Perihematomal Edema Volume Research Articles

Early decompressive surgery improves long-term prognosis in patients with intracerebral hemorrhage.

Multiple studies have shown that early decompressive surgery in patients with intracerebral hemorrhage can effectively limit hematoma expansion, reduce perihematomal edema, and improve prognosis. However, these studies are limited by small sample sizes and short follow-up times. To analyze the effect of early decompressive surgery on the long-term prognosis of patients with cerebral hemorrhage and identify the influencing factors for poor prognosis. A retrospective analysis of 78 patients with cerebral hemorrhage admitted between January 2020 and December 2022 was conducted. Patients were divided into early and delayed surgery groups for comparison of outcomes such as mortality rate, modified Rankin Scale score, and Short Form-36 scores. Additionally, factors influencing long-term prognosis were analyzed through logistic regression based on significant differences observed between groups. The early decompressive surgery group showed superior outcomes with lower mortality rates, modified Rankin Scale (mRS) scores, hematoma expansion rates, and perihematomal edema volumes compared to the delayed surgery group (P< 0.05). Additionally, age, preoperative Glasgow Coma Scale (GCS) score, preoperative hematoma volume, and a history of hypertension or diabetes were identified as independent prognostic factors for patients with cerebral hemorrhage, with odds ratios (ORs) greater than 1. Early decompressive surgery can improve the long-term prognosis and quality of life of patients with cerebral hemorrhage, reduce mortality rates, and decrease hematoma expansion and perihematomal edema. Older patients, those with higher preoperative hematoma volume and GCS score, and those with coexisting hypertension and diabetes should be given special attention to decrease the occurrence of adverse prognosis.

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.

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

Introduction: 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. Methods: 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. Results: 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. Conclusions: 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.

Neutrophil-to-lymphocyte ratio on admission predicts early perihematomal edema growth after intracerebral hemorrhage.

Poor functional outcome is associated with perihematomal edema (PHE) expansion after intracerebral hemorrhage (ICH). The inflammatory response is crucial for the onset and progression of PHE. This study aimed to determine the connection between admission neutrophil-lymphocyte ratio (NLR) and early PHE development. We retrospectively analyzed patients with ICH admitted to the Chaohu Affiliated Hospital of Anhui Medical University from January 2021 to December 2022. The primary outcome measure was absolute PHE, defined as the volume of the follow-up PHE minus admission PHE. A semiautomated measurement tool (3D Slicer) was used to calculate the volumes of cerebral hematoma and cerebral edema. Spearman's correlation analysis determined the relationship between NLR and absolute PHE. The multiple linear regression model was constructed to analyze the predictive relation of admission NLR on early PHE expansion. A total of 117 patients were included. The median hematoma and PHE volumes on admission were 9.38 mL (interquartile range [IQR], 4.53-19.54) and 3.54 mL (IQR, 1.33-7.1), respectively. The median absolute PHE was 2.26 mL (IQR, 1.25-4.23), and the median NLR was 3.10 (IQR, 2.26-3.86). Spearman's correlation test showed a positive correlation between admission NLR and absolute PHE (r = .548, P < .001). Multiple linear regression analyses suggested that for every 1-unit increase in admission NLR (B = .176, SE = .043, Beta = .275, P < .001), there was a 0.176 mL increase in absolute PHE. Admission neutrophil-to-lymphocyte ratio (NLR) significantly and positively predicted early perihematomal edema (PHE) expansion.

Sex Differences in Perihematomal Edema Volume and Outcome After Intracerebral Hemorrhage.

