To determine associations between cerebral microbleed (CMB) burden with recurrent ischemic stroke (IS) and intracerebral hemorrhage (ICH) risk after IS or TIA.
We identified prospective studies of ...patients with IS or TIA that investigated CMBs and stroke (ICH and IS) risk during ≥3 months follow-up. Authors provided aggregate summary-level data on stroke outcomes, with CMBs categorized according to burden (single, 2-4, and ≥5 CMBs) and distribution. We calculated absolute event rates and pooled risk ratios (RR) using random-effects meta-analysis.
We included 5,068 patients from 15 studies. There were 115/1,284 (9.6%) recurrent IS events in patients with CMBs vs 212/3,781 (5.6%) in patients without CMBs (pooled RR 1.8 for CMBs vs no CMBs; 95% confidence interval CI 1.4-2.5). There were 49/1,142 (4.3%) ICH events in those with CMBs vs 17/2,912 (0.58%) in those without CMBs (pooled RR 6.3 for CMBs vs no CMBs; 95% CI 3.5-11.4). Increasing CMB burden increased the risk of IS (pooled RR 95% CI 1.8 1.0-3.1, 2.4 1.3-4.4, and 2.7 1.5-4.9 for 1 CMB, 2-4 CMBs, and ≥5 CMBs, respectively) and ICH (pooled RR 95% CI 4.6 1.9-10.7, 5.6 2.4-13.3, and 14.1 6.9-29.0 for 1 CMB, 2-4 CMBs, and ≥5 CMBs, respectively).
CMBs are associated with increased stroke risk after IS or TIA. With increasing CMB burden (compared to no CMBs), the risk of ICH increases more steeply than that of IS. However, IS absolute event rates remain higher than ICH absolute event rates in all CMB burden categories.
•With differences between SVD and LVD, the prevalences of SVDs were associated with severe CA stenoses.•SVD includes white matter lesions, LI and CMBs, however CMBs were not associated with severe CA ...stenoses.•Hyperlipidemia related to atherosclerosis might reduce the prevalence of deep CMBs and mixed CMBs.
Small vessel diseases (SVDs) are often asymptomatic. However, SVDs significantly influence the prognosis in patients with large vessel diseases (LVDs). We investigated asymptomatic cerebral findings on 3-Tesla MRI in patients with severe carotid artery (CA) stenoses, compared to peoples without a past history of neurological disorders, including strokes.
We retrospectively analyzed the prevalences of various asymptomatic cerebral findings which were intracerebral hemorrhages (ICHs), cortical superficial siderosis, ventricular dilatation (Evans’ index) and SVDs including cerebral microbleeds (CMBs), lacunar infarctions (LIs), deep white matter hyperintensities (WMHs), periventricular hyperintensities (PVHs). The prevalence of each finding was compared using multivariate logistic regression models with adjustment for stroke risk factors.
We evaluated the findings in 54 patients with severe CA stenosis treated by stenting (CA stenosis group) and 200 adults with health screening tests of the brain and no past history of neurological disorders (control group). Multivariate analyses adjusted for age ≥ 65 years old, female gender, hypertension, hyperlipidemia, diabetes mellitus, alcohol consumption, and smoking index revealed that the prevalences of severe PVHs, severe deep WMHs, asymptomatic deep ICHs, and asymptomatic LIs were significantly higher in the CA stenosis group than the control group. However, there were no significant differences in the prevalences of CMBs, or the remaining asymptomatic findings described above.
With pathological differences between SVD and LVD, asymptomatic SVDs except CMBs and deep ICHs often co-exists severe CA stenosis as a presentative LVD.
To assess the association between cerebral microbleeds (CMBs) and future spontaneous intracerebral hemorrhage (ICH) risk in ischemic stroke patients with nonvalvular atrial fibrillation (AF) taking ...oral anticoagulants.
This was a meta-analysis of cohort studies with >50 patients with recent ischemic stroke and documented AF, brain MRI at baseline, long-term oral anticoagulation treatment, and ≥6 months of follow-up. Authors provided summary-level data on stroke outcomes stratified by CMB status. We estimated pooled annualized ICH and ischemic stroke rates from Poisson regression. We calculated odds ratios (ORs) of ICH by CMB presence/absence, ≥5 CMBs, and CMB topography (strictly lobar, mixed, and strictly deep) using random-effects models.
