Presence Of Cerebral Microbleeds Research Articles

Association between pulse wave velocity and cerebral microbleeds: a systematic review and meta-analysis.

Cerebral microbleeds are associated with events that are among the highest mortality and disability events combined worldwide, as well as with hypertensive vasculopathy. The aim of the present study was to investigate the relationship between a marker of hypertensive vasculopathy, arterial stiffness assessed by pulse wave velocity, and cerebral microbleeds. A systematic review and meta-analysis was performed using PubMed, Scopus, and Web of Science, according to the Meta-analysis of Observational Studies in Epidemiology (MOOSE) and Cochrane Collaboration Handbook statements. Data extraction, quality assessment and statistical analyses were performed following pre-established criteria. Twenty-one studies involving 18,436 participants were included. Higher levels of pulse wave velocity were associated with a higher presence of cerebral microbleeds p-OR = 1.26 (95% CI; 1.09-1.45), with considerable heterogeneity; even adjusting for potential confounding variables p-OR = 1.12 (95% CI, 1.05-1.20), with substantial heterogeneity. Only the percentage of women was related to p-OR in the adjusted model. Sensitivity analyses confirmed the robustness of our results. Adjusted models showed publication bias. Higher levels of arterial stiffness are associated with greater presence of cerebral microbleeds. This phenomenon may be caused by damage to the brain under higher blood flow loads, in turn due to age-induced reversal of the stiffness gradient between large and small vessels. As the world's population is undergoing demographic ageing, our results underline the importance of establishing pulse wave velocity as a cardiovascular marker for early screening and delaying the onset of the characteristic signs of both diseases.

Sex Differences in Frequency, Severity, and Distribution of Cerebral Microbleeds

Cerebral small vessel disease (SVD) is associated with various cerebrovascular outcomes, but data on sex differences in SVD are scarce. To investigate whether the frequency, severity, and distribution of cerebral microbleeds (CMB), other SVD markers on magnetic resonance imaging (MRI), and outcomes differ by sex. This cohort study used pooled individual patient data from the Microbleeds International Collaborative Network, including patients from 38 prospective cohort studies in 18 countries between 2000 and 2018, with clinical follow-up of at least 3 months (up to 5 years). Participants included patients with acute ischemic stroke or transient ischemic attack with available brain MRI. Data were analyzed from April to December 2023. Outcomes of interest were presence of CMB, lacunes, and severe white matter hyperintensities determined on MRI. Additionally, mortality, recurrent ischemic stroke, and intracranial hemorrhage during follow-up were assessed. Multivariable random-effects logistic regression models, Cox regression, and competing risk regression models were used to investigate sex differences in individual SVD markers, risk of recurrent cerebrovascular events, and death. A total of 20 314 patients (mean [SD] age, 70.1 [12.7] years; 11 721 [57.7%] male) were included, of whom 5649 (27.8%) had CMB. CMB were more frequent in male patients, and this was consistent throughout different age groups, locations, and in multivariable models (female vs male adjusted odds ratio [aOR], 0.86; 95% CI, 0.80-0.92; P < .001). Female patients had fewer lacunes (aOR, 0.82; 95% CI, 0.74-0.90; P < .001) but a higher prevalence of severe white matter hyperintensities (aOR, 1.10; 95% CI, 1.01-1.20; P = .04) compared with male patients. A total of 2419 patients (11.9%) died during a median (IQR) follow-up of 1.4 (0.7-2.5) years. CMB presence was associated with a higher risk of mortality in female patients (hazard ratio, 1.15; 95% CI, 1.02-1.31), but not male patients (hazard ratio, 0.95; 95% CI, 0.84-1.07) (P for interaction = .01). A total of 1113 patients (5.5%) had recurrent ischemic stroke, and 189 patients (0.9%) had recurrent intracranial hemorrhage, with no sex differences. This cohort study using pooled individual patient data found varying frequencies of individual SVD markers between female and male patients, indicating potential pathophysiological differences in manifestation and severity of SVD. Further research addressing differences in pathomechanisms and outcomes of SVD between female and male patients is required.

Association Between Cerebral Microbleeds and Neurological Outcomes in Patients Who Underwent Extracorporeal Membrane Oxygenation.

