Risk Of Future Intracerebral Hemorrhage Research Articles

Risk of intracranial hemorrhage in patients using anticoagulant therapy for atrial fibrillation after cerebral microbleeds combined with acute ischemic stroke: a meta-analysis.

To evaluate intracerebral hemorrhage (ICH) risk in patients with ischemic stroke (IS) and cerebral microbleeds (CMBs) undergoing anticoagulation therapy for non-valvular atrial fibrillation (AF). We conducted a comprehensive search across multiple databases, including Embase, PubMed, Cochrane, UpToDate, Scopus, WOS, and SinoMed. The search covered observational literature published from each database inception until February 1, 2023. We analyzed the prevalence of CMBs during the follow-up period, compared future ICH risk between patients with and without baseline CMBs (CMBs presence/absence, ≧5 CMBs), and examined factors influencing ICH occurrence in patients with CMBs. Also studied recurrent stroke during anticoagulation therapy, the risk of future ICH when white matter hyperintensity (WMH) and CMBs coexist, and the effects of anticoagulants vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs) on future ICH. We included 7 articles involving 5,134 participants. The incidence of CMBs was 24%; baseline CMBs were associated with an increased ICH risk compared to patients without CMBs. ICH-risk was more significant in patients with baseline ≥5 CMBs. After anticoagulant therapy, ICH risk was higher than that of recurrent IS. The risk of future ICH was significantly increased with anticoagulant VKAs compared with NOAC. Anticoagulant therapy for ischemic stroke patients with non-valvular AF and CMBs increases future ICH risk. Discontinuing anticoagulation due to ICH risk should be avoided. NOACs are safe and effective for patients with CMBs and IS.

Is statin therapy after ischaemic stroke associated with increased intracerebral hemorrhage? The association may be dependent on intensity of statin therapy.

There has been concern that statin therapy may be associated with an increased risk of intracerebral hemorrhage (ICH). We investigated whether the intensity and type of statin therapy instituted after ischemic stroke (IS) were associated with risk of future ICH in a region of northern China with a high incidence of stroke. Newly diagnosed IS patients who were not treated with lipid-lowering drugs in the Beijing Employee Medical Claims Data database from 2010 to 2017 were included. The primary exposure variable was any statin prescription within 1 month of the first documented stroke diagnosis. High-intensity statin therapy was defined as atorvastatin ⩾ 80 mg, simvastatin ⩾ 80 mg, pravastatin ⩾ 40 mg, and rosuvastatin ⩾ 20 mg per day or equivalent combination. An adjusted Cox proportional hazards model was used to estimate the hazard ratio (HR) for ICH during follow-up in groups exposed and not exposed to statins. Of 62,252 participants with IS and 628 ICH readmissions were recorded during a median follow-up of 3.17 years. The risk of ICH among statin users (N = 43,434) was similar to that among nonusers (N = 18,818) with an adjusted HR and 95% confidence interval (CI) of 0.86 (0.73, 1.02). Compared with non-statin therapy, patients with low/moderate-intensity therapy had a lower risk of ICH (0.62: 0.52, 0.75), while patients with high-intensity therapy had a substantially higher risk (2.12: 1.72, 2.62). For patients with different types of statin therapy, adherence to rosuvastatin had the lowest risk of ICH compared to adherence to atorvastatin (0.46: 0.34, 0.63), followed by simvastatin (0.60: 0.45, 0.81). In patients with IS, any statin therapy was not associated with an increased risk of ICH. However there appeared to be differential risk according to the dose of statin with high-intensity statin therapy being associated with an increased risk of ICH, while low/moderate-intensity therapy was associated with a lower risk.