Although larger hematoma volume is associated with worse outcome after intracerebral hemorrhage (ICH), the association between perihematomal edema (PHE) volume and outcome remains uncertain, as does the impact of sex on PHE and outcome. Here we aimed to determine whether larger PHE volume is associated with worse outcome and whether PHE volume trajectories differ by sex. We conducted a post hoc analysis of the Factor VIIa for Acute Hemorrhagic Stroke Treatment (FAST) trial, which randomized patients with ICH to receive recombinant activated factor VIIa or placebo. Computerized planimetry calculated PHE and ICH volumes on serial computed tomography (CT) scans (at baseline [within 3h of onset], at 24h, and at 72h). Generalized estimating equations examined interactions between sex, CT time points, and FAST treatment arm on PHE and ICH volumes. Mixed and multivariable logistic models examined associations between sex, PHE, and outcomes. A total of 781 patients with supratentorial ICH (mean age 65years) were included. Compared to women (n = 296), men (n = 485) had similar median ICH (14.9 vs. 13.6mL, p = 0.053) and PHE volumes (11.1 vs. 10.5mL, p = 0.56) at baseline but larger ICH and PHE volumes at 24h (19.0 vs. 14.0mL, p < 0.001; 22.2 vs. 15.7mL, p < 0.001) and 72h (16.0 vs. 11.8mL, p < 0.001; 28.7 vs. 19.9mL, p < 0.001). Men had higher absolute early PHE expansion (p < 0.001) and more hematoma expansion (growth ≥ 33% or 6mL at 24h, 33% vs. 22%, p < 0.001). An interaction between sex and CT time points on PHE volume (p < 0.001), but not on ICH volume, confirmed a steeper PHE trajectory in men. PHE expansion (per 5mL, odds radio 1.19, 95% confidence interval 1.10-1.28), but not sex, was associated with poor outcome. Early PHE expansion and trajectory in men were significantly higher. PHE expansion was associated with poor outcomes independent of sex. Mechanisms leading to sex differences in PHE trajectories merit further investigation.

Abstract TMP84: Multi-Institutional Validation of an Automated Segmentation Tool for Intracerebral Hemorrhage (ICH) and Peri-Hematomal Edema (PHE) on Head CT

Objective: In patients with acute intracerebral hemorrhage (ICH), the volume of hemorrhage, and perihematomal edema (PHE) are representative of primary, and secondary brain injury, respectively. Automated quantification of ICH and PHE volumes from admission non-contrast head CT can facilitate evaluation of large stroke datasets, and expedite treatment triage when volume cutoffs are applied. We aimed to train and externally validate an automated model for segmentation and quantification of ICH and PHE volumes on non-contrast head CT scans. Methods: For training of the model, we used the data from multicentric ATACH-2 clinical trial with head CTs from eleven medical institutes in six countries. The model was then exported and tested on two external datasets from Yale and University of Berlin. We designed an automated pipeline for extracting brain window from 3D non-contrast head CT, skull stripping, resampling to homogenous voxel size, and segmentation. For segmentation we applied a deep learning model based on 3D full resolution nnUNet. We used the Dice Similarity Coefficient (DSC), Hausdorff Distance (HD), and Volume Similarity (VS) between automated segmentation and ground truth manual segmentation volumes to evaluate the models’ performance. Results: A total of 854 patients from the ATACH-2 trial (854 х2, baseline and follow-up CT scans) were used for training of the model in 5-fold cross-validation. In validation folds, the model achieved a mean DSC=0.90±0.10, HD =1.42±16.0mm, and VS=0.95±0.10 for ICH; and DSC=0.74±0.12, HD =3.0±16.5 mm, and VS=0.91±0.12 for PHE. In the externaltesting cohort from Yale (200 patients х2, baseline and follow-up CT scans), the model archieved median DSC=0.93, HD=0.98 mm, and VS=0.97 for ICH; and median DSC=0.69, HD=4.52 mm, and VS=0.84 for PHE. In the externaltesting cohort from Charité Hospital, University of Berlin (915 baseline CT scans), the model archived median DSC=0.87, HD=4 mm, and VS=0.90 for ICH; and median DSC=0.65, HD=5 mm, VS=0.85 for PHE. Conclusion: We trained, validated, and externally tested an end-to-end automated tool for segmentation of both ICH and PHE on non-contrast head CT. Such tool can facilitate treatment triage for trials when volume cutoffs are applied for enrollment.

