Treatment Of Acute Cerebral Hemorrhage Research Articles

Predicting hematoma expansion using machine learning: An exploratory analysis of the ATACH 2 trial

IntroductionHematoma expansion (HE) in patients with intracerebral hemorrhage (ICH) is a key predictor of poor prognosis and potentially amenable to treatment. This study aimed to build a classification model to predict HE in patients with ICH using deep learning algorithms without using advanced radiological features. MethodsData from the ATACH-2 trial (Antihypertensive Treatment of Acute Cerebral Hemorrhage) was utilized. Variables included in the models were chosen as per literature consensus on salient variables associated with HE. HE was defined as increase in either >33% or 6 mL in hematoma volume in the first 24 h. Multiple machine learning algorithms were employed using iterative feature selection and outcome balancing methods. 70% of patients were used for training and 30% for internal validation. We compared the ML models to a logistic regression model and calculated AUC, accuracy, sensitivity and specificity for the internal validation models respective models. ResultsAmong 1000 patients included in the ATACH-2 trial, 924 had the complete parameters which were included in the analytical cohort. The median [interquartile range (IQR)] initial hematoma volume was 9.93.mm3 [5.03–18.17] and 25.2% had HE. The best performing model across all feature selection groups and sampling cohorts was using an artificial neural network (ANN) for HE in the testing cohort with AUC 0.702 [95% CI, 0.631–0.774] with 8 hidden layer nodes The traditional logistic regression yielded AUC 0.658 [95% CI, 0.641–0.675]. All other models performed with less accuracy and lower AUC. Initial hematoma volume, time to initial CT head, and initial SBP emerged as most relevant variables across all best performing models. ConclusionWe developed multiple ML algorithms to predict HE with the ANN classifying the best without advanced radiographic features, although the AUC was only modestly better than other models. A larger, more heterogenous dataset is needed to further build and better generalize the models.

Radiomic Features of Acute Cerebral Hemorrhage on Non-Contrast CT Associated with Patient Survival.

The mortality rate of acute intracerebral hemorrhage (ICH) can reach up to 40%. Although the radiomics of ICH have been linked to hematoma expansion and outcomes, no research to date has explored their correlation with mortality. In this study, we determined the admission non-contrast head CT radiomic correlates of survival in supratentorial ICH, using the Antihypertensive Treatment of Acute Cerebral Hemorrhage II (ATACH-II) trial dataset. We extracted 107 original radiomic features from n = 871 admission non-contrast head CT scans. The Cox Proportional Hazards model, Kaplan-Meier Analysis, and logistic regression were used to analyze survival. In our analysis, the "first-order energy" radiomics feature, a metric that quantifies the sum of squared voxel intensities within a region of interest in medical images, emerged as an independent predictor of higher mortality risk (Hazard Ratio of 1.64, p < 0.0001), alongside age, National Institutes of Health Stroke Scale (NIHSS), and baseline International Normalized Ratio (INR). Using a Receiver Operating Characteristic (ROC) analysis, "the first-order energy" was a predictor of mortality at 1-week, 1-month, and 3-month post-ICH (all p < 0.0001), with Area Under the Curves (AUC) of >0.67. Our findings highlight the potential role of admission CT radiomics in predicting ICH survival, specifically, a higher "first-order energy" or very bright hematomas are associated with worse survival outcomes.

Abstract TMP74: Association Between Hematoma Volume After Risk of Subsequent Ischemic Stroke: A MISTIE III and ATACH-2 Analysis