Abstract 123: In Vivo Permeability Of The Aging Brain With Cerebral Microbleeds

Introduction: Age-related cerebral microbleeds (CMBs) are vascular changes associated with an increased risk of intracerebral hemorrhage (ICH) and neurocognitive decline. CMBs share a strikingly similar appearance on MRI to cerebral cavernous malformations (CCMs), which are leaky capillary lesions predisposing patients to brain bleeding. Our team had previously shown increased vascular permeability in CCM and in the brain of older subjects, with common circulating biomarkers of angiogenesis and inflammation. We examine here whether vascular permeability is greater in the aging brain harboring CBMs. Methods: Dynamic Contrast-Enhanced Quantitative Perfusion (DCEQP) MRI, which assesses vascular permeability, was acquired for 7 patients with CMBs (>50 years old), 10 old (>50 years old), and 9 young (18-30 years old) healthy subjects without CMBs. Cases with active brain disease, stroke or seizure in the prior year were excluded. DCEQP scans were co-registered onto their respective T1-weighted images, normalized using the Desikan-Killiany atlas, and finally segmented into white and gray matter within frontal, temporal, parietal, and occipital lobes. The mean permeability was calculated within each segmented area, and values were compared between the 3 groups of interest. Results: Increased permeability was observed within the frontal white and gray matter as well as the parietal gray matter of patients with CMBs compared to age matched old healthy controls (both: p<0.05). In addition, greater background brain permeability was also observed in old healthy controls compared to young healthy controls, in the occipital white matter, as well as the white and gray matter in the temporal and parietal lobes (all: p<0.05). Conclusion: We confirm that the human brain exhibits increased vascular permeability with aging, and this is more pronounced in brains harboring CMBs. This may provide insight into the pathogenesis of CMBs, potentially reflecting end stage age-related failure of the blood brain barrier, associated with frank bleeding. These results offer a starting point for the development of diagnostic and prognostic imaging biomarkers of CMBs, which can help stratify patients at higher risk of future ICH and cognitive decline.

Abstract WP132: Cerebral Amyloid Angiopathy And Risk Of Ischemic And Hemorrhagic Stroke

Introduction: Cerebral amyloid angiopathy (CAA), a condition characterized by beta amyloid deposition in the cerebral vasculature, is a common cause of intracerebral hemorrhage (ICH) in elderly patients. Radiographic features of CAA such as white matter hyperintensities and cerebral microbleeds are also associated with an increased risk of ischemic stroke. However, there are limited population-based data regarding the risk of incident ischemic and hemorrhagic stroke associated with clinically diagnosed CAA. Methods: We performed a retrospective cohort study using inpatient and outpatient claims from 2016 to 2018 from a nationally representative 5% sample of Medicare beneficiaries. The study exposure was a diagnosis of CAA identified using ICD-10-CM code I68.0. Participants with prevalent stroke were excluded. The primary outcome was any stroke (ischemic or hemorrhagic), and secondary outcomes were ICH, subarachnoid hemorrhage (SAH), and ischemic stroke, assessed separately. These outcomes were identified using validated ICD-10-CM diagnosis codes. Cox proportional hazards regression was used to determine the association between CAA and outcomes after adjustment for demographics and vascular comorbidities. Results: Of the 1.3 million Medicare beneficiaries included, 436 had clinically documented CAA without a prior or concurrent stroke. During a median follow-up of 3.0 years (IQR, 2.3-3.0), incident ischemic stroke occurred in 29,545 patients (2.28%), SAH in 3,340 (0.26%), and ICH in 4,338 (0.34%). In adjusted Cox models, CAA was significantly associated with an increased risk of any stroke (HR, 3.4; 95% CI, 2.5-4.7), ICH (HR, 17.1; 95% CI, 11.1-26.3), and SAH (HR, 6.2; 95% CI, 2.7-13.9). There was a nonsignificant association with ischemic stroke (HR, 1.4; 95% CI, 0.8-2.4). Conclusions: In a nationally representative cohort of Medicare beneficiaries, CAA was associated with a significantly increased risk of future ICH and SAH, but was not significantly associated with an increased risk of future ischemic stroke.

