Imaging markers of intracerebral hemorrhage expansion in patients with unclear symptom onset

Background: Hematoma expansion (HE) is common and associated with poor outcome in intracerebral hemorrhage (ICH) with unclear symptom onset (USO). Aims: We tested the association between non-contrast computed tomography (NCCT) markers and HE in this population. Methods: Retrospective analysis of patients with primary spontaneous ICH admitted at five centers in the United States and Italy. Baseline NCCT was analyzed for presence of the following markers: intrahematoma hypodensities, heterogeneous density, blend sign, and irregular shape. Variables associated with HE (hematoma growth > 6 mL and/or > 33% from baseline to follow-up imaging) were explored with multivariable logistic regression. Results: Of 2074 patients screened, we included 646 subjects (median age = 75, 53.9% males), of whom 178 (27.6%) had HE. Hypodensities (odds ratio (OR) = 2.67, 95% confidence interval (CI) = 1.79–3.98), heterogeneous density (OR = 2.16, 95% CI = 1.46–3.21), blend sign (OR = 2.28, 95% CI = 1.38–3.75) and irregular shape (OR = 1.82, 95% CI = 1.21–2.75) were independently associated with a higher risk of HE, after adjustment for confounders (ICH volume, anticoagulation, and time from last seen well (LSW) to NCCT). Hypodensities had the highest sensitivity for HE (0.69), whereas blend sign was the most specific marker (0.90). All NCCT markers were more frequent in early presenters (time from LSW to NCCT ⩽ 6 h, n = 189, 29.3%), and more sensitive in this population as well (hypodensities had 0.77 sensitivity). Conclusion: NCCT markers are associated with HE in ICH with USO. These findings require prospective replication and suggest that NCCT features may help the stratification of HE in future studies on USO patients.

Ultraearly Hematoma Growth in Acute Spontaneous Intracerebral Hemorrhage Predicts Early and Long-Term Poor Clinical Outcomes: A Prospective, Observational Cohort Study

Aims: Although prognostic importance of ultraearly hematoma growth (uHG) in acute, non-traumatic intracerebral hemorrhage (ICH) has been established for early outcomes, longer-term clinical outcomes are lacking. We aimed to determine the association of uHG with early and 1-year clinical outcomes after acute ICH in a larger and broader range of patients.Methods: We studied 589 patients with acute (<6 h) spontaneous ICH. uHG was defined as baseline ICH volume/onset-to-imaging time (OIT) (ml/h). Multivariable logistic regression analyses were performed to determine the association of uHG with in-hospital mortality, 90-day, and 1-year poor outcome [3 ≤ modified Rankin Scale (mRS)] after ICH.Results: The median speed of uHG was 4.8 ml/h. uHG > 9.3 ml/h was independently related to in-hospital mortality [odds ratio (OR) 2.81, 95% CI 1.52–5.23], 90-day poor outcome (OR 3.34, 95% CI 1.87–5.95), and 1-year poor outcome (OR 3.59, 95% CI 2.01–6.40) after ICH. The sensitivity of uHG > 9.3 ml/h in the prediction of in-hospital mortality, 90-day poor outcome, and 1-year poor outcome was 68.8, 48.0, and 51.1%, respectively.Conclusions: Ultraearly hematoma growth was a useful predictor of in-hospital mortality, 90-day, and 1-year poor outcome after acute ICH. The combination of both uHG and baseline ICH volume could allow better selection of patients with ICH at high risk of poorest clinical outcomes for future clinical trials to improve early- and long-term clinical outcomes.

Higher Cerebral Blood Flow Predicts Early Hematoma Expansion in Patients With Intracerebral Hemorrhage: A Clinical Study

