Baseline Hematoma Volume Research Articles

Early minimally invasive image-guided eNdoscopic evacuation of iNTracerebral hemorrhage: a phase II pilot trial.

Whether minimally invasive endoscopic surgery (ES) improves survival and functional outcome in people with spontaneous supratentorial intracerebral hemorrhage (SSICH) is unknown. This is a single-center pilot study performed between July 2021 to January 2023. Any supratentorial hematoma with a volume between 20 mL and 100 mL was endoscopically evacuated within 24 h after bleeding onset. Participants were followed-up for 6 months, assessing clinical and radiological outcomes. The primary feasibility outcome was satisfactory hematoma removal (<15 mL residual volume on the first postinterventional CT study) and the primary efficacy outcome was reaching a modified Rankin Scale 0-3 (mRS) at 6 months. Secondary outcomes were mortality and morbidity rates. Ten participants (median age 72.5 years [IQR 67-81], 70% male, median baseline hematoma volume 34.1 [IQR 25.5-58.0]) were included. Satisfactory hematoma evacuation was achieved in 70% (7/10) with a median evacuation percentage of 69.5% [IQR 45.3-93.9%]. The median duration of surgery was 91 min [IQR 73-111]. Favorable outcome at 6 months was observed in 60% of the participants and improved from within 24 h before the intervention to the last follow-up (6 months). Five participants (50%) experienced a total of six complications, two recurrent bleedings, three pneumonias and one epilepsy. Mortality rate was 30%, while one participant died from pneumonia, one from a recurrent bleeding, and one participant due to a glioblastoma. ES appears to be feasible, with satisfactory hematoma removal being achieved in the majority of participants. Based on the descriptive results of this pilot trial, a national multicenter RCT comparing ES to best medical treatment is currently ongoing. https://clinicaltrials.gov/, identifier NCT05681988.

A Five-Point Score Grading System for Predicting Early Hematoma Expansion in Patients with Spontaneous Intracerebral Hemorrhage

Background: Stroke is the second leading cause of mortality and morbidity worldwide, with spontaneous Intracranial Hemorrhage (ICH) accounting for 9%-27% of all strokes. The study evaluates clinical and NCCT markers to predict early Hematoma Expansion (HE) in patients with Intracranial Hemorrhage (ICH), focusing on directing management objectives. Methods: We prospectively evaluated 96 patients with spontaneous ICH who underwent a baseline NCCT within four hours of admission, followed by a follow-up scan within six hours or at the time of clinical deterioration, whichever was earlier. Hematoma volumes were determined using baseline and follow-up CT images and imaging characteristics that predicted HE were evaluated. A grading system score was created to predict HE. Results: Of the ninety-six patients studied, 29 displayed black hole signs, 31 had island signs and 22 had swirl signs on baseline NCCT. On follow-up scans, the total incidence of HE in ICH patients was 53 out of 96 (55.2%). The average baseline hematoma volume in HE patients was 44.1 ml, compared to 12.2 ml in non-hematoma expansion patients. Of the 53 patients with HE, 29 had black hole sign, 16 had swirl sign and 28 had island sign. A higher grading system score (P &lt; 0.001) was associated with a higher likelihood of HE.

Leakage sign based on contrast-enhanced CT is a predictive marker for hematoma expansion and poor prognosis in primary brainstem hemorrhage

BackgroundAlthough hematoma expansion is a poor prognostic factor in patients with intracerebral hemorrhage (ICH), its effect on primary brainstem hemorrhage (PBSH) remains unclear. Since we previously observed the “leakage sign” (LS) on computed tomography (CT) to be a significant predictor for hematoma expansion, we herein investigated the effect of LS in PBSH. MethodsBetween January 2013 and August 2023, 515 patients with ICH were admitted to our institute. Thirty-six patients with PBSHs met the inclusion criteria, who were then divided into LS-positive (LS+) and LS-negative (LS-) groups based on the presence of LS. We evaluated hematoma expansion and prognosis at discharge. ResultsPatients in the LS+ group had larger baseline hematoma volume and lower Glasgow Coma Scale scores on admission and significantly poor prognosis at discharge. Subgroup analysis revealed that LS was frequently observed within 100 min after the onset of symptoms in patients with a hematoma size of >10 mm3 on CT; additionally, patients in the LS+ group more frequently experienced hematoma expansion and had poor prognosis at discharge. ConclusionLS is a significant predictive marker for disease severity at admission, hematoma expansion, and poor prognosis at discharge.