Cerebral microbleeds (CMBs) are common and varied in patients receiving extracorporeal membrane oxygenation (ECMO). Here, the authors describe CMB findings in patients receiving ECMO and their association with clinical factors. A total of 138 patients receiving ECMO were enrolled and categorized as venovenous and venoarterial. Blood coagulation profiles during ECMO support and Glasgow Coma Scale (GCS) scores within 7 days were recorded. Patients with CMBs exhibited prolonged activated clotting time (P<0.001), decreased fibrinogen levels (P<0.001), reduced platelet counts (P<0.001), and extended prothrombin time (P<0.001). A significant correlation (P<0.05) was observed between the presence of CMBs and most coagulation parameters among all patients. Patients with venoarterial ECMO had significantly higher activated partial thromboplastin time, activated clotting time, and prothrombin time compared with those with venovenous ECMO (all P<0.05). Patients with a less severe CMB burden exhibited higher GCS scores and better neurological injury outcomes at both 7 and 90 days. CMB burden in all patients with ECMO was significantly correlated (P<0.05) with most blood coagulation profiles and neurological injury. CMB burdens after ECMO are common, varied, and associated with a variety of clinical conditions. These findings may guide ECMO management.

Cerebral small vessel disease was associated with the prognosis in ischemic stroke with atrial fibrillation.

The purpose of this study was to explore the relationship between atrial fibrillation (AF), cerebral small vessel disease (CSVD), and ischemic stroke. Data were extracted from China's Third National Stroke Registry (CNSR-III), which registered 15,166 patients in China. A total of 12,180 ischemic stroke patients were included excluding those diagnosed with TIA or without MRI. Logistic regression was to explore the relationship between AF, CSVD, and poor functional outcomes at 12-month follow-up. Cox regression is to explore AF, CSVD, and stroke recurrence as well as all-cause mortality at 12-month follow-up. The average age was 62.40 ± 11.22 years old, and 8362 (68.65%) were men at baseline. Patients with AF had an increased risk of stroke recurrence and all-cause mortality at 12-month follow-up. Those with AF and CSVD imaging such as lacunes, white matter hyperintensity (WMH), and the presence of cerebral microbleeds (CMBs) had an increased risk of poor prognosis. And those with both AF and CSVD burden had an increased risk of worse prognosis at 12-month follow-up. Among Chinese patients with acute ischemic stroke, those with AF were associated with a higher risk of 12-month mortality and stroke recurrence. When AF was combined with some CSVD imaging features such as lacunes, WMH, presence of CMBs or burdens, the 12-month poor prognosis worsened.

Logistic regression model for predicting risk factors and contribution of cerebral microbleeds using renal function indicators.

The brain and kidneys share similar low-resistance microvascular structures, receiving blood at consistently high flow rates and thus, are vulnerable to blood pressure fluctuations. This study investigates the causative factors of cerebral microbleeds (CMBs), aiming to quantify the contribution of each risk factor by constructing a multivariate model via stepwise regression. A total of 164 hospitalized patients were enrolled from January 2022 to March 2023 in this study, employing magnetic susceptibility-weighted imaging (SWI) to assess the presence of CMBs. The presence of CMBs in patients was determined by SWI, and history, renal function related to CMBs were analyzed. Out of 164 participants in the safety analysis, 36 (21.96%) exhibited CMBs and 128 (78.04%) did not exhibit CMBs, and the median age of the patients was 66 years (range: 49-86 years). Multivariate logistic regression identified hypertension (OR = 13.95%, 95% CI: 4.52, 50.07%), blood urea nitrogen (BUN) (OR = 1.57, 95% CI: 1.06-2.40), cystatin C (CyC) (OR = 4.90, 95% CI: 1.20-22.16), and urinary β-2 microglobulin, (OR = 2.11, 95% CI: 1.45-3.49) as significant risk factors for CMBs. The marginal R-square ( ) was 0.25. Among all determinants, hypertension (47.81%) had the highest weight, followed by UN (11.42%). Quasi-curves plotted using the bootstrap method (999 times) showed good agreement between the predictive model and actual observations. Hypertension, BUN, urinary β-2 microglobulin, CyC were risk factors for CMBs morbidity, and controlling the above indicators within a reasonable range will help to reduce the incidence of CMBs.