Nonalcoholic fatty liver disease and risk of intracerebral hemorrhage

Background and aimsThis study aimed to investigate the association between the steatosis severity of nonalcoholic fatty liver disease (NAFLD) and future intracerebral hemorrhage (ICH) risk. Methods and resultsWe used data from the Kailuan study. Participants without a history of stroke, myocardial infarction, cancer, other liver diseases or alcohol abuse were enrolled. NAFLD and the severity of liver steatosis were assessed by abdominal ultrasonography. We stratified the participants into different groups according to the severity changes in liver steatosis status across the first 4-year follow-up period. The outcome was the first occurrence of ICH during the next 6-year follow-up period. Hazard ratios (HRs) and 95% CI of ICH were estimated using Cox models adjusted for potential risk factors. A total of 49,906 participants were enrolled in this study. During a median of 6.79 years of follow-up, 193 incident ICH cases were identified. Compared with persistent nonfatty liver participants, the hazard ratios (HRs) for participants with persistent mild steatosis, persistent moderate steatosis, persistent severe steatosis, alleviating steatosis, and aggravating steatosis were 1.28 (95% CI, 0.75–2.18), 2.33 (95% CI, 1.24–4.38), 1.63 (95% CI, 0.22–12.11), 1.41 (95% CI, 0.91–2.18), and 1.37 (95% CI, 0.94–2.00), respectively, in the fully adjusted model. ConclusionsNAFLD with persistent moderate steatosis was significantly related to an increased risk of future ICH, independent of other conventional risk factors.

Association between antiplatelet medication and cerebral microbleeds in stroke-free population.

BACKGROUNDCerebral microbleeds (CMBs) may increase the risk of future intracerebral hemorrhage and ischemic stroke. However, It is unclear whether antiplatelet medication is associated with CMBs. This study aimed to investigate the association between antiplatelet medication and CMBs in a community-based stroke-free population.METHODSIn this cross-sectional study, stroke-free participants aged 18–85 years were recruited from a community in Beijing, China. Demographic, clinical, and antiplatelet medication data were collected through a questionnaire, and all participants underwent blood tests and brain magnetic resonance imaging at 3.0T. The presence, count, and location of CMBs were evaluated using susceptibility-weighted imaging. The association between antiplatelet medication and the presence of CMBs was analyzed using multivariable logistic regression. The associations between antiplatelet medication and CMBs by location (lobar, deep brain or infratentorial, and mixed regions) were also analyzed using multinomial logistic regression. A linear regression analysis was conducted to determine the association between antiplatelet medication and the log-transformed number of CMBs.RESULTSOf the 544 participants (mean age: 58.65 ± 13.66 years, 217 males), 119 participants (21.88%) had CMBs, and 64 participants (11.76%) used antiplatelet medication. Antiplatelet medication was found to be associated with CMBs at any location [odds ratio (OR) = 2.39, 95% CI: 1.24–4.58] and lobar region (OR = 2.83, 95% CI: 1.36–5.86), but not with the number of CMBs (β = 0.14, 95% CI: -0.21–0.48). Among antiplatelet medications, aspirin use was found to be associated with any CMB (OR = 3.17, 95% CI: 1.49–6.72) and lobar CMBs (OR = 3.61, 95% CI: 1.57–8.26).CONCLUSIONSAntiplatelet medication was associated with CMBs in stroke-free participants, particularly lobar CMBs. Among antiplatelet medications, aspirin use was associated with any CMB and lobar CMBs. Our findings suggest that it might be essential to optimize the management of antiplatelet medication in the stroke-free population with a higher burden of vascular risk factors to reduce the potential risk of CMBs.

Factors associated with the new appearance of cerebral microbleeds after endovascular treatment for unruptured intracranial aneurysms.

Endovascular treatment of unruptured intracranial aneurysms may increase cerebral microbleeds (CMBs) in postprocedural T2*-weighted MRIs, which may be a risk for future intracerebral hemorrhage. This study examined the characteristics of postprocedural CMBs and the factors that cause their increase. The patients who underwent endovascular treatment for unruptured intracranial aneurysms from April 2016 to February 2018 were retrospectively analyzed. Treatment techniques for endovascular treatment included simple coiling, balloon-assisted coiling, stent-assisted coiling, or flow diverter placement. To evaluate the increase in CMBs, a head MRI including diffusion-weighted imaging and T2*-weighted MRIs was performed on the preprocedural day; the first postprocedural day; and at 1, 3, and 6months after the procedure. Among the 101 aneurysms that were analyzed, 38 (37.6%) showed the appearance of new CMBs. In the multivariate analysis examining the causes of the CMB increases, chronic kidney disease, a higher number of preprocedural CMBs, and a higher number of diffusion-weighted imaging-positive lesions on the first postprocedural day were independent risk factors. Furthermore, a greater portion of the increased CMBs was found in cortical and subcortical lesions of the treated vascular perfusion area within 1month after the procedure. In endovascular treatment for unruptured intracranial aneurysms, CMBs tended to increase in patients with small vessel disease before the procedure, and it was also implicated in hemorrhagic changes after periprocedural microinfarction.