Timing of Spot Sign Appearance, Spot Sign Volume, and Leakage Rate among Phases of Multiphase CTA Predict Intracerebral Hemorrhage Growth.

The presence of spot sign is associated with a high risk of hematoma growth. Our aim was to investigate the timing of the appearance, volume, and leakage rate of the spot sign for predicting hematoma growth in acute intracerebral hemorrhage using multiphase CTA. In this single-center retrospective study, multiphase CTA in 3 phases was performed in acute intracerebral hemorrhage (defined as intraparenchymal ± intraventricular hemorrhages). Phases of the spot sign first appearance, spot sign volumes (microliter), and leakage rates among phases (microliter/second) were measured. Associations between baseline clinical and imaging variables including spot sign volume parameters (volume and leakage rate divided by median) and hematoma growth (>6 mL) were investigated using regression models. Receiver operating characteristic analysis was used as appropriate. Two hundred seventeen patients (131 men; median age, 70 years) were included. The spot sign was detected in 21.7%, 30.0%, and 29.0% in the first, second, and third phases, respectively, with median volumes of 19.7, 31.4, and 34.8 μl in these phases. Hematoma growth was seen in 44 patients (20.3%). By means of modeling, the following variables, namely the spot sign appearing in the first phase, first phase spot sign volume, spot sign appearing in the second or third phase, and spot sign positive and negative leakage rates, were associated with hematoma growth. Among patients with a spot sign, the absolute leakage rate accounting for both positive and negative leakage rates was also associated with hematoma growth (per 1-μl/s increase; OR, 1.26; 95% CI, 1.04-1.52). Other hematoma growth predictors were stroke history, baseline NIHSS score, onset-to-imaging time, and baseline hematoma volume (all P values < .05). The timing of the appearance of the spot sign, volume, and leakage rate were all associated with hematoma growth. Development of automated software to generate these spot sign volumetric parameters would be an important next step to maximize the potential of temporal intracerebral hemorrhage imaging such as multiphase CTA for identifying those most at risk of hematoma growth.

The relationship between perihematomal edema and hematoma expansion in acute spontaneous intracerebral hemorrhage: an exploratory radiomics analysis study.

The relationship between early perihematomal edema (PHE) and hematoma expansion (HE) is unclear. We investigated this relationship in patients with acute spontaneous intracerebral hemorrhage (ICH), using radiomics. In this multicenter retrospective study, we analyzed 490 patients with spontaneous ICH who underwent non-contrast computed tomography within 6 h of symptom onset, with follow-up imaging at 24 h. We performed HE and PHE image segmentation, and feature extraction and selection to identify HE-associated optimal radiomics features. We calculated radiomics scores of hematoma (Radscores_HEA) and PHE (Radscores_PHE) and constructed a combined model (Radscore_HEA_PHE). Relationships of the PHE radiomics features or Radscores_PHE with clinical variables, hematoma imaging signs, Radscores_HEA, and HE were assessed by univariate, correlation, and multivariate analyses. We compared predictive performances in the training (n = 296) and validation (n = 194) cohorts. Shape_VoxelVolume and Shape_MinorAxisLength of PHE were identified as optimal radiomics features associated with HE. Radscore_PHE (odds ratio = 1.039, p = 0.032) was an independent HE risk factor after adjusting for the ICH onset time, Glasgow Coma Scale score, baseline hematoma volume, hematoma shape, hematoma density, midline shift, and Radscore_HEA. The areas under the receiver operating characteristic curve of Radscore_PHE in the training and validation cohorts were 0.808 and 0.739, respectively. After incorporating Radscore_PHE, the integrated discrimination improvements of Radscore_HEA_PHE in the training and validation cohorts were 0.009 (p = 0.086) and -0.011 (p < 0.001), respectively. Radscore_PHE, based on Shape_VoxelVolume and Shape_MinorAxisLength of PHE, independently predicts HE, while Radscore_PHE did not add significant incremental value to Radscore_HEA.

Influence of Time to Achieve Target Systolic Blood Pressure on Outcome After Intracerebral Hemorrhage: The Blood Pressure in Acute Stroke Collaboration.

