Baseline Intracerebral Hemorrhage Volume Research Articles

Cognitive Outcome after Acute Spontaneous Intracerebral Hemorrhage: Analysis of the iDEF Randomized Trial.

The impact of intracerebral hemorrhage (ICH) on cognition and the determinants of cognitive recovery early after ICH remain elusive. In this post hoc analysis of the intracerebral hemorrhage deferoxamine (iDEF) trial, we examined the trajectories of cognitive impairment and the determinants of early cognitive recovery after ICH. We examined baseline factors associated with a 90-day cognitive outcome and constructed generalized linear mixed models to examine the trajectory of cognitive function over time among iDEF participants. Cognition was measured by the Montreal Cognitive Assessment (MoCA) scores on days 7, 30, and 90. 291 were available for analysis under the trial's modified intention-to-treat definition (38% female, mean age 60.3 ± 12.0 years, median NIHSS 13, IQR 8-18). The median baseline ICH volume was 12.9 IQR (6.4-26.0) mL; 59 (20%) of the ICH cases were lobar, 120 (41%) had intraventricular extension. There was an overall significant increase in total MOCA score with time (p < 0.0001). Total MOCA score increased by an estimated 3.9 points (95% CI: 3.1, 4.7) between the day 7 and day 30 assessments and by an additional 2.9 points (95% CI: 2.2, 3.6) between the day 30 and day 90 assessments. Despite the overall improvement, 134 of 205 (65%) patients with an available 90-day MoCA score remained cognitively impaired with a score <26 on day 90. Older age, higher NIHSS score, baseline ICH volume, intraventricular hemorrhage, and perihematoma edema had an adjusted negative impact on cognitive recovery. Although ICH survivors exhibit significant improvement of cognitive status over the first 3 months, cognitive performance remains impaired in the majority of patients. Among factors independently associated with worse cognitive recovery, higher baseline ICH, intraventricular blood and perihematomal edema volumes, are potential therapeutic targets that merit further exploration.

Baseline perihematomal edema, C-reactive protein, and 30-day mortality are not associated in intracerebral hemorrhage.

The relationship between baseline perihematomal edema (PHE) and inflammation, and their impact on survival after intracerebral hemorrhage (ICH) are not well understood. Assess the association between baseline PHE, baseline C-reactive protein (CRP), and early death after ICH. Analysis of pooled data from multicenter ICH registries. We included patients presenting within 24 h of symptom onset, using multifactorial linear regression model to assess the association between CRP and edema extension distance (EED), and a multifactorial Cox regression model to assess the association between CRP, PHE volume and 30-day mortality. We included 1,034 patients. Median age was 69 (interquartile range [IQR] 59-79), median baseline ICH volume 11.5 (IQR 4.3-28.9) mL, and median baseline CRP 2.5 (IQR 1.5-7.0) mg/L. In the multifactorial analysis [adjusting for cohort, age, sex, log-ICH volume, ICH location, intraventricular hemorrhage (IVH), statin use, glucose, and systolic blood pressure], baseline log-CRP was not associated with baseline EED: for a 50% increase in CRP the difference in expected mean EED was 0.004 cm (95%CI 0.000-0.008, p = 0.055). In a further multifactorial analysis, after adjusting for key predictors of mortality, neither a 50% increase in PHE volume nor CRP were associated with higher 30-day mortality (HR 0.97; 95%CI 0.90-1.05, p = 0.51 and HR 0.98; 95%CI 0.93-1.03, p = 0.41, respectively). Higher baseline CRP is not associated with higher baseline edema, which is also not associated with mortality. Edema at baseline might be driven by different pathophysiological processes with different effects on outcome.

Abstract WMP82: Peri-Hematomal Edema (PHE) Shape Features as Independent Predictors of the 3-month Outcome in Acute Supratentorial Intracerebral Hemorrhage (ICH)

Background: Perihematomal edema (PHE) is a marker of post-ICH secondary brain injury and a potential treatment target. However, different studies have reported equivocal results regarding the optimal metrics of PHE volume in relation to clinical outcomes - such as absolute, and relative baseline PHE volume, or the rate of PHE volume growth over the first 24- and 72-hours post-ICH. In this study, we examined the association of different PHE shape features at baseline and 24-hour with outcome at 3-month follow-up. Methods: We used the data from ATACH-2 trial. We manually segmented ICH and PHE on baseline and follow-up CTs, and extracted 14 shape features. We explored the association of baseline, follow-up, difference (baseline subtracted from follow-up) and temporal rate (difference divided by time gap) of PHE shape changes with 3-month mRS. We applied Spearman correlation to assess univariate associations, and multivariate stepwise regression to evaluate if PHE shape features independently predict outcome adjusting for age, sex, NIHSS, GCS, baseline ICH volume, and treatment. Results: 796 patients were included. Baseline PHE maximum diameters across various planes, main axes, volume, surface and sphericity correlated with 3-month mRS after adjusting for multiple comparisons. The 24-hour difference and temporal change rates of these features also had significant association with outcome - but not the 24-hour absolute values. In multivariate regression, baseline PHE shape sphericity (p=0.029) and voxel volume (p=0.026), alongside admission NIHSS (p< 0.001), ICH volume (p=0.002), and age (p<0.001) were independent predictors of favorable outcomes. Conclusion: Aside from metrics of volume, PHE sphericity at baseline is an independent prognostic factor, with less spheric (more irregular) shape associated with worse outcome. In addition, baseline PHE shape features - compared to changes over the first 24 hours post-ICH - had stronger prognostic associations.

