Presence Of Cerebral Microbleeds Research Articles

Recurrent cerebrovascular events after recent small subcortical infarction.

Recent small subcortical infarcts (RSSI) are the neuroimaging hallmark feature of small vessel disease (SVD)-related acute lacunar stroke. Long-term data on recurrent cerebrovascular events including their aetiology after RSSI are scarce. This retrospective study included all consecutive ischaemic stroke patients with an MRI-confirmed RSSI (in the supply area of a small single brain artery) at University Hospital Graz between 2008 and 2013. We investigated associations between clinical and SVD features on MRI (STRIVE criteria) and recurrent cerebrovascular events, using multivariable Cox regression adjusted for age, sex, vascular risk factors and MRI parameters. We analysed 332 consecutive patients (mean age 68years, 36% women; median follow-up time 12years). A recurrent ischaemic cerebrovascular event occurred in 70 patients (21.1%; 54 ischaemic strokes, 22 transient ischaemic attacks) and was mainly attributed to SVD (68%). 26 patients (7.8%) developed intracranial haemorrhage. In multivariable analysis, diabetes (HR 2.43, 95% CI 1.44-3.88), severe white matter hyperintensities (HR 1.97, 95% CI 1.14-3.41), and cerebral microbleeds (HR 1.89, 95% CI 1.32-3.14) on baseline MRI were related to recurrent ischaemic stroke/TIA, while presence of cerebral microbleeds increased the risk for intracranial haemorrhage (HR 3.25, 95% CI 1.39-7.59). A widely used SVD summary score indicated high risks of recurrent ischaemic (HR 1.22, 95% CI 1.01-1.49) and haemorrhagic cerebrovascular events (HR 1.57, 95% CI 1.11-2.22). Patients with RSSI have a substantial risk for recurrent cerebrovascular events-particularly those with coexisting chronic SVD features. Recurrent events are mainly related to SVD again.

Literature Review on the Association between Cerebral Large Artery Disease and Cerebral Microbleeds

CMBs are small areas of hemorrhage in the brain, often seen on neuroimaging studies, that have been associated with various cerebrovascular pathologies. Large-artery atherosclerosis and resulting vascular stenosis are major contributors to ischemic stroke. Given the structural continuity between intracranial large and small vessels, their susceptibility to hemodynamic influences, and their shared risk factors, they may coexist in the same individual. This article reviews recent advances in understanding the interplay between large artery atherosclerosis (LAA) and cerebral microbleeds (CMB). Methods: A comprehensive search of electronic databases including PubMed, MEDLINE, and Google Scholar was conducted using relevant keywords such as "cerebral large artery disease," "cerebral microbleeds," "arterial stenosis," and "atherosclerosis." Articles published in English between [2010] and [2024] were considered for inclusion. Studies investigating the relationship between LAA and CMBs through neuroimaging, pathological examination, or clinical correlations were selected for review. Results: The review identified a range of studies exploring the association between LAA and CMBs. Several cross-sectional imaging studies have demonstrated a significant correlation between LAA severity and the presence, number, and distribution of CMBs. Histopathological investigations have revealed microvascular alterations in regions affected by LAA, potentially contributing to CMB formation. The evidence indicates a correlation between cerebrovascular microbleeds (CMBs) and large artery diseases, impacting the prognosis of individuals with cerebral infarction resulting from large artery atherosclerosis (LAA). Keywords: Cerebral infarction; Large-artery atherosclerosis; Cerebral microbleeds.

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.

Statin Therapy for Secondary Prevention in Ischemic Stroke Patients With Cerebral Microbleeds.

