Hematoma Expansion Research Articles

Potential of Satellite Sign for Prediction of Hematoma Expansion in Small Spontaneous Hematoma within 7 Days' Follow-Up.

Background Hematoma expansion (HE) is the most important modifiable predictor that can change the clinical outcome of intracerebral hemorrhage (ICH) patients. The study aimed to investigate the potential of satellite sign for prediction of HE in spontaneous ICH patients who had follow-up non-contrast computed tomography (NCCT) within 7 days after the initial CT scan. Methods We retrospectively reviewed data and NCCT from 142 ICH patients who were treated at our hospital at Bangkok, Thailand. All included patients were treated conservatively, had baseline NCCT within 12 hours after symptom onset, and had follow-up NCCT within 168 hours after baseline NCCT. HE was initially estimated by two radiologists, and then by image analysis software. Association between satellite sign and HE was evaluated. Results HE occurred in 45 patients (31.7%). Patients with HE had significantly higher activated partial thromboplastin time ( p = 0.001) and baseline hematoma volume ( p = 0.001). The prevalence of satellite sign was 43.7%, and it was significantly independently associated with HE ( p = 0.021). The sensitivity, specificity, and accuracy of satellite sign for predicting HE was 57.8, 62.9, and 61.3%, respectively. From image analysis software, the cutoff of greater than 9% relative growth in hematoma volume on follow-up NCCT had the highest association with satellite sign ( p = 0.024), with a sensitivity of 55%, specificity of 64.6%, and accuracy of 60.5%. Conclusion Satellite sign, a new NCCT predictor, was found to be significantly associated with HE in Thai population. With different context of Thai population, HE was found in smaller baseline hematoma volume. Satellite sign was found more common in lobar hematoma. Further studies to validate satellite sign for predicting HE and to identify an optimal cutoff in Thai population that is correlated with clinical outcomes are warranted.

Predictive value of hyperglycemia on prognosis in spontaneous intracerebral hemorrhage patients

BackgroundSpontaneous intracerebral hemorrhage (ICH) is the second most common cause of stroke and accounts for approximately 15–20% of all new stroke cases. Hematoma expansion is a potentially important therapeutic target that is amenable to treatment and independently predict outcome. Hyperglycemia is frequent in ICH patients, and affects cerebrovascular function, increasing the risk of cerebral vascular rupture. We recruited 170 ICH patients to explore the high risk factors of mortality and the association between hyperglycemia and early hematoma expansion. MethodsA retrospective analysis of 170 patients with ICH who were grouped by survival and blood glucose level, death group (35 cases) and survival group (135 cases); 77 cases in the hyperglycemic group and 93 cases in the normoglycemic group. Recorded parameters, such as age, gender, past medical history, blood glucose, serum calcium, hematoma volume, and hematoma expansion. Group comparison used t-test, rank sum test and Fisher exact test. After these, logistic regression analysis and receiver operating characteristic (ROC) curves were performed. ResultsAmong 170 ICH subjects(130 males and 40 females)，35 died and 77 exhibited hyperglycaemia. Compared with the survival group, the death group presented with higher Original Intracerebral Hemorrhage Scale (OICH) score, greater blood glucose, larger hemorrhage volume and lower Glasgow Coma Scale (GCS) score. The occurrence of hematoma expansion and massive hemorrhage volume in the hyperglycemic group were higher than in the normoglycemic group(P < 0.05). After adjustment for confounders variables, multivariate logistic analysis showed that blood glucose was an independent predictor of hematoma expansion (adjusted odd ratio:8.04, 95%CI:3.89–16.63, P < 0.01). Fasting blood glucose had better predictive value for hematoma expansion (AUC:0.95, 95%CI:0.92–0.99, P < 0.01). ConclusionHyperglycemia is associated with higher mortality risk and could be a potential marker in the prediction of hematoma expansion.

