Cerebral Microbleeds In Patients Research Articles

COVID-19-associated cerebral microbleeds in the general population

Abstract Cerebral microbleeds are frequent incidental findings on brain MRI and have previously been shown to occur in Coronavirus Disease 2019 (COVID-19) cohorts of critically ill patients. We aimed to determine the risk of having microbleeds on medically indicated brain MRI and compare non-hospitalized COVID-19-infected patients with non-infected controls. In this retrospective case-control study, we included patients over 18 years of age, having an MRI with a susceptibility-weighted sequence, between 1 January 2019 and 1 July 2021. Cases were identified based on a positive reverse transcriptase polymerase chain reaction test for SARS-CoV-2 and matched with three non-exposed controls, based on age, sex, body mass index and comorbidities. The number of cerebral microbleeds on each scan was determined using artificial intelligence. We included 73 cases and 219 matched non-exposed controls. COVID-19 was associated with significantly greater odds of having cerebral microbleeds on MRI [odds ratio 2.66 (1.23–5.76, 95% confidence interval)], increasingly so when patients with dementia and hospitalized patients were excluded. Our findings indicate that cerebral microbleeds may be associated with COVID-19 infections. This finding may add to the pathophysiological considerations of cerebral microbleeds and help explain cases of incidental cerebral microbleeds in patients with previous COVID-19.

Clinical significance of the Microbleed Anatomical Rating Scale score in ischemic stroke patients treated with intravenous thrombolysis.

Conflicting results were shown on the relationship between cerebral microbleeds (CMBs) burden and functional outcomes in patients treated with intravenous tissues plasminogen activator (IV tPA). We aimed to investigate the relationship between CMBs burden and functional outcomes using the Microbleed Anatomical Rating Scale (MARS) and determine its optimal cutoff value. A retrospective study was conducted to include patients treated with IV tPA in our stroke center, and the MARS was used to assess the CMBs burden. Other clinical data including demographic factors, stroke severity, vascular risk factors, and clinical outcomes were also documented. Another mediation analysis was performed to investigate whether early neurological improvement could mediate the association between MARS and functional outcomes. A total of 408 patients were included. A cutoff value of 1.5 could predict functional outcomes in patients treated with IV tPA. Based on that cutoff value, MARS showed an independent relationship with functional outcomes [adjusted OR (Odds Ratio) 0.841, 95% confidence interval (CI) 0.720-0.982, P = .029]. A shift analysis showed that higher MARS score (MARS ≥1.5) was related with poor functional outcome according to mRS score distribution (OR = 0.519, 95% CI 0.336-0.803, P = .003). Total effect (indirect + direct effect) was calculated and showed in figure. Early neurological improvement mediated 24% of the effect of MARS score on functional outcomes. Our study showed that MARS could be a potential method to assess the functional outcome based on CMBs in patients treated with IV tPA, and MARS score ≥ 1.5 might be an optimal threshold for poor functional outcome.

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 < 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.

Predictive Values of the CHA2DS2-VASc Score and Left Atrial Diameter for Cerebral Small Vessel Disease in Geriatric Patients With Atrial Fibrillation.

Objective The objective of this study was to determine whether the CHA2DS2-VASc (congestive heart failure, hypertension, age, diabetes mellitus, stroke, vascular disease, age, sex) score and left atrial diameter (LAD) could predict the presence of cerebral small vessel disease (cSVD) in patients older than 65 years with atrial fibrillation as the cause of ischemic stroke. Materials and methods In this study, we included patients over 65 years of age who had suffered an ischemic stroke caused by atrial fibrillation within 30 days after the onset of symptoms. The data recordedincluded demographics, electrocardiograms, Holter monitors, and echocardiography reports. The anteroposterior LAD, determined by transthoracic echocardiography, was analyzed. Each patient's CHA2DS2-VASc score was calculated. Brain magnetic resonance imaging (MRI) assessed white matter hyperintensities (WMH) on fluid-attenuated inversion recovery (FLAIR) images and cerebral microbleeds (CMBs) on susceptibility-weighted sequences. The Fazekas score, based on WMH on MRI, was used to grade the severity of gliosis. Participants were categorized into three groups according to their quantitative CMB burden. Findings The study included 60 participants, with a mean age of 80 years (range 65-99), and 43.3% (n = 26) were male. The CHA2DS2-VASc score had a mean value of 4.21 (range 2-8), and the mean LAD was 4.17 (range 2.6-5.3) cm. The CHA2DS2-VASc score did not predict CMBs (OR, 1.389; 95% CI, 0.961-2.008, p = 0.08) in geriatric stroke patients with atrial fibrillation. However, in the subgroup of patients with diabetes mellitus, the CHA2DS2-VASc score was higher in those with CMB 1-4 and CMB ≥ 5 than in those without CMB. Additionally, the risk of CMBs 1-4 increased with higher LAD compared to patients withoutLAD. Conclusion The LAD and CHA2DS2-VASc scores were not significantly associated with CMB prediction in elderly stroke patients with atrial fibrillation. In a diabetes mellitus subgroup, the CHA2DS2-VASc score was indicative of CMB. An increased LAD elevates the risk of CMBs in patients with coronary artery disease.