To investigate whether an earlier time to achieving and maintaining systolic blood pressure (SBP) at 120 to 140 mm Hg is associated with favorable outcomes in a cohort of patients with acute intracerebral hemorrhage. We pooled individual patient data from randomized controlled trials registered in the Blood Pressure in Acute Stroke Collaboration. Time was defined as time form symptom onset plus the time (hour) to first achieve and subsequently maintain SBP at 120 to 140 mm Hg over 24 hours. The primary outcome was functional status measured by the modified Rankin Scale at 90 to 180 days. A generalized linear mixed models was used, with adjustment for covariables and trial as a random effect. A total of 5761 patients (mean age, 64.0 [SD, 13.0], 2120 [36.8%] females) were included in analyses. Earlier SBP control was associated with better functional outcomes (modified Rankin Scale score, 3-6; odds ratio, 0.98 [95% CI, 0.97-0.99]) and a significant lower risk of hematoma expansion (0.98, 0.96-1.00). This association was stronger in patients with bigger baseline hematoma volume (>10 mL) compared with those with baseline hematoma volume ≤10 mL (0.006 for interaction). Earlier SBP control was not associated with cardiac or renal adverse events. Our study confirms a clear time relation between early versus later SBP control (120-140 mm Hg) and outcomes in the one-third of patients with intracerebral hemorrhage who attained sustained SBP levels within this range. These data provide further support for the value of early recognition, rapid transport, and prompt initiation of treatment of patients with intracerebral hemorrhage.

Andexanet alfa versus non-specific treatments for intracerebral hemorrhage in patients taking factor Xa inhibitors - Individual patient data analysis of ANNEXA-4 and TICH-NOAC.

Data comparing the specific reversal agent andexanet alfa with non-specific treatments in patients with non-traumatic intracerebral hemorrhage (ICH) associated with factor-Xa inhibitor (FXaI) use are scarce. The study aimed to determine the association between the use of andexanet alfa compared with non-specific treatments with the rate of hematoma expansion and thromboembolic complications in patients with FXaI-associated ICH. We performed an individual patient data analysis combining two independent, prospective studies: ANNEXA-4 (180 patients receiving andexanet alfa, NCT02329327) and TICH-NOAC (63 patients receiving tranexamic acid or placebo ± prothrombin complex concentrate, NCT02866838). The primary efficacy outcome was hematoma expansion on follow-up imaging. The primary safety outcome was any thromboembolic complication (ischemic stroke, myocardial infarction, pulmonary embolism, or deep vein thrombosis) at 30 days. We used binary logistic regression models adjusted for baseline hematoma volume, age, calibrated anti-Xa activity, times from last intake of FXaI, and symptom onset to treatment, respectively. Among 243 participants included, the median age was 80 (IQR 75-84) years, baseline hematoma volume was 9.1 (IQR 3.4-21) mL and anti-Xa activity 118 (IQR 78-222) ng/mL. Times from last FXaI intake and symptom onset to treatment were 11 (IQR 7-16) and 4.7 (IQR 3.0-7.6) h, respectively. Overall, 50 patients (22%) experienced hematoma expansion (ANNEXA-4: n=24 (14%); TICH-NOAC: n=26 (41%)). After adjusting for pre-specified confounders (baseline hematoma volume, age, calibrated anti-Xa activity, times from last intake of FXaI, and symptom onset to treatment, respectively), treatment with andexanet alfa was independently associated with decreased odds for hematoma expansion (aOR 0.33, 95% CI 0.13-0.80, p = 0.015). Overall, 26 patients (11%) had any thromboembolic complication within 30 days (ANNEXA-4: n=20 (11%); TICH-NOAC: n=6 (10%)). There was no association between any thromboembolic complication and treatment with andexanet alfa (aOR 0.70, 95% CI 0.16-3.12, p = 0.641). The use of andexanet alfa compared to any other non-specific treatment strategy was associated with decreased odds for hematoma expansion, without increased odds for thromboembolic complications.

Prediction of Hematoma Expansion in Intracerebral Hemorrhage in 24 Hours by Machine Learning Algorithm