Inflammatory score predicts early hematoma expansion and poor outcomes in patients with intracerebral hemorrhage

This study aimed to develop a prediction score named inflammatory score based on proper integration of several inflammatory markers and investigate whether it was associated with hematoma expansion and poor outcomes in patients with intracerebral hemorrhage (ICH). This study involved a consecutive series of spontaneous ICH patients of two cohorts admitted within 24 hours after symptom onset. Inflammatory score (0-9) was developed with the combination of neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, systemic immune-inflammation index, lactate dehydrogenase, and C-reactive protein. The authors investigated the association between inflammatory score and hematoma expansion and poor outcomes by using univariate and multivariate logistic regression analyses. The optimal cutoff point of inflammatory score was determined by receiver operating characteristic analysis in the development cohort and then validated. A total of 301 and 154 ICH patients were enrolled in the development and validation cohorts. Inflammatory score was significantly higher in patients with hematoma expansion and poor outcomes. The multivariate logistic regression analysis revealed inflammatory score was independently associated with hematoma expansion, secondary neurological deterioration within 48 hours, 30-day mortality, and 3-month poor modified Rankin scale (4-6). The diagnostic accuracy of inflammatory score exhibited by area under the curve showed numerically or statistically higher than most of the individual indicators. Moreover, inflammatory score greater than or equal to 5 was selected as the optimal cutoff point, which was further prospectively validated with high diagnostic accuracy. The inflammatory score is a reliable predictor for early hematoma expansion and short-term and long-term poor outcomes with good diagnostic accuracies in ICH patients.

Abstract Number ‐ 252: High Mortality in Patients with Spontaneous Intracerebral Hemorrhage Experiencing Neurological Decline on Mobile Stroke Unit

Introduction Spontaneous intracranial hemorrhage (ICH) is associated with significant morbidity and mortality. Mobile Stroke Unit (MSU) provides a unique opportunity to assess patients in the hyperacute phase of ICH to track outcomes. Methods Methods: We conducted a retrospective review of patients with spontaneous ICH diagnosed on two different MSUs in the United States. Patients were divided into three groups based on symptom onset/last known well (LKW): Group 1: 0–1 hours from LKW, Group 2: 1–2 hours from LKW, and Group 3: 2–4 hours from LKW. We compared neurological decline (ND) rates between MSU and Emergency Department (ED) arrival for patients in the three groups. Neurological decline was defined as a decrease in GCS by ≥ 2 points or an increase in NIHSS ≥ 4 points between MSU and ED examination. χ2 test was used to compare the proportion of patients who experience ND between MSU and ED transport. We also assessed and compared pre‐defined factors that could be associated with ND in the three groups. CT scans done on MSU were compared to those done on ED arrival. Results Results: Fifty‐fourpatients met the study criteria. The mean age was 62, and 69% were male. Median MSU NIHSS was 18, and median ED NIHSS was 19. The mean MSU GCS was 14, and ED GCS was 12. The mean hematoma volume on the MSU CT head was 21 cc and 24 cc on the ED CT head. Mean MSU MAP was 136, and MAP on ED arrival was 120. Thirty‐three percent (18/54) of patients experienced ND between MSU and ED transport. Forty percent (n = 10/25) patients in group 1, 22% (n = 4/18) in group 2 and 36%(n = 4/11) in group 3 had ND (chi‐square 0.45). Overall, patients with ND experienced significantly high mortality (OR 5.091, p = 0.029, CI 1.24‐20.78). On univariate analysis, variables significantly associated with ND were MSU NIHSS, hematoma volume, and presence of hydrocephalus on MSU CT scan. No variables were significant to predict ND on multivariate analysis (Hematoma Expansion OR 1.028, CI 0.99‐1.05; Hydrocephalus OR 3.70 CI 0.67‐20.43) Conclusions Conclusion: One‐thirdof ICH patients experience neurological decline between MSU and ED transport within four hours of symptom onset and are at a significantly higher risk of mortality. Higher ND rates are likely due to earlier diagnosis of ICH on MSU. Due to the smaller sample size, we did not find significant variables associated with ND. However, various ways of providing rapid medical and surgical treatment to these patients should be explored in future studies to assess the effect on functional outcomes.