Abstract 149: Different Response to Blood Pressure Reduction in Lobar and Deep Intracerebral Hemorrhage

Background: Blood pressure (BP) reduction is associated with better neuroimaging and clinical outcomes in patients with spontaneous, non-traumatic intracerebral hemorrhage (ICH). Because this evidence comes from studies that overwhelmingly enrolled deep hemorrhages, the impact of BP reduction in patients with lobar ICH remains understudied. Methods: We re-analyzed data from the pivotal Antihypertensive Treatment of Acute Cerebral Hemorrhage-2 (ATACH-2) study. We included all patients with available neuroimaging data. Participants were randomized to either intensive (systolic BP target 110-139 mmHg) or standard (systolic BP target 140-179 mmHg) acute BP lowering. The main outcome measures were hematoma expansion > 6 mL in the first 24 hours (HE), poor functional outcome (3-month mRS 4-6) and renal adverse events (RAE) until day 7 or hospital discharge. We fitted multivariable logistic regression models to test for association between the intervention and our outcomes of interest. Covariates included sex, age, race and ethnicity, and baseline ICH volume. Results: Among 1,000 patients enrolled in ATACH-2, 875 (87.5%) with complete data were included (88.9% deep hemorrhages and 11.1% lobar hemorrhages). The baseline characteristics of the intensive and standard treatment groups remained balanced as in the original study (all comparisons p >0.05). Multivariable logistic regression showed that intensive BP reduction decreased the risk of HE (OR 0.60, 95%CI 0.39-0.90; p=0.02) and increased the risk of RAE (OR 2.53, 95%CI 1.40-4.77; p=0.003) in patients with deep, but not lobar ICH (HE, OR: 0.89; 95% CI= 0.31 - 2.52; p=0.83 and RAE, OR: 0.46; 95% CI= 0.04 - 5.10; p=0.53). Intensive BP reduction was not associated with improved mRS in either deep (OR: 0.96; 95 % CI= 0.68 - 1.37; p= 0.82) nor lobar (OR: 0.66; 95% CI= 0.16 - 2.42; p= 0.54) ICH. Conclusion: The impact of intensive blood pressure lowering differs in deep and lobar ICH. These results emphasize the need for a better understanding about biologic differences in ICH, which may have therapeutic implications.

Short-term functional outcomes of patients with acute intracerebral hemorrhage in the native and expatriate population.

Functional outcomes in patients with intracerebral hemorrhage (ICH) have not been well characterized in the Middle East and North Africa Region. We report the 30 and 90-day clinical outcomes in the native and expatriate of Qatar with ICH. We evaluated the Glasgow Coma Scale (GCS), NIHSS, and imaging in the Qatar Stroke Registry (2013-22). The outcome measures were a modified Rankin Scale (mRS) at 90 days and mortality at 30 and 90 days. Unfavorable outcome was defined as mRS of 4-6. We performed non-parametric ROC analyses to measure the concordance index (C-index) to assess the goodness-of-fit of ICH score for predicting 30 day and 90-day mortality and functional outcome. 1,660 patients (median age of 49 (41.5-58) years; male 83.1%, expatriates 77.5%) with ICH, including supratentorial deep in 65.2%, cortical in 16.2%, infratentorial 16% and primary intraventricular in 2.5% were studied. The median baseline ICH volume was 7.5 (3.2-15.8) ml. An unfavorable outcome was seen in 673 (40.5%) patients at 90 days. The unfavorable 90-day outcome (mRS 4-6) was 49.2% in the native population vs. 44.4% in Africans, 39.0% in South Asian, 35.3% in Far Eastern, and 7.7% in Caucasians, p < 0.001. Mortality at 30 days and 90 days was 10.4 and 15.1%. Increasing age [OR (95% CI), 1.02 (1.00-1.03)], lower GCS [0.77 (0.73-0.80)], prior use of antiplatelet medications [1.82 (1.19-2.08)], higher ICH volume [1.03 (1.02-1.04)], and presence of any intraventricular hemorrhage [1.57(1.19-2.08)], were associated with unfavorable outcome. In this relatively younger ICH cohort more than 75% were expatriates. The ICH volume, 90-day unfavorable outcome and mortality was lower in the expatriates compared to the local Arab population, likely related to the younger age and smaller size of the hemorrhages. Prognostic scoring systems may have to be modified in this population to avoid early withdrawal of care.