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.

Correlation between lipid-lowering therapy and cerebral microbleeds.

To investigate if there is a correlation between lipid-lowering treatment with statins and the occurrence, number, and location of cerebral microbleeds (CMBs) among patients with ischemic cerebrovascular disease (ICVD), and also to compare treatment with atorvastatin and rosuvastatin in terms of the occurrence of CMBs and their differences. In this retrospective study, we included patients who were diagnosed with ICVD and underwent susceptibility weighted imaging (SWI) in a grade A tertiary hospital from October 1, 2014 to October 1, 2022. We collected information on previous statin use, past medical history, clinical test indicators, and imaging data. We found that out of 522 patients, 310 patients (59.4%) had no CMB and 212 patients (40.6%) had CMBs. There was no statistically significant correlation between prior statin use, the occurrence, and number of CMBs in patients diagnosed with ICVD (P < 0.05). As for the location of CMB, there was a statistically significant correlation between prior statin use and lobar CMBs (P < 0.048). However, there was no statistically significant correlation between the use of atorvastatin and rosuvastatin and the occurrence of CMBs (P > 0.05). There was no independent correlation between previous statin use, and the occurrence, and number of CMBs in patients with ICVD. As for CMBs in different locations, there was a correlation between previous use of statin and lobar CMBs. There was no significant difference between atorvastatin and rosuvastatin in the occurrence of CMBs in patients with ICVD.

Association of statin use and lipid levels with cerebral microbleeds and intracranial hemorrhage in patients with atrial fibrillation: A prospective cohort study.

An increased risk of intracranial hemorrhage (ICH) associated with statins has been reported, but data on the relationship between statin use and cerebral microbleeds (CMBs) in patients with atrial fibrillation (AF), a population at high bleeding and cardiovascular risk, are lacking. To explore the association between statin use and blood lipid levels with the prevalence and progression of CMBs in patients with AF with a particular focus on anticoagulated patients. Data of Swiss-AF, a prospective cohort of patients with established AF, were analyzed. Statin use was assessed during baseline and throughout follow-up. Lipid values were measured at baseline. CMBs were assessed using magnetic resonance imagining (MRI) at baseline and at 2 years follow-up. Imaging data were centrally assessed by blinded investigators. Associations of statin use and low-density lipoprotein (LDL) levels with CMB prevalence at baseline or CMB progression (at least one additional or new CMB on follow-up MRI at 2 years compared with baseline) were assessed using logistic regression models; the association with ICH was assessed using flexible parametric survival models. Models were adjusted for hypertension, smoking, body mass index, diabetes, stroke/transient ischemic attack, coronary heart disease, antiplatelet use, anticoagulant use, and education. Of the 1693 patients with CMB data at baseline MRI (mean ± SD age 72.5 ± 8.4 years, 27.6% women, 90.1% on oral anticoagulants), 802 patients (47.4%) were statin users. The multivariable adjusted odds ratio (adjOR) for CMBs prevalence at baseline for statin users was 1.10 (95% CI = 0.83-1.45). AdjOR for 1 unit increase in LDL levels was 0.95 (95% CI = 0.82-1.10). At 2 years, 1188 patients had follow-up MRI. CMBs progression was observed in 44 (8.0%) statin users and 47 (7.4%) non-statin users. Of these patients, 64 (70.3%) developed a single new CMB, 14 (15.4%) developed 2 CMBs, and 13 developed more than 3 CMBs. The multivariable adjOR for statin users was 1.09 (95% CI = 0.66-1.80). There was no association between LDL levels and CMB progression (adjOR 1.02, 95% CI = 0.79-1.32). At follow-up 14 (1.2%) statin users had ICH versus 16 (1.3%) non-users. The age and sex adjusted hazard ratio (adjHR) was 0.75 (95% CI = 0.36-1.55). The results remained robust in sensitivity analyses excluding participants without anticoagulants. In this prospective cohort of patients with AF, a population at increased hemorrhagic risk due to anticoagulation, the use of statins was not associated with an increased risk of CMBs.