We established an international collaboration and pooled data from 8 centers including 1,552 patients. The crude CMB prevalence was 30% and 7% for ≥5 CMBs. Baseline CMB presence (vs no CMB) was associated with ICH during follow-up (OR 2.68, 95% confidence interval CI 1.19-6.01,
= 0.017). Presence of ≥5 CMB was related to higher future ICH risk (OR 5.50, 95% CI 2.07-14.66,
= 0.001). The pooled annual ICH incidence increased from 0.30% (95% CI 0.04-0.55) among CMB-negative patients to 0.81% (95% CI 0.17-1.45) in CMB-positive patients (
= 0.01) and 2.48% (95% CI 1.2-6.2) in patients with ≥5 CMBs (
= 0.001). There was no association between CMBs and recurrent ischemic stroke.
The presence of CMB on MRI and the dichotomized cutoff of ≥5 CMBs might identify subgroups of ischemic stroke patients with AF with high ICH risk and after further validation could help in risk stratification, in anticoagulation decisions, and in guiding randomized trials and ongoing large observational studies.
Cerebral microbleeds (MB) are potential risk factors for intracerebral hemorrhage (ICH), but it is unclear if they are a contraindication to using antithrombotic drugs. Insights could be gained by ...pooling data on MB frequency stratified by antithrombotic use in cohorts with ICH and ischemic stroke (IS)/transient ischemic attack (TIA).
We performed a systematic review of published and unpublished data from cohorts with stroke or TIA to compare the presence of MB in: (1) antithrombotic users vs nonantithrombotic users with ICH; (2) antithrombotic users vs nonusers with IS/TIA; and (3) ICH vs ischemic events stratified by antithrombotic use. We also analyzed published and unpublished follow-up data to determine the risk of ICH in antithrombotic users with MB.
In a pooled analysis of 1460 ICH and 3817 IS/TIA, MB were more frequent in ICH vs IS/TIA in all treatment groups, but the excess increased from 2.8 (odds ratio; range, 2.3-3.5) in nonantithrombotic users to 5.7 (range, 3.4-9.7) in antiplatelet users and 8.0 (range, 3.5-17.8) in warfarin users (P difference=0.01). There was also an excess of MB in warfarin users vs nonusers with ICH (OR, 2.7; 95% CI, 1.6-4.4; P<0.001) but none in warfarin users with IS/TIA (OR, 1.3; 95% CI, 0.9-1.7; P=0.33; P difference=0.01). There was a smaller excess of MB in antiplatelet users vs nonusers with ICH (OR, 1.7; 95% CI, 1.3-2.3; P<0.001), but findings were similar for antiplatelet users with IS/TIA (OR, 1.4; 95% CI, 1.2-1.7; P<0.001; P difference=0.25). In pooled follow-up data for 768 antithrombotic users, presence of MB at baseline was associated with a substantially increased risk of subsequent ICH (OR, 12.1; 95% CI, 3.4-42.5; P<0.001).
The excess of MB in warfarin users with ICH compared to other groups suggests that MB increase the risk of warfarin-associated ICH. Limited prospective data corroborate these findings, but larger prospective studies are urgently required.
Cerebral microbleeds (MBs) originate from hypertensive microangiopathy or amyloid angiopathy. However, small intracerebral bleeds associated with other diseases or head traumas are also reported as ...MBs, in the absence of MB criteria. MBs are divided into two groups, lobar areas and deep areas including posterior fossae. MBs in these two areas are investigated each for related diseases and risk factors. Recently, apolipoprotein ε4 or inflammation were reported to influence MBs. MBs originate from multiple factors. In people with MBs, the incidence or recurrent rate of strokes, in particular intracerebral hemorrhages or lacunar infarctions, are higher than those without MB. MBs might be a surrogate marker for strokes. However, there are no guidelines for anti-platelet or anti-coagulant drug use, for people with MBs. Further studies are needed to investigate antithrombotic drug uses in patients with MBs. MBs are reported to be associated with neuro-cognitive disorders, including Alzheimer’s disease and vascular dementia.
