Primary Intracerebral Hemorrhage Research Articles

Circle of Willis Morphology in Primary Intracerebral Hemorrhage

We aimed to study the distribution of Circle of Willis (CoW) morphology and its association with intracerebral hemorrhage (ICH) etiology and cerebral small vessel disease (CSVD) burden. Patients with primary ICH who had brain MRIs were consecutively enrolled between March 2012 and January 2021. CoW morphology, CSVD features and the combined CSVD burden (including global CSVD burden, total hypertensive arteriopathy [HA] burden, and total cerebral amyloid angiopathy [CAA] burden) were assessed. CoW morphology included poor CoW (defined as CoW score 0–2), incomplete CoW, and complete fetal-variant of the posterior communicating artery (CFPcoA). Among 296 patients enrolled, 215 were included in the analysis. There was no significant difference among HA-, CAA-, and mixed-ICH in each CoW morphology. Exploratory subgroup analyses suggested that poor CoW was associated with a greater incidence of HA-ICH and low incidence of mixed ICH in patients aged < 60 years, while mixed ICH occurred more frequently in patients with CFPcoA, especially in those without hypertension history (all p < 0.050). Additionally, incomplete CoW was correlated with a larger incidence of lacunes (adjusted OR [adOR] 2.114, 95% CI 1.062–4.207), microbleeds ≥ 5 (adOR 2.437, 95% CI 1.187–5.002), and therefore the combined CSVD burden (adOR 1.194, 95% CI 1.004–1.419 for global CSVD burden, adOR 1.343, 95% CI 1.056–1.707 for total CAA burden), independent of modifiable vascular risk factors, but not age and sex. The CoW might therefore have a potential impact on ICH etiology and is associated with a greater CSVD burden. Our findings are novel, and need to be verified in future studies.

Contemporary Trends in the Nationwide Incidence of Primary Intracerebral Hemorrhage.

We report contemporary trends in nationwide incidence of intracerebral hemorrhage (ICH) across demographic and regional strata over a 15-year period. Utilizing the Nationwide Inpatient Sample (2004-2018) and US Census Bureau data, we calculated ICH incidence rates for age, race/ethnicity, sex, and hospital region sub-cohorts across 5 consecutive 3-year periods (2004-2006 to 2016-2018). We fit Poisson and log binomial regression models to evaluate demographic and regional differences in ICH incidence and trends in prevalence of hypertension and past/current anticoagulant use among hospitalized ICH patients. Overall, the annual incidence rate (95% CI) of ICH per 100 000 was 23.15 (23.10-23.20). The 3-year incidence of ICH (per 100 000) increased from 62.79 in 2004 to 2006 to 78.86 in 2016 to 2018 (adjusted incidence rate ratio, CI: 1.11 [1.02-1.20]), coinciding with increased 3-year prevalence of hypertension and anticoagulant use among hospitalized ICH patients (adjusted risk ratio, CI: hypertension-1.16 [1.15-1.17]; anticoagulant use-2.30 [2.14-2.47]). We found a significant age-time interaction, whereby ICH incidence increased significantly faster among those aged 18 to 44 years (adjusted incidence rate ratio, CI: 1.10 [1.05-1.14]) and 45 to 64 years (adjusted incidence rate ratio, CI: 1.08 [1.03-1.13]), relative to those aged ≥75 years. Rising ICH incidence among young and middle-aged Americans warrants ICH prevention strategies targeting these economically productive age groups.

A Nomogram for Individualized Prediction of Stress-Related Gastrointestinal Bleeding in Critically Ill Patients with Primary Intracerebral Hemorrhage.