Background: Non-traumatic intracerebral hemorrhage (ICH) is independently associated with long-term increased risk of major arterial ischemic events. Whether hematoma volume influences this risk is poorly understood. Methods: We pooled individual patient data from the MISTIE III (Minimally Invasive Surgery Plus Alteplase for Intracerebral Hemorrhage Evacuation phase 3) and the ATACH-2 (Antihypertensive Treatment of Acute Cerebral Hemorrhage) trials. The exposure was hematoma volume. In the primary analysis, hematoma volume was treated as a continuous measure after natural logarithmic transformation to approximate linearity, and in the secondary analysis, it was dichotomized by the median. The outcome was an ischemic stroke, adjudicated centrally within each trial. We evaluated the association between hematoma volume and the risk of an ischemic stroke using Cox regression analyses after adjustment for demographics, vascular comorbidities, and ICH characteristics. Results: Of 1,499 ICH patients, the mean age was 61.7 (SD, 12.8) years and 574 (38.3%) were female. The median hematoma volume was 17.3 mL (IQR, 7.2-35.7). During a median follow up of 107 days (IQR, 91-140), 30 ischemic strokes occurred of which 22 were in patients with median ICH volume &gt; 17.3 mL with a cumulative incidence of 4.6% (95% CI, 3.1-7.1). Among patients with median ICH volume &lt; 17.3 mL, there were 8 ischemic strokes with a cumulative incidence of 3.1% (95% CI, 1.7-6.0). Using adjusted Cox regression models, log-transformed ICH volume (continuous measure) was associated with an increased risk of ischemic stroke (HR, 1.5 per log-unit increase; 95% CI, 1.1-2.8). Similarly, ICH volume &gt; 17.3 mL was associated with an increased risk of ischemic stroke (HR, 2.5; 95% CI, 1.1-7.2), compared to those with an ICH volume &lt; 17.3 mL. Conclusions: In a heterogeneous cohort of ICH patients, initial hematoma volume was associated with a heightened risk of subsequent ischemic stroke.

Intensive Blood Pressure Reduction is Associated with Reduced Hematoma Growth in Fast Bleeding Intracerebral Hemorrhage A Secondary Analysis of the ATACH-2 Randomized Clinical Trial.

Spontaneous intracerebral hemorrhage (ICH) patients at highest risk of hematoma growth are those with the most potential to benefit from anti-expansion treatment. Large clinical trials have not definitively shown a clear benefit of blood pressure (BP) reduction. We aim to determine whether intensive blood pressure reduction could benefit patients with fast bleeding ICH. An exploratory analysis of data from the Antihypertensive Treatment of Acute Cerebral Hemorrhage 2 (ATACH-2) randomized controlled trial was performed. In order to capture not just early bleeding (even if a small amount), but the rate of bleeding (mL/hour), we restricted the study to "Fast bleeding ICH," defined as an ICH volume/onset-to-CT time >5mL/hr. Hematoma growth, as defined as an increase of hematoma volume > 33% between baseline and 24 hours. A total of 940 patients were included (mean age 62.1 years, 61.5% male), of whom 214 (22.8%) experienced hematoma expansion. Of these, 567(60.3%) met the definition of "fast bleeding" with baseline ICH volume/time to presentation of at least 5mL/hr. Intensive blood pressure reduction was associated with a significantly lower rate of hematoma growth in fast bleeding patients (20.6% vs 31.0%, p=0.005). In a subgroup of 266 (46.9%) fast-bleeding patients who received treatment within 2 hours after symptom onset, intensive BP lowering was associated with improved functional independence (OR, 1.98; 95% CI,1.06-3.69; p=0.031). Our results suggest that early use of intensive BP reduction may reduce hematoma growth and improve outcome in fast bleeding patients. This article is protected by copyright. All rights reserved.

Abstract TMP79: Deep Learning Model For Prediction Of Supratentorial Intracerebral Hemorrhage (ich) Expansion

Purpose: Hematoma expansion (HE) is associated with early clinical deterioration, worse long-term outcome, and higher mortality in ICH. Identification of patients at risk of HE may allow targeted anti-expansion therapies in future trials. We aimed to train and validate a deep learning model for prediction of HE based on admission non-contrast head CT. Methods: We utilized the clinical and imaging information from the Antihypertensive Treatment of Acute Cerebral Hemorrhage II (ATACH-2) trial and Yale ICH registry. All patients with spontaneous supratentorial ICH who had baseline head CT (&lt;24 h from last know well), follow-up scan (within 16-48 h of baseline), axial slice thickness &lt;5.7 mm, and slices numbers &gt;28 were included. The HE was defined as an increase volume &gt;33% or 6 ml. We trained a DenseNet121-based 3D convolutional neural network for prediction of HE (pipeline summarized in the Figure). Results: A total of 749 patients (610 from ATACH-2 and 183 from Yale) were randomly split (4:1) into 634 training/cross-validation (368 (58%) male, mean age of 62.8±13.1 years, median NIHSS 10, and 144 (23%) with HE); and 159 independent test set (92 (58%) male, mean age of 62.5±14.6 years, median NIHSS 12, and 36 (23%) with HE). The average of validation AUC in five-fold training/cross-validation was 0.62, with the best performing model achieving an AUC of 0.71 in validation fold. We then tested this model in the independent validation cohort isolated from training process, achieving an AUC of 0.67 in predicting HE. The attention heatmaps (Figure) confirm that deep learning model predictions were based on head CT regions containing ICH and perilesional edema. Conclusion: We could train, and independently validate a deep learning model for identification of supratentorial ICH patients at risk of impending HE. Compared to visual markers (including CTA spot sign), such model can provide an automated objective tool for future trial enrollment based on readily available non-contrast CT