Abstract Number ‐ 230: Mobile Stroke Unit Experience With Anticoagulant Related Intracranial Hemorrhage

Introduction The advent of mobile stroke units (MSU) provide a golden opportunity to rapidly reverse anticoagulant related intracranial hemorrhage (AC‐ICH) in the pre‐hospital setting. The timely reversal of anticoagulants is crucial in halting hematoma expansion and achieving good clinical outcomes. It is known that AC‐ICH is associated with higher mortality rate and higher hematoma expansion than spontaneous ICH. Multiple studies showed that rapid reversal of AC‐ICH is associated with better outcomes and more stability of the hematoma size. Studies showed there is delay in initiation of therapy and revere the anticoagulants in ICH cases, [1,2}. Here, we report 3 cases of AC‐ICH diagnosed on the MSU with pre‐hospital use of reversal agents. To our knowledge, this is the first case series of Non vitamin K antagonist oral anticoagulants (NOACS) on the MSU. Methods We reviewed the MSU data from May 2016 to December 2020 and those with AC‐ICH were selected. Baseline demographics and clinical presentation were obtained including clinical outcome. Results A total of 3 patients were identified. Patient 1 is a96 year‐oldfemale with history of Atrial fibrillation (AF) that presented with AC‐ICH related to Apixaban and was treated with Prothrombin complex concentrate (PCC). The time of MSU examination to treatment (MSUe‐T) was 41 minutes.The patient was neurologically intact and discharged home after 4 days, no further images were indicated as the patient was stable and back to baseline. Patient 2 is a68 year‐oldmale with history of deep vein thrombosis that presented with AC‐ICH related to Warfarin and was treated with PCC. TheMSUe‐T was 64 minutes. Repeated CT head in the ED was stable. Neurological exam improved and the patient discharged to a skilled nursing facility. Patient 3 is a79 year oldmale with history of AF that presented with AC‐ICH related to Rivaroxaban and was treated with PCC. TheMSUe‐T was 50 minutes. Repeated CT head after 3 days was stable. According to FASTEST trial, the average time from onset to treatment of AC‐ICH was 90–120 min.In this trial, the growth of the ICH during the first hours was associated with increase mortality rate,{3} Conclusions Our data demonstrated that management of AC‐ICH on the MSU is feasible and provides an ample opportunity to reverse AC in the hyper‐early stage of ICH. MSU might have an important role in reducing the mortality for AC‐ICH patients. Larger comparative studies between Emergency department and MSU are needed.

Hematological indices as predictors of intracerebral hematoma expansion detected on serial computed tomography

ObjectiveHematoma expansion is associated with unfavourable neurological outcomes in intracranial haemorrhage. We aimed to study association of red blood cell (RBC) indices, platelet indices, and their ratios with hematoma expansion, detected by serial computed tomography (CT). MethodsHospital-based observational study of 88 patients with intracerebral hematoma referred for serial CT head with patients grouped as having progression/ no change/ resolution of hematoma. Baseline hematological indices and ratios were analysed. Results40 patients (45.5 %) had resolution, 20 patients (22.7 %) had no change and 28 patients (31.8 %) had progression of hematoma. RBC distribution width (RDW) (p value 0.001) and Plateletcrit (p-value 0.009) showed statistically significant difference among the groups. RBC distribution width (RDW) to PC ratio (RPR)showed statistically significant increase (p < 0.001) in patients with progression.Receiver operating characteristic curve with RPR as test variable in predicting progression of hematoma showed cut-off value as 0.0615 (64.3 % sensitivity, 63.3 % specificity). Patients with RPR > 0.0615 had greater chances of hematoma progression {OR 3.1 (95 % CI 1.22 to 7.91); p = 0.0174} ConclusionRaised RPR was most significant parameter with higher RDW, lower plateletcrit values in patients with progression of intra-parenchymal hematoma. These readily available indices can aid in prompt prognostication of intracerebral haemorrhage cases.

Intracranial and Blood Pressure Variability and In-Hospital Outcomes in Intracranial Device-Monitored Patients with Spontaneous Intracerebral Hemorrhage.