The association between statin use and the risk of intracranial hemorrhage (ICrH) following ischemic stroke (IS) or transient ischemic attack (TIA) in patients with cerebral microbleeds (CMBs) remains uncertain. This study investigated the risk of recurrent IS and ICrH in patients receiving statins based on the presence of CMBs. We conducted a pooled analysis of individual patient data from the Microbleeds International Collaborative Network, comprising 32 hospital-based prospective studies fulfilling the following criteria: adult patients with IS or TIA, availability of appropriate baseline MRI for CMB quantification and distribution, registration of statin use after the index stroke, and collection of stroke event data during a follow-up period of ≥3 months. The primary endpoint was the occurrence of recurrent symptomatic stroke (IS or ICrH), while secondary endpoints included IS alone or ICrH alone. We calculated incidence rates and performed Cox regression analyses adjusting for age, sex, hypertension, atrial fibrillation, previous stroke, and use of antiplatelet or anticoagulant drugs to explore the association between statin use and stroke events during follow-up in patients with CMBs. In total, 16,373 patients were included (mean age 70.5 ± 12.8 years; 42.5% female). Among them, 10,812 received statins at discharge, and 4,668 had 1 or more CMBs. The median follow-up duration was 1.34 years (interquartile range: 0.32-2.44). In patients with CMBs, statin users were compared with nonusers. Compared with nonusers, statin therapy was associated with a reduced risk of any stroke (incidence rate [IR] 53 vs 79 per 1,000 patient-years, adjusted hazard ratio [aHR] 0.68 [95% CI 0.56-0.84]), a reduced risk of IS (IR 39 vs 65 per 1,000 patient-years, aHR 0.65 [95% CI 0.51-0.82]), and no association with the risk of ICrH (IR 11 vs 16 per 1,000 patient-years, aHR 0.73 [95% CI 0.46-1.15]). The results in aHR remained consistent when considering anatomical distribution and high burden (≥5) of CMBs. These observational data suggest that secondary stroke prevention with statins in patients with IS or TIA and CMBs is associated with a lower risk of any stroke or IS without an increased risk of ICrH. This study provides Class III evidence that for patients with IS or TIA and CMBs, statins lower the risk of any stroke or IS without increasing the risk of ICrH.

Hippocampal amide proton transfer values are associated with cerebral small vessel disease imaging markers and total burden: a community-based cross-sectional study.

Neurodegeneration has been suggested to be associated with cerebral small vessel disease (CSVD). The association between different CSVD imaging markers and the extent of neurodegeneration could be indirectly confirmed by examining the relationship between CSVD imaging markers and the hippocampal amide proton transfer (APT) values. The associations between hippocampal APT values with CSVD imaging markers and CSVD total load need to be further validated. The aim of this study was to investigate potential variations in hippocampal APT values among individuals with CSVD imaging markers and varying degrees of CSVD total burden. A cross-sectional study (retrospective analysis of prospectively-acquired data) was conducted at Nanxishan Hospital of Guangxi Zhuang Autonomous Region. From May 2020 to June 2021, 165 individuals (age, 40-76 years; male/female, 103/62) were included in this study. The inclusion criteria for the participants were as follows: The presence of lacunar infarction (LI), and/or cerebral microbleed (CMB); moderate-to-severe enlarged perivascular space (EPVS) (>20); deep white matter hyperintensity (WMH) > Fazekas 2 or periventricular WMH > Fazekas. The exclusion criteria comprised the following: History of craniocerebral operation; Cases with significant pathology incidentally identified during magnetic resonance (MR) scan; Drug or alcohol abuse. The differences of hippocampal APT values between CSVD imaging makers presence or absence groups and different CSVD total burden groups were compared using independent t-test and one-way analysis of variance (ANOVA). The correlations between APT values and CSVD imaging markers were analyzed using Pearson correlation analysis. A mediation analysis model was used to investigate the mediating effect of the hippocampal APT values in the association between CSVD total loads and Montreal Cognitive Assessment (MoCA) score was assessed. The hippocampal APT values among different CSVD total load groups were significantly different (P<0.001). The hippocampal APT values were significantly different between the imaging markers presence and absence groups. The P values for the LI, WMH EPVS, and CMB presence or absence groups were <0.001, <0.001, 0.034, and 0.002, respectively. The hippocampal APT values were significantly correlated with CMB (P<0.01), LI (P<0.01) and WMH (P<0.01). The mediation models demonstrated that the APT values of the hippocampus partially mediated the association between CSVD total load and MoCA score, the proportion of mediation attributable was calculated as 17.50%. Hippocampal APT values were associated with CSVD imaging markers and total burden. Hippocampal APT values may serve as a biomarker for the early detection of neurodegeneration in CSVD patients.

Cerebral microbleeds and risk of symptomatic hemorrhagic transformation following mechanical thrombectomy for large vessel ischemic stroke.

