Intracerebral Hemorrhage Growth Research Articles

Hematoma Expansion Following Intracerebral Hemorrhage: Mechanisms Targeting the Coagulation Cascade and Platelet Activation.

Hematoma expansion (HE), defined as a greater than 33% increase in intracerebral hemorrhage (ICH) volume within the first 24 hours, results in significant neurological deficits, and enhancement of ICH-induced primary and secondary brain injury. An escalation in the use of oral anticoagulants has led to a surge in the incidences of oral anticoagulation-associated ICH (OAT-ICH), which has been associated with a greater risk for HE and worse functional outcomes following ICH. The oral anticoagulants in use include vitamin K antagonists, and direct thrombin and factor Xa inhibitors. Fibrinolytic agents are also frequently administered. These all act via differing mechanisms and thus have varying degrees of impact on HE and ICH outcome. Additionally, antiplatelet medications have also been increasingly prescribed, and result in increased bleeding risks and worse outcomes after ICH. Aspirin, thienopyridines, and GPIIb/IIIa receptor blockers are some of the most common agents in use clinically, and also have different effects on ICH and hemorrhage growth, based on their mechanisms of action. Recent studies have found that reduced platelet activity may be more effective in predicting ICH risk, hemorrhage expansion, and outcomes, than antiplatelet agents, and activating platelets may thus be a novel target for ICH therapy. This review explores how dysfunctions or alterations in the coagulation and platelet cascades can lead to, and/or exacerbate, hematoma expansion following intracerebral hemorrhage, and describe the mechanisms behind these effects and the drugs that induce them. We also discuss potential future therapy aimed at increasing platelet activity after ICH.

Intensive Blood Pressure Reduction and Spot Sign in Intracerebral Hemorrhage

The computed tomographic angiography (CTA) spot sign is associated with intracerebral hemorrhage (ICH) expansion and may mark those patients most likely to benefit from intensive blood pressure (BP) reduction. To investigate whether the spot sign is associated with ICH expansion across a wide range of centers and whether intensive BP reduction decreases hematoma expansion and improves outcome in patients with ICH and a spot sign. SCORE-IT (Spot Sign Score in Restricting ICH Growth) is a preplanned prospective observational study nested in the Antihypertensive Treatment of Acute Cerebral Hemorrhage II (ATACH-II) randomized clinical trial. Participants included consecutive patients with primary ICH who underwent a CTA within 8 hours from onset at 59 sites from May 15, 2011, through December 19, 2015. Data were analyzed for the present study from July 1 to August 31, 2016. Patients in ATACH-II were randomized to intensive (systolic BP target, <140 mm Hg) vs standard (systolic BP target, <180 mm Hg) BP reduction within 4.5 hours from onset. Expansion of ICH was defined as hematoma growth of greater than 33%, and an unfavorable outcome was defined as a 90-day modified Rankin Scale score of 4 or greater (range, 0-6). The association among BP reduction, ICH expansion, and outcome was investigated with multivariable logistic regression. A total of 133 patients (83 men [62.4%] and 50 women [37.6%]; mean [SD] age, 61.9 [13.1] years) were included. Of these, 53 (39.8%) had a spot sign, and 24 of 123 without missing data (19.5%) experienced ICH expansion. The spot sign was associated with expansion with sensitivity of 0.54 (95% CI, 0.34-0.74) and specificity of 0.63 (95% CI, 0.53-0.72). After adjustment for potential confounders, intensive BP treatment was not associated with a significant reduction of ICH expansion (relative risk, 0.83; 95% CI, 0.27-2.51; P = .74) or improved outcome (relative risk of 90-day modified Rankin Scale score ≥4, 1.24; 95% CI, 0.53-2.91; P = .62) in spot sign-positive patients. The predictive performance of the spot sign for ICH expansion was lower than in prior reports from single-center studies. No evidence suggested that patients with ICH and a spot sign specifically benefit from intensive BP reduction. clinicaltrials.gov Identifier: NCT01176565.