Frequency of deep-seated cerebral microbleeds in patients with lobar hemorrhages and histopathological evidence for cerebral amyloid angiopathy.

Cerebral amyloid angiopathy (CAA) is a common disease and the most common cause of lobar hemorrhages in the elderly. Usually, deep-seated microhemorrhages preclude the diagnosis of CAA. In this study, we sought to estimate the frequency of deep-seated microbleeds on MRI in patients with lobar hemorrhages and histopathological evidence for cerebral amyloid angiopathy. In addition, we describe a cohort of patients with cortical and deep-seated microbleeds on MRI and a histopathological specimen available from lobar hematoma evacuation. Retrospective database search for histopathological specimens from lobar hematoma evacuation and review of imaging findings (CT and MRI) and patient charts was performed. Between 1 January 2012 and 31 December 2020, 88 specimens from 88 patients were available. A total of 56 specimens were excluded (no brain tissue in the specimen n = 4, other diagnosis n = 8, no MRI n = 43, and no BOLD-based sequence n = 1). Of the remaining 32 patients, 25 patients (78%) did not harbor deep-seated lesions on MRI, of which 17 patients had histopathological features of CAA. A total of seven patients harbored deep-seated CMB. Of these seven patients, three (3/20, 15%) had histopathological features of CAA. Approximately 15% of patients with histopathologically diagnosed CAA harbor deep-seated microbleeds. This finding may add to the discussion on how to identify patients with CAA and deep-seated CMB.

Correlation between insulin resistance and cerebral microbleeds among Chinese patients with cerebral small vessel disease

Background and objectivesInsulin resistance (IR) plays an important role in the pathogenesis of cerebral small vessel disease (CSVD); however, little is known about the relationship between IR and the incidence of cerebral microbleeds (CMBs) in Asian populations. The aim of this study is to investigate the relationship between CMBs and IR in Chinese patients with CSVD. MethodsThis retrospective study included 240 patients with CSVD. Patients were categorized by the homeostatic model assessment of insulin resistance (HOMA-IR): Quartile 1 (≤1.26), Quartile 2 (1.27–1.92), Quartile 3 (1.93–2.89), and Quartile 4 (>2.89). The medical record of each patient was reviewed, and demographic, clinical and laboratory information was abstracted. All patients completed an MRI scan, and CMBs were defined as round or ovoid hypointense lesions on SWI sequence. ResultsCMBs were present in 82 (34.17%) of the 240 patients that were included in the study (mean age, 71 years; male, 54.89%). After adjustment for potential confounding variables, insulin resistance was associated with the presence of CMBs (adjusted odds ratio 2.298, 95% confidence interval 1.017–5.194 for Q4:Q1; P = 0.046). According to receiver operating characteristic analysis, the best discriminating factor for CMBs was a HOMA-IR level ≥2.215 (area under the curve 0.595; sensitivity 51.2%; specificity 65.2%). ConclusionsIR is significantly associated with the presence of CMBs, suggesting the potential role of IR as a predictive marker for CMBs in patients with CSVD.

Correlation between blood pressure variability and deep cerebral microbleeds in patients with acute ischemic stroke.