Abstract 101: Predicting Hematoma Expansion Using An Artificial Neural Network: An Exploratory Analysis Of The Atach 2 Trial

Introduction: Hematoma expansion (HE) in patients with intracerebral hemorrhage (ICH) is a key predictor of poor prognosis and potentially amenable to treatment. Current clinical scoring models, radiological markers, and labs have limited ability to predict HE. This study aimed to create a more robust classification model to predict HE in patients with ICH using a deep learning algorithm, an artificial neural network (ANN). Methods: Data from the ATACH 2 trial (Antihypertensive Treatment of Acute Cerebral Hemorrhage) was utilized. Variables included in the models were chosen as per literature consensus on salient factors associated with HE and clinical expertise. HE was defined as increase in either &gt;33% or 6mL in hematoma volume in the first 24 hours. A multi-layer feedforward ANN was trained using the back-propagation method to minimize the loss function with 5-fold cross validation. 80% of patients were used for training and 20% for testing. The ANN was compared to a logistic regression model (GLM). Given the imbalance in patients with HE, AUPRC (area under the precision-recall curve), recall and precision were calculated for the respective models. Results: Of the 963 patients in the study (mean age 62±13.0, 38.5% female), 31% had hematoma expansion. The median [interquartile range (IQR)] initial hematoma volume was 10.5mm 3 [5.16 - 20.25], median admission SBP [IQR] was 200 [184-217], median platelet count [IQR] was 213 [178-256], median INR [IQR] was 1.0 [0.9-1.0], and median admission GCS [IQR] was 15 [13-15]. The GLM model had AUPRC of 0.38 with recall of 0.60 and precision of 0.38 in the testing cohort. The ANN training model demonstrated AUPRC of 0.92 with recall of 0.72 with precision of 0.39 during testing. Initial ICH volume, platelets, INR, and GCS had the highest feature importance. Conclusion: We developed an ANN to predict HE in ICH patients performing with improved sensitivity and similar positive predictive value when compared to GLM. We support that ANN can capture complex associations between variables not attainable in classic regression models. This model may help identify patients at risk for HE who warrant careful monitoring and aggressive treatment upfront including those suitable for clinical trials for treatments.

J-shape relation of blood pressure reduction and outcome in acute intracerebral hemorrhage: A pooled analysis of INTERACT2 and ATACH-II individual participant data.

The aim of this study was to better define the shape of association between the degree ("magnitude") of early (< 1 h) reduction in systolic blood pressure (SBP) and outcomes in patients with acute intracerebral hemorrhage (ICH) through pooled analysis of the second Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT2) and second Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH-II) datasets. Association of the continuous magnitude of SBP reduction described using cubic splines and an ordinal measure of the functional outcome on the modified Rankin scale (mRS) scores at 90 days were analyzed in generalized linear mixed models. Models were adjusted for achieved (mean) and variability (standard deviation, SD) of SBP between 1 and 24 h, various baseline covariates, and trial as a random effect. Among 3796 patients (mean age 63.1 (SD = 13.0) years; female 37.4%), with a mean magnitude (< 1 h) of SBP reduction of 28.5 (22.8) mmHg, those with larger magnitude were more often non-Asian and female, had higher baseline SBP, received multiple blood pressure (BP) lowering agents, and achieved lower SBP levels in 1-24 h. Compared to those patients with no SBP reduction within 1 h (reference), the adjusted odds of unfavorable functional outcome, according to a shift in mRS scores, were lower for SBP reductions up to 60 mmHg with an inflection point between 32 and 46 mmHg, but significantly higher for SBP reductions > 70 mmHg. Similar J-shape associations were evident across various time epochs across 24 h and consistent according to baseline hematoma volume and SBP and history of hypertension. A moderate degree of rapid SBP lowering is associated with improved functional outcome after ICH, but large SBP reductions over 1 h (e.g. from > 200 to target < 140 mmHg) were associated with reduction, or reversal, of any such benefit.