In patients with acute ischemic stroke (AIS) treated with endovascular therapy (EVT), the association of pre-existing cerebral small vessel disease (cSVD) with symptomatic intracerebral hemorrhage (sICH) remains controversial. We tested the hypothesis that the presence of cerebral microbleeds (CMBs) and their burden would be associated with sICH after EVT of AIS. We conducted a retrospective study combining cohorts of patients that underwent EVT between January 1st 2015 and January 1st 2020. CMB presence, burden, and other cSVD markers were assessed on a pre-treatment MRI, evaluated independently by two observers. Primary outcome was the occurrence of sICH. 445 patients with pretreatment MRI were included, of which 70 (15.7%) demonstrated CMBs on baseline MRI. sICH occurred in 36 (7.6%) of all patients. Univariate analysis did not demonstrate an association between CMB and the occurrence of sICH (7.5% in CMB+ group vs 8.6% in CMB group, p = 0.805). In multivariable models, CMBs' presence was not significantly associated with increased odds for sICH (-aOR- 1.19; 95% CI [0.43-3.27], p = 0.73). Only ASPECTs (aOR 0.71 per point increase; 95% CI [0.60-0.85], p < 0.001) and collaterals status (aOR 0.22 for adequate versus poor collaterals; 95% CI [0.06-0.93], p 0.019) were independently associated with sICH. CMB presence and burden is not associated with increased occurrence of sICH after EVT. This result incites not to exclude patients with CMBs from EVT. The risk of sICH after EVT in patients with more than10 CMBs will require further investigation. Registration-URL: http://www. gov ; Unique identifier: NCT01062698.

Associations of Growth-Associated Protein 43 with Cerebral Microbleeds: A Longitudinal Study.

Cerebral microbleeds (CMB) play an important role in neurodegenerative pathology. The present study aims to test whether cerebrospinal fluid (CSF) growth-associated protein 43 (GAP-43) level is linked to CMBs in elderly people. A total of 750 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) who had measurements of GAP-43 and CMBs were included in the study. According to the presence and extent of CMBs, participants were stratified into different groups. Regression analyses were used to assess cross-sectional and longitudinal associations between GAP-43 and CMBs. Participants with CMB were slightly older and had higher concentrations of CSF GAP43. In multivariable adjusted analyses for age, gender, APOEɛ4 status, and cognitive diagnoses, higher CSF GAP-43 concentrations were modestly associated with CMB presence (OR = 1.169, 95% CI = 1.001-1.365) and number (β= 0.020, SE = 0.009, p = 0.027). Similarly, higher CSF GAP43 concentrations were accrual of CMB lesions, associated with higher CMB progression (OR = 1.231, 95% CI = 1.044-1.448) and number (β= 0.017, SE = 0.005, p = 0.001) in the follow up scan. In stratified analyses, slightly stronger associations were noted in male participants, those 65 years and older, carriers of APOEɛ4 alleles, and with more advanced cognitive disorders. CSF GAP-43 was cross-sectionally associated with the presence and extent of CMBs. GAP-43 might be used as a biomarker to track the dynamic changes of CMBs in elderly persons.

Abstract WP170: Patients With Cerebral Microbleeds Are More Likely to Have Poor Collaterals at the Time of Mechanical Thrombectomy

Introduction: Collateral cerebrovasculature is important for the survival of penumbral tissue in patients with large vessel occlusive (LVO) stroke, and adequate collateralization is associated with favorable outcomes. The presence of cerebral microbleeds (CMB) have been implicated in vessel wall remodeling and impaired vasoreactivity. We investigated whether the presence of deep and/or lobar CMB predicts poor collateral recruitment in patients with LVO stroke who underwent thrombectomy (MT). Methods: We performed a retrospective, single-center study of adults who presented with LVO stroke and had MT between January 2012-June 2020. CT angiography of head prior to MT was used to assess collateral status with poor status defined as ≤50% filling and good status as &gt;50% filling. CMBs were assessed using T2*-weighted gradient echo or susceptibility weighted magnetic resonance images. Location of CMB was further characterized as deep vs. lobar using consensus definitions. Poor stroke outcome was defined as modified Rankin Scale (mRS) ≥3 at 90 days. Multivariable logistic regressions were performed to evaluate the associations between CMB, CMB types (lobar, deep, lobar+deep) and poor collaterals after adjusting for vascular risk factors. Results: Consecutive 151 subjects were included (mean age 68±15 years, 47% women), with a median NIHSS of 18. CMB were identified in 57 subjects (37.4%). Of these, 20.5% had lobar CMB, 5.3% had deep CMB and 11.9% had combined lobar &amp; deep CMB. Patients with CMB had higher odds of having poor collaterals compared to those without CMB (OR 1.56, 95% CI 1.09-2.23, P=0.015). The association of CMB with poor collaterals was strongest in patients with combined lobar &amp; deep CMB (OR 4.78, 95% CI 1.43-15.93, P=0.011), compared with those with exclusively deep CMB (OR 2.78, 95% CI 0.44-17.62, P=0.278) or lobar CMB (OR 0.52, 95% CI 0.19-1.38, P=0.188). Patients with poor collaterals were more likely to have poor outcome compared with those with good collaterals (48.4% vs. 31.0%, P=0.03). Conclusion: Cerebral microbleeds are independently associated with poor collateral recruitment when adjusted for traditional vascular risk factors. Further study is warranted to elucidate the differential effects of CMB types on collateral recruitment.