Spontaneous intracerebral hemorrhage (sICH) is a major health concern and has high mortality rates up to 52%. Despite a decrease in its incidence, fatality rates remain unchanged; understanding and preventing of factors associated with mortality and treatments for theseare needed. Blood pressure variability (BPV) has been shown to be a potential modifiable factor associated with clinical outcomes in patients with traumatic intracerebral hemorrhage and sICH. Few data are available on the effect of intracranial pressure (ICP) variability (ICPV) and outcomes in patients with sICH. The goal of our study was to investigate the association between ICPV and BPV during the first 24h of intensive care unit (ICU) admission and external ventricular drain (EVD) placement, and mortality in patients with sICH who were monitored with an EVD. We conducted a single-center retrospective study of adult patients admitted to an ICU with a diagnosis of sICH who required EVD placement during hospitalization. We excluded patients with ICH secondary to other pathological conditions such as trauma, underlying malignancy, or arteriovenous malformation. Blood pressure and ICP measurements were collected and recorded hourly during the first 24h of ICU admission and EVD placement, respectively. Measures of variability used were standard deviation (SD) and successive variation (SV). Primary outcome of interest was in-hospital mortality, and secondary outcomes were hematoma expansion and discharge home (a surrogate for good functional outcome at discharge). Descriptive statistics and multivariable logistic regressions were performed. We identified 179 patients with sICH who required EVD placement. Of these, 52 (29%) patients died, 121 (68%) patients had hematoma expansion, and 12 (7%) patients were discharged home. Patient's mean age (± SD) was 56 (± 14), and 87 (49%) were women. The mean opening ICP (± SD) was 21 (± 8) and median ICH score (interquartile range) was 2 (2-3). Multivariable logistic regression found an association between ICP-SV and ICP-SD and hematoma expansion (odds ratio 1.6 [1.03-2.30], p = 0.035 and odds ratio 0.77 [0.63-0.93] p = 0.009, respectively). Our study found an association between ICPV and hematoma expansion in patients with sICH monitored with an EVD. Measures of ICPV relating to rapid changes in ICP (ICP-SV) were associated with a higher odds of hematoma expansion, whereas measures relating to tight control of ICP (ICP-SD) were associated with a lower odds of hematoma expansion. One measure of BPV, sytolic blood pressure maximum-minimum (SBPmax-min), was found to be weakly associated with discharge home (a surrogate for good functional outcome at hospital discharge). More research is needed to support these findings.

Hypodensities within hematoma predict outcome after spontaneous intracerebral hemorrhage

Background and objective:&#x0D; Not much is known about the prevalence and significance of hypodensities within hematoma after spontaneous intracerebral hemorrhage (ICH). The objective of this study was to determine the prevalence of hypodensities within hematoma after spontaneous ICH and their significance to predict poor outcome after ICH.&#x0D; Methods:&#x0D; This observational cross sectional study was conducted in the Department of Neurology, Pakistan Institute of Medical Sciences, Islamabad, from October 2021 to June 2022. Total 140 patients of acute stroke were included. Inclusion criteria was any patient of &gt;20 years of age with confirmed diagnosis of ICH on imaging, non-traumatic, who presented within 24 hours after onset of symptoms. Data was analyzed by SPSS ver.23.0.&#x0D; Results: &#x0D; Total 150 patients were included in the study. The mean age of patients was 52.28 ± 1.29 years. There were 100 (71.4%) males and 40 (28.6%) females. Hypertension was the most common comorbid present in 87 patients (62.1%).55% of patients had on presentation National Institute of Health Stroke Scale (NIHSS) and modified Rankin Scale score of moderate severity. The mean ICH score on presentation was 2.64 +1.26. Hematoma expansion was present in 55(39.3%) patients while interventricular extension was seen in 100(71.4%) patients. Hypodensities were seen in 125(89.3%) patients( p value 0.001). When hematoma volume were compared in both groups it was also significant (p value 0.002).&#x0D; Conclusion: &#x0D; We conclude that hypodensities within hematoma are a reliable marker of hematoma expansion after spontaneous ICH. Such reliable marker can be easily employed in resource-poor countries where CT angiography is not available everywhere. The higher NIHSS score and low GCS are significantly associated with hypodensities within hematoma.