ObjectiveThe significance of non-contrast computer tomography (CT) image markers in predicting hematoma expansion (HE) following intracerebral hemorrhage (ICH) within different time intervals in the initial 24 hours after onset may be uncertain. Hence, our objective was to examine the predictive value of clinical factors and CT image markers for HE within the initial 24 hours using machine learning algorithms. MethodsFour machine learning algorithms, including extreme gradient boosting (XGBoost), support vector machine, random forest, and logistic regression, were employed to assess the predictive efficacy of HE within every 6-hour interval during the first 24 hours post-ICH. The area under the receiver operating characteristic curves was utilized to appraise predictive performance across various time periods within the initial 24 hours. ResultsA total of 604 patients were included, with 326 being male, and 112 experiencing HE. The findings from machine learning algorithms revealed that CT image markers, baseline hematoma volume, and other factors could accurately predict HE. Among these algorithms, XGBoost demonstrated the most robust predictive model results. XGBoost's accuracy at different time intervals was 0.89, 0.82, 0.87, and 0.94, accompanied by F1-scores of 0.89, 0.80, 0.87, and 0.93, respectively. The corresponding area under the curve was 0.96, affirming the precision of the predictive capability. ConclusionsCT imaging markers and clinical factors could effectively predict HE within the initial 24 hours across various time periods by machine learning algorithms. In the expansive landscape of big data and multimodal cerebral hemorrhage, machine learning held significant potential within the realm of neuroscience.

Early blood pressure lowering therapy is associated with good functional outcome in patients with intracerebral hemorrhage

BackgroundThe implementation of a care bundle might improve functional outcome for patients with intracerebral hemorrhage (ICH). However, the impact of anti-hypertensive treatment on ICH outcomes remains uncertain. Our objective is to examine whether early blood pressure (BP) lowering therapy within first 12 h is associated with good outcome in ICH patients.MethodsWe included acute ICH patients who had baseline computed tomography (CT) scans within 6 h after onset of symptoms between October 2013 and December 2021. Early BP reduction was defined as use of anti-hypertensive agents within 12 h after onset of symptom. The clinical characteristics were compared between patients who received early BP lowering therapy and those without. The associations between early BP lowering and good outcome and functional independence at 3 months were assessed by using multivariable logistic regression analyses.ResultsA total of 377 patients were finally included in this study for outcome analysis. Of those, 212 patients received early BP reduction within 12 h after ICH. A total of 251 (66.6%) patients had good outcome. After adjustment for age, admission systolic BP, admission GCS score, baseline hematoma volume, hematoma expansion, and presence of intraventricular hemorrhage, early BP lowering therapy was associated with functional independence (adjusted odd ratio:1.72, 95% confidence interval:1.03–2.87; P = 0.039) and good outcome (adjusted odd ratio: 2.02, 95% confidence interval:1.08–3.76; P = 0.027).ConclusionsIn ICH patients presenting within 6 h after symptom onset, early BP reduction within first 12 h is associated with good outcome and functional independence when compared to those who do not undergo such early intervention. Implementation of quality measures to ensure early BP reduction is crucial for management of ICH.

Prothrombin Complex Concentrate vs Conservative Management in ICH Associated With Direct Oral Anticoagulants.

Intracerebral hemorrhage (ICH) associated with direct oral anticoagulant (DOAC) use carries extremely high morbidity and mortality. The clinical effectiveness of hemostatic therapy is unclear. To compare the clinical and radiological outcomes of DOAC-associated ICH treated with prothrombin complex concentrate (PCC) vs conservative management. In this population-based, propensity score-weighted retrospective cohort study, patients who developed DOAC-associated ICH from January 1, 2016, to December 31, 2021, in Hong Kong were identified. The outcomes of patients who received 25 to 50 IU/kg PCC with those who received no hemostatic agents were compared. Data were analyzed from May 1, 2022, to June 30, 2023. The primary outcome was modified Rankin scale of 0 to 3 or returning to baseline functional status at 3 months. Secondary outcomes were mortality at 90 days, in-hospital mortality, and hematoma expansion. Weighted logistic regression was performed to evaluate the association of PCC with study outcomes. In unweighted logistic regression models, factors associated with good neurological outcome and hematoma expansion in DOAC-associated ICH were identified. A total of 232 patients with DOAC-associated ICH, with a mean (SD) age of 77.2 (9.3) years and 101 (44%) female patients, were included. Among these, 116 (50%) received conservative treatment and 102 (44%) received PCC. Overall, 74 patients (31%) patients had good neurological recovery and 92 (39%) died within 90 days. Median (IQR) baseline hematoma volume was 21.7 mL (3.6-66.1 mL). Compared with conservative management, PCC was not associated with improved neurological recovery (adjusted odds ratio [aOR], 0.62; 95% CI, 0.33-1.16; P = .14), mortality at 90 days (aOR, 1.03; 95% CI, 0.70-1.53; P = .88), in-hospital mortality (aOR, 1.11; 95% CI, 0.69-1.79; P = .66), or reduced hematoma expansion (aOR, 0.94; 95% CI, 0.38-2.31; P = .90). Higher baseline hematoma volume, lower Glasgow coma scale, and intraventricular hemorrhage were associated with lower odds of good neurological outcome but not hematoma expansion. In this cohort study, Chinese patients with DOAC-associated ICH had large baseline hematoma volumes and high rates of mortality and functional disability. PCC treatment was not associated with improved functional outcome, hematoma expansion, or mortality. Further studies on novel hemostatic agents as well as neurosurgical and adjunctive medical therapies are needed to identify the best management algorithm for DOAC-associated ICH.