Predictors and Prognostic Impact of Hematoma Expansion in Infratentorial Cerebral Hemorrhage.

Hematoma expansion (HE) is common and predicts poor outcome in patients with supratentorial intracerebral hemorrhage (ICH). We investigated the predictors and prognostic impact of HE in infratentorial ICH. We conducted a retrospective analysis of patients with brainstem and cerebellar ICH admitted at seven sites. Noncontrast computed tomography images were analyzed for the presence of hypodensities according to validated criteria, defined as any hypodense region strictly encapsulated within the hemorrhage with any shape, size, and density. Occurrence of HE (defined as > 33% and/or > 6-mL growth) and mortality at 90days were the outcomes of interest. Their predictors were investigated using logistic regression with backward elimination at p < 0.1. Logistic regression models for HE were adjusted for baseline ICH volume, antiplatelet and anticoagulant treatment, onset to computed tomography time, and presence of hypodensities. The logistic regression model for mortality accounted for the ICH score and HE. A total of 175 patients were included (median age 75years, 40.0% male), of whom 38 (21.7%) had HE and 43 (24.6%) died within 90days. Study participants with HE had a higher frequency of hypodensities (44.7 vs. 24.1%, p = 0.013), presentation within 3h from onset (39.5 vs. 24.8%, p = 0.029), and 90-day mortality (44.7 vs. 19.0%, p = 0.001). Hypodensities remained independently associated with HE after adjustment for confounders (odds ratio 2.44, 95% confidence interval 1.13-5.25, p = 0.023). The association between HE and mortality remained significant in logistic regression (odds ratio 3.68, 95% confidence interval 1.65-8.23, p = 0.001). Early presentation and presence of noncontrast computed tomography hypodensities were independent predictors of HE in infratentorial ICH, and the occurrence of HE had an independent prognostic impact in this population.

Association Between Hematoma Expansion Severity and Outcome and Its Interaction With Baseline Intracerebral Hemorrhage Volume.

Hematoma expansion (HE) is a major determinant of neurologic deterioration and poor outcome in intracerebral hemorrhage (ICH) and represents an appealing therapeutic target. We analyzed the prognostic effect of different degrees of HE. This was a retrospective analysis of patients with ICH admitted at 8 academic institutions in Italy, Germany, Canada, China, and the United States. All patients underwent baseline and follow-up imaging for HE assessment. Relative HE (rHE) was classified as follows: none (<0%), mild (0%-33%), moderate (33.1%-66%), and severe (>66%). Absolute HE (aHE) was classified as none (<0 mL), mild (0-6.0 mL), moderate (6.1-12.5 mL), and severe (>12.5 mL). Predictors of poor functional outcome (90 days modified Rankin Scale 4-6) were explored with logistic regression. We included 2,163 patients, of whom 1,211 (56.0%) had poor outcome. The occurrence of severe aHE or rHE was more common in patients with unfavorable outcome (13.9% vs 6.5%, p < 0.001 and 18.3% vs 7.2%, p < 0.001 respectively). This association was confirmed in logistic regression (rHE odds ratio [OR] 1.98, 95% CI 1.38-2.82, p < 0.001; aHE OR 1.73, 95% CI 1.23-2.45, p = 0.002) while there was no association between mild or moderate HE and poor outcome. The association between severe HE and poor outcome was significant only in patients with baseline ICH volume below 30 mL. The strongest association between HE and outcome was observed in patients with smaller initial volume experiencing severe HE. These findings may inform clinical trial design and guide clinicians in selecting patients for antiexpansion therapies.

Associations of Cerebral Small Vessel Disease on the Features of Hematoma and Hematoma Expansion in Intracerebral Hemorrhage.

Several early noncontrast CT (NCCT) signs of spontaneous intracerebral hemorrhage (ICH) can predict hematoma expansion (HE). However, the associations of underlying cerebral small vessel disease (SVD) on early NCCT signs and HE have been less explored. We conducted an analysis of all patients with spontaneous supratentorial ICH and received follow-up imaging between 2016 and 2020 at a stroke center. The early NCCT signs were categorized as shape or density signs. HE was defined as an increase in hematoma volume ≥6 mL or 33% from baseline. The severity of SVD was assessed by both a 3-point CT-based and a 4-point magnetic resonance imaging (MRI)-based SVD score. Regression models were used to examine the associations between SVD score and hematoma volume, NCCT signs, and HE. A total of 328 patients (median age: 64 years; 38% female) were included. The median baseline ICH volume was 8.6 mL, with 38% of the patients had shape signs and 52% had density signs on the initial NCCT. Higher MRI-SVD scores were associated with smaller ICH volumes (p = 0.0006), fewer shape (p = 0.001), or density signs (p = 0.0003). Overall, 16% of patients experienced HE. A higher MRI-SVD score was inversely associated with HE (adjusted odds ratio 0.71, 95% CI: 0.53-0.96). Subgroup analysis revealed that this association was primarily observed in patients who were younger (&lt;65 years), male, had deep hemorrhage, or did not meet the criteria for cerebral amyloid angiopathy diagnosis. In patients with spontaneous ICH, a more severe SVD was associated with smaller hematoma volume, fewer NCCT signs, and a lower risk of HE. Further research is required to investigate why a higher burden of severely diseased cerebral small blood vessels is associated with less bleeding.