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

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

Abstract TP127: Application Of Machine Learning Algorithms For Prediction Of Hematoma Expansion In Spontaneous Intracerebral Hemorrhage

Introduction: Hematoma expansion (HE) is a known prognostic indicator of spontaneous intracerebral hemorrhage (sICH). Although several scores exist for prediction of HE, universal adoption has been limited due to their lack of sensitivity and specificity. As machine learning (ML) algorithms have shown promise in the stroke field, here we examine the predictive accuracy of several ML algorithms for HE in sICH patients. Methods: We retrospectively analyzed demographic, clinical data, and radiographic signs of patients with sICH in our 2-hospital database. A total of 61 clinical, imaging, and treatment variables were included in the study. Nine ML models were applied: Adaptive Boost (AdaBoost), Bernoulli Naïve Bayes (BNB), Decision Tree (DT), Gaussian Naïve Bayes (GNB), Logistic Regression (LR), Multi-Layer Perceptron (MLP), Multinomial Naïve Bayes models (MNB), Random Forest (RF), and Extreme Gradient Boosting (XGBoost). All models were trained to predict HE. Model accuracy was assessed using the area under characteristic curve (AUC). Results: Of the 301 patients with sICH, 63 developed HE (21.93%). Of the 9 models studied, MLP had the highest AUC score (0.93±0.042), followed by XGBoost (0.80±0.06). All models demonstrated moderate to high predictive accuracy (AUC 0.64-0.93) for HE. The top predictors in MLP were Baseline NIHSS score, HDL, aPPT, time from last known well to ER, initial hematoma volume, and island sign. MLP had moderate sensitivity of 0.46±0.17 and high specificity of 0.99±0.02. GNB, however, showed the highest sensitivity at 0.86±0.06 and a moderate specificity of 0.65±0.07. Five of the 9 models ranked time last known well to ER presentation as a predictor of HE. Conclusion: In our study, we found all ML models applied had moderate to high predictive accuracy for prediction of HE in sICH, with MLP having the highest accuracy of all models. Future studies examining the use of these algorithms are warranted.

Abstract TP120: Noncontrast Ct, Single-phase Cta, And Multiphase Cta Intracerebral Hemorrhage Expansion Scores

Background: Several noncontrast computed tomography (NCCT), single-phase computed tomography angiography (CTA), and multiphase CTA markers of intracerebral hemorrhage (ICH) expansion have been previously proposed. We derived and validated three scores for the prediction of hematoma expansion depending on the use of NCCT, single-phase CTA, or multiphase CTA markers of hematoma expansion. Methods: We prospective studied 276 consecutive patients with ICH within 6 hours from symptom onset. After deriving NCCT, single-phase CTA, and multiphase CTA scores in a 5-year period population (n=156), we validated them in a different 3-year period population (n=120). Outcome parameters included substantial hematoma expansion &gt;6 mL or &gt;33% at 24 hours (primary outcome) and poor outcome (mRS score &gt;2) at 90 days. Results: The most accurate marker of hematoma expansion was spot sign in phase 1 of multiphase CTA (80.3%). The four independent predictors of substantial hematoma expansion included in the different scores were ultraearly hematoma growth (uHG) &gt;5 mL/h, heterogeneous density, spot sign in phase 1 of multiphase CTA, and spot sign in any phase of multiphase CTA (Table). On each of the three scores, the proportion of patients that experienced substantial hematoma expansion increased with each point increase. C-index for both substantial hematoma expansion and poor outcome in the derivation and validation cohort was lower in NCCT expansion score than in single-phase CTA expansion score which, in turn, was lower than in multiphase CTA expansion score (Table). Conclusions: This study demonstrates the added prognostic value of more advanced CT modalities in acute ICH evaluation. Single-phase CTA score and, especially, multiphase CTA score, are more robust than NCCT score in the prediction of hematoma expansion and poor outcome. These scores may help to refine the selection of patients at risk of expansion and poorest outcomes in different decision-making scenarios.

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 WP126: Predictors Of Intracranial Hemorrhage Volume Expansion In Patients Receiving Factor Xa Inhibitors In The Annexa-4 Trial