Abstract WP174: A Reassessment of Cost Effectiveness and Clinical Effectiveness of Anticoagulation Reversal in Direct Oral Anticoagulant - Related Intracerebral Hemorrhage

Introduction: Anticoagulation use is associated with increased risk of hematoma expansion (HE) in patients with intracerebral hemorrhage (ICH). We sought to assess rates of HE in patients with ICH on direct oral anticoagulants (DOAC) and annual cost associated with anticoagulation reversal and occurrence of HE. Methods: We performed an observational cohort study on consecutive patients with ICH on DOAC admitted to a Comprehensive Stroke Center over 3 years, using data from an institutional ICH registry. We prospectively collected baseline demographic and clinical variables, neuroimaging data on baseline and follow-up hematoma volumes (HV) and HE and outcomes on discharge via modified Rankin scale (mRS). Hemostatic efficacy on hematoma size was adjudicated based on the Andexanet Alfa, a Novel Antidote to the Anticoagulation Effects of Factor Xa Inhibitors-4 (ANNEXA-4) trial, with a ≤20% increase in HV compared to baseline considered “excellent” and a ≤ 35% increase in HV compared to baseline considered “good.” Weighted hematoma expansion cost was estimated based on common odds ratio of mRS increase with HE and distributions of mRS with HE. Results: We identified 103 patients who met inclusion criteria: mean age 75.8 (± 11.4) years, 55.3% female. 92 patients (89.3%) received anticoagulation reversal with prothrombin complex concentrate (PCC), of which 19 (20.7%) had HE. A more severe coagulopathy (antiXa &gt; 0.5) was associated with increased risk of HE (p&lt;0.05). 74 patients (80.4%) achieved good or excellent hemostasis. Use of PCC was associated with a 19.6% hematoma expansion rate using the definition above, which translates into a $6700 increase in annual cost per every ICH patient attributed to HE. Conclusion: Cost effective and clinically effective treatments for anticoagulation reversal are needed to reduce the risk and cost associated with HE in anticoagulation-related ICH.

Value of Image Biomarkers Based on Dual-Energy Computed Tomography Angiography Material Separation Technique in Predicting Early Hematoma Expansion in Spontaneous Intracerebral Hemorrhage

ObjectiveThis study aims to investigate the connection between the leakage sign (LS) and hematoma expansion (HE) in cases of spontaneous intracerebral hemorrhage (ICH). The investigation employs dual-energy computed tomography angiography (DECTA). MethodsA prospective cohort study was conducted, in which clinical and DECTA imaging data were collected from ICH patients within 6 hours of onset between January 2021 and June 2023. Exposure factors included DE-LS and traditional imaging biomarkers. The occurrence of HE on CT rescanned within 24 hours was the observed outcome. Exposed and confounding factors were considered in both univariate and multivariate regression analyses based on the results. Logistic and adjusted Poisson regressions were employed, and odds ratios (OR) and relative risks (RR) were calculated with 95% confidence intervals (CI). ResultsThe study enrolled a total of 90 patients, of whom 32 cases manifested HE, while 58 cases did not exhibit HE. Univariate analysis revealed statistically significant differences in parameters such as admission SBP, CRP, GCS, baseline hematoma volume, and imaging biomarkers likeDE-SS, and DE-LS. The OR value of DE-LS was determined as 48.21, with an RR value of 7.51. Multivariate adjusted Poisson regression analysis demonstrated that DE-LS was a robust independent predictor(RR = 4.11, 95% CI: 1.49 - 11.35; P < 0.001). ConclusionsDECTA-based DE-LS stands out as an independent predictor of HE. The utilization of RR values over OR values is endorsed when assessing the risk of HE prediction.

Clinical Significance of Stiffness during Endoscopic Surgery for Intracerebral Hemorrhage: A Retrospective Study.