PurposeTo establish and validate a nomogram model for predicting stress-related gastrointestinal bleeding in critically ill patients with primary intracerebral hemorrhage.Patients and MethodsFrom January 2018 to March 2021, we conducted a hospital-based study by screening eligible patients with acute intracerebral hemorrhage. Univariate and multivariate logistic regression analyses were performed to determine the predictors for stress-related gastrointestinal bleeding in patients with primary intracerebral hemorrhage. The nomogram was constructed on the basis of multivariate logistic model and was internally validated by bootstrap resampling. The discriminative performance of the nomogram was evaluated using the calibration and concordance index (C-index), which was equal to the area under the curve of receiver-operating characteristics. Hosmer-Lemeshow test was performed to check the model’s goodness of fit. A decision curve analysis was used to assess its clinical utility.ResultsA total of 410 patients were enrolled in this study. Stress-related gastrointestinal bleeding occurred in 115 patients (28.0%). Multivariate analysis demonstrated that gastric pH at admission [odds ratio (OR): 0.52, 95% confidence interval (CI): 0.41–0.66, P < 0.001], ICH volume (OR: 1.03, 95% CI: 1.02–1.05, P < 0.001) and sepsis (OR: 2.56, 95% CI: 1.54–4.25, P < 0.001) were independent predictors for stress-related gastrointestinal bleeding in critically ill patients with ICH. The nomogram including gastric pH at admission, ICH volume and sepsis presented good discrimination with C-index of 0.770 (95% CI: 0.716 to 0.822), which was confirmed to be 0.764 through bootstrapping validation. The calibration plot showed good agreement between the predicted and observed outcomes. The Hosmer–Lemeshow test showed a goodness-of-fit (Chi-Square = 8.085, DF = 8, P = 0.425). Decision curve analysis demonstrated that the nomogram was clinically beneficial.ConclusionThe proposed nomogram based on gastric pH at admission, ICH volume and sepsis can accurately predict the risk of stress-related gastrointestinal bleeding in critically ill patients with primary intracerebral hemorrhage.

Abstract WP128: Race Heterogeneity Potentially Drives The Association Between Hypercholesterolemia And In-hospital Mortality Among Patients With Primary Intracerebral Hemorrhage: Analysis Of 15-year Nationwide Data

Background: The evidence of association between Intracerebral Hemorrhage (ICH) outcomes and hypercholesterolemia (HC) is equivocal. We provide nationwide estimates of ICH in-hospital mortality (IHM) among patients with HC, across race/ethnicity subgroups. Methods: In a pooled cross-sectional analysis of adult (≥ 18 years) primary ICH patients in the National Inpatient Sample (2004 - 2018), we used ICD 9 / 10 codes to identify patients with HC. We fit survey design multivariable logistic regression models to provide nationwide estimates of the association between IHM and HC as adjusted odds ratio (aOR) and 95% confidence interval (CI). Results: Among a total of 803,230 ICH hospitalizations, we identified 56,635 HC ICH patients. HC patients, compared to patients with no hypercholesterolemia (NHC), were older (72.3 vs. 68.7 years), had higher proportional (%) burden of diabetes (35.8 vs. 26.4), hypertension (90.0 vs. 80.9), obesity (9.2 vs. 8.0), atrial fibrillation (22.1 vs. 19.3) and past / current use of anticoagulation (11.9 vs. 9.8). However, HC patients (vs. NHC) were less likely to have extreme loss of function (21.4 vs. 28.7) or receive invasive treatment, including extra-ventricular drain (5.2 vs. 7.6), invasive ventilation (5.7 vs. 7.9), tracheostomy (2.4 vs. 4.2) and gastric tube placement (6.0 vs. 8.5). Overall, and non-Hispanic whites (NHW), non-Hispanic black and Hispanic, HC patients (vs. NHC) had lower IHM (aOR, CI for overall effect: 0.85, 0.81 - 0.90) (Figure 1). The HC - IHM association was significantly modified by age among NHW, whereby the likelihood of IHM among HC (vs. NHC) significantly increased with advancing age (aOR, CI: 1.01, 1.00 - 1.02) (Figure 2). Conclusion: HC is associated with lower ICH severity and IHM, albeit with significant race/ethnic variations. Further evaluation of potential role of genetic, environmental and treatment factors, across race/ethnicity sub-groups, in the relationship between HC and ICH outcomes is warranted.

Abstract WP138: Delirium Is Associated With Higher Rates Of 90-day Hospital Readmission Among Patients With Primary Intracerebral Hemorrhage