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&lt; 0.001), ICH volume (p=0.002), and age (p&lt;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 WP172: A Novel Score to Predict Early Time From Symptom Onset to Hospital Arrival in Patients With Intracerebral Hemorrhage

Introduction: Up to 40% of ICH patients have unknown onset time, leading to uncertainty regarding the use of hyperacute ICH treatments and their exclusion from acute ICH treatment trials. We aimed to develop a prediction score that can reliably identify ICH patients presenting within 3 hours of symptom onset. Methods: Spontaneous ICH patients participating in the iDEF trial with available prerequisite data were analyzed. A stepwise multivariable logistic regression model was used to determine predictors of early presentation (symptom onset-to-baseline CT scan time ≤3 hours) with a p-value &lt; 0.15. To develop the prediction score, we allocated scores proportional to the standardized odds ratio (OR) of each binary variable. Continuous variables were dichotomized using the lowest threshold above which there was no additional gain in the positive predictive value (PPV) for early presentation. Results: Of 291 iDEF participants, 132 (45%) presented early. Baseline NIHSS (OR 1.05 per 1-score increase; 95% CI, 0.99-1.11), Glasgow Coma Scale (1.18 per 1-score increase; 1.01-1.39), ICH volume (1.17 per 10-ml increase; 0.98-1.39), absolute perihematomal edema volume (0.81 per 10-ml increase; 0.66-1.00), irregular hematoma shape (2.24; 1.12-4.48), blend sign (0.45; 0.21-0.97), white blood cell count (0.89 per 10 3 cell/ml increase; 0.82-0.96), and blood glucose levels (0.91 per mmol/l increase; 0.82-0.99) were associated with early presentation (c-statistic=0.71). The PPV for an early ICH presentation score (Figure) of &gt;7 was 69%. Conclusion: This novel early ICH presentation score using readily available clinical, neuroimaging, and laboratory data has good performance for identification of ICH patients presenting within 3 hours of symptom onset. If validated in external datasets, the early ICH presentation score can be used to improve recruitment feasibility in acute ICH trials and support clinical decision-making in ICH patients with an unknown symptom onset time.

Peri-hematomal edema shape features related to 3-month outcome in acute supratentorial intracerebral hemorrhage.

Perihematomal edema (PHE) represents secondary brain injury and a potential treatment target in intracerebral hemorrhage (ICH). However, studies differ on optimal PHE volume metrics as prognostic factor(s) after spontaneous, non-traumatic ICH. This study examines associations of baseline and 24-h PHE shape features with 3-month outcomes. We included 796 patients from a multicentric trial dataset and manually segmented ICH and PHE on baseline and follow-up CTs, extracting 14 shape features. We explored the association of baseline, follow-up, difference (baseline/follow-up) and temporal rate (difference/time gap) of PHE shape changes with 3-month modified Rankin Score (mRS) - using Spearman correlation. Then, using multivariable analysis, we determined if PHE shape features independently predict outcome adjusting for patients' age, sex, NIH stroke scale (NIHSS), Glasgow Coma Scale (GCS), and hematoma volume. Baseline PHE maximum diameters across various planes, main axes, volume, surface, and sphericity correlated with 3-month mRS adjusting for multiple comparisons. The 24-h difference and temporal change rates of these features had significant association with outcome - but not the 24-h absolute values. In multivariable regression, baseline PHE shape sphericity (OR = 2.04, CI = 1.71-2.43) and volume (OR = 0.99, CI = 0. 98-1.0), alongside admission NIHSS (OR = 0.86, CI = 0.83-0.88), hematoma volume (OR = 0.99, CI = 0. 99-1.0), and age (OR = 0.96, CI = 0.95-0.97) were independent predictors of favorable outcomes. In acute ICH patients, PHE shape sphericity at baseline emerged as an independent prognostic factor, with a less spherical (more irregular) shape associated with worse outcome. The PHE shape features absolute values over the first 24 h provide no added prognostic value to baseline metrics.