Studies regarding hematoma stiffness and removal difficulty are scarce. This study explored the association between hematoma stiffness and surgical results of endoscopic hematoma removal for intracerebral hemorrhage. It also aimed to clarify factors associated with hematoma stiffness. We classified intracerebral hematoma as either soft or firm stiffness by retrospectively evaluating operative videos by two neurosurgeons. The interobserver reliability of the classification was assessed by calculating the κ values. We investigated the relationship between hematoma stiffness and surgical results. Favorable hematoma removal (FHR) was defined as a residual hematoma volume of ≤15 mL or removal rate of ≥70%. Furthermore, we compared the background characteristics, imaging findings, and laboratory data between the two groups. Forty patients were included in this study. The mean baseline hematoma volume was 69.9 mL (range, 41.3-97.6 mL). FHR was accomplished in 35 cases (87.5%). Thirty-four patients (85%) were in the soft hematoma group (group S). Six patients (15%) were in the firm hematoma group (group F). Classification of hematoma stiffness demonstrated an excellent degree of interobserver agreement (κ score = 0.91). Patients in group S had a high FHR rate (p = 0.018) and short endoscopic procedure times (p = 0.00034). The island sign was present in group S (p = 0.030). Patients in group F had significantly high fibrinogen levels (p = 0.049) and low serum total calcium (p = 0.032), hemoglobin (p = 0.041), and hematocrit (p = 0.011) levels. Hematoma stiffness during endoscopic surgery for intracerebral hemorrhage correlates with surgical results, including the endoscopic procedure time and accomplishing rate of FHR.

Prediction of Basal Ganglia Hematoma Expansion Based on Radiomics and Clinical Characteristics: A Novel Multivariate Predictive Nomogram

Background. This study is aimed at formulating and authenticating a pioneering nomogram integrating noncontrast computed tomography (NCCT) mean CT densities (m-CTD) of hematoma, morphological indicators from NCCT hematoma, and clinical manifestations to foresee hematoma expansion (HE) in patients suffering from spontaneous basal ganglia hemorrhage (BGH). Methods. A predictive model was constructed by retrospectively evaluating the data from 406 patients. This model was externally validated using an independent dataset of 174 patients. Multivariate logistic regression analysis was deployed to discern independent prognostic indicators and to generate a nomogram for HE prediction. Model calibration was examined using 1000 bootstrap samples for internal validation. Results. Multivariate logistic regression disclosed that m-CTD (odds ratio (OR) 0.846, 95% confidence interval (CI) 0.782-0.909), baseline hematoma volume (BHV) (OR 1.055, 95% CI 1.017-1.095), NCCT blend sign (BS) (OR 3.320, 95% CI 1.704-6.534), NCCT black hole sign (BHS) (OR 2.468, 95% CI 1.293-4.729), systolic blood pressure (SBP) (OR 1.027, 95% CI 1.014-1.040), and homocysteine (Hcy) (OR 1.075, 95% CI 1.038-1.114) were independent predictors of HE. The area under the curve (AUC) for the training and validation datasets yielded 0.874 and 0.883, respectively. The calibration curve for the nomogram closely approximated the optimal diagonal. The decision curve analysis (DCA) indicated that the prediction model offers substantial net benefits. Conclusions. The innovative predictive nomogram, leveraging radiomics and clinical traits of hematoma, presents a potent and noninvasive tool for HE risk stratification. The method of quantifying mean hematoma density holds significant prognostic value in forecasting HE.

Tranexamic Acid for Intracerebral Hemorrhage in Patients on Non-Vitamin K Antagonist Oral Anticoagulants (TICH-NOAC): A Multicenter, Randomized, Placebo-Controlled, Phase 2 Trial.