Von Willebrand factor, ABO blood group, and risk of first-ever intracerebral hemorrhage: A prospective nested case-control study

Background and purposeLow levels of von Willebrand factor (VWF) were associated with intracerebral hemorrhage (ICH) in a previous study. Persons with blood group O have lower VWF levels than other ABO blood groups. This study aimed to investigate the association between VWF and the risk of ICH in adults, as well as the association between ABO blood group and risk of ICH. MethodsThis population-based, nested case-control study was conducted using data and blood samples from health examinations between 1985 and 2007. All participants were followed, and cases with first-ever ICH were identified and validated. One or two controls were matched to each case. ResultsDuring a median follow-up time from blood sampling to ICH of 5.6 years, 176 cases with ICH were identified. The mean age at health examination was 57 years; 50% of participants were women. There was an association between hypertension and risk of ICH, but there was no association between VWF level and risk of ICH. There was no association between blood group O and risk of ICH. ConclusionsTo our knowledge this is the largest prospective study investigating the association between VWF, ABO blood group and ICH. We found no association between VWF or blood group O and risk of future ICH.

Phosphatidylethanol Levels, As a Marker of Alcohol Consumption, Are Associated With Risk of Intracerebral Hemorrhage.

Previous observational studies have shown a moderately increased risk of intracerebral hemorrhage (ICH) with high self-reported alcohol consumption. However, self-reported data tend to underestimate alcohol consumption. Phosphatidylethanol is a specific biomarker reflecting alcohol intake during the last month and correlates with the amount of alcohol consumed. The present study aimed to investigate the association between phosphatidylethanol levels and the risk of future ICH. This population-based nested case-referent study was conducted within the Northern Sweden Health and Disease Cohort. At baseline, all participants underwent a health examination, including a questionnaire with questions about alcohol consumption. A blood sample was collected and stored at -80°C, and phosphatidylethanol 16:0/18:1 levels were measured in packed erythrocytes. Cases (n=97) were diagnosed with a first-ever ICH between 1985 and 2007. Two referents (n=180) were matched to each case. The mean age at baseline was 55 years, 39% of participants were women, and the mean time from blood sampling to ICH was 7.3 years. Only phosphatidylethanol and hypertension remained independently associated with ICH in a multivariable model. Participants with phosphatidylethanol >0.30 μmol/L had an increased risk of ICH compared with those with phosphatidylethanol <0.01 μmol/L (odds ratio, 4.64 [95% CI, 1.49-14.40]). High blood concentrations of phosphatidylethanol were associated with an increased risk of future ICH. This association was independent of hypertension and other risk factors for ICH. Our findings suggest that phosphatidylethanol, as a marker of alcohol consumption, may be used as a risk marker of future ICH.

Cortical superficial siderosis progression in cerebral amyloid angiopathy: Prospective MRI study.

To investigate the prevalence, predictors, and clinical relevance of cortical superficial siderosis (cSS) progression in cerebral amyloid angiopathy (CAA). Consecutive patients with symptomatic CAA meeting Boston criteria in a prospective cohort underwent baseline and follow-up MRI within 1 year. cSS progression was evaluated on an ordinal scale and categorized into mild (score 1-2 = cSS extension within an already present cSS focus or appearance of 1 new cSS focus) and severe progression (score 3-4 = appearance of ≥2 new cSS foci). Binominal and ordinal multivariable logistic regression were used to determine cSS progression predictors. We investigated future lobar intracerebral hemorrhage (ICH) risk in survival analysis models. We included 79 patients with CAA (mean age, 69.2 years), 56 (71%) with lobar ICH at baseline. cSS progression was detected in 23 (29%) patients: 15 (19%) patients had mild and 8 (10%) severe progression. In binominal multivariable logistic regression, ICH presence (odds ratio [OR], 7.54; 95% confidence interval [CI], 1.75-53.52; p = 0.016) and baseline cSS (OR, 10.41; 95% CI, 2.84-52.83; p = 0.001) were independent predictors of cSS progression. In similar models, presence of disseminated (but not focal) cSS at baseline (OR, 5.58; 95% CI, 1.81-19.41; p = 0.004) was an independent predictor of cSS progression. Results were similar in ordinal multivariable logistic regression models. In multivariable Cox regression analysis, severe cSS progression was independently associated with increased future ICH risk (HR, 5.90; 95% CI, 1.30-26.68; p = 0.021). cSS evolution on MRI is common in patients with symptomatic CAA and might be a potential biomarker for assessing disease severity and future ICH risk. External validation of these findings is warranted.