Abstract TMP79: Magnetic Resonance Imaging Elements Predict Incident Intracerebral Hemorrhage

Introduction: Incident intracerebral hemorrhage (ICH) is an uncommon medical event that can lead to devastating outcomes, including death. Small vessel disease (SVD), as measured by cerebral microbleeds (CMBs) and white matter hyperintensities (WMH), has been associated with risk factors and might be a predictor of incident ICH. CMBs result from irregularities in brain vessel structure due to chronic hypertension and cerebral amyloid angiopathy. These microhemorrhages are a possible risk factor for ICH. Methods: A cohort of ARIC (Atherosclerosis Risk in Communities) participants underwent 3T MRI at visit 5 (2011-2013). CMBs were assessed using a T2* gradient echo. CMBs are homogenous hypointense lesions ≤10 mm in diameter. WMH volumes were derived from FLAIR images using an automated program to measure the volumetric burden of leukoaraiosis. During 10 years of follow-up, incident ICH was noted in 7 (0.4%) out of 1,656 participants were dichotomized based on the presence of CMB and the median of WMH volume. Results: ARIC subjects (n=1656, mean age=76±5 years; 40% men; 26% African American race) underwent MRI. CMBs were present in 385 (23.25%) patients out of 1656. ICH occurred in 0.16% and 1.30% of patients without CMBs and with CMBs, respectively. Kaplan Meier (KM) survival analysis between CMBs and ICH was significant (logrank p=0.002). Cox Regression yielded a significant crude hazards ratio (HR 8.7, 95% CI 1.7-44.7, p=0.010). Adjustment for age, gender, race, and hypertension was also significant (HR 9.9, 95% CI 1.9-52.0, p=0.07). KM survival analysis between WMH median (11.68 cm 3 ) and ICH was significant (logrank p=0.006). Figure 1 displays the KM curves of those with and without CMBs and the incidence of ICH as well as those below and above WMH median and incidence of ICH. Conclusion: CMBs and WMH detected by MRI appear to be an important predictor for the occurrence of incident ICH. Further research is needed to observe if MRI could be used to screen subjects at high-risk for elevated risk of incident ICH.

Abstract TP233: Cerebral Microbleeds Are More Frequent With BRCA Mutations: A Single-Center Retrospective Study

Introduction: Breast cancer susceptibility gene (BRCA) mutations are well-known causes of systemic cancers. We have previously identified that those with BRCA mutations have a higher likelihood of cerebral microbleeds (CMBs) on brain MRI compared to BRCA wildtype. We aimed to confirm our prior findings in a subsequent cohort. Methods: We performed a single-center retrospective review of all individuals with a confirmed diagnosis of BRCA 1 or 2 mutation and a standard-of-care brain MRI. All individuals were ≥ 18 years old, without intracranial radiation, cerebral metastases, or other cerebral processes which may impact interpretation. Our comparative cohort were individuals with breast cancer who have a genetically confirmed BRCA wildtype status. The primary outcome was the presence of CMBs, defined by consensus criteria. Standard descriptive techniques were used. Likelihood ratios were calculated by binary logistic regression and adjusted for significant variables. Results: We identified 49 individuals who met inclusion criteria: 15 with BRCA mutation and 34 with BRCA wildtype. Only one patient was with aspirin use in the BRCA mutation cohort. All cancers were of breast origin with 4 BRCA mutations patients with cancer staging ≥ 3 compared with 14 in the BRCA wildtype cohort. Chemotherapy rates did not differ. Patients with BRCA were younger, less often with hyperlipidemia, and more commonly had CMBs, Table 1. The presence of BRCA mutation trended towards higher odds of having a CMB (OR 5.8, 95%CI 0.93 - 36.16, p = 0.059) after adjustment for age and hyperlipidemia. Conclusion: We found that CMBs were more common in the BRCA mutation cohort, with a trend towards a 5-fold higher likelihood in the regression analysis. While underpowered, our findings support prior data highlighting this association. Further studies with larger sample sizes are warranted.