Prognostic significance of perihematomal edema in basal ganglia hemorrhage after minimally invasive endoscopic evacuation.

Spontaneous basal ganglia hemorrhage is a common type of intracerebral hemorrhage (ICH) with no definitive treatment. Minimally invasive endoscopic evacuation is a promising therapeutic approach for ICH. In this study the authors examined prognostic factors associated with long-term functional dependence (modified Rankin Scale [mRS] score ≥ 4) in patients who had undergone endoscopic evacuation of basal ganglia hemorrhage. In total, 222 consecutive patients who underwent endoscopic evacuation between July 2019 and April 2022 at four neurosurgical centers were enrolled prospectively. Patients were dichotomized into functionally independent (mRS score ≤ 3) and functionally dependent (mRS score ≥ 4) groups. Hematoma and perihematomal edema (PHE) volumes were calculated using 3D Slicer software. Predictors of functional dependence were assessed using logistic regression models. Among the enrolled patients, the functional dependence rate was 45.50%. Factors independently associated with long-term functional dependence included female sex, older age (≥ 60 years), Glasgow Coma Scale score ≤ 8, larger preoperative hematoma volume (OR 1.02), and larger postoperative PHE volume (OR 1.03, 95% CI 1.01-1.05). A subsequent analysis evaluated the effect of stratified postoperative PHE volume on functional dependence. Specifically, patients with large (≥ 50 to < 75 ml) and extra-large (≥ 75 to 100 ml) postoperative PHE volumes had 4.61 (95% CI 0.99-21.53) and 6.75 (95% CI 1.20-37.85) times greater likelihood of long-term dependence, respectively, than patients with a small postoperative PHE volume (≥ 10 to < 25 ml). A large postoperative PHE volume is an independent risk factor for functional dependence among basal ganglia hemorrhage patients after endoscopic evacuation, especially with postoperative PHE volume ≥ 50 ml.

Clinical Trial Protocol for BEACH: A Phase 2a Study of MW189 in Patients with Acute Nontraumatic Intracerebral Hemorrhage

Patients with acute spontaneous intracerebral hemorrhage (ICH) develop secondary neuroinflammation and cerebral edema that can further damage the brain and lead to increased risk of neurologic complications. Preclinical studies in animal models of acute brain injury have shown that a novel small-molecule drug candidate, MW01-6-189WH (MW189), decreases neuroinflammation and cerebral edema and improves functional outcomes. MW189 was also safe and well tolerated in phase 1 studies in healthy adults. The proof-of-concept phase 2a Biomarker and Edema Attenuation in IntraCerebral Hemorrhage (BEACH) clinical trial is a first-in-patient, multicenter, randomized, double-blind, placebo-controlled trial. It is designed to determine the safety and tolerability of MW189 in patients with acute ICH, identify trends in potential mitigation of neuroinflammation and cerebral edema, and assess effects on functional outcomes. A total of 120 participants with nontraumatic ICH will be randomly assigned 1:1 to receive intravenous MW189 (0.25 mg/kg) or placebo (saline) within 24 h of symptom onset and every 12 h for up to 5 days or until hospital discharge. The 120-participant sample size (60 per group) will allow testing of the null hypothesis of noninferiority with a tolerance limit of 12% and assuming a “worst-case” safety assumption of 10% rate of death in each arm with 10% significance and 80% power. The primary outcome is all-cause mortality at 7 days post randomization between treatment arms. Secondary end points include all-cause mortality at 30 days, perihematomal edema volume after symptom onset, adverse events, vital signs, pharmacokinetics of MW189, and inflammatory cytokine concentrations in plasma (and cerebrospinal fluid if available). Other exploratory end points are functional outcomes collected on days 30, 90, and 180. BEACH will provide important information about the utility of targeting neuroinflammation in ICH and will inform the design of future larger trials of acute central nervous system injury.

Association of serum occludin levels and perihematomal edema volumes in intracranial hemorrhage patients.