The early hematoma expansion of intracerebral hemorrhage (ICH) indicates a poor prognosis. This paper studies the relationship between cerebral blood flow (CBF) around the hematoma and hematoma expansion (HE) in the acute stage of intracerebral hemorrhage. A total of 50 patients with supratentorial cerebral hemorrhage were enrolled in this study. They underwent baseline whole-brain CTP within 6 h after intracerebral hemorrhage, and non-contrast CT within 24 h. Absolute hematoma growth and relative hematoma growth were calculated, respectively. A relative growth of Hematoma volume >33% was considered to be hematoma expansion. The Ipsilateral peri-edema CBF and Ipsilateral edema CBF were calculated by CTP maps in patients with and without hematoma expansion, respectively. In this study the incidence of hematoma expansion in the early stage of supratentorial cerebral hemorrhage was 32%; The CBF of the hematoma expansion group was higher than that of the patients without hematoma expansion (23.5 ± 12.5 vs. 15.1 ± 7.4, P = 0.004). After adjusting for age, gender, Symptom onset to NCCT and Baseline hematoma volume, ipsilateral peri-edema CBF was still an independent risk factor for early HE (or = 1.095, 95% CI = 1.01–1.19, P = 0.024). Here, we concluded that higher cerebral blood flow predicts early hematoma expansion in patients with intracerebral hemorrhage.

Impact of Intraventricular Hemorrhage on Classification of Hematoma Expansion and Development of Radiomics Prediction Models

Background: To investigate the impact of intraventricular hemorrhage (IVH) on the classification of hematoma expansion (HE), and the development of radiomics models using features extracted from the baseline hematoma to predict HE.Methods: Eighty-four patients with baseline and follow-up non-contrast CT within 4~24 hours were included. The intraparenchymal hemorrhage (IPH) and IVH were separately outlined by an experienced neuroradiologist. HE was defined as an absolute hematoma growth >6 mL or percentage growth >33%. HE was determined based on two criteria, using IPH alone (HEP) or IPH+IVH (HEP+V). The radiomics analysis was performed by using PyRadiomics to extract features, followed by random forest algorithm to select features, and lastly the decision tree to build classification models. Results: The classification of expansion showed 37 (44%) HEP and 47 (56%) non-HEP based on IPH alone, and similar results of 38 (45%) HEP+V and 46 (55%) non-HEP+V based on IPH+IVH. The majority, >94% of HE patients, had a poor outcome (death or mRS>3 at discharge). Three radiomics analysis (RA) models were built. The first model using baseline IPH to predict HEP (RAP-P) showed an accuracy of 80% but loss of correlation with the clinical outcome; the second model using IPH+IVH to predict HEP (RAPV-V) had a slightly higher accuracy of 81% and resumed the poor outcome association with HE; and the third model using IPH+IVH to predict HEP+V (RAPV-PV) had the highest accuracy of 86% with preserved clinical outcome correlation of HE. The sensitivity, specificity, and accuracy of three decision trees (RAP-P, RAPV-P, RAPV-PV) were 0.8/ 0.68/ 0.89; 0.81/ 0.92/ 0.72 and 0.86/ 0.82/ 0.89, respectively.Conclusions: The proposed radiomics approach with additional IVH information could be used to classify the expansion status highly associated with the clinical outcome and provide a robust tool for the enrollment of high-risk ICH cases in the anti-expansion trials.

Novel Predictive Markers on Computed Tomography for Predicting Early Epidural Hematoma Growth in Pediatric Patients

Objective Epidural hematoma (EDH), most often caused by rupture of the middle meningeal artery secondary to head trauma with fracture of the temporal bone, is a potentially fatal condition that can lead to elevated intracranial pressure, herniation, and death within hours following the inciting traumatic incident, unless surgical evacuation is accomplished. Several markers have been found to be associated with hematoma expansion in intracerebral hemorrhage (ICH) patients, including: the CT Blend Sign, Swirl Sign, and Black Hole Sign. This study aims to examine these markers, along with intradural air close to or in the region of an EDH and/or close to a significant fracture, fractures involving the skull base, and complicated (i.e., comminuted or displaced) fractures for possible associations to EDH growth in the pediatric population. Predicting hematoma growth is a crucial part of patient management, as surgery can be a life-saving intervention. Methods Scans from all pediatric patients with EDH from 2012 to 2019 across two separate health systems were examined and measurements were taken to determine whether these additional factors are of predictive value. Specifications such as length, transverse, and height measurements were taken from CT images. Statistical Analysis The average percent change in the hematoma measurements was used to determine which predictive factors were associated with a “noteworthy increase,” namely, an increase of greater than 25%. Additionally, the average percent change in hematoma size was evaluated for patients whose original imaging showed either all three CT signs or intradural air in all three specified locations. Results Most of the proposed markers were associated with EDH growth in this cohort. The established CT signs were also supported. This is notable, as most of the research on these signs has been in adult populations rather than pediatric. Conclusions Adding these novel imaging signs could aid in the decision to operate on versus observe PEDH patients, thereby preventing unnecessary procedures or preserving brain function quickly when surgery is indicated. This study serves as a starting point for several other investigations into the validity of the proposed markers as well as a reevaluation of the current signs in the pediatric population.

