Intracerebral Hemorrhage Volume Research Articles

Location-Specific Hematoma Volume Cutoff and Clinical Outcomes in Intracerebral Hemorrhage.

Major intracerebral hemorrhage (ICH) trials have largely been unable to demonstrate therapeutic benefit in improving functional outcomes. This may be partly due to the heterogeneity of ICH outcomes based on their location, where a small strategic ICH could be debilitating, thus confounding therapeutic effects. We aimed to determine the ideal hematoma volume cutoff for different ICH locations in predicting ICH outcomes. We retrospectively analyzed consecutive ICH patients enrolled in the University of Hong Kong prospective stroke registry from January 2011 to December 2018. Patients with premorbid modified Rankin Scale score >2 or who underwent neurosurgical intervention were excluded. ICH volume cutoff, sensitivity, and specificity in predicting respective 6-month neurological outcomes (good [modified Rankin Scale score 0-2], poor [modified Rankin Scale score 4-6], and mortality) for specific ICH locations were determined using receiver operating characteristic curves. Separate multivariate logistic regression models were also conducted for each location-specific volume cutoff to determine whether these cutoffs were independently associated with respective outcomes. Among 533 ICHs, the volume cutoff for good outcome according to ICH location was 40.5 mL for lobar, 32.5 mL for putamen/external capsule, 5.5 mL for internal capsule/globus pallidus, 6.5 mL for thalamus, 17 mL for cerebellum, and 3 mL for brainstem. ICH smaller than the cutoff for all supratentorial sites had higher odds of good outcomes (all P<0.05). Volumes exceeding 48 mL for lobar, 41 mL for putamen/external capsule, 6 mL for internal capsule/globus pallidus, 9.5 mL for thalamus, 22 mL for cerebellum, and 7.5 mL for brainstem were at greater risk of poor outcomes (all P<0.05). Mortality risks were significantly higher for volumes that exceeded 89.5 mL for lobar, 42 mL for putamen/external capsule, and 21 mL for internal capsule/globus pallidus (all P<0.001). All receiver operating characteristic models for location-specific cutoffs had good discriminant values (area under the curve >0.8), except in predicting good outcome for cerebellum. ICH outcomes differed with location-specific hematoma size. Location-specific volume cutoff should be considered in patient selection for ICH trials.

Non-contrast computed tomography features predict intraventricular hemorrhage growth

ObjectivesNon-contrast computed tomography (NCCT) markers are robust predictors of parenchymal hematoma expansion in intracerebral hemorrhage (ICH). We investigated whether NCCT features can also identify ICH patients at risk of intraventricular hemorrhage (IVH) growth.MethodsPatients with acute spontaneous ICH admitted at four tertiary centers in Germany and Italy were retrospectively included from January 2017 to June 2020. NCCT markers were rated by two investigators for heterogeneous density, hypodensity, black hole sign, swirl sign, blend sign, fluid level, island sign, satellite sign, and irregular shape. ICH and IVH volumes were semi-manually segmented. IVH growth was defined as IVH expansion > 1 mL (eIVH) or any delayed IVH (dIVH) on follow-up imaging. Predictors of eIVH and dIVH were explored with multivariable logistic regression. Hypothesized moderators and mediators were independently assessed in PROCESS macro models.ResultsA total of 731 patients were included, of whom 185 (25.31%) suffered from IVH growth, 130 (17.78%) had eIVH, and 55 (7.52%) had dIVH. Irregular shape was significantly associated with IVH growth (OR 1.68; 95%CI [1.16–2.44]; p = 0.006). In the subgroup analysis stratified by the IVH growth type, hypodensities were significantly associated with eIVH (OR 2.06; 95%CI [1.48–2.64]; p = 0.015), whereas irregular shape (OR 2.72; 95%CI [1.91–3.53]; p = 0.016) in dIVH. The association between NCCT markers and IVH growth was not mediated by parenchymal hematoma expansion.ConclusionsNCCT features identified ICH patients at a high risk of IVH growth. Our findings suggest the possibility to stratify the risk of IVH growth with baseline NCCT and might inform ongoing and future studies.Clinical relevance statementNon-contrast CT features identified ICH patients at a high risk of intraventricular hemorrhage growth with subtype-specific differences. Our findings may assist in the risk stratification of intraventricular hemorrhage growth with baseline CT and might inform ongoing and future clinical studies.Key Points• NCCT features identified ICH patients at a high risk of IVH growth with subtype-specific differences.• The effect of NCCT features was not moderated by time and location or indirectly mediated by hematoma expansion.• Our findings may assist in the risk stratification of IVH growth with baseline NCCT and might inform ongoing and future studies.