Clinical Relevance of Cerebral Small Vessel Diseases.

Clinical Relevance of Cerebral Small Vessel Diseases.

Cortical superficial siderosis and bleeding risk in cerebral amyloid angiopathy: A meta-analysis.

To assess the association of cortical superficial siderosis (cSS) presence and extent with future bleeding risk in cerebral amyloid angiopathy (CAA). This was a meta-analysis of clinical cohorts of symptomatic patients with CAA who had T2*-MRI at baseline and clinical follow-up for future intracerebral hemorrhage (ICH). We pooled data in a 2-stage meta-analysis using random effects models. Covariate-adjusted hazard ratios (adjHR) from multivariable Cox proportional hazard models were used. We included data from 6 eligible studies (n = 1,239). cSS pooled prevalence was 34% (95% confidence interval [CI] 26%-41%; I 2 87.94%; p < 0.001): focal cSS prevalence was 14% (95% CI 12%-16%; I 2 6.75%; p = 0.37), and disseminated cSS prevalence was 20% (95% CI 13%-26%; I 2 90.39%; p < 0.001). During a mean follow-up of 3.1 years (range 1-4 years), 162/1,239 patients experienced a symptomatic ICH-pooled incidence rate 6.9% per year (95% CI 3.9%-9.8% per year; I 2 83%; p < 0.001). ICH incidence rates per year according to cSS status were 3.9% (95% CI 1.7%-6.1%; I 2 70%; p = 0.018) for patients without cSS, 11.1% (95% CI 7%-15.2%; I 2 56.8%; p = 0.074) for cSS presence, 9.1% (95% CI 5.5%-12.8%; I 2 0%; p = 0.994) for focal cSS, and 12.5% (95% CI 5.3%-19.7%; I 2 73.2%; p = 0.011) for disseminated cSS. In adjusted pooled analysis, any cSS presence was independently associated with increased future ICH risk (adjHR 2.14; 95% CI 1.19-3.85; p < 0.0001). Focal cSS was linked with ICH risk (adjHR 2.11; 95% CI 1.31-2.41; p = 0.002), while disseminated cSS conferred the strongest bleeding risk (adjHR 4.28; 95% CI 2.91-6.30; p < 0.0001). In patients with CAA, cSS presence and extent are the most important MRI prognostic risk factors for future ICH, likely useful in treatment planning. This study provides Class III evidence that in symptomatic CAA survivors with baseline T2*-MRI, cSS (particularly if disseminated, i.e., affecting >3 sulci) increases the risk of future ICH.

Incidence of Convexal Subarachnoid Hemorrhage in the Elderly: The Mayo Clinic Study of Aging

ObjectivesNontraumatic convexal subarachnoid hemorrhages in the elderly can be a manifestation of cerebral amyloid angiopathy associated with a high risk of future intracerebral hemorrhage. The incidence in the elderly population is unknown. Our objectives were to: 1) determine the incidence of convexal subarachnoid hemorrhage in a population-based study, and, 2) to compare apopolipoprotein-E genotype and amyloid positron emission tomographic (PET) imaging for those with versus without hemorrhage. MethodsBetween 11/29/2004 and 3/11/2017, 4462 individuals without hemorrhage at baseline participated in the population-based Mayo Clinic Study of Aging. We used the Rochester Epidemiology Project medical records-linkage system to identify intracerebral hemorrhages. Records and images were reviewed to identify convexal subarachnoid hemorrhage. Neuroimaging characteristics, demographics, medications, and apopolipoprotein-E genotype were recorded. ResultsFour cases were identified. The incidence of convexal subarachnoid hemorrhage was 14.1 per 100,000 person years. Three occurred in women, median age, 79 (range: 71-84). One patient had coexisting cerebral microbleeds. Two participants developed a subsequent lobar intracerebral hemorrhage at a median of 4.75 years after convexal subarachnoid hemorrhage. The apopolipoprotein-E -allele combinations of the 4 were: 3/3, 3/3, 2/2, and 2/3. On Pittsburgh Compound B-PET imaging, median standardized uptake value ratio with convexal subarachnoid hemorrhage was 1.86 (range: 1.38-2.34). ConclusionsConvexal subarachnoid hemorrhage is rare in the older population, occurring with an incidence of about 14 per 100,000 person years. Yet, when present, it may be associated with a high risk of future intracerebral hemorrhage.