Introduction: Andexanet, a specific reversal agent for FXa inhibitors, showed an effective hemostasis in 82% of patients with major bleeding in the ANNEXA-4 trial. However, little is known about the predictors associated with hematoma expansion in patients with FXa inhibitor-associated intracranial hemorrhage (ICrH) receiving andexanet. Methods: ANNEXA-4 was a prospective, single-arm, open-label study of andexanet in patients with acute major bleeding within 18h after taking a FXa inhibitor. Hematoma volumes at baseline and 12h after andexanet treatment were measured utilizing a computerized-assisted volumetric method. Univariate and multivariate logistic regression analyses of baseline clinical and non-clinical parameters were performed to identify factors predictive of different volumes of hematoma expansion. Results: A total of 305 patients with both baseline and follow-up imaging were included (mean age 80 years; 60.2% with intracerebral hemorrhage; 55.4% taking apixaban; 32.5% taking rivaroxaban). Overall median baseline hematoma volume was 10.4 mls (IQR 2.7-28.1) and time from symptom onset to baseline CT was 3.3h (1.5-6.8). Mean baseline anti-FXa activity levels were 148 ng/mL (SD 107.5). In follow up scans, 48 cases (15.7%) showed evidence of ICrH expansion ≥6 mls. Utilizing a four category ICrH Expansion Scale as the dependent variable, ordinal logistic regression identified Glasgow Coma Scale (GCS) score (OR 0.79; 95% CI 0.64-0.97), baseline ICrH volume (OR 1.02; 95% CI 1.01-1.04) and time from symptom onset to CT (OR 0.73 (0.53-0.99) as significant predictors of ICrH expansion. Baseline anti-FXA activity (OR 1.54; 95% CI 0.95-2.51; p value 0.08) and multiple compartment ICrH (OR 2.32; 95% CI 0.98-5.51; p value 0.06) showed trend as predictors of ICrH expansion. ICrH expansion dichotomized by ≥6 mls or &lt;6 mls as dependent variable, identified similar predictors of ICrH expansion. Conclusions: Shorter time from onset of symptoms to CT, lower GCS score and larger hematoma volumes at presentation increased the probability of ICrH expansion in FXa-associated ICrH treated with andexanet. These findings can inform the eligibility criteria of clinical trials targeting hemostatic efficacy in patients with FXa-associated ICrH.

Abstract TP130: Effect Of Antifibrinolytic Medication On Hematoma Expansion In Acute Ischemic Stroke Patients With Post Thrombolytic Intracerebral Hemorrhages

Background and Purpose: Antifibrinolytic medications such as the synthetic lysine analogs tranexamic acid and ε-aminocaproic acid inhibit fibrinolysis by attaching to the lysine-binding site of the plasminogen molecule. However, the efficacy of intravenous (IV) antifibrinolytic medication in the prevention of hematoma expansion in acute ischemic stroke patients who develop post thrombolytic intracerebral hemorrhage (ICH) is unclear. Methods: We analyzed the effect of antifibrinolytic medication in acute ischemic stroke patients with post thrombolytic ICH on hematoma expansion over an 8-year period. The Region-of-Interest; method on a Horos Medical Image Viewer (Version 3.3.6) was utilized for hematoma volume measurement on serial computed tomographic scans. We compared changes in hemorrhage volume in patients who did and did not receive IV antifibrinolytic medication. Results: A total of 53 patients (mean age 69.7±14.3, 53% were men) with post thrombolytic ICH were analyzed. Twenty-six patients received antifibrinolytic treatment: 20 and 6 patients received a single IV dose of ε-aminocaproic acid (5 g) or tranexamic acid (1 g), respectively. Ten patients (38%) had a reduction or stabilization in hematoma volume (overall pre and post-treatment volumes were 17.43±16.23 cm3 and 25.14±26.57 cm3 respectively). Mean fibrinogen level in the antifibrinolytic medication group was 277 mg/dL; 3 patients had levels &lt;200 mg/dL. In patients that did not receive antifibrinolytics, 16 (59%) out of 27 patients had a reduction or stabilization in hematoma volume (overall pre and post-treatment volumes were 19.74±32.32 cm3 and 27.15±52.58 cm3 respectively). The mean percent change in hematoma volume with antifibrinolytic medication treatment was 48% and without was 27%. [Figure 1] Conclusion: We did not identify any reduction in any of the measures of hematoma expansion with antifibrinolytic treatment in acute ischemic stroke patients with post thrombolytic ICH.

Abstract TP129: Increased Levels Of Matrix Metalloproteinases-induced BBB Dysfunction May Be Responsible For Increased Post-sich Hematoma Growth In Nicotine-exposed Rats.