Abstract 350: Activation of Platelet CLEC-2 in Hematoma Expansion After Intracerebral Hemorrhage: Finding an Effective Dose

Intracerebral hemorrhage (ICH) is the least treatable and one of the most disabling stroke subtypes, with both the primary and secondary brain injuries mainly due to hematoma expansion (HE) within the first few hours, followed by an inflammatory and oxidative injury. Almost all ICH patients experience some degree of expansion, and ICH volume can be an independent determinant of mortality and functional outcome. Previous studies found that reduced platelet activity is associated with early ICH growth and worse functional outcomes. The platelet C-type lectin-like receptor 2 (CLEC-2) elicits robust platelet activation upon stimulation. Thus, we hypothesized that activation of CLEC-2 would result in activation and aggregation of platelets, reducing HE, and improving functional outcomes after ICH. We administered two CLEC-2 agonists (Fucoidan and the endogenous ligand Podoplanin) at varying doses after murine ICH and measured hemorrhage volume, brain water content, and behavior. We also collected blood from podoplanin-treated mice and conducted hematologic tests. We further tested Rhodocytin, a known CLEC-2 activator, for whole blood clotting times, platelet functions, and soluble fibrin in human blood samples. We found that treatment with Fucoidan did not reduce hemorrhage volume or brain water content and had no effect on neurological function, compared to vehicle. Further, Podoplanin treatment showed a tendency to reduce brain water content but did not affect hematoma volume or behavior. Our in vitro studies showed lower fibrinogen levels with podoplanin treatment, compared to sham and vehicle, but no effect on partial thromboplastin time, prothrombin time, or INR. At higher doses, Rhodocytin resulted in immediate clotting, while at lower doses, it significantly increased soluble fibrin, consistent with initiation of clotting seen in the higher doses. In conclusion, our findings indicate that activation of CLEC-2 at the doses tested does not reduce ICH volume or improve outcomes, but did affect hemostatic parameters. Thus, the agonists may produce favorable outcomes with a different dosing regimen. Further studies are needed to confirm the mechanism by which CLEC-2 is acting in ICH, effective doses, and the effect of altered bleeding parameters.

Tranexamic acid for acute intracerebral hemorrhage growth predicted by spot sign trial: Rationale and design.

Rationale Acute intracerebral hemorrhage inflicts a high-economic and -health burden. Computed tomography angiography spot sign is a predictor of hematoma expansion, is associated with poor clinical outcome and is an important stratifying variable for patients treated with haemostatic therapy. Aims We aim to compare the effect of treatment with tranexamic acid to placebo for the prevention of hemorrhage growth in patients with high-risk acute intracerebral hemorrhage with a positive spot sign. Design The tranexamic acid for acute intracerebral hemorrhage growth predicted by spot sign (TRAIGE) is a prospective, multicenter, placebo-controlled, double-blind, investigator-led, randomized clinical trial that will include an estimated 240 participants. Patients with intracerebral hemorrhage demonstrating symptom onset within 8 h and with the spot sign as a biomarker for ongoing hemorrhage, and no contraindications for antifibrinolytic therapy, will be enrolled to receive either tranexamic acid or placebo. The primary outcome measure is the presence of hemorrhage growth defined as an increase in intracerebral hemorrhage volume >33% or >6 ml from baseline to 24 ± 2 h. The secondary outcomes include safety and clinical outcomes. Conclusion The TRAIGE trial evaluates the efficacy of haemostatic therapy with tranexamic acid in the prevention of hemorrhage growth among high-risk patients with acute intracerebral hemorrhage.

Abstract 215: Does the CT Angiography Spot Sign Identify Intracerebral Hemorrhage Patients More Likely to Benefit From Intensive Blood Pressure Reduction?