Abstract TP166: White Matter Hyperintensity Burden Associated With Stroke Severity, Aphasia, and Motor Deficits During Intracerebral Hemorrhage Hospitalization

Introduction: Cerebral Small Vessel Disease (CSVD) is associated with cognitive disruptions after intracerebral hemorrhage (ICH), however evidence connecting CSVD to specific neurological deficits after ICH is limited. Methods: Electronic medical record data were retrieved for adult patients (&gt;18 years) with admission for primary non-traumatic ICH, available admission NIHSS scores, and CSVD assessment. CSVD burden was graded from 0-4, with 1 point assessed for: 1) deep Fazekas white matter hyperintensity (WMH) score of 2-3 or periventricular (PV) Fazekas score of 3; 2) cerebral microbleed presence; 3) lacune presence; 4) &gt; 20 basal ganglia perivascular spaces. Severe CSVD was assessed scores ≥ 3, and individual marker severity was assessed using the same criteria. The primary outcome was moderate-severe stroke (total NIHSS score ≥5). Secondary outcomes were severe motor deficit (motor score &gt;12), complete aphasia (language score = 3), and cortical deficit (any impairment in language, extinction, and gaze). Associations between CSVD and NIHSS were determined using multivariable logistic regression, adjusting for major clinical and demographic factors. Adjusted odds ratios (aOR) and 95% confidence interval (CI) are reported. Results: The cohort included 1024 patients (median age [interquartile range]: 71 [61-79], 53% male). Patients were 22% Hispanic and had a racial distribution of 61% White, 24% Black, 8% Asian, 7% other. The median NIHSS score was 4 [1-11]; 477 (47%) showed moderate-severe NIHSS scores and 262 (26%) showed severe CSVD. Severe PV WMH burden was independently associated with moderate-severe NIHSS score (vs non-severe; aOR, 95% CI: 1.55, [1.02-2.36]). Severe deep WMH burden (vs non-severe) was independently associated with aphasia (1.97, [1.02-3.81]), and motor deficit (3.95, [1.22-12.73]) (Figure 1). Conclusion: Severe WMH burdens increase odds of neurological deficit among patients with primary ICH.

Abstract WMP22: Higher Burden of Cerebral Small Vessel Disease is Associated With Risk of Incident Stroke in Community-Dwelling Individuals

Background: Mild manifestations of individual cerebral small vessel disease (CSVD) markers are common and may not denote increased risk, but high CSVD burden identifies individuals at increased risk of stroke and dementia. Scores incorporating multiple CSVD markers may better identify a person’s risk, but it remains unclear if they offer benefit beyond tools based on clinical factors alone such as the revised Framingham Stroke Risk Profile (FSRP). Therefore, we related a multi-marker CSVD score to risk of incident stroke and compared the findings with the FSRP in community-dwelling individuals. Methods: Framingham Heart Study (FHS) participants aged ≥55 years, free of stroke and dementia and with brain magnetic resonance imaging (MRI) ratings of CSVD markers were included. A multi-marker CSVD score reflecting increasing CSVD burden was used (one point each for presence of cerebral microbleeds, severe perivascular spaces, extensive white matter hyperintensities, covert brain infarcts, and cortical superficial siderosis, ranging 0-5). Multivariable Cox proportional hazards regression analyses were used to relate CSVD score to incident stroke. Results: Among 1,154 participants (46% male, mean age 70.9±8.7), 590 (51%) had score 0, 352 (31%) had score 1, 164 (14%) had score 2, and 48 (4%) had score ≥ 3. Over a median follow-up of 8.2 years (Q1-Q3: 5.1-12.5) from the time of MRI, 92 (8%) developed stroke. In models adjusting for time interval between clinic exam and MRI, FHS cohort, and FSRP score, number of CSVD manifestations was associated with increased risk of stroke in a dose-dependent manner: score 1 (HR: 1.73; 95% CI 1.05-2.84), score 2 (HR 1.83; 95% CI: 1.01-3.30), and score ≥ 3 (HR: 3.31; 95% CI: 1.50-7.28) in relation to participants with no CSVD markers. In comparison, a 5-percent increase in FSRP alone was associated with increased risk of stroke (HR: 1.25; 95% CI 1.15-1.36). Interpretation: Higher CSVD burden is associated with increased risk of stroke, beyond the effect explained by risk factors in the FSRP. These findings support consideration of CSVD burden to identify risk of stroke in community-dwelling individuals.

Abstract WP161: Characterizing the Underlying Microangiopathy of Deep Cerebellar Intracerebral Hemorrhage