Clinical Strategies Against Early Hematoma Expansion Following Intracerebral Hemorrhage

Hematoma volume is the strongest predictor of morbidity and mortality after intracerebral hemorrhage. Protection against early hematoma growth is therefore the mainstay of therapeutic intervention for acute intracerebral hemorrhage, but the current armamentarium is restricted to early blood pressure lowering and emergent reversal for anticoagulant agents. Although intensive lowering of systolic blood pressure to <140 mmHg appears likely to prevent hematoma growth, two recent randomized trials, INTERACT-2 and ATACH-2, demonstrated non-significant trends of reduced hematoma enlargement by intensive blood pressure control, with only a small magnitude of benefit or no benefit for clinical outcomes. While oral anticoagulants can be immediately reversed by prothrombin complex concentrate, or the newly developed idarucizumab for direct thrombin inhibitor or andexanet for factor Xa inhibitors, the situation regarding reversal of antiplatelet agents is not yet quite as advanced. However, considering at most the approximately 10% rate of anticoagulant use among patients with intracerebral hemorrhage, what is most essential for patients with intracerebral hemorrhage in general is early hemostatic therapy. Tranexamic acid may safely reduce hematoma expansion, but its hemostatic effect was insufficient to be translated into improved functional outcomes in the TICH-2 randomized trial with 2,325 participants. In this context, recombinant activated factor VII (rFVIIa) is a candidate to be added to the armory against hematoma enlargement. The FAST, a phase 3 trial that compared doses of 80 and 20 μg/kg rFVIIa with placebo in 841 patients within 4 h after the stroke onset, showed a significant reduction in hematoma growth with rFVIIa treatment, but demonstrated no significant difference in the proportion of patients with severe disability or death. However, a post hoc analysis of the FAST trial suggested a benefit of rFVIIa in a target subgroup of younger patients without extensive bleeding at baseline when treated earlier after stroke onset. The FASTEST trial is now being prepared to determine this potential benefit of rFVIIa, reflecting the pressing need to develop therapeutic strategies against hematoma enlargement, a powerful but modifiable prognostic factor in patients with intracerebral hemorrhage.

Aspirin does not Affect the Hematoma Volume and Growth in Severe Spontaneous Intracranial Hematoma

Baseline hematoma volume (HV) and hematoma growth (HG) affect the prognosis of spontaneous intracranial hematoma (ICH), but there is still a lack of evidence on the effects of aspirin (acetylsalicylic acid, ASA) on HV and HG in patients with severe ICH. This study retrospectively analyzed patients with severe ICH who met the inclusion and exclusion criterias in Beijing Tiantan Hospital, Capital Medical University between January 1, 2015 and July 31, 2019. Severe ICH patients were divided into ASA group and nASA group according to ASA usage, and the effects of prior ASA on HV and HG were evaluated respectively. And possible risk factors for HG were screened. Totally, 221 patients with severe ICH were consecutively enrolled into this study. There were 72 (32.58%) patients in ASA group and 149 patients (67.42%) in nASA group. Although the baseline HV of the nASA group was significantly higher than that of the ASA group (45.51±29.76 VS 32.67±25.85, p=0.001), after adjusting for confounding factors, the prior ASA did not significantly affect the baseline HV (p = 0.057). Similarly, although the incidence of HG in nASA group was higher than that in ASA group (36.2% VS 25.0%, p = 0.095), ASA did not significantly affect the occurrence of HG (p =0.057). In addition, we found that admission high blood pressure and GCS were risk factors for HG. Prior ASA does not increase the baseline HV and the incidence of HG in severe ICH patients. In addition, admission high blood pressure and GCS were risk factors for HG.