We investigated differences in the anatomical distribution of cerebral microbleeds (CMBs) on MRI, hypothesized to indicate the type of underlying cerebral small vessel disease (SVD), between Eastern ...and Western general populations.
We analyzed data from 11 studies identified by a PubMed search between 1996 and April 2014 according to the Preferred Reporting Items for a Systematic Review and Meta-analysis of Individual Participant Data. Study quality measures indicated low or medium risk of bias. We included stroke-free participants from populations aged between 55 and 75 years, categorized by geographic location (Eastern or Western). We categorized CMB distribution (strictly lobar, deep and/or infratentorial D/I, or mixed i.e., CMBs located in both lobar and D/I regions). We tested the hypothesis that Eastern and Western populations have different anatomical distributions of CMBs using multivariable mixed effects logistic regression analyses adjusted for age, sex, and hypertension and clustering by institution.
Among 8,595 stroke-free individuals (mean age SD 66.7 5.6 years; 48% male; 42% from a Western population), 624 (7.3%) had CMBs (strictly lobar in 3.1%; D/I or mixed in 4.2%). In multivariable mixed effects models, Eastern populations had higher odds of D/I or mixed CMBs (adjusted odds ratio 2.78, 95% confidence interval CI 1.77-4.35) compared to Western populations. Eastern populations had a higher number of D/I or mixed CMBs (adjusted prevalence ratio 2.83, 95% CI 1.27-6.31).
Eastern and Western general populations have different anatomical distributions of CMBs, suggesting differences in the spectrum of predominant underlying SVDs, with potential implications for SVD diagnosis and treatment.
Objective Deep intracerebral hematoma (ICH) is frequently associated with microbleed (MB) arising from degenerated MB. Increased numbers of MB are correlated with increased age, and we examined a ...possible relationship between MB number and ICH onset in younger patients. Methods Excluding patients with ICH and a history of ICH, we examined the number of MB and other risk factors in 195 patients with deep ICH (97 male, 98 female) consecutively admitted to our hospital. The patients were equally divided into 3 subgroups according to age (groups A, B, and C). Odds ratios were estimated from logistic regression analyses. Results The number (percentage) of MB in group A (≤60 years old, n = 64) 5.0 ± 9.6 (65.6%) was less than group B (61-69 years old, n = 63) 6.6 ± 9.1 (79.4%) or group C (≥70 years old, n = 68) 6.0 ± 7.0 (86.8%). Multivariate analyses demonstrated that MB greater than or equal to 3 was significantly associated with higher age in group A versus B (odds ratio: 2.3; 95% confidence interval: 1.01-5.3; P = .046) and in group A versus C (odds ratio: 2.6; 95% confidence interval: 1.1-6.2; P =.030). Conclusions Our findings suggest that risk factors for the development of ICH may differ with age, and younger patients with deep ICH have fewer MB.
A 58-year-old male presented with severe consciousness disturbance and left hemiparesis. Computed tomography (CT) revealed subarachnoid hemorrhage (SAH) and acute subdural hematoma caused by a ...ruptured right middle cerebral artery aneurysm. The aneurysm was clipped and the hematoma was evacuated. The patient had almost recovered without new neurological deficits on the next day. Arterial systolic blood pressure was postoperatively controlled within 120 to 150 mmHg. Continuous ventricular and cisternal drainage from the level 10 cm above the external auditory meatus was performed to drain bloody cerebrospinal fluid and prevent vasospasm. Three days after surgery, the patient suddenly lapsed into a coma. CT demonstrated diffuse SAH and bilateral intraventricular hemorrhage caused by rupture of an anterior communicating artery aneurysm. Neck clipping was performed immediately. Unfortunately, the patient died of primary damage due to SAH 3 days after the second surgery. In this case, cisternal drainage was probably important in the aneurysm rupture because of decreased intracranial pressure and change in the perianeurysm environment. Postoperative management of patients with residual untreated aneurysms must consider the possibility that cisternal drainage may result in higher transmural pressure, leading to rupture of the untreated aneurysms.
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.
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