Risk of Intracerebral Hemorrhage and Mortality After Convexity Subarachnoid Hemorrhage in Cerebral Amyloid Angiopathy.

Background and Purpose- Convexity subarachnoid hemorrhage (cSAH) is an increasingly recognized presentation of cerebral amyloid angiopathy (CAA), usually revealed by transient symptoms, but data on its outcome are limited. We compared the risk of future intracerebral hemorrhage (ICH), cSAH, and death in patients with CAA after cSAH and after lobar ICH. Methods- Consecutive patients with probable CAA, based on the Boston criteria, presenting with cSAH (CAA-cSAH) or lobar ICH (CAA-ICH) were included. We obtained baseline clinical and magnetic resonance imaging data and follow-up information. Univariable and multivariable analyses were used to compare incidence rate for symptomatic ICH, symptomatic cSAH, and late-death (beyond 30 days) between patients with CAA-cSAH and CAA-ICH. Results- Among 105 patients (mean age, 76.7±7.5 years) enrolled, 44 participants presented with CAA-cSAH and 61 with CAA-ICH. The median follow-up was 22.2 months (interquartile range, 12.6-34.4). The symptomatic ICH rate (per person-year) was 10.5% (95% CI, 5.6-19.4) in patients with CAA-cSAH compared with 8.5% (95% CI, 4.4-16.4) in those with CAA-ICH (adjusted hazard ratio, 1.05; 95% CI, 0.32-3.43). The annual incidence rates of symptomatic cSAH (9.9% versus 3.8%; adjusted hazard ratio, 1.77; 95% CI, 0.43-7.28) and death (9.5% versus 17.8%; adjusted hazard ratio, 0.56; 95% CI, 0.22-1.43) were not significantly different between patients with CAA-cSAH and those with CAA-ICH. Conclusions- Patients with CAA-related cSAH have a poor outcome, with similar high risk of future ICH and long-term mortality than CAA patients after lobar ICH. Our findings may have important prognostic implication and guide management of patients with cSAH in CAA.

Abstract WP346: Frequency of Convexal Subarachnoid Hemorrhage in the General Population

Background: Non-traumatic convexal subarachnoid hemorrhages (cSAH) in the elderly can be a manifestation of cerebral amyloid angiopathy (CAA) and predict future intracerebral hemorrhage risk. The frequency of cSAH in the elderly population is unknown. Our objective was to determine the frequency of convexal subarachnoid hemorrhage in a population-based study among individuals who underwent amyloid PET imaging. Methods: Between 11/29/2004 and 3/11/2017 there were 1,687 participants ages 50-years and older in the population-based Mayo Clinic Study of Aging (MCSA) with Pittsburgh compound B (PiB) PET imaging. All intracerebral hemorrhages among participants were identified utilizing the Rochester Epidemiology Project’s records linkage system, and records and images were reviewed to identify those with both symptomatic and asymptomatic convexal subarachnoid hemorrhage. Neuroimaging characteristics, demographics, medications, and ApoE genotype were recorded. Results: Four (0.23%) cSAHs were identified among the individuals who underwent PiB PET imaging. Three were women and median age was 73 (range: 67-84). cSAH occurred in the following locations: right frontal (3), and right parieto-occipital (1). Two went on to develop a lobar intracerebral hemorrhage at a median of 4.75 years after cSAH. Coexisting cerebral microbleeds were identified in one case. The APOE allele combinations of the four participants were: 3/3, 3/3, 2/2, and 2/3. On PiB PET imaging, the median SUVR was 1.81 (range: 1.38-2.34). Conclusion: cSAH is a relatively rare manifestation of CAA occurring in less than 1% of the general population, but may represent a subset with a high risk of future intracerebral hemorrhage. Half of the participants with cSAH had an APOE e2 allele.