Predictors of cerebral microbleeds in patients with autosomal dominant polycystic kidney disease

ObjectivesIndividuals with autosomal dominant polycystic kidney disease (ADPKD) can present with vascular abnormalities, including intracranial aneurysms. However, whether ADPKD is associated with cerebral small-vessel disease, such as cerebral microbleeds (CM), remains unclear. The study analyzes the prevalence of CM and the associated clinical and radiological factors in patients with ADPKD. MethodsThe retrospective study enrolled 140 consecutive patients with ADPKD from July 2014 to May 2023. Brain MRIs were analyzed for the presence of CM with susceptibility-weighted imaging (SWI), which were categorized based on lesion location (lobar, deep, or infratentorial). ResultIn this study, the prevalence of CM is 26.4%. Chronic kidney disease (CKD) stage (odds ratio [OR]: 1.40, 95% confidence interval [CI]: 1.04–1.88, p = 0.027) and leukoaraiosis grade (OR: 3.29, 95% CI: 1.43–7.56, p = 0.005) were strongly associated with CM. Additionally, both CKD stage (OR: 1.48, 95% CI: 1.06–2.07, p = 0.023) and leukoaraiosis grade (OR: 2.81, 95% CI: 1.30–6.05, p = 0.008) were associated with lobar microbleeds, whereas only leukoaraiosis grade was also related to deep (OR: 9.00, 95% CI: 3.06–26.44, p < 0.001) and infratentorial (OR: 2.48, 95% CI: 1.10–5.61, p = 0.029) microbleeds. The prediction model based on age, CKD stage and leukoaraiosis grade had diagnostic performance with area under curve: 0.804, 0.688, 0.697, respectively. ConclusionWe recommend that patients with ADPKD who are aged 58 or older, and who have CKD of at least stage 3, undergo brain MRI for detection of CM.

Risk factors and prognosis of acute ischemic stroke complicated with cerebral microbleeds

Objective: To observe the risk factors and prognosis of patients with acute ischemic stroke complicated with cerebral microbleeds (CMBs) to provide a theoretical basis for better prevention and treatment of acute ischemic stroke and reduction of bleeding risk. Methods: The clinical data of 200 patients with acute ischemic stroke who completed susceptibility weighted imaging (SWI) were retrospectively analyzed. They were divided into a CMB group and a non CMB group. Univariate analysis and multivariate logistic regression analysis were used to analyze the risk factors and prognosis of acute ischemic stroke. Results: Univariate analysis showed that systolic blood pressure, fasting plasma glucose, free triiodothyronine (FT3), infarct site in the cerebral lobe and total anterior circulation infarct (TACI) (using the Oxfordshire Community Stroke Project (OCSP) classification) were correlated with acute ischemic stroke complicated with CMBs (P &lt; 0.05). Multivariate logistic regression analysis showed that systolic blood pressure (OR: 1.02, 95% CI: 1.009–1.032), fasting blood glucose (OR: 1.174, 95% CI: 1.082–1.274) and infarct site in the cerebral lobe (OR: 12.925, 95% CI: 7.412–22.540) were independent risk factors for acute ischemic stroke complicated with CMBs (P &lt; 0.05). TACI (OR: 0.004, 95% CI: 0.002–0.007) may not be an independent risk factor (P &lt; 0.05). Conclusion: Systolic blood pressure, fasting blood glucose and infarct site in the cerebral lobe, but likely not TACI, were independent risk factors for acute ischemic stroke complicated with CMBs. The presence or absence of CMBs did not affect the prognosis of acute ischemic stroke.

GGC repeat expansions in NOTCH2NLC cause uN2CpolyG cerebral amyloid angiopathy.