Introduction: Superficial (gray matter, vermis) cerebellar intracerebral hemorrhage (cICH) is associated with strictly lobar supratentorial cerebral microbleeds—a strong marker for cerebral amyloid angiopathy. However, for deep (white matter, deep nuclei, cerebellar peduncle) cICH, it is unclear whether hypertensive cerebral small vessel disease (HTN-cSVD) is the underlying microangiopathy. Hypothesis: We hypothesized that left ventricular hypertrophy (LVH), a marker for hypertensive end-organ damage, and non-hemorrhagic imaging markers of HTN-cSVD such as peri-basal ganglia (BG) white matter hyperintensity (WMH) pattern, deep lacunes, and severe BG enlarged perivascular spaces (EPVS) would be associated with deep vs. superficial cICH. Methods: Brain MRI scans from a prospective database of consecutive non-traumatic ICH patients admitted to a single referral center (2003 to 2019) were analyzed for the presence of cerebral microbleeds (CMBs) and non-hemorrhagic neuroimaging markers. The presence of clinical risk factors, LVH, and neuroimaging markers were compared between patients with deep and superficial cICH in univariate and multivariable models. Results: Of 1,791 patients with spontaneous ICH, 129 (7%) were found to have cICH (mean age 73±12 years, 46% female). Of these, 83 (64%) patients had deep cICH and 46 (36%) patients had superficial cICH. Hypertension (94% vs. 67%, p &lt; 0.01) and LVH (60% vs. 28%, p &lt; 0.01) were more common among patients with deep vs. superficial cICH. Among those who received a brain MRI (74%), the frequency of peri-BG WMH pattern (24% vs. 5%, p = 0.02), deep lacunes (59% vs. 14%, p &lt; 0.01), severe BG EPVS (27% vs. 3%, p &lt; 0.01), deep CMBs (51% vs. 16%, p &lt; 0.01), and mixed location CMBs (37% vs. 11%, p &lt; 0.01) was greater among patients with deep cICH compared to superficial cICH. When these variables were entered into a multivariable regression model, LVH (OR 3.10, 95% CI [1.07-8.97], p = 0.04) and deep lacunes (OR 4.38, 95% CI [1.25-15.31], p = 0.02) remained significantly associated with deep cICH. Conclusions: Because supratentorial HTN-cSVD imaging markers are common in deep cICH, and deep lacunes and LVH are independently associated with deep cICH, it is likely that HTN-cSVD is the underlying microangiopathy of deep cICH.

Serum Placental Growth Factor as a Marker of Cerebrovascular Disease Burden in Alzheimer's Disease.

Concomitant cerebrovascular diseases (CeVD) have been identified as an important determinant of Alzheimer's disease (AD) progression. Development of robust blood-based biomarkers will provide critical tools to evaluate prognosis and potential interventional strategies for AD with CeVD. This study investigated circulating placental growth factor (PlGF), a potent pro-angiogenic factor related to endothelial dysfunction and vascular inflammation, in an Asian memory clinic cohort of non-demented individuals as well as AD, including its associations with neuroimaging markers of CeVD. 109 patients with AD, 76 cognitively impaired with no dementia (CIND), and 56 non-cognitively impaired (NCI) were included in this cross-sectional study. All subjects underwent 3T brain magnetic resonance imaging to assess white matter hyperintensities (WMH), lacunes, cortical infarcts, and cerebral microbleeds (CMBs). Serum PlGF concentrations were measured by electrochemiluminescence immunoassays. Serum PlGF was elevated in AD, but not CIND, compared to the NCI controls. Adjusted concentrations of PlGF were associated with AD only in the presence of significant CeVD. Elevated PlGF was significantly associated with higher burden of WMH and with CMBs in AD patients. Serum PlGF has potential utility as a biomarker for the presence of CeVD, specifically WMH and CMBs, in AD. Further studies are needed to elucidate the underlying pathophysiological mechanisms linking PlGF to CeVD, as well as to further assess PlGF's clinical utility.

Diagnostic Performance Using a Combination of MRI Findings for Evaluating Cognitive Decline.

We investigated potentially promising imaging findings and their combinations in the evaluation of cognitive decline. This retrospective study included 138 patients with subjective cognitive impairments, who underwent brain MRI. We classified the same group of patients into Alzheimer's disease (AD) and non-AD groups, based on the neuropsychiatric evaluation. We analyzed imaging findings, including white matter hyperintensity (WMH) and cerebral microbleeds (CMBs), using the Kruskal-Wallis test for group comparison, and receiver operating characteristic (ROC) curve analysis for assessing the diagnostic performance of imaging findings. CMBs in the lobar or deep locations demonstrated higher prevalence in the patients with AD compared to those in the non-AD group. The presence of lobar CMBs combined with periventricular WMH (area under the ROC curve [AUC] = 0.702 [95% confidence interval: 0.599-0.806], p < 0.001) showed the highest performance in differentiation of AD from non-AD group. Combinations of imaging findings can serve as useful additive diagnostic tools in the assessment of cognitive decline.