To observe the 24-h ambulatory blood pressure characteristics of patients with acute ischemic stroke and explore the correlation between blood pressure variability and strictly deep cerebral microbleeds (CMBs). A convenient sampling method was used to enrol 131 patients with acute ischemic stroke in the Department of Neurology between April 2021 and May 2022. Hospitalised patients with acute ischemic stroke were assessed retrospectively; their ambulatory blood pressure was monitored continuously for 24 h, and the relevant parameters were recorded. Magnetic susceptibility-weighted imaging was used to divide the CMBs into a strictly deep CMB group ( n = 24) and a non-CMB group ( n = 107) according to the location of the CMBs. A logistic regression analysis was performed to determine the independent correlation between the 24-h ambulatory blood pressure parameters and strictly deep CMBs. The receiver operating characteristic (ROC) was further used to analyse the predictive value of the ambulatory blood pressure parameters for strictly deep CMBs in patients with acute ischemic stroke. The results showed that the night systolic blood pressure standard deviation and the night diastolic blood pressure standard deviation (NDBP-SD) in the strictly deep CMB group were higher than those in the non-CMB group ( p < 0.05). The multiple logistic regression analysis indicated that the NDBP-SD (odds ratio [OR] = 1.205, 95% confidence interval [CI]: 1.011-1.436, p = 0.038) was an independent risk factor for strictly deep CMBs in patients. The ROC curve analysis revealed that the area under the curve value of the NDBP-SD was 0.682, and the intercept was 7.81. When NDBP-SD is ≥ 7.81, the occurrence of strictly deep CMBs is closely related (OR = 3.872, 95% CI: 1.347-11.125, p = 0.012). The NDBP-SD is an independent risk factor for strictly deep CMBs in patients with acute ischemic stroke. When NDBP-SD is > 7.81, it may promote the production of strictly deep CMBs.

High Blood Pressure Increases the Risk of Cerebral Microbleeds in Hypertensive Individuals

Introduction: Hypertension is the leading preventable risk factor for major cardiovascular diseases worldwide. Recently, compelling evidence has emerged associating hypertension with cerebral microbleeds (CMBs), which are subclinical hemorrhages in the brain resulting from structural abnormalities in the small vessels that supply the brain. In addition to overall elevated blood pressure (BP), elevation in individual parameters such as systolic BP, diastolic BP, pulse pressure and mean arterial pressure could also individually be important risk factors for CMBs. This study aimed to assess the association between CMBs and blood pressure, and assess blood pressure parameters that could be possible risk factors for CMB. Methods: A retrospective case-control study was conducted from August 2021 to September 2022 on patients who underwent MRI due to primary complaints of limb disorders, loss of consciousness, persistent dizziness, and intermittent headaches. The patients were divided according to MRI results into 52 cases (those who had CMBs) and 52 controls (those who had no CMBs). Extracted data were analyzed in SPSS. Chi-square test, binary logistic regression, and Spearman’s correlation analysis were conducted. Results: In total, 104 cases and control patients were assessed, with mean (±SD) age 70.6 ± 8.56 vs 68.9 ± 8.93 years respectively (p > 0.05). CMB patients had more cases of stroke, hyperlipidemia and diabetes than non-CMB patients. Systolic blood pressure (SBP), diastolic blood pressure, pulse pressure (PP) and mean arterial pressure (MAP) were all considerably raised in CMB patients than non-CMBs patients. Blood pressure grades were positively correlated with the severity of CMBs (r = 0.22; p = 0.044). Logistic regression analysis showed that SBP and MAP were independent risk factors for CMBs (age and sex adjusted odds ratio = 1.420; 95% CI: 1.030 - 1.851, and 1.310; 95% CI: 1.011 - 1.631 respectively). Conclusions: In summary, this study found that hypertension was positively correlated with CMBs severity, and that SBP and MAP are independent risk factors for CMBs in patients with hypertension.

Sex differences in the progression of cerebral microbleeds in patients with concomitant cerebral small vessel disease.

Sex differences in cerebral microbleeds (CMBs) are not well-known. We aimed to assess the impact of sex on the progression of CMBs. The CHALLENGE (Comparison Study of Cilostazol and Aspirin on Changes in Volume of Cerebral Small Vessel Disease White Matter Changes) database was analyzed. Out of 256 subjects, 189 participants with a follow-up brain scan were included in the analysis. The linear mixed-effect model was used to compare the 2-year changes in the number of CMBs between men and women. A total of 65 men and 124 women were analyzed. There were no significant differences in the prevalence (70.8 vs. 71.8%; P = 1.000) and the median [interquartile range (IQR)] number of total CMBs [1 (0-7) vs. 2 (0-7); P = 0.810] at baseline between men and women. The median (IQR) increase over 2 years in the number of CMBs was statistically higher in women than in men [1 (0-2) vs. 0 (0-1), P = 0.026]. The multivariate linear mixed-effects model showed that women had a significantly greater increase in the number of total, deep, and lobar CMBs compared to men after adjusting for age and the baseline number of CMBs [estimated log-transformed mean of difference between women and men: 0.040 (P = 0.028) for total CMBs, 0.037 (P = 0.047) for deep CMBs, and 0.047 (P = 0.009) for lobar CMBs]. The progression of CMB over 2 years was significantly greater in women than in men.