Abstract WP131: Association Between Intercellular Adhesion Molecule-1 And Intracerebral Hemorrhage: A Post-hoc Analysis Of The Fast Trial

Introduction: Neutrophil-mediated inflammation in the acute phase of intracerebral hemorrhage (ICH) worsens outcome in pre-clinical studies. Intercellular adhesion molecule-1 (ICAM-1), an inducible ligand for integrins and cell-cell adhesion molecules, is critical for neutrophil extravasation. We aimed to determine whether serum levels of ICAM-1 are associated with worse outcomes after ICH. Methods: We conducted a post-hoc analysis of the randomized controlled FAST (Factor-VII-for-Acute-Hemorrhagic-Stroke-Treatment) trial. The study exposure was serum level of ICAM-1, ascertained at admission. The co-primary outcomes were mortality, and death or major disability (modified Rankin Score 4-6) at 90 days. Secondary radiological outcomes were baseline ICH volume, perihematomal edema volume (PHE), and hematoma expansion at 24 hours (ICH volume increase of ≥33% or 6mL). Multivariable linear and logistic regression analyses, adjusted for age, sex, baseline ICH volume, ICH location, and trial treatment arm, were used to test for associations between ICAM-1 and outcomes. Results: Of 841 patients, we included 507 (60%) with complete data (mean age 64 years, 37% women). Hematoma expansion occurred in 169 (34%), while 242 (48%) had a poor outcome. In multivariable analyses, ICAM-1 was associated with mortality (OR, 1.02; 95% confidence interval, CI, 1.01-1.05; p=0.02) and poor outcome (OR, 1.02; CI, 1.01-1.04; p=0.04). In multivariable analyses of radiological outcomes, ICAM-1 was associated with hematoma expansion (OR, 1.03, CI, 1.01-1.07) and baseline PHE (beta, 0.02; SE, 0.001, p=0.01), but was not associated with baseline ICH volume. Conclusions: In this post-hoc analysis of the FAST trial in patients with ICH, admission serum levels of ICAM-1 were associated with hematoma expansion, PHE, and poor outcome. These findings highlight the need to further explore the role of early inflammatory biomarkers in prognostication and as potential therapeutic targets.

Abstract TP119: Relationships Of Female Sex With Intracerebral Hemorrhage Characteristics And Outcomes

Introduction: Biological sex is known to impact cerebrovascular disease characteristics and clinical outcomes. While in intracerebral hemorrhage (ICH) it is known that biological sex impacts ICH incidence, it is less clear whether biological sex impacts ICH outcomes. Hypothesis: Female sex will be associated with ICH characteristics and clinical outcomes. Methods: Spontaneous ICH patients enrolled into a prospective observational ICH cohort study between 2009-2020 were assessed. Patients with prior anticoagulant use and secondary etiologies of ICH were excluded from the analysis. Female sex was assessed as the primary exposure variable. Primary analyses assessed relationships of female sex with radiographic outcomes: ICH location, ICH volume, hematoma expansion (&gt;33% and/or &gt;6mL). Secondary analyses assessed relationships of female sex with clinical outcomes: poor discharge neurological outcome (modified Rankin 4-6), and poor discharge disposition (skilled nursing facility, hospice, or inpatient death). Separate multivariable regression models assessed these relationships after adjusting for relevant covariates. Results: Of 504 ICH patients analyzed, mean age was 67 (SD 14.9), 46% were female, and median baseline ICH volume was 14.6 mL (IQR 4.98-35.0). In primary analyses, female sex was not associated with ICH volume or hematoma expansion but was associated with lobar ICH location (adjusted OR 1.72, 95% CI: 1.09-2.70). In secondary analyses, female sex was not associated with poor discharge neurological outcomes (adjusted OR 1.40, 95% CI: 0.74-2.64) after adjusting for race, ICH severity, and ICH location. However, there was an association of female sex with poor discharge disposition (adjusted OR 1.91, 95% CI: 1.15-3.16) after adjusting for similar covariates. Conclusions: While there were no clear intergroup sex differences in ICH severity or neurological outcomes, female sex was associated with worse discharge disposition. Further work is required to clarify whether these disposition differences are due to disease specific complications, characteristics, or if there are other social disparities responsible for these outcome differences.