Background: Delirium in-hospital (DIH) results in poor in-patient outcomes. However, it’s longer-term effects among intracerebral hemorrhage (ICH) patients are not well characterized. We sought to evaluate the association between DIH and 90-day readmission (RA) among primary ICH patients. Method: Clinical, imaging and outcomes data, from May 2016 to June 2021, were obtained from the Neurological Outcomes Registry for ICH (NEURO-RICH) ; an informatics pipeline across 7 comprehensive and primary stroke centers which implement protocolized delirium assessments via 4AT / CAM-ICU scales. Demographic (age, sex, race, ethnicity, marital status), Glasgow Coma Scale (GCS), systolic and diastolic blood pressure (S/DBP), sepsis, systemic inflammatory response syndrome, and comorbidity data were analyzed. Survival analysis for time-to-90-Day RA was performed with death modeled as a competing risk. Sub hazard ratios (SHR) and 95% confidence intervals (CI) are reported. Subgroup with imaging data (ICH score and cerebral small vessel disease) was analyzed. Results: Final analyses included 1,434 ICH patients (mean age: 66.0 years, 47.2% female, 24.8% non-Hispanic Black, 19.9% Hispanic, median GCS: 13.2, SBP: 163 mmHg). In the fully adjusted model, DIH was significantly associated with higher rates of 90-Day RA (SHR, CI: 2.24, 1.04 - 4.81) (Figure 1A). Anticoagulant therapy (1.36, 1.03 - 1.80), hypertension (1.95, 1.38 - 2.74), diabetes (1.13, 1.09 - 1.17), and Charlson Comorbidity Index (1.08, 1.04 - 1.13) were also independently associated with 90-Day RA (SHR, CI reported). In the imaging subgroup of 523 patients, DIH retained independent association with 90-Day RA (SHR: 3.94 [1.37 - 11.36]) (Figure 1B). Discussion: In addition to traditional predictors of poor outcomes among ICH patients, DIH demonstrated strong and independent association with 90-day RA. Screening, identification, and active management of DIH is critical to reduce long-term disease burden of ICH.

Abstract TP137: Ethnic/racial Variations Of Intracerebral Hemorrhage Genetics (erich-gene) Study Protocol

Introduction: Epidemiologic studies of intracerebral hemorrhage (ICH) have consistently demonstrated variation in incidence, location, comorbidity burden, age-of-onset, and outcome by race and ethnicity, and genetic studies have identified differences in risk mediated by genetic risk factors such as Apolipoprotein E (APOE). We report the design and methods of the largest multi-ethnic genome-wide association study (GWAS) of ICH risk and outcome conducted to date. Methods: The Ethnic/Racial Variations of ICH Genetics (ERICH-GENE) study is an international, multi-center, genetic case-control study of ICH. Cases are individuals with confirmed primary ICH with biosample availability and consent compatible with shareable genome-wide genotyping or previous genotyping. Central neuroimaging phenotype harmonization of case status, hemorrhage location, and imaging characteristics of cerebral small vessel disease including leukoaraiosis, atrophy, microbleeds, intraventricular hemorrhage severity and volume of ICH measurements will be performed. Controls are ICH-free individuals of compatible age and race/ethnicity from existing studies and biorepositories. Results: As of August 2021, 2,002 ICH cases have been collected and genotyped, in addition to 2,558 already-genotyped ICH cases from the multi-ethnic ERICH study. 5,600 total new ICH cases will be genotyped under ERICH-GENE, with planned meta-analyses across existing ICH GWAS datasets and international biobanks totaling &gt;20,000 cases. We are on schedule to meet our genotyping goal within the study period. Non-European ancestry cases are being prioritized for genotyping and ~66% of the previously genotyped ERICH cases are black or Hispanic. From available cases, a total of 10,621 neuroimaging studies have been uploaded for central adjudication to date with 6,278 having undergone harmonization. Conclusions: ERICH-GENE is a large, multi-ethnic, international, centrally harmonized GWAS of ICH risk and outcome that will identify genetic risk factors across diverse populations for biological discovery and population-specific risk stratification.

Association Between Serum Lactate Dehydrogenase Level and Hematoma Expansion in Patients with Primary Intracerebral Hemorrhage: A Propensity-Matched Analysis

The present study aimed to explore whether a higher serum lactate dehydrogenase (sLDH) level on admission is associated with hematoma expansion (HE) in patients with primary intracerebral hemorrhage (ICH). This single-center prospective observational study of patients with primary ICH aged 19 years or older was conducted at the Dehua County Hospital from January 2018 to May 2021. Clinical data and demographic information and outcomes were collected and analyzed. The association between increased sLDH levels and HE was assessed in univariate and multivariate analyses. Propensity-score matching (PSM) analysis was implemented to reduce baseline differences between the groups. Of 609 patients with ICH screened, 360 who metall eligibility criteria were enrolled in the study (mean age, 59.83 ± 12.64 years; 60.28% female patients), of whom 69 (19.17%) developed early HE. sLDH levels were statistically higher in the HE group compared with the non-HE group (236.0 [222.30-275.50] U/L vs. 209.6 [179.30-253.8] U/L; P < 0.001). Multivariable analysis showed that higher sLDH levels were still statistically associated with HE (odds ratio [OR], 0.08; 95% confidence interval, 0.03-0.210; P < 0.001). After PSM, the matched HE group had a significantly higher sLDH level than did the matched non-HE group (236.0 [222.0-279.10] vs. 216.30 [173.0-278.7] U/L; P= 0.003). The area under the curve of 0.704 (95% confidence interval, 0.654-0.751; P < 0.0001) (sensitivity, 92.75%; specificity, 52.58%), and the optimal cutoff value for sLDH level as a predictor for HE in patients with primary ICH was determined as 211.0U/L. The area under the curve of the logistic regression model based on these predictors (the TsL (time from onset to initial computed tomography,sLDH) modelbased on these predictors: sLDH, time from onset to initial computed tomography) was 0.817, with a sensitivity of 84.06% and specificity of 72.51% for HE. The TsL model produced the best ability to predict HE compared with single sLDH. sLDH levels were statistically correlated with poor outcome. The current PSM analysis study shows that increased serum LDH level is statistically associated with HE. Our findings indicate that the TsL model constructed by sLDH and time from onset to initial computed tomography markedly enhances the prediction of HE after ICH.