Background and Purpose: the computed tomography angiography (CTA) spot sign is a strong predictor of intracerebral hemorrhage (ICH) expansion, and may mark those most likely to benefit from intensive blood pressure (BP) reduction. The Spot Sign score in restricting ICH growth (SCORE-IT) study analyzed whether intensive BP reduction improved outcome in Spot Sign positive patients enrolled in the Antihypertensive Treatment of Acute Cerebral Hemorrhage II (ATACH-2) clinical trial. Methods: In ATACH-2, patients with ICH were randomly assigned to intensive (systolic BP target: 110-139 mmHg) versus standard (systolic BP target: 140-179 mmHg) BP treatment within 4.5 h from stroke onset. This analysis included patients with a CTA performed within 8 hours from onset. The association between intensive BP lowering, ICH expansion and functional outcome was investigated with a multivariable logistic regression model. Results: 133 subjects met the inclusion criteria, of whom 53 (39.9%) had a spot sign and 24/123 (19.5%) experienced ICH expansion. A total of 56/123 patients had a 90 day modified Rankin scale (mRS) &gt;3 (45.5%). Among Spot positive patients, 74.1% of those in the intensive BP lowering group had poor outcome, compared with 50.0% of those in the standard group (p=0.31). After adjustment for potential confounders, intensive BP lowering was not associated with a significant reduction of ICH expansion (odds ratio [OR] 0.83, 95% confidence interval [CI] 0.27 - 2.51, p = 0.74) or improved functional outcome (OR for mRS&gt;3 1.24, 95% CI 0.53 - 2.91, p = 0.62) in spot sign positive ICH patients. Conclusions: We found no evidence that ICH patients with a spot sign specifically benefit from intensive BP reduction.

Abstract WP372: The Acute ICH Growth Score: Simple and Accurate Predictor of Hematoma Expansion in Patients with Acute Intracerebral Hemorrhage

Background and Purpose: Acute intracerebral hemorrhage (ICH) hematoma expansion predicts high mortality and morbidity, occurring in a third of patients presenting with this condition. Recent studies correlated ultra-early hematoma growth and hematoma morphologic appearance with ICH expansion. Our purpose was to develop simple and clinically useful score that would predict ICH hematoma expansion accurately. Methods: This cohort included patients with primary or anticoagulation-associated ICH patients presenting &lt;6 hours post ictus prospectively enrolled in the PREDICT study. Patients underwent baseline CT, CT angiography and 24-hour CT for hematoma expansion analysis. A risk score model was developed for predicting hematoma expansion (&gt; 6 ml or &gt; 33%). A 7-point acute ICH growth score was based on ultra-early hematoma growth &gt; 5 mL/hour (yes=1), irregular morphology (yes=1), density heterogeneity (yes=1), presence of fluid-blood levels (yes=1), spot sign (yes=1), and use of anticoagulation (yes=2). Discrimination of the expansion score was assessed. Results: We retrospectively studied 301 primary or anticoagulation-associated intracerebral hemorrhage patients. The 7-point acute ICH growth score demonstrated good discrimination for hematoma expansion&gt;6 mL or 33% (area under the curve of 0.76). Median and significant HE are shown in the table below (p&lt;0.001). Conclusions: In a multicenter prospective study, the ICH expansion score demonstrate good correlation with hematoma expansion, and included recently reported variables such as morphology and ultraearly growth.

Intracerebral haemorrhage growth is influenced by anticoagulation intensity

Intracerebral haemorrhage growth is influenced by anticoagulation intensity

Statistical analysis plan for the PlAtelet Transfusion in Cerebral Haemorrhage (PATCH) trial: a multicentre randomised controlled trial.