Correlation of lipoprotein-associated phospholipase A2 and cerebral microbleeds in patients with acute ischaemic stroke

Background and aimsCerebral microbleeds (CMBs) increase the risk of stroke occurrence and recurrence,and affect the prognosis of stroke patients. Therefore, identifying biological markers that predict CMBs after stroke is urgently needed. This study explored whether high levels of lipoprotein-associated phospholipase A2(Lp-PLA2) are associated with an increased risk of CMBs in patients with acute ischaemic stroke (AIS).MethodsFrom April 2020 to October 2021, we enrolled 242 patients with AIS. At admission, the plasma levels of Lp-PLA2 were measured in all patients as well as the number of CMBs and white matter lesions. According to the results of the Susceptibility Weighted Imaging (SWI), the patients were divided into a CMB group and a no-CMB group. The groups were compared with univariate and multivariate analyses to clarify the correlation between Lp-PLA2 levels and CMBs, and the optimal cut-off value of Lp-PLA2 that predicted CMBs was determined from the receiver-operating characteristic curve.ResultsCMBs were detected in 71 (29.3%) of the 242 AIS patients. The median Lp-PLA2 level was 182.79 ng/ml. Using the 1st quartile of Lp-PLA2 levels (the lowest levels) as the reference group, univariate logistic regression analysis showed that individuals in the 4th quartile (the highest levels) had a higher risk of CMBs (odds ratio [OR] = 1.460, 95% confidence interval [CI]: 1.188–1.795, P = 0.000). This correlation persisted after adjusting for relevant risk factors (OR = 1.370, 95% CI: 1.096–1.713, P = 0.006). The optimal cut-off value of Lp-PLA2 that predicted the occurrence of CMBs was 184.36 ng/ml; at this threshold, the sensitivity was 69.0%, and the specificity was 60.2%.ConclusionsOur data suggest that a high level of Lp-PLA2 in patients with AIS is a potential risk factor for CMBs.

Presence of cerebral microbleeds is associated with cognitive decline in acromegaly.

Cognitive decline in acromegaly has gained increasing attention. Cerebral microbleeds (CMBs) as radiographic markers for microvascular injury have been linked to various types of cognitive decline. However, the association between CMB formation and acromegaly has not yet been quantified. This study is designed to investigate the prevalence and the radiographic patterns of CMBs and the association between cognitive function and acromegaly-related CMBs in growth hormone (GH)-secreting pituitary adenoma, which is characterized by acromegaly. In a cohort of 55 patients with GH-secreting pituitary adenoma (acromegaly) and 70 healthy control (HC) patients, we determined the presence of CMBs using a 3.0-T MRI scanner. The numbers, locations, and grades of CMBs were determined via susceptibility-weighted imaging (SWI) and the Microbleed Anatomical Rating Scale. Obstructive sleep apnea (OSA) was assessed using the criteria of the American Academy of Sleep Medicine (AASM) Scoring Manual Version 2.2. The Montreal Cognitive Assessment (MoCA) was used to assess cognitive performance within 3days of admission. The association between CMBs and cognitive function as well as clinical characteristics was explored. The incidence of CMBs was 29.1%, whereas that of OSA was 65.5% in acromegaly. There was a statistically significant difference in the prevalence of CMBs between subjects with and without acromegaly (29.1% and 5.3%, respectively) (p<0.01). The age of acromegaly patients with CMBs was much younger compared with HCs with CMBs. Compared with HCs, a significant cognitive decline and the occurrence of OSA were demonstrated in patients with acromegaly (p<0.01). Binary logistic regression analysis adjusted for age, education, and body mass index (BMI) revealed that CMB was an independent risk factor for cognitive impairment in patients with acromegaly (OR=3.19, 95% CI 1.51-6.76, p=0.002). Furthermore, in the logistic regression models adjusted for age, BMI, diabetes, and hypertension, OSA was independently associated with the occurrence of CMBs in patients with acromegaly (OR=13.34, 95% CI 3.09-57.51, p=0.001). A significant increase of CMBs was demonstrated in patients with acromegaly, which may be a result of OSA in acromegaly. The present study indicated that increasing CMBs are responsible for cognitive decline in patients with acromegaly.