Perihematomal edema (PHE) is one of the severe secondary damages following intracranial hemorrhage (ICH). Studies showed that blood-brain barrier (BBB) injury contributes to the development of PHE. Previous studies showed that occludin protein is a potential biomarker of BBB injury. In the present study, we investigated whether the levels of serum occludin on admission are associated with PHE volumes in ICH patients. This cross-sectional study included 90ICH patients and 32 healthy controls.The volumes of hematoma and PHE were assessed using non-contrast cranial CT within 30 min of admission. Blood samples were drawn on admission, and the levels of baseline serum occludin were detected using enzyme-linked immunosorbent assay. Partial correlation analysis and multiple linear regression analysis were performed to evaluate the association between serum occludin levels and PHE volumes in ICH patients. The serum occludin levels in ICH patients were much higher than health controls (median 0.27 vs. 0.13 ng/mL, p < 0.001). At admission, 34 ICH patients (37.78%) had experienced a severe PHE (≥30 mL), and their serum occludin levels were higher compared to those with mild PHE (<30 mL) (0.78 vs. 0.21 ng/mL, p < 0.001). The area under the receiver operating characteristics curve (ROC) of serum occludin level in predicting severe PHE was 0.747 (95% confidence interval CI 0.644-0.832, p < 0.001). There was a significant positive correlation between serum occludin levels and PHE volumes (partial correlation r = 0.675, p < 0.001). Multiple linear regression analysis showed that serum occludin levels remained independently associated with the PHE volumes after adjusting other confounding factors. The present study showed that serum occludin levels at admission were independently correlated with PHE volumes in ICH patients, which may provide a biomarker indicating PHE volume change.

Perihematomal edema after minimally invasive surgery: a matter of concern to neurosurgeons.

The purpose of this study is to explore the evolution of brain edema after minimally invasive surgery in deep spontaneous cerebral hemorrhage (DSICH) treatment and to analyze the differences in edema after different surgical methods. The clinical data of 105 patients with DSICH treated at Renmin Hospital of Wuhan University from January 2020 to June 2022 were analyzed retrospectively. Among them, 54 patients were treated with minimally invasive puncture and drainage surgery (MIPDS group), and 51 were treated with neuroendoscopic surgery (NES group). Continuous computed tomography images of patients in the hospital and 3D Slicer software were used to quantitatively calculate the edematous area to explore the changes in perihematomal edema volume in the two groups after the operation. The peak volume of postoperative edema (37.36±10.51 mL) in the MIPDS group was more extensive than that in the NES group, and its net increase in edema volume was 16.86±10.01 mL more than that in the NES group. The relative edema index (0.86±0.26) was lower in the NES group than in the MIPDS group (P < 0.05). The peak of postoperative edema in the MIPDS group was at 6-8 days after the operation, and that in the NES group was most often at 3-5 days after the operation. There are differences in perihematomal edema of DSICH treated by different minimally invasive methods. Compared with the MIPDS group, the NES group showed earlier peak of cerebral edema and lower degree of cerebral edema. The absolute regression volume of edema in the MIDPs group was greater than that in the NEs group, but there was no difference in the regression rate of edema between the two groups.

An updated systematic review and meta-analysis investigating perihematomal edema and clinical outcome after intracerebral hemorrhage