Total intracranial volume as a covariate for predicting prognosis in patients with primary intracerebral hemorrhage

ObjectivesThe initial hematoma volume is reliable and stable imaging predictor for the outcome of patients with intracerebral hemorrhage, and the total intracranial volume varies between patients. However, the role of total intracranial volume in predicting the prognosis of spontaneous intracerebral hemorrhage has not been previously addressed. Methods782 patients with spontaneous intracerebral hemorrhage were selected in this retrospective cohort at the Neurosurgery Emergency Unit of The First Affiliated Hospital of Harbin Medical University. Due to missing CT images, initial CT exceeding 24 h, traumatic cerebral hemorrhage, and aneurysm, 145 patients were excluded and the remaining 637 patients were included in our analysis. Functional outcome was assessed using the modified Rankin Scale(mRS) and mortality at 3-months after spontaneous intracerebral hemorrhage. CT image datasets were calculated by 3D-Slicer. The initial hematoma volume was normalized to the total intracranial volume to evaluate poor functional outcomes (mRS, 4–6) and mortality. ResultsThe results demonstrated that normalized initial hematoma volume can be used as an indicator of poor functional outcome (mRS, 4–6) (AUCNrIHV=0.753, 95%-CI:0.710–0.795, p < 0.001), mortality (AUCNrIHV=0.808, 95%-CI:0.754–0.862, p < 0.001) and hematoma expansion (AUCNrIHV=0.690, 95%-CI:0.613–0.767, p < 0.001). Meanwhile, the initial hematoma volume in predicting poor functional outcome (AUCIHV=0.749, 95%-CI:0.707–0.792, p < 0.001), mortality (AUCIHV=0.816, 95%-CI: 0.763–0.870, p < 0.001) and hematoma expansion (AUCIHV=0.704, 95%-CI: 0.626–0.782, p < 0.001) was similar to the normalized initial hematoma volume. ConclusionsThe normalized initial hematoma volume has no apparent benefit in predicting the prognosis of patients with cerebral hemorrhage compared with initial hematoma volume.

Oral Care in Acute Stroke

Purpose:Stroke impacts independent activities, particularly personal care such as oral hygiene. Existing guidelines lack details about how to provide effective oral care. This study explores the frequency of oral care based on staff adherence to oral care policies.Method:As part of a quality improvement initiative, we conducted a retrospective chart review of 30 consecutive stroke admissions to an acute care hospital. Patients with primary intracerebral hemorrhage or ischemic stroke were eligible. Sources of information included a decision support database and an electronic chart review. Data collection included length of hospitalization, stroke type, presence of infections, oral mechanism exam, dysphagia evaluations, and daily personal care provision by nursing staff (e.g., oral care and bathing).Results:Twenty-seven patients met the inclusion criteria. They had a mean age of 74 years, and 52% were men. Most had supratentorial stroke (86%) with comparable frequencies of right (48%) and left (52%) hemisphere lesions. In over half of the cases, provision of oral care was not documented at any point during the patients' hospitalization (Mdn= 128 hr). Pericare and bathing were about twice and 4 times more frequent than oral care, respectively.Conclusions:Oral care after stroke is challenging. Existing oral care recommendations from stroke guidelines lack sufficient detail and warrant reconsideration for optimal and routine implementation particularly in acute settings. Education around oral care and associated protocols are necessary to advance oral care practices and improve stroke recovery.

Imaging markers of intracerebral hemorrhage expansion in patients with unclear symptom onset.