Abstract WP122: Effect Of Prior Exposure To Statin Therapy On Clinical And Radiological Features Of Intracerebral Hemorrhage: A Post-hoc Analysis Of The I-def Trial

Background: Conflicting data exist regarding the relationship between prior statin use and perihematomal edema (PHE) in patients with intracerebral hemorrhage (ICH). We performed a post-hoc analysis of the ICH Deferoxamine (i-DEF) trial to examine whether there is an association between statin use prior to the onset of ICH and baseline PHE volume and its growth on 72-96 hour follow-up scans. Methods: Statin use prior to the study enrollment was assessed, and CT scans were performed at presentation and after 24 hours after the completion of a 3-day infusion of either saline or deferoxamine (DFO). ICH volumes and various PHE parameters were measured semi-quantititavely using Analyze imaging software. Multivariable logistic regression model was created, adjusting for the variables that were significantly different on univariable analyses, to assess for any associations between prior statin use and measures of ICH and PHE. Bonferroni correction was applied for multiple testing. Results: Seventy-four (25.4%) of 291 participants in i-DEF used statin prior to ICH onset. On univariable analyses, those with prior statin use had higher prevalences of hypertension, diabetes, and prior ischemic stroke, as well as concomitant antihypertensive and antiplatelet uses. Patients with prior statin use had smaller baseline ICH volume, absolute PHE (aPHE) volume, and edema extension distance (EED). Greater hematoma volume growth, baseline relative PHE (rPHE) volume, and reduction in rPHE volume from baseline to follow-up scans were also seen in those with prior statin use. On multivariable analysis, none of the measures of ICH and PHE was significantly associated with prior statin use, after adjusting for multiple testing. Conclusion: In this post-hoc analysis of a randomized controlled trial with standardized imaging and functional assessments, we did not find significant associations between pre-ICH statin use and measures of ICH or PHE volumes and their growth.

Using Noncontrast Computed Tomography to Improve Prediction of Intracerebral Hemorrhage Expansion.

Noncontrast computed tomography hypodensities are a validated predictor of hematoma expansion (HE) in intracerebral hemorrhage and a possible alternative to the computed tomography angiography (CTA) spot sign but their added value to available prediction models remains unclear. We investigated whether the inclusion of hypodensities improves prediction of HE and compared their added value over the spot sign. Retrospective analysis of patients admitted for primary spontaneous intracerebral hemorrhage at the following 8 university hospitals in Boston, US (1994-2015, prospective), Hamilton, Canada (2010-2016, retrospective), Berlin, Germany (2014-2019, retrospective), Chongqing, China (2011-2015, retrospective), Pavia, Italy (2017-2019, prospective), Ferrara, Italy (2010-2019, retrospective), Brescia, Italy (2020-2021, retrospective), and Bologna, Italy (2015-2019, retrospective). Predictors of HE (hematoma growth >6 mL and/or >33% from baseline to follow-up imaging) were explored with logistic regression. We compared the discrimination of a simple prediction model for HE based on 4 predictors (antitplatelet and anticoagulant treatment, baseline intracerebral hemorrhage volume, and onset-to-imaging time) before and after the inclusion of noncontrast computed tomography hypodensities, using receiver operating characteristic curve and De Long test for area under the curve comparison. A total of 2465 subjects were included, of whom 664 (26.9%) had HE and 1085 (44.0%) had hypodensities. Hypodensities were independently associated with HE after adjustment for confounders in logistic regression (odds ratio, 3.11 [95% CI, 2.55-3.80]; P<0.001). The inclusion of noncontrast computed tomography hypodensities improved the discrimination of the 4 predictors model (area under the curve, 0.67 [95% CI, 0.64-0.69] versus 0.71 [95% CI, 0.69-0.74]; P=0.025). In the subgroup of patients with a CTA available (n=895, 36.3%), the added value of hypodensities remained statistically significant (area under the curve, 0.68 [95% CI, 0.64-0.73] versus 0.74 [95% CI, 0.70-0.78]; P=0.041) whereas the addition of the CTA spot sign did not provide significant discrimination improvement (area under the curve, 0.74 [95% CI, 0.70-0.78]). Noncontrast computed tomography hypodensities provided a significant added value in the prediction of HE and appear a valuable alternative to the CTA spot sign. Our findings might inform future studies and suggest the possibility to stratify the risk of HE with good discrimination without CTA.

Predicting Hemorrhage Progression in Deep Intracerebral Hemorrhage: A Multicenter Retrospective Cohort Study

Hemorrhage progression in deep intracerebral hemorrhage (ICH) involves not only the growth of parenchymal hematoma but also an increase in intraventricular hemorrhage (IVH). The search for methods that predict both the increased risk of parenchymal hematoma and IVH growth is warranted. We conducted a retrospective cohort study at multiple centers. Participants with deep ICH were enrolled from January 2018 to December 2021. Prediction models based on logistic regression analysis included clinical as well as routine radiographic and radiomics variables, separately or in combination. The performance of each model was evaluated using discrimination measures (e.g., area under the curve [AUC]). Evaluation of clinical utility was performed using decision curve analysis (DCA). Overall, 647 individuals across 4 stroke centers were included. A total of 429 (66%) patients from 3 centers were assigned to the primary cohort and 218 (34%) from another center were placed in the validation cohort. Multivariate analysis showed that the Glasgow Coma Scale score, baseline ICH volume, IVH, blend sign, and radiomics score were associated with hemorrhage progression in the primary cohort. The clinical-radiomics model (AUC= 0.852 and 0.835) improved the prediction performance of hemorrhage progression compared to the Noncontrast computed tomography signs model (AUC= 0.666 and 0.618) in both the primary and validation cohorts, with similar results in the decision curve analysis curves. The clinical-radiomics model outperformed the routine Noncontrast computed tomography signs model in predicting the progression of deep ICH. The clinical benefit of screening patients using this model may assist in risk stratification.