Clinical significance of cerebral microbleeds on MRI: A comprehensive meta-analysis of risk of intracerebral hemorrhage, ischemic stroke, mortality, and dementia in cohort studies (v1).

Background Cerebral microbleeds can confer a high risk of intracerebral hemorrhage, ischemic stroke, death and dementia, but estimated risks remain imprecise and often conflicting. We investigated the association between cerebral microbleeds presence and these outcomes in a large meta-analysis of all published cohorts including: ischemic stroke/TIA, memory clinic, "high risk" elderly populations, and healthy individuals in population-based studies. Methods Cohorts (with > 100 participants) that assessed cerebral microbleeds presence on MRI, with subsequent follow-up (≥3 months) were identified. The association between cerebral microbleeds and each of the outcomes (ischemic stroke, intracerebral hemorrhage, death, and dementia) was quantified using random effects models of (a) unadjusted crude odds ratios and (b) covariate-adjusted hazard rations. Results We identified 31 cohorts ( n = 20,368): 19 ischemic stroke/TIA ( n = 7672), 4 memory clinic ( n = 1957), 3 high risk elderly ( n = 1458) and 5 population-based cohorts ( n = 11,722). Cerebral microbleeds were associated with an increased risk of ischemic stroke (OR: 2.14; 95% CI: 1.58-2.89 and adj-HR: 2.09; 95% CI: 1.71-2.57), but the relative increase in future intracerebral hemorrhage risk was greater (OR: 4.65; 95% CI: 2.68-8.08 and adj-HR: 3.93; 95% CI: 2.71-5.69). Cerebral microbleeds were an independent predictor of all-cause mortality (adj-HR: 1.36; 95% CI: 1.24-1.48). In three population-based studies, cerebral microbleeds were independently associated with incident dementia (adj-HR: 1.35; 95% CI: 1.00-1.82). Results were overall consistent in analyses stratified by different populations, but with different degrees of heterogeneity. Conclusions Our meta-analysis shows that cerebral microbleeds predict an increased risk of stroke, death, and dementia and provides up-to-date effect sizes across different clinical settings. These pooled estimates can inform clinical decisions and trials, further supporting cerebral microbleeds role as biomarkers of underlying subclinical brain pathology in research and clinical settings.

Statin Treatment in Patients With Intracerebral Hemorrhage.

Ever since the publication of the SPARCL trial (Stroke Prevention by Aggressive Reduction in Cholesterol Levels) in 2006, neurologists became aware of the fact that statins may increase the risk for future intracerebral hemorrhage (ICH) in patients with previous ischemic stroke or ICH.1,2 At the same time, observational studies reported an increased risk for hemorrhagic transformation or even symptomatic bleeding in ischemic stroke patients undergoing thrombolysis who were pretreated with statins.3,4 As a consequence, many physicians were very careful to administer statins in patients with ICH and often stopped statin medication immediately after hospital admission in those who had been taking the medication before the event. In 2011, Westover et al5 provided a Markov decision model that came to the conclusion that statins should be avoided in patients with a history of ICH, particularly in those cases with a lobar location. In clinical practice, this often results in the somewhat counterintuitive situation that after an ICH, statins are often permanently discontinued, whereas platelet inhibitors or even oral anticoagulants are resumed depending on the underlying comorbidity.6 Statins exert many pleiotropic effects in addition to cholesterol lowering. These properties may contribute to both its protective effects and also some unwanted side effects, including an increased risk for bleeding.7,8 On the other hand, however, sudden discontinuation of statins may lead to rebound effects which may impair vascular function and induce adverse clinical effects in patients with acute vascular events.9–12 Some years ago, we formulated the recommendation that statins should not be paused and acutely discontinued in ischemic stroke patients undergoing thrombolysis and inferred—based on only sparse clinical data—that this probably also applies for patients after acute ICH.13 In the meantime, a relevant number of research articles including 2 …

Brain microbleeds, anticoagulation, and hemorrhage risk

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, p = 0.017). Presence of ≥5 CMB was related to higher future ICH risk (OR 5.50, 95% CI 2.07-14.66, p = 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 (p = 0.01) and 2.48% (95% CI 1.2-6.2) in patients with ≥5 CMBs (p = 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.