Abstract 17284: Prognostic Impact of Silent Cerebral Microbleeds in Patients Undergoing Transcatheter Aortic Valve Replacement

Introduction: Cerebral microbleeds (CMBs) are known to be associated with age, various cardiovascular risk factors, cognitive impairment, the use of antithrombotic drugs, and future neurological or cardiovascular events. Transcatheter aortic valve implantation (TAVR) has emerged as a rapidly evolving treatment for patients with severe aortic stenosis (AS). However, data on CMBs in those patients are scarce. Hypothesis: We hypothesized that the presence of CMBs in patients with severe aortic stenosis (AS) undergoing TAVR may be associated with some clinical factors or have prognostic implications. Methods: A retrospective analysis was conducted on data from 137 consecutive patients (mean age: 84 ± 5 years, 55 male) with severe AS who underwent T2*-weighted brain magnetic resonance imaging (MRI) prior to TAVR. The brain MRI was assessed by researchers blinded to the patients' clinical information. Additionally, conventional echocardiography was performed to evaluate left ventricular function and valvular abnormalities. Results: CMBs were identified in 42 out of 137 patients (31%). No significant differences were observed between patients with and without CMBs in age, gender, serum BNP levels, or antiplatelet/anticoagulant therapy. However, there were significant differences in left ventricular ejection fraction (LVEF) and left ventricular end-systolic volume (LVESV) between the two groups (LVEF: 58 ± 14% vs. 64 ± 10%, p = 0.01; LVESV: 38 ± 25 ml vs. 28 ± 16 ml, p &lt; 0.01, respectively). Over a median follow-up period of 618 days, patients with CMBs had a higher incidence of major adverse cardiac events (defined as death or heart failure re-hospitalization) compared to those without CMBs (24.0% vs. 13.0%, log-rank test, p = 0.04). (Figure). Conclusions: Our study reveals a high prevalence of CMBs in patients with severe AS. The presence of CMBs is associated with lower LVEF, increased LVESV, and poor prognosis following TAVR.

Abstract 194: Impact of Pre‐treatment Cerebral Microbleeds on the Outcomes of Endovascular Thrombectomy

Introduction Endovascular thrombectomy (EVT) is the gold standard treatment for patients with acute ischemic stroke (AIS) caused by large vessel occlusion (LVO), and there are several factors that can influence the outcomes of EVT in AIS‐LVO patients. We conducted this meta‐analysis to investigate the effect of cerebral microbleeds (CMBs) on the functional and safety outcomes of EVT in patients with AIS caused by LVO. Methods We followed the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines. We included observational studies that recruited AIS‐LVO patients, used susceptibility‐sensitive magnetic resonance imaging (MRI) to detect CMBs, and examined the association between them and predefined outcome events. The outcomes of interest included functional independence, revascularization success, and hemorrhagic adverse events. We conducted a meta‐analysis using the Mantel‐Haenszel method and calculated the risk ratios. Results Four studies involving 1,514 patients were included. A significant reduction in the likelihood of achieving a favorable functional outcome, as measured by the modified Rankin Scale (mRS), was observed in patients with CMBs (Risk Ratio (RR) 0.70, 95% Confidence Interval (CI): 0.53 ‐ 0.91, P=0.01). No significant differences were observed between the two groups in terms of successful revascularization (RR 0.93, 95% CI [0.74 to 1.17], P=0.51), mortality (RR 0.93, 95% CI [0.74 to 1.17], P=0.51), hemorrhagic transformation (RR 0.93, 95% CI [0.59 to 1.45], P=0.74), and parenchymal hematoma (RR 1.23, 95% CI [0.79 to 1.91], P=0.35). Conclusion The presence of CMBs significantly reduced the likelihood of achieving a favorable functional outcome after EVT in AIS‐LVO patients. However, CMBs did not impact the rates of successful revascularization, mortality, or the occurrence of various hemorrhagic complications. Future research should explore the mechanisms of this association and strategies to mitigate its impact.

The Role of Extracellular Matrix and Inflammation in the Stratification of Bleeding and Thrombotic Risk of Atrial Fibrillation on Oral Anticoagulant Therapy: Insights from Strat-Af Study.