Brain-derived neurotrophic factor contributes to neurogenesis after intracerebral hemorrhage: a rodent model and human study.

Intracerebral hemorrhage (ICH) enhances neurogenesis in the subventricular zone (SVZ); however, the mechanism is not fully understood. We investigated the role of brain-derived neurotrophic factor (BDNF) in post-ICH neurogenesis in a rodent model and in patients with ICH using cerebrospinal fluid (CSF). A rat model of ICH was constructed via stereotaxic injection of collagenase into the left striatum. Patients with ICH receiving an external ventricular drain were prospectively enrolled. CSF was collected from rats and patients at different post-ICH times. Primary cultured rat neural stem cells (NSCs) were treated with CSF with or without BDNF-neutralized antibody. Immunohistochemistry and immunocytochemistry were used to detect NSC proliferation and differentiation. The BDNF concentration in CSF was quantified using enzyme-linked immunosorbent assays (ELISA). In the rat model of ICH, the percentage of proliferating NSCs and neuroblasts in SVZ was elevated in bilateral hemispheres. The cultured rat NSCs treated with CSF from both rats and patients showed an increased capacity for proliferation and differentiation toward neuroblasts. BDNF concentration was higher in CSF collected from rats and patients with ICH than in controls. Blocking BDNF decreased the above-noted promotion of proliferation and differentiation of cultured NSCs by CSF treatment. In patients with ICH, the BDNF concentration in CSF and the neurogenesis-promoting capacity of post-ICH CSF correlated positively with ICH volume. BDNF in CSF contributes to post-ICH neurogenesis, including NSC proliferation and differentiation toward neuroblasts in a rat model and patients with ICH.

NCCT Markers of Intracerebral Hemorrhage Expansion Using Revised Criteria: An External Validation of Their Predictive Accuracy.

Several NCCT expansion markers have been proposed to improve the prediction of hematoma expansion. We retrospectively evaluated the predictive accuracy of 9 expansion markers. Patients admitted for intracerebral hemorrhage within 24 hours of last seen well were retrospectively included from April 2016 to April 2020. The primary outcome was revised hematoma expansion, defined as any of a ≥6-mL or ≥33% increase in intracerebral hemorrhage volume, a ≥ 1-mL increase in intraventricular hemorrhage volume, or de novo intraventricular hemorrhage. We assessed the predictive accuracy of expansion markers and determined their association with revised hematoma expansion. We included 124 patients, of whom 51 (41%) developed revised hematoma expansion. The sensitivity of each marker for the prediction of revised hematoma expansion ranged from 4% to 78%; the specificity, 37%-97%; the positive likelihood ratio, 0.41-7.16; and the negative likelihood ratio, 0.49-1.06. By means of univariable logistic regressions, 5 markers were significantly associated with revised hematoma expansion: black hole (OR = 8.66; 95% CI, 2.15-58.14; P = .007), hypodensity (OR = 3.18; 95% CI, 1.49-6.93; P = .003), blend (OR = 2.90; 95% CI, 1.08-8.38; P = .04), satellite (OR = 2.84; 95% CI, 1.29-6.61; P = .01), and Barras shape (OR = 2.41, 95% CI; 1.17-5.10; P = .02). In multivariable models, only the black hole marker remained independently associated with revised hematoma expansion (adjusted OR = 5.62; 95% CI, 1.23-40.23; P = .03). No single NCCT expansion marker had both high sensitivity and specificity for the prediction of revised hematoma expansion. Improved image-based analysis is needed to tackle limitations associated with current NCCT-based expansion markers.