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.

Race/ethnicity and response to blood pressure lowering treatment after intracerebral hemorrhage.

It is unknown if race/ethnicity modifies the response to blood pressure (BP) lowering treatment after intracerebral hemorrhage (ICH). We aimed to examine the race/ethnicity differences in the response to BP lowering treatment after ICH. This is a post hoc analysis of the Antihypertensive Treatment of Acute Cerebral Hemorrhage II (ATACH-2) trial. The primary outcome is good outcome, defined as 90-day modified Rankin Scale 0-3. The primary predictor is race/ethnicity for which we included non-Hispanic categories of White, Black, Asian, and the category of Hispanic. We fit adjusted logistic regression models with the predictor of race/ethnicity and models with the interaction term of treatment*race/ethnicity. We included a total of 953 patients in our analysis (White = 213, Black = 112, Asian = 554, and Hispanic = 74). In the models with the interaction between race/ethnicity and treatment, we found that White patients assigned to the intensive treatment arm had lower predicted probability of good outcome than those assigned to the standard treatment arm (Model 1: 56.2% vs. 68.1%, p = .027; Model 2: 53.4% vs. 68.3%, p = .009). When divided into White and non-White groups, intensive treatment was associated with higher odds of serious adverse events in White group but not in the non-White group. In addition, there was an association between intensive treatment and higher risk of hematoma expansion in White patients and lower risk of hematoma expansion in non-White patients. In the ATACH-2, there was an interaction between race/ethnicity and response to BP lowering treatment after ICH, with White patients having an association between intensive blood pressure reduction and worse outcome.

Admission computed tomography radiomic signatures outperform hematoma volume in predicting baseline clinical severity and functional outcome in the ATACH-2 trial intracerebral hemorrhage population.

Radiomics provides a framework for automated extraction of high-dimensional feature sets from medical images. We aimed to determine radiomics signature correlates of admission clinical severity and medium-term outcome from intracerebral hemorrhage (ICH) lesions on baseline head computed tomography (CT). We used the ATACH-2 (Antihypertensive Treatment of Acute Cerebral Hemorrhage II) trial dataset. Patients included in this analysis (n=895) were randomly allocated to discovery (n=448) and independent validation (n=447) cohorts. We extracted 1130 radiomics features from hematoma lesions on baseline noncontrast head CT scans and generated radiomics signatures associated with admission Glasgow Coma Scale (GCS), admission National Institutes of Health Stroke Scale (NIHSS), and 3-month modified Rankin Scale (mRS) scores. Spearman's correlation between radiomics signatures and corresponding target variables was compared with hematoma volume. In the discovery cohort, radiomics signatures, compared to ICH volume, had a significantly stronger association with admission GCS (0.47 vs. 0.44, p=0.008), admission NIHSS (0.69 vs. 0.57, p<0.001), and 3-month mRS scores (0.44 vs. 0.32, p<0.001). Similarly, in independent validation, radiomics signatures, compared to ICH volume, had a significantly stronger association with admission GCS (0.43 vs. 0.41, p=0.02), NIHSS (0.64 vs. 0.56, p<0.001), and 3-month mRS scores (0.43 vs. 0.33, p<0.001). In multiple regression analysis adjusted for known predictors of ICH outcome, the radiomics signature was an independent predictor of 3-month mRS in both cohorts. Limited by the enrollment criteria of the ATACH-2 trial, we showed that radiomics features quantifying hematoma texture, density, and shape on baseline CT can provide imaging correlates for clinical presentation and 3-month outcome. These findings couldtrigger a paradigm shift where imaging biomarkers may improve current modelsfor prognostication, risk-stratification, and treatment triage of ICH patients.

Hematoma Expansion Shift Analysis to Assess Acute Intracerebral Hemorrhage Treatments.