Hematoma expansion (HE) is common and associated with poor outcome in intracerebral hemorrhage (ICH) with unclear symptom onset (USO). We tested the association between non-contrast computed tomography (NCCT) markers and HE in this population. Retrospective analysis of patients with primary spontaneous ICH admitted at five centers in the United States and Italy. Baseline NCCT was analyzed for presence of the following markers: intrahematoma hypodensities, heterogeneous density, blend sign, and irregular shape. Variables associated with HE (hematoma growth > 6 mL and/or > 33% from baseline to follow-up imaging) were explored with multivariable logistic regression. Of 2074 patients screened, we included 646 subjects (median age = 75, 53.9% males), of whom 178 (27.6%) had HE. Hypodensities (odds ratio (OR) = 2.67, 95% confidence interval (CI) = 1.79-3.98), heterogeneous density (OR = 2.16, 95% CI = 1.46-3.21), blend sign (OR = 2.28, 95% CI = 1.38-3.75) and irregular shape (OR = 1.82, 95% CI = 1.21-2.75) were independently associated with a higher risk of HE, after adjustment for confounders (ICH volume, anticoagulation, and time from last seen well (LSW) to NCCT). Hypodensities had the highest sensitivity for HE (0.69), whereas blend sign was the most specific marker (0.90). All NCCT markers were more frequent in early presenters (time from LSW to NCCT ⩽ 6 h, n = 189, 29.3%), and more sensitive in this population as well (hypodensities had 0.77 sensitivity). NCCT markers are associated with HE in ICH with USO. These findings require prospective replication and suggest that NCCT features may help the stratification of HE in future studies on USO patients.

Clinical and Brain Computed Tomographic Profile of Stroke Patients in a Tertiary Hospital, North Central Nigeria

Background: Stroke is a common neurological disorder associated with high morbidity and mortality worldwide. Aim: The study set out to characterize the clinico-radiologic pattern of stroke patients as well as to determine the correlation between the clinical and computed tomographic (CT) scan findings in a tertiary hospital in Makurdi, North central Nigeria. Method: This was a retrospective study of 145 patients with clinically suspected stroke, who underwent CT imaging at the Benue State University Teaching Hospital, Makurdi Nigeria between December 2020 and June 2022. Data were analyzed using Statistical Package for Social Sciences (SPSS) version 26. Results: Of the 145 clinically diagnosed cases of stroke, 122 (84.1%) were confirmed on CT. 7 (4.8%) were stroke mimics and 16 (11.0%) were normal. There were 65 (53.3%) males and 57 (46.7%) females with a male: female ratio of 1.1:1. The mean age at presentation was 58.7 ± 12.87 years with age range of 69 - 78 years being affected most. Few cases of stroke were seen below the age of fifty years. Ischaemic stroke was the commonest 77 (63.1%) followed by primary intracerebral haemorrhage (ICH) 38 (31.4%) then sub arachnoid haemorrhage (SAH) 5 (4.1%). Most infarcts were below 10 cm2, while for ICH volume those below 10 cm3 and above 100 cm3 occurred in equal proportion. Hypertension was the main risk factor for stroke with respective frequency of 31 (21.4%) and 94 (64.8%) in isolation or associated with other risk factors like Diabetes mellitus (DM), hyperlipidemia, alcohol, and smoking among others. There was significant correlation between clinical and radiological diagnosis of stroke (p Conclusion: The result showed slight male preponderance with majority of suspected stroke confirmed by CT; these were mostly of ischaemic type. There was significant correlation between clinical and radiologic diagnosis of stroke while hypertension was the main risk factor identified.

Cerebral Microbleeds and Acute Hematoma Characteristics in the ATACH-2 and MISTIE III Trials.

To study the relationship between the presence of cerebral microbleeds (CMBs) and acute hematoma characteristics among patients with primary intracerebral hemorrhage (ICH). We pooled individual patient data from the Antihypertensive Treatment of Acute Cerebral Hemorrhage 2 (ATACH-2) trial and the Minimally Invasive Surgery Plus Alteplase for Intracerebral Hemorrhage Evacuation phase 3 (MISTIE III) trial. We included individuals with a brain MRI scan. Exposure was the presence of a CMB. The coprimary outcomes were admission ICH volume and hematoma expansion. Mixed-effects linear and logistic regression models were used, with demographics and comorbid conditions considered fixed effects and the study cohort treated as a random effect. Additional analyses assessed the relationship between CMB topography and number and hematoma characteristics. Of the 1,499 patients with ICH enrolled in the parent trials, 466 (31.1%) were included in this analysis, and 231 (49.6%) patients had CMBs. In adjusted models, presence of CMBs was associated with smaller ICH volume (β = -0.26, 95% confidence interval [CI] -0.44 to -0.08) and lower odds of hematoma expansion (odds ratio 0.65, 95% CI 0.40-0.95; p = 0.04). The strength of association between CMBs and hematoma characteristics increased with increasing number of CMBs. The location of the CMBs and the severity of leukoaraiosis did not modify these results. In a pooled cohort of patients with ICH, our results are consistent with the hypothesis that more severe underlying small vessel disease, as represented by CMBs, leads to smaller baseline hematoma volumes and reduced hematoma expansion. Underlying cerebral small vessel disease may be of prognostic significance after ICH. ClinicalTrials.gov Identifier: NCT01176565 and NCT01827046. This study provides Class II evidence that the presence of microbleeds on MRI is associated with a smaller ICH volume at presentation and a lower rate of hematoma expansion on follow-up imaging.

