27.55; p < 0.01) and hypertension (OR 3.31; 95% CI 1.19-9.15; p = 0.021) were significantly associated with cSS. cSS is observed in patients diagnosed with AD and AD with a vascular component, being independently associated with multiple CMB and hypertension.

Cerebral Microbleeds and Chronic Kidney Disease in Acute Ischemic Stroke Patients with Atrial Fibrillation

Background: Cerebral microbleeds (CMBs) are associated with the risk of intracerebral hemorrhage in stroke patients with atrial fibrillation (AF). We investigated the association between CMBs and chronic kidney disease (CKD) in patients with acute ischemic stroke and AF. Methods: We retrospectively examined consecutive patients with acute ischemic stroke and AF who underwent brain gradient-echo T2*-weighted magnetic resonance imaging. The number and distribution (lobar, deep or infratentorial, and mixed) of CMBs were assessed. Kidney function was assessed according to the estimated glomerular filtration rate (eGFR), which was calculated using a modified version of the Modification of Diet in Renal Disease equation. Results: Of the 357 included patients, 105 (29.4%) had CMBs. CKD (eGFR < 60 mL/min/1.73 m2) was found in 131 (36.7%) patients. Patients with CKD showed a higher prevalence of any form of CMB (41.2% versus 22.6%, P < .001), deep or infratentorial CMBs (19.9% versus 9.3%, P < .01), and mixed CMBs (14.5% versus 5.3%, P < .01) than those without CKD. After adjusting for age and other confounding factors, CKD was found to be independently associated with the presence of any form of CMB (odds ratio 1.89, P = .02) and mixed CMBs (odds ratio 3.10, P < .01). Moreover, moderate to severe CKD (eGFR < 45 mL/min/1.73 m2) was independently associated with the presence of multiple CMBs (odds ratio 2.31, P = .04). Conclusions: CMBs and CKD are common in acute ischemic stroke patients with AF, and CKD may be a risk factor for CMBs. Further longitudinal studies are needed to evaluate whether maintaining kidney function can prevent the development of CMBs.

Increased Presence of Cerebral Microbleeds Correlates With Ventricular Enlargement and Increased White Matter Hyperintensities in Alzheimer's Disease.

Objective: To investigate whether the number of cerebral microbleeds (CMB) could be a useful indicator to predict glymphatic system dysfunction in Alzheimer’s disease (AD) patients, by comparing the degree of cerebral spinal fluid (CSF) and interstitial fluid (ISF) stasis.Methods: Forty probable AD patients were included, with those exhibiting two or more CMB were included in the multiple CMB group (mCMB, n = 21, mean = 11.1), and none or one CMB included in the non-multiple CMB group (nmCMB, n = 19, mean = 0.84). CMB was defined in axial gradient recalled echo (GRE) T2*-weighted images. Evans index (EI) was calculated to measure lateral ventricle enlargement, Voxel-based Specific Regional Analysis System for Alzheimer’s Disease (VSRAD) software was used to determine the extent of gray and white matter atrophy, and Fazekas scale (FS) was used to determine white matter hyperintensities (WMH).Results: EI was significantly larger in mCMB than in nmCMB, while the gray and white matter volume was not different between groups. Thus, the difference in lateral ventricle enlargement between AD with and without multiple CMB reflects a combination of the degree of brain atrophy and the extent of CSF stasis. FS was higher in mCMB than in the nmCMB, suggesting the failure of ISF elimination was more severe in mCMB cases.Conclusion: The difference in lateral ventricle enlargement and WMH between AD with or without multiple CMB may reflect a difference in the degree of CSF/ISF stagnation.

Sickle cell disease related cerebral fat embolism: Characterizing the clinical syndrome

To characterize the clinical syndrome of sickle cell disease (SCD) related cerebral fat embolism syndrome (CFES) SCD-related CFES results from bonemarrow embolism in the absence of trauma and except for a few single case reports, its clinico-imaging spectrum has not been fully characterized. Twelve SCD patients (6 women and 6 men, aged 28.4±9.9 years), were evaluated for neurological complications such as altered sensorium (n=12) and seizures (n=2) in the setting of acute chest syndrome, fever and no preceding trauma (n=12). Laboratory findings included high CRP (11 out of 11 tested) and thrombocytopenia (n=12), normal CSF findings (n=2 out of 2 tested). EEG showed non-specific diffuse slowing in 9 out of 10 cases and occasional left temporal spike discharges (n=1). Cerebral PET scan obtained in a single case showed globally reduced glucose uptake. Lipid laden macrophages were demonstrated in the broncho-alveolar lavage in two cases. CFES was diagnosed based on the characteristic finding of multiple cerebral microbleeds in the splenium and subcortical location on susceptibility weighted imaging (SWI). Our patients received exchange transfusion, antibiotics, ventilatory assistance (n=12) and anticonvulsant (n=2). One patient died, while the others survived with variable functional disability. In SCD patients presenting with acute chest syndrome, altered mental status and fever, the presence of thrombocytopenia and high CRP provides important clue to the possibility of CFES. The diagnosis is confirmed with SWI MRI that usually demonstrates multiple microbleeds in the splenium and subcortical areas. SCD-related CFES carries considerable short-term morbidity and occasional mortality.

Cerebral Microbleeds Are Associated with Cerebral Hypoperfusion in Patients with Alzheimer's Disease.

Although cerebral microbleeds (CMBs) are commonly observed in patients with Alzheimer's disease (AD), their clinical relevance for AD remains unclear. We investigated the significance of CMBs in AD by examining the relationship between CMBs and cerebral blood flow (CBF) in patients with AD. Thirty-four patients (aged 77.9±7.6 years; 17 men) with probable AD and multiple (≥8) CMBs were selected from 394 consecutive patients. For each lobe of the brain, the correlation between the number of CMBs observed on susceptibility-weighted images and the decrease in CBF observed on single-photon emission computed tomography was assessed. The number of microbleeds was significantly correlated with the severity of decrease in the occipital lobe (Spearman's r = 0.531, p < 0.001) and temporal lobe (r = 0.437, p < 0.001) but not in the frontal lobe (r = 0.201, p = 0.101) and parietal lobe (r = 0.178, p = 0.146). These results were unchanged in the partial correlational analysis after controlling the effect of other small vessel disease such as lacunars and white matter hyperintensities. Multiple CMBs are associated with cerebral hypoperfusion in AD. The effects of CMBs on CBF differed according to brain location, possibly reflecting different distributions of the underlying cerebral amyloid angiopathy and AD-related histopathology, such as neurofibrillary tangles.