Spontaneous intracerebral hemorrhage (sICH) is the deadliest type of stroke, accounting for as high as 28% of all strokes. Tobacco use is one of the major risk factors of sICH, and it also worsens outcomes following sICH. In our earlier study, we observed that nicotine exposure increases TNFα levels in brain vessels, impairs BBB integrity, and increases post-sICH hematoma volume in a TNFα-dependent manner compared to saline-exposed controls. Earlier studies have demonstrated interactions between MMPs and TNFα. Increased levels of matrix metalloproteinases (MMPs) have been found in sICH patients and nicotine-exposed individuals. MMPs are involved in BBB breakdown, edema formation, hematoma expansion, and neuronal loss that follow hematoma development after sICH. In the present study, we tested the hypothesis that nicotine exposure-induced increase in TNFα is responsible for increased post-sICH hematoma volume in a MMP-dependent manner. To test our hypothesis, young male and female rats were exposed to chronic nicotine treatment for 2-3 weeks using osmotic pumps containing either saline or nicotine (4.5 mg/kg/day). Levels of MMPs (2, 3, 9, and 12) and GAPDH were evaluated in brain homogenates using Western blot. Nicotine-treated female rats showed a 37% (100±7 vs. 137±10, p&lt;0.05), 144% (100±18 vs. 244±16, p&lt;0.01), 29% (100±7 vs. 129±9, p&lt;0.05), 22% (100±6 vs. 122±6, p&lt;0.05), and 24% (100±6 vs. 124±7, p&lt;0.05) increase in levels of pro and cleaved forms of MMP-3, cleaved form of MMP-9, pro and cleaved forms of MMP-12, respectively, compared to saline-treated female rats. We are in the process of evaluating levels of MMPs in male samples. Considering the role of MMP-9 in BBB integrity, using both TNFα and MMP-9 inhibitors, we are also in the process of evaluating if TNFα increases post-sICH hematoma growth in nicotine-exposed rats via increased levels of MMP-9. The results so far imply that increased TNFα levels in nicotine-exposed rats may be responsible for increased post-sICH hematoma growth in a MMP-dependent manner. Support: James Esther King Biomedical Research Grant 9JK08 and PK is a recipient of the Lois Pope Neuroscience Summer Research Fellowship.

Abstract TMP80: Sex Is Associated With Location, Severity And Outcome Of Intracerebral Hemorrhage: A Combined Analysis Of Four Landmark Studies

Background and objective: Small, single-center studies point to biological and clinical differences in women and men who sustain a spontaneous, non-traumatic intracerebral hemorrhage (ICH). Leveraging data from four landmark studies of ICH, we investigated the impact of sex on risk factors, location, severity and outcome of ICH. Design: Individual patient data meta-analysis of four studies of ICH, including three randomized clinical trials and one multi-ethnic observational study. Setting: Academic medical centers in the United States. Patients: Patients with neuroimaging confirmed ICH. Measurements: We conducted an individual patient data meta-analysis of four landmark studies of ICH: ERICH, ATACH-II, FAST and MISTIE-III. We evaluated whether sex was associated with specific risk factor profiles, hemorrhage location (deep or lobar), neuroimaging severity (hematoma volume and expansion), and poor 90-day functional outcomes (defined as a modified Rankin scale 4 to 6). Main Results: A total of 4,812 ICH patients were evaluated (mean age 62, 60% males). Men with ICH were younger, more likely to be smokers and diabetics, and less likely to be on anticoagulants (all p&lt;0.05). In multivariable analyses, male sex was associated with non-lobar location (odds ratio [OR], 1.69; 95% CI, 1.42-2.01; p&lt;0.001), larger hemorrhages (beta, 0.21; 95% CI, 0.14-0.28; p&lt;0.001) and a higher risk of hematoma expansion (OR, 1.31; 95% CI, 1.10-1.56; p=0.003). Despite the larger hemorrhage volume and higher risk of expansion, male sex was associated with a 22% lower risk of poor outcomes (OR, 0.78; 95% CI, 0.67-0.91; p=0.001). Conclusions: Men with ICH are more likely to have vascular risk factors, have larger hemorrhage volumes, and have higher risk of hemorrhage expansion. They are also more likely to have a good outcome at 90 days compared to women.