Prestroke physical activity is associated with admission haematoma volume and the clinical outcome of intracerebral haemorrhage

BackgroundPrestroke physical activity (PA) has been linked to improved outcomes after intracerebral haemorrhage (ICH), but its association with ICH volume is unknown. We aimed to investigate associations of prestroke PA...

Safety and technical efficacy of early minimally invasive endoscopy-guided surgery for intracerebral haemorrhage: the Dutch Intracerebral haemorrhage Surgery Trial pilot study

BackgroundPrevious randomised controlled trials could not demonstrate that surgical evacuation of intracerebral haemorrhage (ICH) improves functional outcome. Increasing evidence suggests that minimally invasive surgery may be beneficial, in particular when performed early after symptom onset. The aim of this study was to investigate safety and technical efficacy of early minimally invasive endoscopy-guided surgery in patients with spontaneous supratentorial ICH.MethodsThe Dutch Intracerebral Haemorrhage Surgery Trial pilot study was a prospective intervention study with blinded outcome assessment in three neurosurgical centres in the Netherlands. We included adult patients with spontaneous supratentorial ICH ≥10mL and National Institute of Health Stroke Scale (NIHSS) score ≥2 for minimally invasive endoscopy-guided surgery within 8 h after symptom onset in addition to medical management. Primary safety outcome was death or increase in NIHSS ≥4 points at 24 h. Secondary safety outcomes were procedure-related serious adverse events (SAEs) within 7 days and death within 30 days. Primary technical efficacy outcome was ICH volume reduction (%) at 24 h.ResultsWe included 40 patients (median age 61 years; IQR 51–67; 28 men). Median baseline NIHSS was 19.5 (IQR 13.3–22.0) and median ICH volume 47.7mL (IQR 29.4–72.0). Six patients had a primary safety outcome, of whom two already deteriorated before surgery and one died within 24 h. Sixteen other SAEs were reported within 7 days in 11 patients (of whom two patients that already had a primary safety outcome), none device related. In total, four (10%) patients died within 30 days. Median ICH volume reduction at 24 h was 78% (IQR 50–89) and median postoperative ICH volume 10.5mL (IQR 5.1–23.8).ConclusionsMinimally invasive endoscopy-guided surgery within 8 h after symptom onset for supratentorial ICH appears to be safe and can effectively reduce ICH volume. Randomised controlled trials are needed to determine whether this intervention also improves functional outcome.Trial registrationClinicaltrials.gov: NCT03608423, August 1st, 2018.

Clinical outcome in patients with acute hypertensive hemorrhagic stroke with intravenous fluid versus no intravenous fluid: a randomized controlled study (P7-5.005)

<h3>Objective:</h3> This study was done to compare the outcome(mRS) of patients with acute hypertensive hemorrhagic stroke receiving intravenous fluid vs. no iv fluids in the acute period <h3>Background:</h3> Intracerebral hemorrhage (ICH) accounts for 10% of all strokes. Dehydration has a poor prognosis for both AIS and ICH patients. No randomized controlled trials have been done on hemorrhagic stroke patients. Studies are needed to see if intravenous fluids given to such individuals can help prevent early or late neurological impairment. <h3>Design/Methods:</h3> This was a prospective, single-center, open-label, randomized controlled trial. The outcome assessment was blinded. The patient’s relatives were informed that they would have full authority to enroll or withdraw from the study. All the patients with clinical features of acute hypertensive hemorrhagic stroke and were diagnosed with imaging findings between February 2021 and February 2022 were screened for eligibility. <h3>Results:</h3> A total of 80 patients were included. All baseline characters, including age, sex, GCS at admission, NIHSS score at admission, ICH volume, ICH score at admission, and mRS at admission, were all comparable between the groups. Out of the total 82 patients included in the analysis, 38 were females (46.3%), and 44 were males (53.7%). The primary outcome was a good functional outcome defined as a mRS of 0–3 at three months of follow-up. We found that those in the IVF group had better and statistically significant good functional outcomes at three months of follow-up than those in the no-IVF group. The mean duration of hospital stay in the IVF group was 7.51±2.81 days and in the no-IVF group, it was 10.49±5.98 days(p&lt;0.001). <h3>Conclusions:</h3> Our findings imply that in patients with acute hypertensive intracerebral hemorrhage, normal saline administered at 100ml per hour in the early period is associated with a better functional outcome at three months, as well as a lower risk of dehydration. <b>Disclosure:</b> Dr. Pathak has nothing to disclose.