Hematoma expansion (HE) is commonly analyzed as a dichotomous outcome in intracerebral hemorrhage (ICH) trials. In this proof-of-concept study, we propose an HE shift analysis model as a method to improve the evaluation of candidate ICH therapies. Using data from the Antihypertensive Treatment of Acute Cerebral Hemorrhage II (ATACH-2) trial, we performed HE shift analysis in response to intensive blood pressure lowering by generating polychotomous strata based on previously established HE definitions, percentile/absolute quartiles of hematoma volume change, and quartiles of 24-hour follow-up hematoma volumes. The relationship between blood pressure treatment and HE shift was explored with proportional odds models. The primary analysis population included 863 patients. In both treatment groups, approximately one-third of patients exhibited no HE. With the use of a trichotomous HE stratification, the highest strata of ≥33% revealed a 5.8% reduction in hematoma growth for those randomized to intensive therapy (adjusted odds ratio [aOR] 0.77, 95% confidence interval [CI] 0.60-0.99). Using percentile quartiles of hematoma volume change, we observed a favorable shift to reduce growth in patients treated with intensive therapy (aOR 0.73, 95% CI 0.57-0.93). Similarly, in a tetrachotomous analysis of 24-hour follow-up hematoma volumes, shifts in the highest stratum (>21.9 mL) were most notable. Our findings suggest that intensive blood pressure reduction may preferentially mitigate growth in patients at risk of high volume HE. A shift analysis model of HE provides additional insights into the biological effects of a given therapy and may be an additional way to assess hemostatic agents in future studies. ClinicalTrials.gov Identifier:NCT01176565.

Abstract 40: Hematoma Expansion Shift Analysis to Assess Acute Intracerebral Hemorrhage Treatments

Background and Purpose: In present-day intracerebral hemorrhage (ICH) trials, hematoma expansion (HE) is often analyzed as a binary variable - present or absent. However, dichotomizing intrinsically wide-ranging variables discards substantial information reflective of treatment effect and can reduce the ability to detect relationships between the exposure and outcome of interest. We explored the concept of a “HE shift analysis” as a novel analytic mode for ICH treatment trials using previously published clinical trial data. Methods: Using data from the Antihypertensive Treatment of Acute Cerebral Hemorrhage II (ATACH-2) trial, patients were stratified by treatment status (intensive vs. standard blood pressure lowering with IV nicardipine) and HE shift was evaluated by generating strata based on a) previously established HE definitions, b) quartiles of 24-hour total hematoma volume, and c) quartiles of 24-hour total hematoma volume (THV) change. The relationship between blood pressure treatment and hematoma expansion shift was explored using proportional odds models and adjusted Wilcoxon testing. Results: The primary analysis population included 863 patients. In both treatment groups, approximately one-third of patients exhibited no hematoma growth. Using a conventional threshold, significant intraparenchymal expansion (≥33%) was reduced by 5.8% in those assigned to the intensive therapy arm (aOR: 0.77 [95% CI: 0.60-0.99], Figure 1A). The stratified quartiles of 24-hour total hematoma volumes were associated with a 5% shift within the highest and lowest strata in the intensive arm, (aOR: 0.83 [0.66-1.05], Figure 1B). Intensive therapy was associated with a 5.2% reduction from &gt; 3 mL to 0.5-3 mL (aOR: 0.86 [0.68-1.09], Figure 1C). Conclusions: A shift analysis model of HE provides additional insights into the biological effects of a given therapy and may be an alternate way to assess hemostatic agents in future hemorrhage trials.

Diffusion-Weighted Imaging Lesions After Intracerebral Hemorrhage and Risk of Stroke: A MISTIE III and ATACH-2 Analysis.

Punctate ischemic lesions noted on diffusion-weighted imaging (DWI) are associated with poor functional outcomes after intracerebral hemorrhage (ICH). Whether these lesions increase long-term risk of stroke is poorly understood. We pooled individual patient data from the ATACH-2 trial (Antihypertensive Treatment of Acute Cerebral Hemorrhage) and the MISTIE III trial (Minimally Invasive Surgery Plus Alteplase for Intracerebral Hemorrhage Evacuation Phase 3). We included subjects with a magnetic resonance imaging scan. The exposure was a DWI lesion. The primary outcome was any stroke, defined as a composite of ischemic stroke or recurrent ICH, whereas secondary outcomes were incident ischemic stroke and recurrent ICH. Using multivariate Cox regression analysis, we evaluated the risk of stroke. Of 505 patients with ICH with magnetic resonance imaging, 466 were included. DWI lesions were noted in 214 (45.9%) subjects, and 34 incident strokes (20 ischemic stroke and 14 recurrent ICH) were observed during a median follow-up of 324 days (interquartile range, 91-374). Presence of a DWI lesion was associated with a 6.9% (95% CI, 2.2-11.6) absolute increase in risk of all stroke (hazard ratio, 2.6 [95% CI, 1.2-5.7]). Covariate adjustment with Cox regression models also demonstrated this increased risk. In the secondary analyses, there was an increased risk of ischemic stroke (hazard ratio, 3.5 [95% CI, 1.1-11.0]) but not recurrent ICH (hazard ratio, 1.7 [95% CI, 0.6-5.1]). In a heterogeneous cohort of patients with ICH, presence of a DWI lesion was associated with a 2.5-fold heightened risk of stroke among ICH survivors. This elevated risk persisted for ischemic stroke but not for recurrent ICH.