Evaluation of Cerebral Microbleeds in Patients with Acute Ischemic Stroke

Evaluation of Cerebral Microbleeds in Patients with Acute Ischemic Stroke

Author Response: Cerebral Microbleeds and Treatment Effect of Intravenous Thrombolysis in Acute Stroke: An Analysis of the WAKE-UP Randomized Clinical Trial.

We are grateful for the interest in our article on the treatment effect of alteplase in acute ischemic stroke patients with preexisting cerebral microbleeds (CMBs).1 The readers point out that new lesions are observed on susceptibility-weighted imaging (SWI) in patients with artificial heart valves that meet the imaging criteria of CMBs and suggest that these lesions should be differentiated from CMBs associated with small vessel disease to better identify patients with an increased bleeding risk.2 Of interest, a previous study showed that new CMBs occurring in acute ischemic stroke patients after receiving IV thrombolysis (IVT) were indeed associated with an increased risk of IVT-related hemorrhagic complications.3 On the other hand, new CMBs were not associated with an increased risk of bleeding in patients undergoing cardiac surgery.2,4 However, IVT may constitute a different bleeding risk than cardiopulmonary bypass and extracorporeal membrane oxygenation, or a prolonged intensive care unit stay. The question of whether CMBs in patients with artificial heart valves represent a different pathophysiologic entity with a different bleeding risk merits further research and would profit from histopathology studies and observational studies in stroke and nonstroke cohorts with long-term follow-up.

Cerebral Microbleeds With Atrial Fibrillation After Ablation Therapy.

BackgroundThe prevalence of cerebral microbleeds (CMBs) is significantly higher in patients with atrial fibrillation (AF) than in those without AF. CMBs in patients with AF have been reported to be primarily of the lobar type, but the exact cause of this remains unknown. We investigated the possibility that hemorrhagic transformation of embolic microinfarction can account for de novo lobar CMBs.MethodsA total of 101 patients who underwent ablation therapy for AF were prospectively registered, and 72 patients completed the assessment with MRI 6 months after catheter ablation. Brain MRI, including diffusion-weighted imaging (DWI) and susceptibility-weighted imaging (SWI), were examined at 1–3 days (baseline) and 6 months after catheter ablation. We quantitatively evaluated the spatial and temporal distribution of embolic microinfarctions and de novo CMBs.ResultsOf the 101 patients, 68 were enrolled in this study. Fifty-nine patients (86.8%) showed embolic microinfarctions on baseline DWI immediately after catheter ablation. There were 137 CMBs in SWI, and 96 CMBs were of the lobar type. Six months later, there were 208 CMBs, including 71 de novo CMBs, and 60 of 71 (84.5%) were of the lobar type. Of the 71 de novo CMBs, 56 (78.9%) corresponded to the location of previous embolic microinfarctions found on baseline DWI. The platelet count was significantly lower and hematocrit/hemoglobin and Fazekas score were higher in the group with de novo CMBs than in the group without de novo CMBs.ConclusionDe novo CMBs frequently appeared after catheter ablation therapy. Our results suggest that embolic microinfarction can cause lobar CMBs.

Intracranial Hemorrhages on Extracorporeal Membrane Oxygenation: Differences Between COVID-19 and Other Viral Acute Respiratory Distress Syndrome.

OBJECTIVES:Extracorporeal membrane oxygenation (ECMO) is a potentially lifesaving procedure in acute respiratory distress syndrome (ARDS) due to COVID-19. Previous studies have shown a high prevalence of clinically silent cerebral microbleeds in patients with COVID-19. Based on this fact, together with the hemotrauma and the requirement of therapeutic anticoagulation on ECMO support, we hypothesized an increased risk of intracranial hemorrhages (ICHs). We analyzed ICH occurrence rate, circumstances and clinical outcome in patients that received ECMO support due to COVID-19–induced ARDS in comparison to viral non-COVID-19–induced ARDS intracerebral hemorrhage.DESIGN:Multicenter, retrospective analysis between January 2010 and May 2021.SETTING:Three tertiary care ECMO centers in Germany and Switzerland.PATIENTS:Two-hundred ten ARDS patients on ECMO support (COVID-19, n = 142 vs viral non-COVID, n = 68).INTERVENTIONS:None.MEASUREMENTS AND MAIN RESULTS:Evaluation of ICH occurrence rate, parameters of coagulation and anticoagulation strategies, inflammation, and ICU survival. COVID-19 and non-COVID-19 ARDS patients showed comparable disease severity regarding Sequential Organ Failure Assessment score, while the oxygenation index before ECMO cannulation was higher in the COVID group (82 vs 65 mm Hg). Overall, ICH of any severity occurred in 29 of 142 COVID-19 patients (20%) versus four of 68 patients in the control ECMO group (6%). Fifteen of those 29 ICH events in the COVID-19 group were classified as major (52%) including nine fatal cases (9/29, 31%). In the control group, there was only one major ICH event (1/4, 25%). The adjusted subhazard ratio for the occurrence of an ICH in the COVID-19 group was 5.82 (97.5% CI, 1.9–17.8; p = 0.002). The overall ICU mortality in the presence of ICH of any severity was 88%.CONCLUSIONS:This retrospective multicenter analysis showed a six-fold increased adjusted risk for ICH and a 3.5-fold increased incidence of ICH in COVID-19 patients on ECMO. Prospective studies are needed to confirm this observation and to determine whether the bleeding risk can be reduced by adjusting anticoagulation strategies.