External validation of the diagnostic value of perihematomal edema characteristics in neoplastic and non-neoplastic intracerebral hemorrhage.

Neoplastic intracerebral hemorrhage (ICH) may be incorrectly identified as non-neoplastic ICH on imaging. Relative perihematomal edema (relPHE) on computed tomography (CT) has been proposed as a marker to discriminate neoplastic from non-neoplastic ICH but has not been externally validated. The purpose of this study was to evaluate the discriminatory power of relPHE in an independent cohort. A total of 291 patients with acute ICH on CT and follow-up magnetic resonance imaging (MRI) were included in this single-center retrospective study. ICH subjects were dichotomized into non-neoplastic or neoplastic ICH based on the diagnosis on the follow-up MRI. ICH and PHE volumes and density values were derived from semi-manually segmented CT scans. Calculated PHE characteristics for discriminating neoplastic ICH were evaluated using receiver-operating characteristic (ROC) curves. ROC curve-associated cut-offs were calculated and compared between the initial and the validation cohort. A total of 116 patients (39.86%) with neoplastic ICH and 175 (60.14%) with non-neoplastic ICH were included. Median PHE volumes, relPHE, and relPHE adjusted for hematoma density were significantly higher in subjects with neoplastic ICH (all p values <0.001). ROC curves for relPHE had an area under the curve (AUC) of 0.72 (95% confidence interval [CI] 0.66-0.78) and an AUC of 0.81 (95% CI 0.76-0.87) for adjusted relPHE. The cut-offs were identical in the two cohorts, with >0.70 for relPHE and >0.01 for adjusted relPHE. Relative perihematomal edema and adjusted relPHE accurately discriminated neoplastic from non-neoplastic ICH on CT imaging in an external patient cohort. These results confirmed the findings of the initial study and may improve clinical decision making.

Remote Diffusion-Weighted Imaging Lesions and Intracerebral Hemorrhage: A Systematic Review and Meta-Analysis.

Remote diffusion-weighted imaging lesions (RDWILs) in the context of spontaneous intracerebral hemorrhage (ICH) are associated with an increased risk of recurrent stroke, worse functional outcome, and death. To update current knowledge on RDWILs, we conducted a systematic review and meta-analysis of the prevalence, associated factors and presumed causes of RDWILs. We searched Pubmed, Embase, and Cochrane up to June 2022 for studies reporting RDWILs in adults with symptomatic ICH of no-identified-cause, assessed by magnetic resonance imaging, and analyzed associations between baseline variables and RDWILs in random-effects meta-analyses. Eighteen observational studies (7 prospective), reporting 5211 patients were included, of whom 1386 had ≥1 RDWIL (pooled prevalence: 23.5% [19.0-28.6]). RDWIL presence was associated with neuroimaging features of microangiopathy, atrial fibrillation (odds ratio, 3.67 [1.80-7.49]), clinical severity (mean difference in National Institutes of Health Stroke Scale score, 1.58 points [0.50-2.66]), elevated blood pressure (mean difference, 14.02 mmHg [9.44-18.60]), ICH volume (mean difference, 2.78 mL [0.97-4.60]), and subarachnoid (odds ratio, 1.80 [1.00-3.24]) or intraventricular (odds ratio, 1.53 [1.28-1.83]) hemorrhage. RDWIL presence was associated with poor 3-month functional outcome (odds ratio, 1.95 [1.48-2.57]). RDWILs are detected in approximately 1-in-4 patients with acute ICH. Our results suggest that most RDWILs result from disruption of cerebral small vessel disease by ICH-related precipitating factors such as elevated intracranial pressure and cerebral autoregulation impairment. Their presence is associated with worse initial presentation and outcome. However, given the mostly cross-sectional designs and heterogeneity in study quality, further studies are needed to investigate whether specific ICH treatment strategies may reduce the incidence of RDWILs and in turn improve outcome and reduce stroke recurrence.