Revised intracerebral hemorrhage expansion definitions: Relationship with care limitations.

Hematoma expansion is an important therapeutic target in intracerebral hemorrhage. Recently proposed hematoma expansion definitions have not been validated, and no previous definition has accounted for withdrawal of care. To externally validate revised definitions of hematoma expansion that incorporate intraventricular hemorrhage, and to test their validity in the context of withdrawal of care. We analyzed data from the Antihypertensive Treatment of Acute Cerebral Hemorrhage II trial, comparing revised definitions of hematoma expansion incorporating intraventricular hemorrhage expansion to the conventional definition of "≥6 mL or ≥33%." Primary outcome was modified Rankin Scale of 4-6 at 90 days. We calculated the incidence, sensitivity, specificity, positive and negative predictive values, and c-statistic for all definitions of hematoma expansion. Definitions were compared using nonparametric methods. Secondary analyses were performed after removing patients with withdrawal of care. Primary analysis included 948 patients. Using the conventional definition, the sensitivity was 37.1% and specificity was 83.2% for the primary outcome. Sensitivity improved with all three revised definitions (53.3%, 48.7%, and 45.3%, respectively), with minimal change to specificity (78.4%, 80.5%, and 81.0%, respectively). The greatest improvement was seen with the definition "≥6 mL or ≥33% or any intraventricular hemorrhage," with increased c-statistic from 60.2% to 65.9% (p < 0.001). Secondary analysis excluded 46 participants who experienced withdrawal of care. The revised definitions similarly outperformed the conventional definition in this population, with the greatest improvement in c-statistic using "≥6 mL or ≥33% or any intraventricular hemorrhage" (58.1% vs. 64.1%, p < 0.001). Revised hematoma expansion definitions incorporating intraventricular hemorrhage expansion outperformed conventional definitions for predicting poor outcome, even after accounting for care limitations.

Ultra-Early Blood Pressure Reduction Attenuates Hematoma Growth and Improves Outcome in Intracerebral Hemorrhage.

The aim was to investigate whether intensive blood pressure treatment is associated with less hematoma growth and better outcome in intracerebral hemorrhage (ICH) patients who received intravenous nicardipine treatment ≤2 hours after onset of symptoms. A post-hoc exploratory analysis of the Antihypertensive Treatment of Acute Cerebral Hemorrhage 2 (ATACH-2) trial was performed. This was a multicenter, international, open-label, randomized clinical trial, in which patients with primary ICH were allocated to intensive versus standard blood pressure treatment with nicardipine ≤4.5 hours after onset of symptoms. We have included 913 patients with complete imaging and follow-up data in the present analysis. Among the 913 included patients, 354 (38.7%) had intravenous nicardipine treatment initiated within 2 hours. In this subgroup of patients treated within 2 hours, the frequency of ICH expansion was significantly lower in the intensive blood pressure reduction group compared with the standard treatment group (p = 0.02). Multivariable analysis showed that ultra-early intensive blood pressure treatment was associated with a decreased risk of hematoma growth (odds ratio, 0.56; 95% confidence interval [CI], 0.34-0.92; p = 0.02), higher rate of functional independence (odds ratio, 2.17; 95% CI, 1.28-3.68; p = 0.004), and good outcome (odds ratio, 1.68; 95% CI, 1.01-2.83; p = 0.048) at 90 days. Ultra-early intensive blood pressure reduction was associated with a favorable shift in modified Rankin Scale score distribution at 3 months (p = 0.04). In a subgroup of ICH patients with elevated blood pressure given intravenous nicardipine ≤2 hours after onset of symptoms, intensive blood pressure reduction was associated with reduced hematoma growth and improved functional outcome. ANN NEUROL 2020;88:388-395.