ObjectivesThe relationship between perihematomal edema (PHE) and intracerebral hemorrhage (ICH) outcomes is uncertain. Given newly published studies, we updated a previous systematic review and meta-analysis assessing the prognostic impact of PHE on ICH outcomes. Materials and methodsDatabases were searched through September 2022 using pre-defined keywords. Included studies used regression to examine the association between PHE and functional outcome (assessed by modified Rankin Scale [mRS]) and mortality. The study quality was assessed using the Newcastle-Ottawa Scale. The overall pooled effect, and secondary analyses exploring different subgroups were obtained by entering the log transformed odds ratios and their confidence intervals into a DerSimonian-Laird random effects meta-analysis. ResultsTwenty-eight studies (n=8655) were included. The pooled effect size for overall outcome (mRS and mortality) was 1.05 (95% CI 1.03, 1.07; p<0.00). In secondary analyses, PHE volume and growth effect sizes were 1.03 (CI 1.01, 1.05) and 1.12 (CI 1.06, 1.19), respectively. Results of subgroup analyses assessing absolute PHE volume and growth at different time points were: baseline volume 1.02 (CI 0.98, 1.06), 72-hour volume 1.07 (CI 0.99, 1.16), growth at 24 hours 1.30 (CI 0.96, 1.74) and growth at 72 hours 1.10 (CI 1.04, 1.17). Heterogeneity across studies was substantial. ConclusionsThis meta-analysis indicates that PHE growth, especially within the first 24 hours after ictus, has a stronger impact on functional outcome and mortality than PHE volume. Definitive conclusions are limited by the large variability of PHE measures, heterogeneity, and different evaluation time points between studies.

CD4+ T cells aggravate hemorrhagic brain injury.

Leukocyte infiltration accelerates brain injury following intracerebral hemorrhage (ICH). Yet, the involvement of T lymphocytes in this process has not been fully elucidated. Here, we report that CD4+ T cells accumulate in the perihematomal regions in the brains of patients with ICH and ICH mouse models. T cells activation in the ICH brain is concurrent with the course of perihematomal edema (PHE) development, and depletion of CD4+ T cells reduced PHE volumes and improved neurological deficits in ICH mice. Single-cell transcriptomic analysis revealed that brain-infiltrating T cells exhibited enhanced proinflammatory and proapoptotic signatures. Consequently, CD4+ T cells disrupt the blood-brain barrier integrity and promote PHE progression through interleukin-17 release; furthermore, the TRAIL-expressing CD4+ T cells engage DR5 to trigger endothelial death. Recognition of T cell contribution to ICH-induced neural injury is instrumental for designing immunomodulatory therapies for this dreadful disease.

Temporal Evolution of Perihematomal Blood-Brain Barrier Compromise and Edema Growth After Intracerebral Hemorrhage

PurposeThe aim of this study was to investigate the temporal evolution of perihematomal blood-brain barrier (BBB) compromise and edema growth and to determine the role of BBB compromise in edema growth.MethodsSpontaneous intracerebral hemorrhage patients who underwent computed tomography perfusion (CTP) were divided into five groups according to the time interval from symptom onset to CTP examination. Permeability-surface area product (PS) maps were generated using CTP source images. Ipsilateral and contralateral mean PS values were computed in the perihematomal and contralateral mirror regions. The relative PS (rPS) value was calculated as a ratio of ipsilateral to contralateral PS value. Hematoma and perihematomal edema volume were determined on non-contrast CT images.ResultsIn the total of 101 intracerebral hemorrhage patients, the ipsilateral mean PS value was significantly higher than that in contralateral region (z = −8.284, p < 0.001). The perihematomal BBB permeability showed a course of dynamic changes including an increase in the hyperacute and acute phases, a decrease in the early subacute phase and a second increase in the late subacute phase and chronic phase. Perihematomal edema increased gradually until the late subacute phase and then slightly increased. There was a relationship between rPS value and edema volume (β = 0.254, p = 0.006).ConclusionThe perihematomal BBB permeability is dynamic changes, and edema growth is gradually increased in patients following intracerebral hemorrhage. BBB compromise plays an essential role in edema growth. The quantitative assessment of BBB compromise may provide valuable information in therapeutic interventions of intracerebral hemorrhage patients.