Development and validation of a novel radiomics-clinical model for predicting post-stroke epilepsy after first-ever intracerebral haemorrhage.

Post-stroke epilepsy (PSE) is associated with increased morbidity and mortality. This study aimed to develop and validate a novel prediction model combining clinical factors and radiomics features to accurately identify patients at high risk of developing PSE after intracerebral haemorrhage (ICH). Researchers performed a retrospective medical chart review to extract derivation and validation cohorts of patients with first-ever ICH that attended two tertiary hospitals in China between 2010 and 2020. Clinical data were extracted from electronic medical records and supplemented by tele-interview. Predictive clinical variables were selected by multivariable logistic regression to build the clinical model. Predictive radiomics features were identified, and a Rad-score was calculated according to the coefficient of the selected feature. Both clinical variables and radiomic features were combined to build the radiomics-clinical model. Performances of the clinical, Rad-score, and combined models were compared. A total of 1571 patients were included in the analysis. Cortical involvement, early seizures within 7days of ICH, NIHSS score, and ICH volume were included in the clinical model. Rad-score, instead of ICH volume, was included in the combined model. The combined model exhibited better discrimination ability and achieved an overall better benefit against threshold probability than the clinical model in the decision curve analysis (DCA). The combined radiomics-clinical model was better able to predict ICH-associated PSE compared to the clinical model. This can help clinicians better predict an individual patient's risk of PSE following a first-ever ICH and facilitate earlier PSE diagnosis and treatment. • Radiomics has not been used in predicting the risk of developing PSE. • Higher Rad-scores were associated with higher risk of developing PSE. • The combined model showed better performance of PSE prediction ability.

Abstract TMP44: Artificial Intelligence-driven Automated Intracerebral Hemorrhage Volume Calculation Is More Accurate Than ABC/2

Introduction: Treatment of spontaneous intracerebral hemorrhage (ICH) requires rapid, accurate estimation of hemorrhage volume to determine appropriate patient care and guide prognosis. ICH volume estimation on Computed Tomography (CT) imaging using the ABC/2 formula is the clinical gold standard, however this method can be inaccurate, suffers from observer scoring variability, and takes time to make the measurement on a workstation. Semi-Autonomous Segmentation (SAS) is the gold standard for hemorrhage volume estimation, however it is not used clinically due to the increased time for analysis. Recently, artificial intelligence (AI) driven segmentation has been developed (Viz.ai, San Francisco, California) to automatically detect ICH and calculate hematoma volume. Objective: Our goal is to validate the accuracy of the Viz.ai ICH segmentation algorithm as a tool for determining hemorrhage volume by comparing its performance to both ABC/2 and SAS. Methods: Seventy head CTs positive for ICH were analyzed with SAS in 3D Slicer to determine ICH volume as the standard reference volume. The same CT scans were then analyzed using the ABC/2 method. Finally, scans were uploaded to Viz.ai for ICH volume analysis. Results: Compared against standard SAS, Viz.ai ICH volumes were more accurate than ABC/2 in 77% of cases. Average difference between Viz.ai ICH volume and SAS ICH volume was 4.9±4.2 mL (R2=0.98). Average difference between ABC/2 ICH volume and SAS ICH volume was 10.6±11.4 mL (R2=0.77). Conclusion: This study indicates that Viz.ai more accurately estimates ICH volume than ABC/2 over a broad range of hematoma volumes when compared to standard SAS, which when coupled with significantly faster analysis compared to SAS justifies the use of AI in ICH triage workflow.

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.