Evidence-based hemostatic treatment for intracerebral hemorrhage (ICH) associated with non-vitamin K antagonist oral anticoagulants (NOACs) is lacking. Tranexamic acid (TXA) is an antifibrinolytic drug potentially limiting hematoma expansion. We aimed to assess the efficacy and safety of TXA in NOAC-ICH. We performed a double-blind, randomized, placebo-controlled trial at 6 Swiss stroke centers. Patients with NOAC-ICH within 12 hours of symptom onset and 48 hours of last NOAC intake were randomized (1:1) to receive either intravenous TXA (1 g over 10 minutes followed by 1 g over 8 hours) or matching placebo in addition to standard medical care via a centralized Web-based procedure with minimization on key prognostic factors. All participants and investigators were masked to treatment allocation. Primary outcome was hematoma expansion, defined as ≥33% relative or ≥6 mL absolute volume increase at 24 hours and analyzed using logistic regression adjusted for baseline hematoma volume on an intention-to-treat basis. Between December 12, 2016, and September 30, 2021, we randomized 63 patients (median age, 82 years [interquartile range, 76-86]; 40% women; median hematoma volume, 11.5 [4.8-27.4] mL) of the 109 intended sample size before premature trial discontinuation due to exhausted funding. The primary outcome did not differ between TXA (n=32) and placebo (n=31) arms (12 [38%] versus 14 [45%]; adjusted odds ratio, 0.63 [95% CI, 0.22-1.82]; P=0.40). There was a signal for interaction with onset-to-treatment time (Pinteraction=0.024), favoring TXA when administered within 6 hours of symptom onset. Between the TXA and placebo arms, the proportion of participants who died (15 [47%] versus 13 [42%]; adjusted odds ratio, 1.07 [0.37-3.04]; P=0.91) or had major thromboembolic complications within 90 days (4 [13%] versus 2 [6%]; odds ratio, 1.86 [0.37-9.50]; P=0.45) did not differ. All thromboembolic events occurred at least 2 weeks after study treatment, exclusively in participants not restarted on oral anticoagulation. In a smaller-than-intended NOAC-ICH patient sample, we found no evidence that TXA prevents hematoma expansion, but there were no major safety concerns. Larger trials on hemostatic treatments targeting an early treatment window are needed for NOAC-ICH. URL: https://clinicaltrials.gov; Unique identifier: NCT02866838.

Clinical characteristics and dynamic evaluation of hematoma morphology in patients with aspirin-related intracerebral hemorrhage.

With the increasing awareness of thrombotic disease prevention and treatment, as well as advancements in cardiac valve replacement and cardiovascular disease resection surgeries, patients undergoing these procedures require antithrombotic medications. This work aimed to explore the dynamic changes in hematoma morphology and volume in aspirin-related intracerebral hemorrhage (ARICH). 43 cases with ARICH were selected as the experimental group and 40 cases of non-antithrombotic drug-related cerebral hemorrhage (non-ATT-ICH) were enrolled in the control group. General information about the two study groups was collected, and the initial laboratory test indices upon admission for each patient were recorded. Hematoma volumes were recorded within 6 hours, 24±3 hours, 72 hours, and 7 days after the onset of the disease. Volume changes were observed, and the absorption rates of the hematoma at 1 day, 3 days, and 7 days after onset were calculated. In the baseline data, the baseline hematoma volume of the experimental group (19.37±3.21) was slightly higher than that of the control group (15.73±2.78), showing a statistically significant difference (p<0.05). In terms of hematoma morphology and location, the hematoma morphology irregularity of the experimental group compared with the control group was 67% vs. 40%. In terms of hematoma growth and expansion, patients with ARICH had a larger volume of hematoma growth within 1 to 3 days of onset. At 3 d and 7 d, the experimental group's absorption rate was higher than the control group, and the experimental group's hematoma absorption rate was faster than the control group. The experimental group's hematoma morphology was mostly irregular, as can be seen (67%). If the hematoma volume increased from 1 d to 3 d after the onset of the disease, the hematoma volume of the patients in the experimental group was larger. The hematoma absorption rate of the experimental group was faster than that of the control group from 72 h to 7 d. The morphology of ARICH hematoma was mainly irregular (67%). In ARICH patients, if the hematoma volume rose within 1-3 days of initiation, the hematoma volume increased even more. Compared with non-ATT-ICH, ARICH had a faster rate of hematoma absorption at 3-7 d.

Clinical characteristics of spontaneous intracranial basal ganglia hemorrhage and risk factors for hematoma expansion in the plateaus of China.

The clinical features of intracranial cerebral hemorrhage (ICH) and the risk factors for hematoma expansion (HE) have been extensively studied. However, few studies have been performed in patients who live on a plateau. The natural habituation and genetic adaptation have resulted in differences in disease characteristics. The purpose of this study was to investigate the differences and consistency of clinical and imaging characteristics of patients in the plateaus of China compared with the plains, and to analyze the risk factors for HE of intracranial hemorrhage in the plateau patients. From January 2020 to August 2022, we undertook a retrospective analysis of 479 patients with first-episode spontaneous intracranial basal ganglia hemorrhage in Tianjin and Xining City. The clinical and radiologic data during hospitalization were analyzed. Univariate and multivariate logistic regression analyzes were used to assess the risk factors for HE. HE occurred in 31 plateau (36.0%) and 53 plain (24.2%) ICH patients, and HE was more likely to occur in the plateau patients compared with the plain (p = 0.037). The NCCT images of plateau patients also showed heterogeneity of hematoma imaging signs, and the incidence of blend signs (23.3% vs. 11.0%, p = 0.043) and black hole signs (24.4% vs. 13.2%, p = 0.018) was significantly higher than in the plain. Baseline hematoma volume, black hole sign, island sign, blend sign, and PLT and HB level were associated with HE in the plateau. Baseline hematoma volume and the heterogeneity of hematoma imaging signs were independent predictors of HE in both the plain and plateau. Compared with the plain, ICH patients in the plateau were more prone to HE. The patients showed the same heterogeneous signs on the NCCT images as in the plain, and also had predictive value for HE.