Demographic Characteristics and Clinical Outcomes of Asian American and Pacific Islander Patients With Primary Intracerebral Hemorrhage

Demographic Characteristics and Clinical Outcomes of Asian American and Pacific Islander Patients With Primary Intracerebral Hemorrhage

Liver fibrosis indices associated with substantial hematoma expansion in Chinese patients with primary intracerebral hemorrhage

BackgroundWhether liver fibrosis is associated with increased risk for substantial hematoma expansion (HE) after intracerebral hemorrhage (ICH) is still uncertain. We evaluated the association between various liver fibrosis indices and substantial HE in a Chinese population with primary ICH.MethodsPrimary ICH patients admitted to West China Hospital within 24 h of onset between January 2015 and June 2018 were consecutively enrolled. Six liver fibrosis indices were calculated, including aspartate aminotransferase (AST)-platelet ratio index (APRI), AST/alanine aminotransferase ratio-platelet ratio index (AARPRI), fibrosis-4 (FIB-4), modified fibrosis-4 (mFIB-4), fibrosis quotient (FibroQ) and Forns index. Substantial HE was defined as an increase of more than 33% or 6 mL from baseline ICH volume. The association of each fibrosis index with substantial HE was analyzed using binary logistic regression.ResultsOf 436 patients enrolled, about 85% showed largely normal results on standard hepatic assays and coagulation parameters. Substantial HE occurred in 115 (26.4%) patients. After adjustment, AARPRI (OR 1.26, 95% CI 1.00-1.57) and FIB-4 (OR 1.15, 95% CI 1.02-1.30) were independently associated with substantial HE in ICH patients within 24 h of onset, respectively. In ICH patients within 6 h of onset, each of the following indices was independently associated with substantial HE: APRI (OR 2.64, 95% CI 1.30-5,36), AARPRI (OR 1.55, 95% CI 1.09-2.21), FIB-4 (OR 1.35, 95% CI 1.08-1.68), mFIB-4 (OR 1.09, 95% CI 1.01-1.18), FibroQ (OR 1.08, 95% CI 1.00-1.16) and Forns index (OR 1.37, 95% CI 1.10-1.69).ConclusionsLiver fibrosis indices are independently associated with higher risk of substantial HE in Chinese patients with primary ICH, which suggesting that subclinical liver fibrosis could be routinely assessed in such patients to identify those at high risk of substantial HE.

Charcot–Bouchard aneurysms revisited: clinicopathologic correlations

Intracerebral hemorrhage (ICH) is a significant cause of morbidity and mortality worldwide. Hypertension and cerebral amyloid angiopathy (CAA) are the most common causes of primary ICH, but the mechanism of hemorrhage in both conditions is unclear. Although fibrinoid necrosis and Charcot–Bouchard aneurysms (CBAs) have been postulated to underlie vessel rupture in ICH, the role and significance of CBAs in ICH has been controversial. First described as the source of bleeding in hypertensive hemorrhage, they are also one of the CAA-associated microangiopathies along with fibrinoid necrosis, fibrosis and “lumen within a lumen appearance.” We describe clinicopathologic findings of CBAs found in 12 patients out of over 2700 routine autopsies at a tertiary academic medical center. CBAs were rare and predominantly seen in elderly individuals, many of whom had multiple systemic and cerebrovascular comorbidities including hypertension, myocardial and cerebral infarcts, and CAA. Only one of the 12 subjects with CBAs had a large ICH, and the etiology underlying the hemorrhage was likely multifactorial. Two CBAs in the basal ganglia demonstrated associated microhemorrhages, while three demonstrated infarcts in the vicinity. CBAs may not be a significant cause of ICH but are a manifestation of severe cerebral small vessel disease including both hypertensive arteriopathy and CAA.