BackgroundUse of antiplatelet therapy shortly before stroke due to spontaneous primary intracerebral haemorrhage (ICH) is associated with higher case fatality in comparison to ICH without prior antithrombotic drug use. The PlAtelet Transfusion in Cerebral Haemorrhage (PATCH) trial aimed to assess the effect of platelet transfusion in patients presenting with ICH while using antiplatelet therapy. The main hypothesis of PATCH was that platelet transfusion would reduce death or dependence by reducing ICH growth.Methods/DesignPATCH was a multicentre prospective, randomised, open, blinded endpoint (PROBE) parallel group trial, conducted at 60 hospitals in The Netherlands, Scotland and France. Forty-one sites enrolled 190 patients with spontaneous supratentorial ICH aged ≥18 years, who had used antiplatelet therapy for ≥7 days preceding ICH, if Glasgow Coma Scale was ≥8. Participants were randomised (1:1, with a secure web-based system using permuted blocks, stratified by study centre and type of antiplatelet therapy pre-ICH) to receive either platelet transfusion within 6 hours of symptom onset and 90 minutes of diagnostic brain imaging, or standard care without platelet transfusion. The primary outcome was modified Rankin Scale (mRS) score assessed blind to treatment allocation at 3 months after ICH. Planned secondary outcomes included ICH growth on brain imaging performed approximately 24 hours after randomisation, survival at 3 months, disability at 3 months scored using the Amsterdam Medical Centre linear disability score, heterogeneity of treatment effect on mRS and ICH growth according to presence of the computed tomography angiography spot sign, causes of poor outcome, and cost-effectiveness. Safety outcomes were transfusion reactions, thromboembolic complications, and serious adverse events occurring during hospitalisation. This statistical analysis plan was written without knowledge of the unblinded data.Trial registrationThe trial was registered with the Netherlands Trial Register on 29 April 2008 (NTR1303).

Audit of CT reporting standards in cases of intracerebral haemorrhage at a comprehensive stroke centre in Australia.

Multiple CT-derived biomarkers that are predictive of intracerebral haemorrhage (ICH) growth and outcome have been described in the literature, but the extent to which these appear in imaging reports of ICH is unknown. The aim of this retrospective process audit was to determine which of the known predictors of ICH outcome was recorded in reports of the disease, with a view to providing reporting recommendations, as appropriate. We examined the initial CT report of patients diagnosed with ICH presenting to a metropolitan comprehensive stroke centre and meeting inclusion criteria during the audit period between 1 March 2013 and 28 February 2014. Each report was assessed for the inclusion of the following ICH characteristics: the number of measurement dimensions; volume; location; hydrocephalus; shape; density; 'CTA spot sign' (where CTA was performed). A total of 100 patients met audit inclusion criteria. At least one ICH dimension was recorded in 90% of reports; however, 39% did not include the measurements in three dimensions and volume was reported in just 6%. No ICH dimension was recorded in 10% of reports. With the exception of density and shape, reporting of other CT features exceeded 95%. Where CTA was performed (58%), 14 (24%) of 58 reported the 'CTA spot sign' status. In this audit, volume was the most under-reported of the established ICH characteristics predictive of ICH outcome. Readily calculated from multiplanar reformats using the ABC/2 technique, the routine reporting of ICH volume is recommended. More reporting attention to ICH density heterogeneity and shape irregularity is encouraged, given their emerging importance. Where acute CTA is performed, the presence of any dynamic haemorrhage (CTA spot sign) should be reported.

Prognostic Significance of Hyponatremia in Acute Intracerebral Hemorrhage: Pooled Analysis of the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial Studies.

To determine the association of hyponatremia at presentation with clinical and imaging outcomes in patients with acute intracerebral hemorrhage. Retrospective pooled analysis of prospectively collected data from 3,243 participants of the pilot and main phases of the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trials 1 and 2 (international, multicenter, open, blinded endpoint, randomized controlled trials designed to assess the effects of early intensive blood pressure lowering in patients with acute intracerebral hemorrhage). Clinical hospital sites in 21 countries. Patients with predominantly mild-moderate severity of spontaneous intracerebral hemorrhage within 6 hours of onset and elevated systolic blood pressure (150-220 mm Hg) were included in the study. Patients were assigned to receive intensive (target systolic blood pressure, < 140 mm Hg within 1 hr) or guideline-recommended (target systolic blood pressure, < 180 mm Hg) blood pressure-lowering therapy. Presentation hyponatremia was defined as serum sodium less than 135 mEq/L. The primary outcome was death at 90 days. Multivariable logistic regression was used to assess the association of hyponatremia with important clinical events. Of 3,002 patients with available data, 349 (12%) had hyponatremia. Hyponatremia was associated with death (18% vs 11%; multivariable-adjusted odds ratio, 1.81; 95% CI, 1.28-2.57; p < 0.001) and larger baseline intracerebral hemorrhage volume (multivariable adjusted, p = 0.046) but not with baseline perihematomal edema volume nor with growth of intracerebral hemorrhage or perihematomal edema during the initial 24 hours. Hyponatremia at presentation is associated with increased mortality in patients with predominantly deep and modest volume intracerebral hemorrhage through mechanisms that seem independent of growth in intracerebral hemorrhage or perihematomal edema.