Intensive Blood Pressure Lowering in Patients with Moderate to Severe Grade Acute Cerebral Hemorrhage: Post Hoc Analysis of Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH)-2 Trial

Objective: To study the effect of intensive blood pressure reduction in patients with moderate to severe intracerebral hemorrhage (ICH) within the subjects recruited in Antihypertensive Treatment of Acute Cerebral Hemorrhage 2 trial. Design: Randomized, multicenter, 2 group, open-label clinical trial. Setting: A total of 110 sites in the USA, Japan, China, Taiwan, South Korea, and Germany. Patients: A total of 1,000 patients underwent randomization from May 2011 till September 2015. Interventions: We analyzed the effect of intensive (goal 110–139 mm Hg) over standard (goal 140–179 mm Hg) systolic blood pressure (SBP) reduction using intravenous nicardipine within 4.5 h of symptom onset in moderate to severe grade subjects with ICH in a non-prespecified analysis. Moderate to severe grade was defined by Glasgow Coma Scale score <13 or baseline National Institutes of Health Stroke Scale score ≥10 or baseline intraparenchymal hemorrhage volume ≥30 mL or presence of intraventricular hemorrhage. The primary outcome was death or disability (score 4–6 on the modified Rankin scale) at 3 months after randomization ascertained by a blinded investigator. Measurements and Main Results: Of a total of 682 subjects who met the definition of moderate to severe grade (mean age 61.9 ± 13.1 years, 62.5% men) with a mean baseline SBP of 174.7 ± 24.8 mm Hg, the frequency of hematoma expansion was significantly lower among subjects randomized to intensive SBP reduction than among subjects randomized to standard SBP reduction (20.4 vs. 27.9%, relative risk [RR]: 0.7; 95% confidence interval [CI]: 0.55–0.96). The primary endpoint of death or disability was observed in 52.5% (170/324) of subjects receiving intensive SBP reduction and 48.9% (163/333) of subjects receiving standard SBP reduction (RR: 1.1; 95% CI: 0.9–1.2). Conclusions: Intensive SBP lowering reduced the frequency of hematoma expansion but did not reduce the rate of death or disability in patients with moderate to severe grade ICH.

Rate and Predictors of Unanticipated Surgical Evacuation in Patients with Intracerebral Hemorrhage: Post Hoc Analysis of ATACH 2 Trial

We performed this analysis to identify the rates, predictors, and associated outcomes of unexpected neurosurgical evacuation in a multicenter randomized clinical trial, Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH)2. The ATACH 2 trial determined the efficacy of antihypertensive treatment in patients with spontaneous supratentorial intracerebral hemorrhages (ICHs) with a Glasgow Coma Scale (GCS) score of ≥5 and intraparenchymal hematoma volume of <60 cm3 on initial computed tomographic scan. We determined the proportion of ICH patients requiring unanticipated surgical evacuation and identified baseline factors associated with evacuation. Among the 992 subjects analyzed, 44 (4.4%) subjects required unanticipated surgical evacuation of hematoma. The proportion of subjects with initial GCS score of 13 or less was significantly higher among those who required surgical evacuation (43.2% vs. 26.8%, P < 0.001). In the logistics regression analysis, hematoma volume ≥18 cm3 (odds ratio, 4.3; 95% confidence interval, 2.1-8.8) and right-sided hematoma (odds ratio, 2.8; 95% confidence interval, 1.3-5.9) were significantly associated with surgical evacuation. Age, location, GCS score strata, and allocated treatment (intensive vs. standard systolic blood pressure reduction) were not associated with surgical evacuation. Among the 44 patients who underwent surgical evacuation, death or disability at 3 months postrandomization was seen in 32 (73%) of 44 subjects. In the large cohort of ATACH 2 subjects with good grade ICH, the rates of unanticipated surgical evacuation were low and were associated with relatively high rates of death or disability at 3 months.

Effects of oxiracetam combined with ginkgo biloba extract in the treatment of acute intracerebral hemorrhage: A clinical study.