In anticoagulated atrial fibrillation (AF) patients, the validity of models recommended for the stratification of the risk ratio between benefits and hemorrhage risk is limited. We hypothesize that both circulating and neuroimaging-based markers might improve the prediction of bleeding and thrombotic risk in anticoagulated AF patients. The Strat-AF study is an observational, prospective, single-center study enrolling 170 patients with AF; recruited patients are evaluated by means of a comprehensive protocol, with clinical, cerebral magnetic resonance imaging and circulating biomarkers assessment. The main outcome is the evaluation of cerebral microangiopathy related to the levels of circulating biomarkers of inflammation and extracellular matrix (ECM) remodeling. At multivariate logistic regression analysis adjusted for age, sex, CHA2DS2-VASc, HAS-BLED and type of anticoagulant, matrix metalloproteinases (MMP)-2 levels were significantly and positively associated with the presence of cerebral microbleeds (CMBs). A significant association between MMP-2, tissue inhibitor of metalloproteinases (TIMP)-1,-2,-4 levels and white matter hyperintensity was also found. Concerning the small vessel disease (SVD) score, MMP-2 and TIMP-1,-2 levels were associated with the presence of two and three or more signs of SVD, whereas TIMP-4 levels were associated with the presence of three signs of SVD with respect to patients with no instrumental signs of SVD. As regarding the presence of enlarged perivascular spaces (EPVS), a significant association was found for high levels of interleukin (IL)-8 and TIMP 1-2-3. These results demonstrate that patients with AF have evidence of impaired ECM degradation, which is an independent risk factor for thrombotic complications of AF patients on oral anticoagulant therapy. The incorporation of these markers in the prognostic schemes might improve their clinical capability in predicting stroke risk and thrombotic complications.

Prevalence, Risk Factors, and Clinical Outcomes of New Cerebral Microbleeds After Intravenous Thrombolysis in Acute Ischemic Stroke: aSystematic Review and Meta-analysis.

Cerebral microbleeds (CMBs) are common in the elderly population, and are associated with an increased risk of stroke and dementia. An acute ischemic stroke event can make CMBs develop rapidly. However, the progression of CMBs after intravenous thrombolysis is not well understood. Following apreviously registered protocol, PubMed, Web of Science, and Embase databases were systematically searched to identify relevant literature up to August 2022. Cohort studies that reported new CMBs in patients with acute ischemic stroke undergoing intravenous thrombolysis were included. Random effects models were used to calculate the pooled estimates. Seven studies with 1079 patients were included in the meta-analysis. The pooled new CMBs prevalence was 7.6% (95% CI 3.9-14.3%) and 63.6% new CMBs were located in the cerebral lobes. Compared with patients without new CMBs, those with new CMBs were older, had ahigher proportion of hypertension, and had higher systolic blood pressure and baseline CMBs burden. The presence of new CMBs increased the likelihood of remote intracerebral hemorrhage (OR 28.75, 95% CI 8.58-96.38) and symptomatic intracerebral hemorrhage (OR 15.49, 95% CI 3.21-74.73) but was not related to functional outcomes or hemorrhagic transformation. The prevalence of new CMBs after intravenous thrombolysis was approximately 7.6%. The presence of new CMBs is associated with remote and symptomatic intracerebral hemorrhage following intravenous thrombolysis. Considering the potential long-term adverse effects of CMBs progression, patients at ahigh risk of developing new CMBs should be identified based on potential risk factors.

The iron burden of cerebral microbleeds contributes to brain atrophy through the mediating effect of white matter hyperintensity

The goal of this work was to explore the total iron burden of cerebral microbleeds (CMBs) using a semi-automatic quantitative susceptibility mapping and to establish its effect on brain atrophy through the mediating effect of white matter hyperintensities (WMH). A total of 95 community-dwelling people were enrolled. Quantitative susceptibility mapping (QSM) combined with a dynamic programming algorithm (DPA) was used to measure the characteristics of 1309 CMBs. WMH were evaluated according to the Fazekas scale, and brain atrophy was assessed using a 2D linear measurement method. Histogram analysis was used to explore the distribution of CMBs susceptibility, volume, and total iron burden, while a correlation analysis was used to explore the relationship between volume and susceptibility. Stepwise regression analysis was used to analyze the risk factors for CMBs and their contribution to brain atrophy. Mediation analysis was used to explore the interrelationship between CMBs and brain atrophy. We found that the frequency distribution of susceptibility of the CMBs was Gaussian in nature with a mean of 201 ppb and a standard deviation of 84 ppb; however, the volume and total iron burden of CMBs were more Rician in nature. A weak but significant correlation between the susceptibility and volume of CMBs was found (r = -0.113, P < 0.001). The periventricular WMH (PVWMH) was a risk factor for the presence of CMBs (number: β = 0.251, P = 0.014; volume: β = 0.237, P = 0.042; total iron burden: β = 0.238, P = 0.020) and was a risk factor for brain atrophy (third ventricle width: β = 0.325, P = 0.001; Evans's index: β = 0.323, P = 0.001). PVWMH had a significant mediating effect on the correlation between CMBs and brain atrophy. In conclusion, QSM along with the DPA can measure the total iron burden of CMBs. PVWMH might be a risk factor for CMBs and may mediate the effect of CMBs on brain atrophy.