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 166: Sex Differences In Perihematomal Edema Volume And Outcome After Intracerebral Hemorrhage

Introduction: Hematoma volume predicts poor outcome after intracerebral hemorrhage (ICH), while outcome associations with perihematomal edema (PHE) remain controversial. Prior studies using non-standardized timing of serial CT imaging reported larger ICH and PHE volumes in men than women, but worse outcome in women. Leveraging data from a cohort with early admission and time-locked follow-up imaging, we investigated the role of sex on PHE and outcomes. Methods: We conducted a post hoc analysis of the randomized FAST (Factor VII for Acute-Hemorrhagic Stroke Treatment) trial. Participants underwent CT imaging within 3 hours of symptom onset, and at 24 and 72 hours. Lesion volumes were calculated using computerized planimetric techniques (AnalyzeDirect). Outcomes (modified Rankin Scale, mRS) were assessed at 90 days. Two-way repeated measures ANOVA tested whether changes in lesion volumes were driven by an interaction between sex and time. Multivariable logistic regression tested for associations between PHE and poor outcome (mRS 4-6). Results: Of 842 subjects, 781 with supratentorial ICH (mean age 65 years, 38% women) were included. Men (n=485) compared to women (n=296) had similar mean ICH and PHE volumes at baseline (p=0.063 and p=0.98) but larger ICH and PHE at 24 hours (p=0.002 and p=0.017) and 72 hours (p=0.002 and p=0.003). All volumes varied over CT time points according to sex (Figure 1 A-C, all three ANOVA: p&lt;0.001). Unlike ICH, PHE expanded between 24 and 72 hours (men: 1.5 ml/h, women: 1.6 ml/h). There was no interaction between PHE changes and FAST-treatment-arm (p=0.85). PHE volume, but not sex, was associated with poor outcome at all CT time points (Figure 1D). Conclusions: Men had greater early lesion expansion than women. In both sexes, PHE expanded beyond 24 hours and was associated with poor outcome. While mechanisms explaining sex differences need further investigation, future ICH studies should be carefully adjusted for sex.

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 HUP19: Sex Differences In Incidence Of Intraventricular Hemorrhage And Hydrocephalus In Patients With Non-traumatic Intracerebral Hemorrhage

Introduction: Non-traumatic Intracerebral Hemorrhage (ICH) accounts for 2 million strokes annually worldwide. This stroke burden disproportionately impacts minorities, and results in severe neurological deficits. Sex differences in brain structure and function, such as a larger mean length of frontal horn in males and increased global cerebral blood flow in women, can contribute to hematoma volume and expansion of ICH into nearby structures. No studies have yet to investigate sex differences in the incidence of Intraventricular Hemorrhage (IVH) and hydrocephalus as sequelae of ICH, both or which correlate with poor long-term outcomes. Methods: A retrospective review of a comprehensive stroke center spontaneous ICH database from 2019-2022 was performed, including patient characteristics such as history of diabetes mellitus, hypertension, coronary artery disease, tobacco use, and anticoagulant use in addition to ICH characteristics such as hematoma location volume, expansion, incidence of IVH and hydrocephalus. A logistic regression model controlling for these covariates was built to investigate sex differences in incidence of IVH and hydrocephalus. Results: This cohort had 100 patients with spontaneous, non-traumatic ICH, of which 39% were female. Overall, 52/100 (52%) patients had IVH and 21/100 (21%) patients developed hydrocephalus. Among males, 29/61(48%) had IVH as opposed to 23/39 (59%) in females, p = 0.264. There was similar development of hydrocephalus in both males 13/61(21%) and females 8/39 (21%). Logistic regression showed females had higher odds of IVH. Higher diastolic blood pressure and anticoagulant use on admission also had higher odds of IVH. Conclusion: This pilot study demonstrates a trend towards higher incidence of IVH among females when controlling for history of diabetes mellitus, hypertension, coronary artery disease, tobacco use, and anticoagulant use. Higher odds of IVH in patients with higher diastolic blood pressure on admission adds to the previously investigated association between systolic blood pressure and ICH hematoma volume. Our sample validated the higher odds of IVH in patients with anticoagulant use on admission.