Disrupted White Matter Integrity and Cognitive Functions in Amyloid-β Positive Alzheimer's Disease with Concomitant Lobar Cerebral Microbleeds.

Lobar cerebral microbleeds (CMBs), which can impair white matter (WM), are often concomitant with definite Alzheimer's disease (AD). To explore the features of cognitive impairments and WM disruptions due to lobar CMBs in patients with AD. There were 310 participants who underwent Florbetapir F18 (AV45) amyloid PET and susceptibility-weighted imaging. Participants with cognitive impairment and amyloid-β positive (ADCI) were included into three groups: ADCI without CMBs, with strictly lobar CMBs (SL-CMBs), and with mixed CMBs (M-CMBs). Tract-based spatial statistics were performed to detect the group differences in WM integrity. There were 82 patients and 29 healthy controls finally included. A decreasing tendency in memory and executive performance can be found among HCs > no CMBs (n = 16) >SL-CMBs (n = 41) >M-CMBs (n = 25) group. Compared to no CMBs, M-CMBs group had significantly decreased fractional anisotropy in left anterior thalamic radiation (ATR), forceps major, forceps minor and inferior longitudinal fasciculus, bilateral inferior fronto-occipital fasciculus (IFOF), and superior longitudinal fasciculus. M-CMBs group also had lower fractional anisotropy in left ATR, IFOF, uncinate fasciculus, and forceps minor compared with SL-CMBs. Furthermore, analysis of Pearson correlation indicated damages in discrepant WMs were positively associated with impairment of memory, executive function, and attention. This study showed lobar CMBs had intensively aggravated cognitive impairments associated with extensive WM damages in definite AD. These findings highlight that lobar CMBs play an important role in AD progression and need to be taken into consideration for the early detection of AD.

White matter changes, duration of hypertension, and age are associated with cerebral microbleeds in patients with different stages of hypertension.

We aimed to investigate risk factors for the presence and number of cerebral microbleeds (CMBs) in patients with different stages of hypertension stages, with an emphasis on the relationship between white matter changes (WMCs) and CMBs. Since 2016, participants aged 40 years or more have been evaluated for the presence of CMBs using enhanced 3D multiecho GE T2*-weighted angiography (ESWAN) sequences. The Mann-Whitney U test and Pearson χ2 test were used to compare the clinical characteristics between the CMB and no-CMB patient groups. Furthermore, we used Spearman's rank correlation analysis to examine the associations between the degree of CMB severity and other important factors. CMBs were detected in 110 (36.7%) of 300 participants. Among patients with stage 2 hypertension, the majority also had CMBs (61.8%, 68/110). CMBs were positively correlated with age, hypertension stage, duration of hypertension, WMCs, and silent cerebral infarction. Patients with grade 3 WMCs were significantly more likely to have CMBs than those without WMCs; this association was true for both patients with stage 1 and those with stage 2 hypertension. In patients with stage 1 or stage 2 hypertension lasting longer than 20 years, the majority had CMBs (69.0%, 29/42; 69.1%, 47/68). The results of binary logistic regression indicated that a more severe hypertension stage, longer duration of hypertension, aging, having silent cerebral infarction and higher values of WMC increase the likelihood of the occurrence of CMBs. CMBs detected in hypertensive patients were more likely to occur in deep structures, and the grade of WMCs and duration of hypertension were more closely associated with the CMB degree than with age.