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 TMP83: Optimal Timing For Resumption Of Anticoagulation After Intracranial Hemorrhage In Patients With Mechanical Heartvalves

Introduction: Anticoagulation in patients with acute intracranial hemorrhage (ICH) and mechanical heart valves (MHV) is often held to mitigate the risk of ICH expansion or recurrence; however there exists a competing risk of acute ischemic stroke (AIS). Optimal timing to resume anticoagulation after ICH remains uncertain. Methods: We retrospectively studied ICH patients with MHV at two academic hospitals from April, 2000-August, 2018. The primary outcome was a composite endpoint of symptomatic hematoma expansion or new ICH, AIS, and intracardiac thrombus up to 30 days post-ICH. The exposure was timing of re-initiation of anticoagulation classified as early if therapeutic anticoagulation was resumed up to 7 days after ICH; late if ≥7 and up to 30 days after ICH; and never if not resumed or resumed after 30-days post-ICH. Cox proportional hazard models were built adjusted for age, sex, and covariates significantly different in univariate analysis at a pre-specified p-value threshold of 0.05. Results: We identified 184 patients with ICH and MHV (65 anticoagulated early, 100 resumed late, 19 not resumed by day 30 post-ICH). We observed 12 AIS, 16 new ICH, and 6 intracardiac thromboses. The mean time from ICH to anticoagulation in the cohort was 12.7 days. Patients resumed early versus late were more likely to have atrial fibrillation (62% versus 42%), and less likely to be reversed (75% versus 94%), to undergo hematoma evacuation (23% versus 43%), have midline shift (27% versus 52.9%), and to have intracerebral involvement (26% versus 49%). There was no significant difference in the hazard of AIS, new or symptomatic ICH expansion, or the composite outcome among those resumed early versus late. Patients not resumed within 30 days post-ICH had a significantly higher risk of AIS compared to those resumed within 30 days (HR 15.9; 95% C.I.1.9-129.7, p=0.0098). Discussion: In this study of ICH patients with MHV, there was no difference in the 30-day thrombotic and hemorrhagic brain-related outcomes in patients anticoagulated within 7 days versus 7-30 days. Withholding anticoagulation within the first 30 days was associated with a significantly higher risk of AIS. Our findings provide a discrete time window to guide resumption of anticoagulation in MHV patients with ICH.

Use of Novel Automated Active Irrigation With Drainage Versus Passive Drainage Alone for Chronic Subdural Hematoma-A Propensity Score-Matched Comparative Study With Volumetric Analysis.

Passive drainage post-surgical evacuation of symptomatic chronic subdural hematoma (cSDH) is currently standard of care. High rates of infection, drain occlusion, and recurrence are associated complications. To explore the use of a novel double-lumen active automated irrigation and aspiration system, IRRAflow (IRRAS), for patients with cSDH and compared procedural and clinical outcomes against passive drainage alone with propensity score matching (PSM) and volumetric analysis. A prospectively maintained database was retrospectively searched for consecutive patients presenting with cSDH. One-to-one PSM of covariates (including baseline comorbidities and presentation hematoma volume) in active and passive irrigation groups was performed to adjust for treatment selection bias. Rates of hematoma clearance, catheter-related occlusion, and infection; number of revisions; and length of hospital stay were recorded. This study included 55 patients: active continuous irrigation-drainage-21 (21 post-PSM) and passive drainage-34 (21 post-PSM). For PSM groups, a significantly higher rate of hematoma clearance was obtained in the active irrigation-drainage group (0.5 ± 0.4 vs 0.4 ± 0.5 mL/day) and in the passive drainage group; odds ratio (OR) = 1.291 (CI: 1.062-1.570, P = .002) and a significantly lower rate of catheter-related infections (OR = 0.051; CI: 0.004-0.697, P = .039). A nonsignificantly lower hematoma expansion rate at discharge was noted in the active irrigation-drainage group (4.8% vs 23.8%; OR = 0.127; P = .186). No statistical difference in all-cause in-hospital mortality or discharge Glasgow Coma Scale score was observed between groups. Active and automated continuous irrigation plus drainage after cSDH surgical evacuation resulted in faster hematoma clearance and led to favorable clinical outcomes and low complication and revision rates compared with passive irrigation.