Predicting Intracerebral Hemorrhage Growth With the Spot Sign: The Effect of Onset-to-Scan Time.

Hematoma expansion after acute intracerebral hemorrhage is common and is associated with early deterioration and poor clinical outcome. The computed tomographic angiography (CTA) spot sign is a promising predictor of expansion; however, frequency and predictive values are variable across studies, possibly because of differences in onset-to-CTA time. We performed a patient-level meta-analysis to define the relationship between onset-to-CTA time and frequency and predictive ability of the spot sign. We completed a systematic review for studies of CTA spot sign and hematoma expansion. We subsequently pooled patient-level data on the frequency and predictive values for significant hematoma expansion according to 5 predefined categorized onset-to-CTA times. We calculated spot-sign frequency both as raw and frequency-adjusted rates. Among 2051 studies identified, 12 met our inclusion criteria. Baseline hematoma volume, spot-sign status, and time-to-CTA were available for 1176 patients, and 1039 patients had follow-up computed tomographies for hematoma expansion analysis. The overall spot sign frequency was 26%, decreasing from 39% within 2 hours of onset to 13% beyond 8 hours (P<0.001). There was a significant decrease in hematoma expansion in spot-positive patients as onset-to-CTA time increased (P=0.004), with positive predictive values decreasing from 53% to 33%. The frequency of the CTA spot sign is inversely related to intracerebral hemorrhage onset-to-CTA time. Furthermore, the positive predictive value of the spot sign for significant hematoma expansion decreases as time-to-CTA increases. Our results offer more precise risk stratification for patients with acute intracerebral hemorrhage and will help refine clinical prediction rules for intracerebral hemorrhage expansion.

Abstract TP368: Prediction of Hemorrhagic Growth Using Textural Pattern Analysis

Introduction: The subjective characterization of non-contrast CT “swirl sign” along with hematoma volume have been used to predict intracerebral hemorrhage (ICH) growth. As early assessment of patients with acute stroke symptoms can be used to optimize treatment, a more robust, quantitative biomarker set could improve patient care. Hypothesis: Quantification of ICH lesion texture from CT scans taken at less than 3 hours from onset could be used to predict hemorrhagic growth at 24 hours. Methods: Baseline and 24-hour CT scans on 71 ICH stroke subjects were obtained from the Virtual International Stroke Trials Archive (VISTA). Semi-automated segmentation of ICH was used to determine lesion volume. Based on treatment effects seen with hemostatic agents, a 6mL absolute increase was initially selected for the growth threshold. First order statistics of CT pixel values within the lesions along with spatial parameters extracted from grey-level co-occurrence matrices (GLCM) were computed, as well as baseline lesion volume, location (deep/lobar), number of connected components, and information about intraventricular hemorrhage. Linear support vector machines were used for classification with 10-fold cross-validation. Results: By the 24-hour scan, 19 subjects showed ICH growth and 52 were stable. In predicting growth based on the initial CT scan, the coefficient of variation and GLCM contrast had the highest sensitivities for discrimination. A combination of textural features provided a classification accuracy of 68% (sensitivity 65%, specificity 68%). Results for classifying “any growth” were comparable. Conclusions: Patterns noted in standard-of-care CT are indicative of an increased risk of hematoma expansion. Imaging biomarkers based on texture analysis can be used to classify patients and may aid in understanding mechanisms of ICH enlargement and acute treatment selection.