Abstract WP121: Can The Extended Glasgow Outcome Scale (e-gos) Augment The Interpretation Of Results From Clinical Trials Of Minimally Invasive Surgery Of Spontaneous Intracerebral Hemorrhage Using The Modified Rankin Scale (mrs): A Secondary Analysis Of The Clear-iii And Mistie-iii Trials

Introduction: Currently, the modified Rankin scale (mRS) is most commonly used to assess functional outcome in clinical trials of interventions for spontaneous intracerebral hemorrhage (ICH). Extended Glasgow Outcome Score (eGOS) is often used to assess global disability/recovery after traumatic brain injury and provides additional discrimination of vegetative state (VS) from lower severe disability (LSD). We compared primary outcomes from 2 clinical trials of minimally invasive surgery for intracerebral and intraventricular hemorrhage (ICH/IVH) at different thresholds of eGOS. Methods: Post-hoc analysis of primary outcomes (PO) from the CLEAR-III trial (intraventricular alteplase [IVtPA] vs. saline for obstructive IVH; N=500; PO: mRS 0-3 at day 180), and MISTIE-III trial (stereotactic thrombolysis [MIS+tPA] vs. conservative management; N=499; PO: mRS 0-3 at day 365). eGOS was derived from functional outcome scales obtained during the trials. Outcomes on eGOS were categorized into 5 subgroups: good outcomes: 7-8 (A), 5-6 (B), 4 (C), and poor outcomes: 3 (D), and 1-2 (E). Generalized, ordered logistic regression analysis was performed, adjusting for age, ICH location, stability ICH and IVH volumes, and randomization GCS. Results: eGOS scales were available in 481 (96%) patients at day 180 in CLEAR-III and 478 (96%) patients at day 365 in MISTIE-III. In CLEAR-III, odds of being in eGOS category D (LSD) or E (death or VS) vs. the others, were approximately 40% lower for IVtPA group compared to saline group (aOR = 0.59; 95% CI, 0.38-0.90; p=0.016), and odds of being in category E (vs. the others) were almost 50% lower (aOR = 0.51; 95% CI, 0.33-0.80; p=0.004). VS occurred in 2.49% of IVtPA and 2.07% of saline group patients. In MISTIE-III, odds of being in eGOS category D or E (vs. the others) were not significantly different for MIS+tPA vs. conservative treatment: aOR = 0.84; 95% CI, 0.55-1.28; p=0.41), as were odds for being in eGOS category E (vs. the others), aOR = 0.77; 95% CI, 0.48-1.24; p=0.29). Conclusions: The 5-category dichotomized eGOS (4-8 vs. 1-3) defines a functional outcome improvement in CLEAR-III at day 180, which was not observed using the PO with mRS. Use of eGOS did not result in a different interpretation of the MISTIE-III trial.

Abstract TP117: Temporal Serum Iron And Hemoglobin Changes In Patients From The High Dose Deferoxamine In Intracerebral Hemorrhage Trial

Introduction: Following intracerebral hemorrhage (ICH), elevated cerebral tissue iron concentrations are seen. It is unclear how peripheral serum iron concentrations change over time and how they relate to anemia after ICH. Given the known impacts of iron concentrations and anemia on clinical outcomes, we explored serum iron biomarker and hemoglobin concentration changes after acute ICH. Methods: A post hoc analysis of patients with available serial (baseline and 5 day) serum biomarker data from the multicenter, High Dose Deferoxamine in Intracerebral Hemorrhage (HI-DEF) trial was performed. Changes of serum hemoglobin, iron, transferrin, and ferritin were assessed using repeated measure ANOVA analyses. Deferoxamine treatment and poor 90 day modified Rankin Scale 4-6 were separately assessed as between subject factors for these laboratory changes. Results: Of 42 ICH patients analyzed, the mean age was 64, 62% were male, median ICH volume was 15.7mL (IQR 5.7-37.5), and baseline anemia was seen in 19%. We identified significant decrements of hemoglobin (mean difference -1.4 g/dL; 95%CI: -1.9 to -0.9; p&lt;0.0001), iron (mean difference -16.9 ug/dL; 95%CI: -29.7 to -4.1; p=0.01), transferrin (mean difference -43.9 ng/mL; 95%CI: -56.6 to -31.3; p&lt;0.0001), and conversely, significant ferritin elevations (mean difference 104.5 ug/L; 95%CI: 52.5-156.6; p&lt;0.0001) at 5 days. Anemia was identified in 43% of patients at 5 days. Deferoxamine did not have a significant impact on these repeated measures. Patients with poor long-term outcomes had greater decrements in hemoglobin compared to those with good outcomes (mean difference: -1.5 g/dL; 95%CI: -2.6 to -0.3; p=0.01). Conclusions: Serum iron and hemoglobin concentrations decrease significantly over time following ICH. Patients with worse long term ICH outcomes had greater hemoglobin decrements during their hospitalization. The aggregate iron biomarker and hemoglobin concentration changes suggest anemia development may be due to anemia of inflammation. Further work is required to address the pathophysiologic difference between systemic and central iron homeostasis mechanisms following ICH and the impacts that ICH has on inflammation, systemic iron homeostasis, anemia, and clinical outcomes.