Noncontrast Computed Tomography Markers of Cerebral Hemorrhage Expansion: Diagnostic Accuracy Meta-Analysis.

Assess the diagnostic accuracy of noncontrast computed tomography (NCCT) markers of hematoma expansion in patients with primary intracerebral hemorrhage. We performed a meta-analysis of observational studies and randomized controlled trials with available data for calculation of sensitivity and specificity of NCCT markers for hematoma expansion (absolute growth >6 or 12.5 mL and/or relative growth >33%). The following NCCT markers were analyzed: irregular shape, island sign (shape-related features); hypodensity, heterogeneous density, blend sign, black hole sign, and swirl sign (density-related features). Pooled accuracy values for each marker were derived from hierarchical logistic regression models. A total of 10,363 subjects from 23 eligible studies were included. Significant risk of bias of included studies was noted. Hematoma expansion frequency ranged from 7% to 40%, mean intracerebral hemorrhage volume from 9 to 27.8 ml, presence of NCCT markers from 9% (island sign) to 82% (irregular shape). Among shape features, sensitivity ranged from 0.32 (95%CI = 0.20-0.47) for island sign to 0.68 (95%CI = 0.57-0.77) for irregular shape, specificity ranged from 0.47 (95%CI = 0.36-0.59) for irregular shape to 0.92 (95%CI = 0.85-0.96) for island sign; among density features sensitivity ranged from 0.28 (95%CI = 0.21-0.35) for black hole sign to 0.63 (95%CI = 0.44-0.78) for hypodensity, specificity ranged from 0.65 (95%CI = 0.56-0.73) for heterogeneous density to 0.89 (95%CI = 0.85-0.92) for blend sign. Diagnostic accuracy of NCCT markers remains suboptimal for implementation in clinical trials although density features performed better than shape-related features. This analysis may help in better tailoring patients' selection for hematoma expansion targeted trials.

High Serum S100A12 Levels Predict Poor Outcome After Acute Primary Intracerebral Hemorrhage.

ObjectiveIntracerebral hemorrhage (ICH) triggers an inflammatory cascade that damages brain tissues and worsens functional outcome. S100A12 functions to promote brain inflammation. We aimed to investigate the relationship between serum S100A12 levels and functional outcome in ICH patients.MethodsSerum S100A12 levels were measured in 101 ICH patients hospitalized within 24 h after symptom onset. Poor functional outcome was defined as a modified Rankin scale of 3 or greater at 3 months after stroke. Early neurologic deterioration was defined as an increase of ≥4 points in the National Institutes of Health Stroke Scale (NIHSS) score or death at 24 hours from symptoms onset.ResultsHigh serum S100A12 levels were independently correlated with NIHSS score (t = 5.384, P < 0.001), hematoma volume (t = 4.221, P < 0.001) and serum C-reactive protein levels (t = 5.068, P < 0.001). Serum S100A12 levels were substantially higher in patients with a poor outcome (median, 66.5 versus 37.7 ng/mL; P < 0.001) or early neurological deterioration (median, 76.5 versus 40.1 ng/mL; P < 0.001) than in the other remainders, independently predicted a poor outcome (odds ratio, 1.035; 95% confidence interval, 1.007–1.064; P = 0.015) and early neurologic deterioration (odds ratio,1.032; 95% confidence interval, 1.003–1.060; P = 0.027), and significantly discriminated a poor outcome (area under curve, 0.794; 95% confidence interval, 0.702–0.868) and early neurologic deterioration (area under curve, 0.760; 95% confidence interval, 0.664–0.839) under receiver operating characteristic curve.ConclusionHigh serum S100A12 levels at admission are highly associated with the extent of inflammatory response, severity, a poor functional outcome and early neurologic deterioration in ICH patients, substantializing serum S100A12 as a promising prognostic biomarker for ICH.

Delayed perihematomal hypoperfusion is associated with poor outcome in intracerebral haemorrhage.