Cerebral Amyloid Angiopathy and the Risk of Hematoma Expansion.

We assessed whether hematoma expansion (HE) and favorable outcome differ according to type of intracerebral hemorrhage (ICH). Among participants with ICH enrolled in the TICH-2 (Tranexamic Acid for Hyperacute Primary Intracerebral Haemorrhage) trial, we assessed baseline scans for hematoma location and presence of cerebral amyloid angiopathy (CAA) using computed tomography (CT, simplified Edinburgh criteria) and magnetic resonance imaging (MRI; Boston criteria) and categorized ICH as lobar CAA, lobar non-CAA, and nonlobar. The main outcomes were HE and favorable functional outcome. We constructed multivariate regression models and assessed treatment effects using interaction terms. A total of 2,298 out of 2,325 participants were included with available CT (98.8%; median age=71 years, interquartile range=60-80 years; 1,014 female). Additional MRI was available in 219 patients (9.5%). Overall, 1,637 participants (71.2%) had nonlobar ICH; the remaining 661 participants (28.8%) had lobar ICH, of whom 202 patients had lobar CAA-ICH (8.8%, 173 participants according to Edinburgh and 29 participants according to Boston criteria) and 459 did not (lobar non-CAA, 20.0%). For HE, we found a significant interaction of lobar CAA ICH with time from onset to randomization (increasing risk with time, pinteraction < 0.001) and baseline ICH volume (constant risk regardless of volume, pinteraction < 0.001) but no association between type of ICH and risk of HE or favorable outcome. Tranexamic acid significantly reduced the risk of HE (adjusted odds ratio=0.7, 95% confidence interval=0.6-1.0, p= 0.020) without statistically significant interaction with type of ICH (pinteraction = 0.058). Tranexamic acid was not associated with favorable outcome. Risk of HE in patients with lobar CAA-ICH was not independently increased but seems to have different dynamics compared to other types of ICH. The time window for treatment of CAA-ICH to prevent HE may be longer. ANN NEUROL 2022;92:921-930.

Diffusion-Weighted Imaging Hyperintensities in Acute and Subacute-Phase Intracerebral Hemorrhage

ObjectiveDiffusion-weighted imaging hyperintensities are observed in intracerebral hemorrhage patients at times and might be associated with unfavorable functional outcomes. However, the suitable time to evaluate diffusion-weighted imaging hyperintensities to influence stroke outcome remains unclear. This study investigated the associations between acute and sub-acute diffusion-weighted imaging hyperintensities and functional outcomes among patients with acute intracerebral hemorrhage. MethodsDiffusion-weighted imaging hyperintensities were evaluated within 24 h (acute phase) and at 14 ± 5 days (sub-acute phase). An unfavorable functional outcome was a score of 5–6 on the modified Rankin Scale at 3 months. ResultsAmong 268 intracerebral hemorrhage patients, diffusion-weighted imaging hyperintensities in the acute phase were observed in 32 (11.9%). Among 227 patients who underwent a second magnetic resonance imaging in the sub-acute phase, diffusion-weighted imaging hyperintensities were observed in 57 (25.1%). Multivariable analysis revealed that the baseline intracerebral hemorrhage volume, history of stroke, and severe white matter lesions were associated with sub-acute diffusion-weighted imaging hyperintensities. The patients with unfavorable outcomes (n = 37) had a higher frequency of sub-acute diffusion-weighted imaging hyperintensities than those without (n = 190) (51.4% vs. 20.0%, P < 0.001); the frequencies of acute diffusion-weighted imaging hyperintensities were not significantly different between the groups (13.5% vs. 10.0%, P = 0.559). Sub-acute diffusion-weighted imaging hyperintensities were independently associated with unfavorable outcomes after adjusting for confounding factors (Odds Ratio, 3.35, 95% CI 1.20–9.35, P = 0.021). ConclusionThe rate of sub-acute diffusion-weighted imaging hyperintensities was higher than acute diffusion-weighted imaging hyperintensities among acute intracerebral hemorrhage patients and likely to be associated with unfavorable outcomes.

Hemorrhage Enlargement Is More Frequent in the First 2 Hours: A Prehospital Mobile Stroke Unit Study.