Edema to Hematoma Ratio is Elevated in COVID-19 ICH Patients (P2-7.002)

<h3>Objective:</h3> The objective of this study was to evaluate whether COVID-19 infection affected perihematomal edema volume in relation to hematoma size in patients with spontaneous intracerebral hemorrhage. <h3>Background:</h3> Perihematomal edema (PHE) is an indicator of secondary brain injury in patients with spontaneous intracerebral hemorrhage (ICH). The complement cascade plays a central role in PHE development. Thus, since COVID-19 infection is known to activate multiple complement cascade pathways, we hypothesized that COVID-19 infection would increase edema to hematoma volume ratio in patients with ICH relative to ICH patients not infected with COVID-19. <h3>Design/Methods:</h3> Patients at Rush University Medical Center with COVID-19 and spontaneous ICH, both diagnosed at admission from April 2020 to June 2021 were identified (N=12) and compared to randomly selected patients with ICH, but without COVID-19 diagnosis in the same time period (N=12). Patient characteristics, presenting factors, and admission CT imaging were abstracted from the electronic health record. Edema and hematoma measurements were made using semiautomatic segmentation software on admission CT scans for greatest accuracy. <h3>Results:</h3> Average hematoma and perihematomal edema volumes were 18.10 mL and 12.12 mL in the non-COVID ICH patients and 18.56 mL and 15.62 mL in COVID ICH patients, respectively (p=0.477, p=0.264). However, edema volume to hematoma volume ratio was 0.75 and 2.47 in non-COVID and COVID patients, respectively (p&lt;0.05). <h3>Conclusions:</h3> Patients with both ICH and COVID-19 have edema volumes significantly greater in relation to their hematoma size compared to ICH patients without COVID-19. As the COVID-19 pandemic has continued, more data is warranted to corroborate these findings and evaluate therapies that minimize edema expansion and promote positive clinical outcomes. <b>Disclosure:</b> Mr. Sim has nothing to disclose. Mr. Pang has nothing to disclose. Dr. Da Silva has nothing to disclose.

The association between blood pressure variability and perihematomal edema after spontaneous intracerebral hemorrhage.

Perihematomal edema (PHE) after spontaneous intracerebral hemorrhage (sICH) is associated with clinical deterioration, but the etiology of PHE development is only partly understood. We aimed to investigate the association between systemic blood pressure (BP) variability (BPV) and formation of PHE. From a multicenter prospective observational study, we selected patients with sICH who underwent 3T brain MRI within 21 days after sICH, and had at least 5 BP measurements available in the first week after sICH. Primary outcome was the association between coefficient of variation (CV) of systolic BP (SBP) and edema extension distance (EED) using multivariable linear regression, adjusting for age, sex, ICH volume and timing of the MRI. In addition, we investigated the associations of mean SBP, mean arterial pressure (MAP), their CVs with EED and absolute and relative PHE volume. We included 92 patients (mean age 64 years; 74% men; median ICH volume 16.8 mL (IQR 6.6-36.0), median PHE volume 22.5 mL (IQR 10.2-41.4). Median time between symptom onset and MRI was 6 days (IQR 4-11), median number of BP measurements was 25 (IQR 18-30). Log-transformed CV of SBP was not associated with EED (B = 0.050, 95%-CI -0.186 to 0.286, p = 0.673). Furthermore, we found no association between mean SBP, mean and CV of MAP and EED, nor between mean SBP, mean MAP or their CVs and absolute or relative PHE. Our results do not support a contributing role for BPV on PHE, suggesting mechanisms other than hydrostatic pressure such as inflammatory processes, may play a more important role.

Advances in Prediction for Perihematomal Edema Growth in Intracerebral Hemorrhage

Perihematomal edema (PHE) has been represented as an important secondary injury after intracerebral hemorrhage (ICH). The evolution of PHE contributed to mass effect, which could induce the increase of intracranial pressure. The volume of PHE increased rapidly in the early stage of ICH and continued to increase for 7 to 11 days after symptom onset, and the edema extension distance (EED) increased rapidly within 24 hours, accounting for 60% of the peak EED [1-2]. For the timepoint of follow-up CT scans was different, the fastest development stage of PHE could also be 48 or 72 hours after symptom onset [3-4]. If patients with ICH could not benefit from early surgical evacuation of the hematoma, anti-edema treatment may bring better therapeutic effect. Thus, the use of anti-edema treatment may need to be considered for reducing PHE volume during the early phase of PHE development. How to appropriately predict PHE growth is important in patients at the early stage of ICH.

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.