The aim of this study was to characterize the temporal evolution and prognostic significance of perihematomal perfusion in acute intracerebral haemorrhage (ICH). A single-centre prospective cohort of patients with primary spontaneous ICH receives computed tomography perfusion (CTP) within 6h from onset (T0) and at 7days (T7). Cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) were measured in the manually outlined perihematomal low-density area. Poor functional prognosis (modified Rankin Scale 3-6) at 90days was the outcome of interest, and predictors were explored with multivariable logistic regression. A total of 150 patients were studied, of whom 52 (34.7%) had a mRS 3-6 at 90days. Perihematomal perfusion decreased from T0 to T7 in all patients, but the magnitude of CBF and CBV reduction was larger in patients with unfavourable outcome (median CBF change -7.8 vs. -6.0ml/100g/min, p<.001, and median CBV change -0.5 vs. -0.4ml/100g, p=.010, respectively). This finding remained significant after adjustment for confounders (odds ratio [OR] for 1ml/100g/min CBF reduction: 1.33, 95% confidence interval [CI] (1.15-1.55), p<.001; OR for 0.1ml/100g CBV reduction: 1.67, 95% CI 1.18-2.35, p=.004). The presence of CBF<20ml/100g/min at T7 was then demonstrated as an independent predictor of poor functional outcome (adjusted OR: 2.45, 95% CI 1.08-5-54, p=.032). Perihaemorrhagic hypoperfusion becomes more severe in the days following acute ICH and is independently associated with poorer outcome. Understanding the underlying biological mechanisms responsible for delayed decrease in perihematomal perfusion is a necessary step towards outcome improvement in patients with ICH.

Prediction of Hematoma Expansion in Patients With Intracerebral Hemorrhage Using Thromboelastography With Platelet Mapping: A Prospective Observational Study

Background and Purpose: The purpose of the study was to evaluate the usefulness of thromboelastography with platelet mapping (TEG-PM) for predicting hematoma expansion (HE) and poor functional outcome in patients with intracerebral hemorrhage (ICH).Methods: Patients with primary ICH who underwent baseline computed tomography (CT) and TEG-PM within 6 h after symptom onset were enrolled in the observational cohort study. We performed univariate and multivariate logistic regression models to assess the association of admission platelet function with HE and functional outcome. In addition, a receiver operating characteristic (ROC) curve analysis investigated the accuracy of platelet function in predicting HE. A mediation analysis was undertaken to determine causal associations among platelet function, HE, and outcome.Results: Of 142 patients, 37 (26.1%) suffered HE. Multivariate logistic regression identified arachidonic acid (AA) and adenosine diphosphate (ADP) inhibition as significant independent predictors of HE. The area under the ROC curves was 0.727 for AA inhibition and 0.721 for ADP inhibition. Optimal threshold for AA inhibition was 41.75% (75.7% sensitivity; 67.6% specificity) and ADP inhibition was 65.8% (73.0% sensitivity; 66.7% specificity). AA and ADP inhibition were also associated with worse 3-month outcomes after adjusting for age, admission Glasgow Coma Scale score, intraventricular hemorrhage, baseline hematoma volume, and hemoglobin. The mediation analysis showed that the effect of higher platelet inhibition with poor outcomes was mediated through HE.Conclusions: These findings suggest that the reduced platelet response to ADP and AA independently predict HE and poor outcome in patients with ICH. Platelet function may represent a modifiable target of ICH treatment.

Soluble triggering receptor expressed on myeloid cells-1 as a serum biomarker of early neurologic deterioration and prognosis in acute supratentorial intracerebral hemorrhage

BackgroundTriggering receptor expressed on myeloid cells-1 (TREM-1) participates in neuroinflammation. We intended to ascertain whether serum soluble TREM-1 (sTREM-1) could be utilized as a biomarker of inflammation, severity, early neurologic deterioration (END) and outcome after primary intracerebral hemorrhage (ICH). MethodsSerum sTREM-1 levels were gauged in 104 ICH patients and 104 healthy controls. END was diagnosed when the National Institutes of Health Stroke Scale (NIHSS) score increased ≥ 4 points or death between admission and 24 h after admission. Patients with a modified Rankin scale score of > 2 at 3 months were considered to have poor outcome. ResultsAs compared to controls, patients exhibited significantly elevated serum sTREM-1 levels (median: 309.0 vs 67.9 pg/ml). Serum sTREM-1 concentrations were intimately correlated with NIHSS score (r = 0.574), hematoma volume (r = 0.554), blood leukocyte count (r = 0.529) and serum C-reactive protein concentrations (r = 0.509). Serum sTREM-1 concentrations > 309.0 pg/ml independently predicted END and poor outcome with odds ratio values of 4.054 and 4.721 respectively. Serum sTREM-1 concentrations distinguished END and poor outcome with areas under receiver operating characteristic curve of 0.789 and 0.813 respectively. ConclusionSerum sTREM-1 may represent a promising inflammatory biomarker for assessment of severity and prediction of END and poor outcome after ICH.