Hematoma enlargement (HE) after intracerebral hemorrhage (ICH) is a therapeutic target for improving outcomes. Hemostatic therapies to prevent HE may be more effective the earlier they are attempted. An understanding of HE in first 1 to 2 hours specifically in the prehospital setting would help guide future treatment interventions in this time frame and setting. Patients with spontaneous ICH within 4 hours of symptom onset were prospectively evaluated between May 2014 and April 2020 as a prespecified substudy within a multicenter trial of prehospital mobile stroke unit versus standard management. Baseline computed tomography scans obtained <1, 1 to 2, and 2 to 4 hours postsymptom onset on the mobile stroke unit in the prehospital setting were compared with computed tomography scans repeated 1 hour later and at 24 hours in the hospital. HE was defined as >6 mL if baseline ICH volume was <20 mL and 33% increase if baseline volume >20 mL. The association between time from symptom onset to baseline computed tomography (hours) and HE was investigated using Wilcoxon rank-sum test when time was treated as a continuous variable and using Fisher exact test when time was categorized. Kruskal-Wallis and Wilcoxon rank-sum tests evaluated differences in baseline volumes and HE. Univariable and multivariable logistic regression analyses were conducted to identify factors associated with HE and variable selection was performed using cross-validated L1-regularized (Lasso regression). This study adhered to STROBE guidelines (Strengthening the Reporting of Observational Studies in Epidemiology) for cohort studies. One hundred thirty-nine patients were included. There was no difference between baseline ICH volumes obtained <1 hour (n=43) versus 1 to 2 hour (n=51) versus >2 hours (n=45) from symptom onset (median [interquartile range], 13 mL [6-24] versus 14 mL [6-30] versus 12 mL [4-19]; P=0.65). However, within the same 3 time epochs, initial hematoma growth (volume/time from onset) was greater with earlier baseline scanning (median [interquartile range], 17 mL/hour [9-35] versus 9 mL/hour [5-23]) versus 4 mL/hour [2-7]; P<0.001). Forty-nine patients had repeat scans 1 hour after baseline imaging (median, 2.3 hours [interquartile range. 1.9-3.1] after symptom onset). Eight patients (16%) had HE during that 1-hour interval; all of these occurred in patients with baseline imaging within 2 hours of onset (5/18=28% with baseline imaging within 1 hour, 3/18=17% within 1-2 hour, 0/13=0% >2 hours; P=0.02). HE did not occur between the scans repeated at 1 hour and 24 hours. No association between baseline variables and HE was detected in multivariable analyses. HE in the next hour occurs in 28% of ICH patients with baseline imaging within the first hour after symptom onset, and in 17% of those with baseline imaging between 1 and 2 hours. These patients would be a target for ultraearly hemostatic intervention.

Association Between Anatomical Location and Hematoma Expansion in Deep Intracerebral Hemorrhage.

ObjectiveTo establish the relationship between hematoma sites of involvement and hematoma expansion (HE) in patients with deep intracerebral hemorrhage (ICH).MethodsEligible patients with deep ICH admitted to hospital within 6 hours of onset between 2018 and 2020 were included in this retrospective multi-center study. Individuals with secondary ICH were excluded. The volume of HE was evaluated based on admission and follow-up computed tomography scans. Associations between deep ICH sites of involvement and HE were examined using multivariable logistic regression analysis while adjusting for confounding covariates of HE.ResultsWe enrolled 583 individuals from three stroke centers. Data from a final total of 460 patients were used in the analysis; of these patients, 159 (34.6%) had HE. In the crude model without adjustment, external capsule, anterior limb of the internal capsule, and posterior limb of the internal capsule (PLIC) involvement were correlated with HE. After fully adjusted models for sex, age, intraventricular hemorrhage, Glasgow Coma Scale admission score, baseline ICH volume, and time from onset to initial computed tomography, multivariable logistic regression revealed that the PLIC is a robust predictor of HE in patients with deep ICH (adjusted odds ratio = 2.73; 95% confidence interval = 1.75–4.26; p < 0.001).ConclusionInvolvement of the posterior limb of the internal capsule in deep hemorrhage could be a promising predictor of HE.

Abstract TP142: Platelet Count And Intracerebral Hemorrhage Expansion In The ATACH 2 Trial

Introduction: The effect of platelet count on hematoma expansion in patients with intracerebral hemorrhage (ICH) has not been sufficiently studied. We performed a secondary analysis of the ATACH 2 trial to examine the association between platelet count and hematoma expansion. Methods: We included patients with a baseline platelet count, volumetric measurement of ICH hematoma volume in mL on a baseline and 24-hour follow-up CT, and excluded those who had surgical evacuation in the first 24 hours. To address the right skew of ICH volume, the primary outcome was the log difference in ICH volume from baseline to 24-hour follow-up. The exposure was baseline platelet count and secondary exposure was the mean of the baseline and a 24-hour platelet count value. We fit unadjusted linear regression models and models adjusted for patient age, sex, race/ethnicity, smoking, baseline ICH volume, GCS, ICH location/side, and randomization arm. Results: We included 945 patients in our primary analysis (mean age 62.3, 62% male, 22.7% white, 57.1% Asian). The mean baseline platelet count was 220.7±61.9 with a standard distribution (Figure 1). There was no association between log difference in ICH volume and baseline platelet count (unadjusted p value=0.616, adjusted p value=0.730) or the mean platelet count over 24 hours (unadjusted p value=0.509, adjusted p value=0.853). The relationships are shown graphically in Figure 2. Conclusion: In patients with supratentorial ICH enrolled in the ATACH-II trial, there was not a significant association between platelet count and hematoma expansion.