A retrospective study about association of dynamic systemic immune-inflammation index (SII) with 180-day functional outcome after basal ganglia intracerebral hemorrhage

ObjectivesThis study aimed to determine whether SII on different days of admission is associated with severity and 180-day functional outcomes after basal ganglia ICH. MethodsIn this retrospective study, data on baseline CT imaging characteristics, mRS, hematoma volume, and laboratory variables were included. The SII and NLR, LMR, and PLR were calculated from laboratory data collected on admission day, day 1, and days 5–7. Both univariate and multivariable logistic regression analyses were used to assess the association between the SII and the outcome. The receiver operating characteristic (ROC) analysis and area under the curve (AUC) were also used to evaluate the ability of the SII to predict outcomes. ResultA total of 245 patients were enrolled in the study. On different days, the NLR, PLR, and SII were significantly lower in patients with favorable outcomes than in those with poor outcomes, and the volume of hemorrhage was positively correlated with the SII. These parameters were associated with outcomes in the univariate logistic regression. In the adjusted analyses, the SII and PLR were independent predictors of basal ganglia ICH outcomes. ROC analysis revealed that the SII showed a stronger ability to predict the 6-month outcomes of patients after basal ganglia ICH than the PLR on different days (AUC = 0.642, 0.804, 0.827 vs. 0.592, 0.725, 0.757; all P < 0.001). ConclusionThe SII independently and strongly predicts the outcome of basal ganglia ICH. A high SII was associated with poor 6-month outcomes in patients with basal ganglia ICH.

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.

Abstract TMP82: Changes In DTI Metrics In The Lateral Ventricle Of Patients With Intraventricular Hemorrhage (IVH)

Objective: To evaluate a non-invasive surrogate imaging marker for blood evacuation in patients with IVH. Clinical Relevance: Extension of intracerebral hemorrhage (ICH) to the ventricles increases the 48 hours mortality by 43%, requiring external ventricular drains (EVD) to mitigate hydrocephalus and monitor intracranial pressures. Blood increases CSF viscosity, altering the diffusion coefficient. We hypothesize change in lateral ventricle (LV) DTI metrics, fractional anisotropy (FA) and mean diffusivity (MD), can be used as a marker for blood removal after IVH. Methods: A sub-cohort of 20 patients in SHRINC trial with ICH and IVH were serially imaged at day 1 (T1=20), 14 (T1=20), 28 (T3=16), and 42 (T4=13) on a 3T MRI system. The serial T1w, segmented LV (JHU WM atlas) volumes, FA, and MD maps were registered. The FA and MD of ipsi and contralesional LV were recorded. Clinical assessment (NIHSS) was associated with the change in FA and MD of LV. A mixed model statistical analysis was performed. Results: We serially imaged 11M/9F with average age 55.4±8.7 years. The baseline hematoma volume and NIHSS were 22.1±18.5 cc and 16.1±8.7 respectively. The patients had basal ganglia (n=12) and thalamic (n=8) ICH extended into LV. The ipsilesional FA was significantly (T1=0.24, T4=0.15, p&lt;0.001) decreased (1.17% /day), and MD was significantly (T1 = 1.49*10 -3 mm 2 /sec, T4 = 2.37 *10 -3 mm 2 /sec, p&lt;0.001) increased (2.4 x 10 -5 mm 2 /sec/day). At T4, there was no relationship (p=0.919) between ipsilesional and contra-MD of LV (Fig-1). Patients with higher baseline NIHSS had a significant temporal decline in FA than those with lower NIHSS (p&lt;0.05). Temporally, ipsilesional MD was negatively associated with the baseline NIHSS (p=0.039). Conclusion: The data suggest that DTI metrics of FA and MD are associated with blood clearance from the ipsilesional ventricle.