Abstract TP125: Relationships Of Female Sex With Viscoelastic Hemostatic Assay Coagulation Characteristics After Intracerebral Hemorrhage

Introduction: There are described differences in coagulation between females and males. Specifically, female sex is associated with greater platelet activation and stronger clotting characteristics. It is unclear whether there are relevant coagulation differences identifiable between female and male patients suffering from intracerebral hemorrhage (ICH). Hypothesis: Female sex will be associated with stronger clotting characteristics on whole blood viscoelastic hemostatic assay testing. Methods: Spontaneous ICH patients admitted and enrolled into a prospective observational ICH cohort study between 2009-2020 and who received baseline viscoelastic hemostatic assay testing (Rotational Thromboelastometry: ROTEM) were assessed. Patients with prior anticoagulant use, patients receiving hemorrhage control therapies prior to ROTEM, and secondary etiologies of ICH were excluded from the analysis. Female sex was assessed as the primary exposure variable. The following ROTEM clotting parameters were assessed as the outcome: Coagulation Time (CT) and Maximum Clot Firmness (MCF). We assessed relationships of female sex with these separate ROTEM parameters using multivariable linear regression analyses after adjusting for relevant covariates. Results: Of 57 ICH patients included for analyses, mean age was 65 (SD 14.1), 47% were female, and the median ICH volume was 20.6 mL (IQR 10.1-43.3). There were no baseline intergroup sex differences in demographics, age, or ICH characteristics. Female sex was associated with increased EXTEM MCF (ß 0.323, p&lt;0.05), signifying greater clotting strength, after adjusting for age, race, baseline hematoma volume, and ICH location. Female sex was not associated with other ROTEM parameters. Conclusions: We identified that female sex was associated with stronger clotting characteristics on ROTEM viscoelastic testing. Further work is required to clarify the clinical significance of these findings and their potential specific impacts on radiographic, complication, and clinical outcomes after ICH.

Deep-learning measurement of intracerebral haemorrhage with mixed precision training: a coarse-to-fine study

To develop a unified deep-learning-based method for automated intracerebral haemorrhage (ICH) segmentation on computed tomography (CT) images with different layer thickness parameters. A total of 134 patients from an internal database (67 patients) and an external database (called CQ500, 67 patients) were employed. The CT examinations included multiple layer thicknesses such as 0.625, 1.25 and 5 mm. ICH segmentation was performed by a coarse-to-fine strategy, including three stages of three-dimensional (3D) skull-stripping segmentation, 3D ICH localisation segmentation, and two-dimensional (2D) ICH fine segmentation. The three stages shared the same sICHNet for segmentation and employed mixed precision training to speed up the training process. In addition, the 3D contextual information from CT was maintained by formatting the consecutive slices into a three-channel image in the 2D ICH fine segmentation. Experimental results demonstrated that the coarse-to-fine segmentation strategy achieved the best performance with a mean Dice coefficient of 0.887. ICH volume consistency was observed (p<0.05) between manual and automatic segmentations, and between segmentations of same individual but with different layer thicknesses in internal dataset and external database. Automated segmentation achieved a relatively consistent segmentation time of 20.01±2.03 seconds no matter the layer thickness of the CT images and the extent of ICH. Longitudinal studies with conservative management and surgical treatment were also visualised. The coarse-to-fine deep learning strategy achieved the best ICH segmentation performance on CT images. The automated segmentation was 5-42 times faster than manual segmentation given ICH of different extents and using different layer thickness parameters.