Tumor Necrosis Factor Receptor 1 and 2 Are Associated With Risk of Intracerebral Hemorrhage

Raised plasma concentrations of tumor necrosis factor receptors (TNFR) have been linked to arterial stiffness, cerebral microbleeds, and vascular events. The aim of this study was to investigate the association of circulating levels of TNFR1 and TNFR2 with risk for future intracerebral hemorrhage (ICH). The population-based MDCS cohort (Malmö Diet and Cancer Study; n=28 449) was conducted in 1991 to 1996. A nested case-control study was performed in the MDCS, including 220 cases who experienced ICH during the follow-up period (mean age at inclusion 62 years, 48% men) and 244 matched controls. Of the 220 ICH cases, 68 died within 28 days. Conditional logistic regression was used to study the association between plasma levels of TNFR1 and TNFR2 and incident ICH, adjusting for known ICH risk factors. Concentrations of both TNFR1 and TNFR2 were significantly higher in subjects who developed ICH during the follow-up. The associations remained after adjustment for ICH risk factors (TNFR1: odds ratio [OR], 2.28; 95% confidence interval [CI], 1.26-4.11; P=0.006; TNFR2: OR, 1.77; CI, 1.16-2.70; P=0.008). ORs were somewhat higher for nonlobar ICH (3.04; CI, 1.29-7.14 and 2.39; CI, 1.32-4.32, respectively) than for lobar ICH (2.03; CI, 0.93-4.41 and 1.35; CI, 0.78-2.37, respectively). TNFR1 and TNFR2 were also associated with increased risk of fatal ICH (TNFR1: OR, 4.42; CI, 1.67-11.6; TNFR2: OR, 2.90; CI, 1.50-5.58) and with poor functional outcome according to the modified Rankin Scale. High plasma levels of TNFR1 and TNFR2 were associated with incident ICH, most clearly with ICH of nonlobar location. The results suggest that tumor necrosis factor-mediated inflammation could be associated with vascular changes preceding ICH.

Intracranial Dural Arteriovenous Fistulae.

Intracranial dural arteriovenous fistulae (dAVFs) are typified by pathological anastomoses between meningeal arteries and dural venous sinuses or cortical veins. These fistulae frequently reside within the dural leaflets surrounding a venous sinus, characteristically at the transverse-sigmoid junction but also at the cavernous sinus (CS), superior sagittal sinus, anterior cranial fossa, tentorium, and other locations. dAVFs are distinguished from their pial counterparts (eg, arteriovenous malformations) by their arterial supply from vessels that perfuse the dura mater and lack of a parenchymal nidus.1 dAVFs are rare lesions, accounting for 10% to 15% of all intracranial vascular malformations: 6% of supratentorial and 35% of infratentorial vascular malformations.2 Most frequently, dAVFs affect patients in their middle-to-later years of life (eg, 50–60 years of age).3 Less commonly, dAVFs occur in younger age groups, including children. There is neither a clear sex predilection nor genetic component to these lesions. Clinical manifestations vary widely and depend on both the hemodynamic properties and location of the fistula. Multiple classification systems have been proposed in an effort to predict which dAVFs are at high risk for new neurological events. Most of these schemes stratify risk based on angiographic appearance of the dAVFs, in particular involvement of a venous sinus and presence or absence of retrograde cortical venous drainage (CVD). Other schemes combine angiographic appearance with mode of presentation, given the impact symptoms related to intracerebral hemorrhage (ICH) and nonhemorrhagic neurological deficits (NHND) have on dAVF natural history.4–6 In the following review and synthesis, the authors describe the pathophysiology, classification, mode of presentation, imaging characteristics, natural history, and therapeutic armamentarium for intracranial dAVFs. Particular attention will be given to recent evidence that certain clinical and angiographic features of dAVFs can be used to help stratify risk of future ICH and NHND in an effort …