PurposeThe present clinical study was conducted to investigate the effect of oxiracetam combined with ginkgo biloba extract in treating patients with acute intracerebral hemorrhage.MethodsNinety‐eight patients with acute cerebral hemorrhage admitted to our hospital were divided into three groups. The differences of brain edema and cerebral hemorrhage were compared between the three groups after 1 and 2 weeks of treatment, and the recovery of neurological function, serum inflammatory factors, AQP‐4, MMP‐9, cognitive function, activities of daily living, and adverse reactions were compared between the three groups after 2 weeks of treatment.ResultsThere was no significant difference among the three groups before treatment (p > .05). After treatment, the recovery of neurological function, serum inflammatory factors, AQP‐4, MMP‐9 levels, cognitive function, and activities of daily living were improved. Among them, the neurological function recovery, serum inflammatory factors, AQP‐4, MMP‐9 levels, cognitive function, and activities of daily living in the combined treatment group and the control group elicited greater results than those in the routine group. The results of the combined treatment group showed the most significant difference (p < .05). The concentration of IL‐6 decreased from 135.98 ± 12.54 to 91.83 ± 7.69 pg/ml, AQP‐4 from 227.55 μg/L ± 21.06 to 114.31 ± 9.22 μg/L, and MMP‐9 from 172.39 ± 9.81 to 94.98 ± 5.01 ng/ml. In addition, the neurological function recovery, the levels of serum inflammatory factors, cognitive function, and activities of daily living in the combined treatment group were better than those in the control group (p < .05). The mean score of MRS in the combined treatment group decreased from 3.36 ± 0.98 at admission to 1.91 ± 0.38.ConclusionOxiracetam combined with Ginkgo biloba extract in the treatment of acute cerebral hemorrhage has a significant improvement effect.

Efficacy of a Combination of Nimodipine and Edaravone in the Treatment of Acute Cerebral Hemorrhage

The present study was aimed at evaluating the clinical efficacy of a combination of nimodipine and edaravone in the treatment of acute cerebral hemorrhage. A total of 180 patients diagnosed with acute cerebral hemorrhage and treated at the Shandong Jiyang Public Hospital were enrolled. The patients were divided into the control group and the research group with 90 patients in each group. Patients in the control group were treated with edaravone, while a combination of nimodipine and edaravone was administered to patients in the research group. Total therapeutic efficacy, neurologic impairment score, quality of life score, hematoma and edema volume were compared between both groups. Results obtained demonstrated that the total therapeutic efficacy of the research group was better than that of the control group (p<0.05). Patients’ hematoma and edema volume before and after treatment on comparison indicated that improvement in the research group after drug administration was significantly better than that of the control group (p<0.05). Moreover, there was a greater decrease in the neurologic impairment score of the research group than that of the control group (p<0.05). Application of a combination of nimodipine and edaravone in the treatment of acute cerebral hemorrhage could achieve greater clinical efficacy as well as significantly improve the therapeutic efficiency.

Late Neurological Deterioration after Acute Intracerebral Hemorrhage: A post hoc Analysis of the ATACH-2 Trial

Background: Neurological deterioration (ND) has a major influence on the prognosis of intracerebral hemorrhage (ICH); however, factors associated with ND occurring after 24 h of ICH onset are unknown. Methods: We performed exploratory analyses of data from the Antihypertensive Treatment of Acute Cerebral Hemorrhage 2 trial, which compared intensive and standard blood pressure lowering treatment in ICH. NDs were captured on the adverse event case report form. Logistic regression analysis was performed to examine the independent predictors of late ND. Results: Among 1,000 participants with acute ICH, 82 patients (8.2%) developed early ND (≤24 h), and 64 (6.4%) had late ND. Baseline hematoma volume (adjusted OR [aOR] per 1-cm³ increase 1.04, 95% CI 1.02–1.06, p < 0.0001), hematoma volume increase in 24 h (aOR 2.24, 95% CI 1.23–4.07, p = 0.008), and the presence of intraventricular hemorrhage (IVH; aOR 2.38, 95% CI 1.32–4.29, p = 0.004) were independent predictors of late ND (vs. no late ND). Late ND was a significant risk factor for poor 90-day outcome (OR 3.46, 95% CI 1.82–6.56). No statistically significant difference in the incidence of late ND was noted between the 2 treatment groups. Conclusions: Initial hematoma volume, early hematoma volume expansion, and IVH are independent predictors of late ND after ICH. Intensive reduction in the systolic blood pressure level does not prevent the development of late ND.