Does tranexamic acid affect intraventricular hemorrhage growth in acute ICH? An analysis of the STOP-AUST trial.

Trials of tranexamic acid (TXA) in acute intracerebral hemorrhage (ICH) have focused on the imaging outcomes of intraparenchymal hematoma growth. However, intraventricular hemorrhage (IVH) growth is also strongly associated with outcome after ICH. Revised definitions of hematoma expansion incorporating IVH growth have been proposed. We sought to evaluate the effect of TXA on IVH growth. We analyzed data from the STOP-AUST trial, a prospective randomized trial comparing TXA to placebo in ICH patients presenting ≤ 4.5h from symptom onset with a CT-angiography spot sign. New IVH development at follow-up, any interval IVH growth, and IVH growth ≥ 1mL were compared between the treatment groups using logistic regression. The treatment effect of TXA against placebo using conventional (> 6mL or 33%), and revised definitions of hematoma expansion (> 6mL or 33% or IVH expansion ≥ 1mL, > 6mL or 33%, or any IVH expansion, and > 6mL or 33% or new IVH development) were also assessed. Treatment effects were adjusted for baseline ICH volume. The analysis population consisted of 99 patients (50 placebo, 49 TXA). New IVH development at follow-up was observed in 6/49 (12%) who received TXA and 13/50 (26%) who received placebo (aOR: 0.38 [95% CI: 0.13-1.13]). Any interval IVH growth was observed in 12/49 (25%) who received TXA versus 26/50 (32%) receiving placebo (aOR: 0.69 [95% CI: 0.28-1.66]). IVH growth ≥ 1mL did not differ between the two groups. Using revised definitions of hematoma expansion, no significant difference in treatment effect was observed between TXA and placebo. IVH may be attenuated by TXA following ICH; however, studies with larger cohorts are required to investigate this further. http://www.clinicaltrials.gov; Unique identifier: NCT01702636.

Intraventricular Hemorrhage Expansion in the CLEAR III Trial: A Post Hoc Exploratory Analysis.

The objective of this study was to evaluate factors associated with intraventricular hemorrhage (IVH) expansion and its association with long-term outcomes. We performed a post hoc analysis of the international, multi-center CLEAR III trial (Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage) which enrolled IVH patients between September 1, 2009, and January 31, 2015. The exposure was IVH expansion, defined as >1 mL increase in volume between baseline and stability computed tomography scans, before treatment randomization. We assessed factors associated with IVH expansion and secondarily assessed the relationship of IVH expansion with clinical outcomes: composite of death or major disability (modified Rankin Scale score, >3), and mortality alone at 6 months. The relationship of IVH expansion on ventriculoperitoneal shunt placement was additionally explored. Multivariable logistic regression was used for all analyses. Of 500 IVH patients analyzed, the mean age was 59 (±11) years old, 44% were female and 135 (27%) had IVH expansion. In multivariable regression models, factors associated with IVH expansion were baseline parenchymal intracerebral hemorrhage (ICH) volume (adjusted odds ratio [OR], 1.04 per 1 mL increase [95% CI, 1.01-1.08]), presence of parenchymal hematoma expansion: >33% (adjusted OR, 6.63 [95% CI, 3.92-11.24]), time to stability head CT (adjusted OR, 0.71 per 1 hour increase [95% CI, 0.54-0.94]), and thalamic hematoma location (adjusted OR, 1.68 [95% CI, 1.01-2.79]) while additionally adjusting for age, sex, and race. In secondary analyses, IVH expansion was associated with higher odds of poor 6-month outcomes (adjusted OR, 1.84 [95% CI, 1.12-3.02]) but not mortality (OR, 1.40 [95% CI, 0.78-2.50]) after adjusting for baseline ICH volume, thalamic ICH location, age, anticoagulant use, Glasgow Coma Scale score, any withdrawal of care order, and treatment randomization arm. However, there were no relationships of IVH expansion on subsequent ventriculoperitoneal shunt placement (adjusted OR, 1.02 [95% CI, 0.58-1.80]) after adjusting for similar covariates. In a clinical trial cohort of patients with large IVH, acute hematoma characteristics, specifically larger parenchymal volume, hematoma expansion, and thalamic ICH location were associated with IVH expansion. Given that IVH expansion resulted in poor functional outcomes, exploration of treatment approaches to optimize hemostasis and prevent IVH expansion, particularly in patients with thalamic ICH, require further study. URL: https://www. gov; Unique identifier: NCT00784134.