The expansion of GGC repeats within NOTCH2NLC leads to the translation of the uN2CpolyG protein, the primary pathogenic factor in neuronal intranuclear inclusion disease (NIID). This study aims to explore the deposition of uN2CpolyG as an amyloid in the vessel wall, leading to uN2CpolyG cerebral amyloid angiopathy (CAA)-related cerebral microbleeds (CMBs). A total of 97 patients with genetically confirmed NIID were enrolled in this study. We analyzed the presence of CMBs using susceptibility-weighted imaging sequences and compared general clinical information, cerebrovascular risk factors, stroke history, antiplatelet medication use, and MRI features between NIID patients with and without CMBs. We further performed hematoxylin and eosin (H&E), Perl's, Congo red, and Thioflavin S staining, ubiquitin, p62 and uN2CpolyG immunostaining on brain tissue obtained from four NIID patients. A total of 354 CMBs were detected among 41 patients with NIID, with nearly half located in the deep brain, one-third in the lobes, and approximately 20% in the infratentorial area. No significant differences in cerebrovascular disease risk factors or history of antiplatelet drug use were observed between patients with and without CMBs. However, patients with CMBs suffered a higher incidence of previous ischemic and hemorrhagic stroke events. This group also had a higher incidence of recent subcortical infarcts and a higher proportion of white matter lesions in the external capsule and temporal pole. Conversely, patients without CMBs showed higher detection of high signals at the corticomedullary junction on diffusion-weighted imaging and more pronounced brain atrophy. H&E staining showed blood vessel leakage and hemosiderin-laden macrophage clusters, and Prussian blue staining revealed brain tissue iron deposition. CMBs occurred more frequently in small vessels lacking intranuclear inclusions, and extensive degeneration of endothelial cells and smooth muscle fibres was observed mainly in vessels lacking inclusions. Congo red-positive amyloid deposition was observed in the cerebral vessels of NIID patients, with disordered filamentous fibres appearing under an electron microscope. Additionally, the co-localization of Thioflavin S-labeled amyloid and uN2CpolyG protein in the cerebral vascular walls of NIID patients further suggested that uN2CpolyG is the main pathogenic protein in this form of amyloid angiopathy. In conclusion, we reviewed patients with GGC repeat expansion of NOTCH2NLC from a novel perspective, providing initial clinical, neuroimaging, and pathological evidence suggesting that uN2CpolyG may contribute to a distinct type of CAA.

Optical Coherence Tomography Angiography Retinal Imaging Associations With Burden of Small Vessel Disease and Amyloid Positivity in the Brain.

Alzheimer disease (AD) and other dementias are associated with vascular changes and amyloid deposition, which may be reflected as density changes in the retinal capillaries. These changes may can be directly visualized and quantified with optical coherence tomography angiography (OCTA), making OCTA a potential noninvasive preclinical biomarker of small vessel disease and amyloid positivity. Our objective was to investigate the feasibility of retinal imaging metrics as noninvasive biomarkers of small vessel disease and amyloid positivity in the brain. We investigated associations between OCTA and neuroimaging and cognitive metrics in 41 participants without dementia from the Mayo Clinic Study of Aging and Alzheimer's Disease Research Center. OCTA metrics included superficial, deep, and full retina capillary density of the fovea, parafovea, and macula as well as the area of the foveal avascular zone (FAZ). Neuroimaging metrics included a high burden of white matter hyperintensity (WMH), presence of cerebral microbleeds (CMB), lacunar infarcts, and amyloid positivity as evidenced on positron emission tomography (PET), whereas cognitive metrics included mini-mental status examination (MMSE) score. We performed generalized estimating equations to account for measurements in each eye while controlling for age and sex to estimate associations between OCTA metrics and neuroimaging and cognitive scores. Associations between OCTA and neuroimaging metrics were restricted to the fovea. OCTA showed decreased capillary density with high burden of WMH in both the superficial (P = 0.003), deep (P = 0.004), and full retina (P = 0.01) in the fovea but not the parafovea or whole macula. Similarly, participants with amyloid PET positivity had significantly decreased capillary density in the superficial fovea (P = 0.027) and deep fovea (P = 0.03) but higher density in the superficial parafovea (P = 0.038). Participants with amyloid PET positivity also had a significantly larger FAZ (P = 0.031), whereas in those with high WMH burden the difference did not reach statistical significance (P = 0.075). There was also a positive association between MMSE and capillary density of the full retina within the fovea (P = 0.037) and in the superficial parafovea (P = 0.046). No associations were found between OCTA metrics and presence of CMB or presence of lacunar infarcts. The associations of lower foveal capillary density with cerebral WMH and amyloid positivity suggest that further research is warranted to evaluate for shared mechanisms of disease between small vessel disease and AD pathologies.

Recurrent cerebrovascular events after recent small subcortical infarction

BackgroundRecent 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.Patients and methodsThis 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.ResultsWe analysed 332 consecutive patients (mean age 68 years, 36% women; median follow-up time 12 years). 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).ConclusionPatients 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.