Abstract WMP85: Significance of Cerebral Small Vessel Disease in Acute Intracerebral Hemorrhage: The INTERACT2 Study

Background: Uncertainty exists over the significance of structural changes arising from cerebral small vessel disease (CSVD), including white matter lesions (WML), lacunes and atrophy, for outcome after acute intracerebral hemorrhage (ICH). We determined associations of CT markers of CSVD and outcomes among participants of the INTERACT2 study. Methods: We graded WML (van Swieten scale), brain atrophy (two linear measurements, frontal ratio [FR] and third ventricle Sylvian fissure distance [TSD]) and the presence of lacunes for 2069/2839 patients with available baseline brain CT (&lt;6hr ICH onset) by three independent neurologists blind to clinical data. Results: WML and brain atrophy were independently associated with death or disability (modified Rankin Scale score 3-6) at 90 days: adjusted odds ratios for WML (grade 3 and 4 vs. 1), FR and TSD (most vs. least severe atrophy quartile) were 1.42 (95% confidence interval 1.02-0.98), 1.47 (1.08-1.99) and 1.64 (1.21-2.22), respectively (all P for trend &lt;0.05). There was no association between lacunes or any CSVD biomarkers and absolute ICH growth, and no significant differences in the effects of intensive BP lowering in each subgroup of CSVD. Conclusions: CSVD manifestations of WML and brain atrophy have prognostic value in acute ICH but they do not appear to influence ICH growth. Intensive BP lowering provided similar treatment effects irrespective of degree of CSVD.

Prognostic significance of delayed intraventricular haemorrhage in the INTERACT studies

Background and purposeIntraventricular extension of intracerebral haemorrhage (ICH) predicts poor outcome, but the significance of delayed intraventricular haemorrhage (dIVH) is less well defined. We determined the prognostic significance of dIVH...

The HEP Score: A Nomogram-Derived Hematoma Expansion Prediction Scale.

Identification of intracerebral hemorrhage (ICH) patients at risk of substantial hematoma expansion (SHE) could facilitate the selection of candidates likely to benefit from therapies aiming to minimize ICH growth. We aimed to develop a grading tool that can be quickly used during the hyperacute phase to predict the risk of SHE. We reviewed data from 237 spontaneous ICH patients who had baseline head CT scan within 12 h of symptom onset and follow-up CT during the following 72 h. We performed logistic regression analyses to determine the predictors of SHE (defined as an absolute increase in ICH volume >6 ml or an increase >33% on follow-up CT). We identified 6 predictors; each was assigned a point in the graphic interface of a nomogram which was used to construct a scoring system-The Hematoma Expansion Prediction (HEP) Score, varying from 0 to 18 points. We evaluated the ability of the model to predict the probability of SHE using c-statistics. SHE occurred in 74 patients (31.2%). The final model to predict SHE included 6 variables: time from onset to baseline CT (<3 vs. 3-12 h), history of dementia, current smoking, antiplatelet use, Glasgow Comma Scale score, and the presence of subarachnoid hemorrhage on baseline scan. The model had satisfactory discrimination ability with a bootstrap corrected c-index of 0.76 (95% CI 0.69-0.83) and good calibration. Patients with a total HEP score >3 were at greatest risk for SHE. We developed and internally validated a novel nomogram and an easy to use score which accurately predict the probability of SHE based on six easily obtainable parameters. This could be useful for treatment decision and stratification. External prospective validation of the HEP score is warranted before its application to other populations.

Abstract W P323: Development of a Nomogram to Predict Hematoma Expansion in Patients with Spontaneous Intracerebral Hemorrhage

Background: Early identification of intracerebral hemorrhage (ICH) patients at risk of significant hematoma expansion (SHE) could facilitate the selection of appropriate patients who are likely to benefit from therapies aiming to minimize ICH growth. Nomograms have been proved to have superior individualized disease-related risk estimations of given outcomes. This study aims to develop a normogram that can be performed during the hyperacute phase to predict the risk of SHE in patients with spontaneous ICH. Methods: We reviewed clinical, laboratory, and radiological data from 237 patients diagnosed with spontaneous ICH who had baseline head CT within 12 hours of symptom onset and follow-up CT during the following 72 hours. SHE was defined as an absolute increase in ICH volume &gt; 6ml or an increase greater than 33% from baseline to follow-up CT. To construct the nomogram, we performed logistic regression analyses to determine the predictors of SHE. Each predictor was assigned a point in the graphic interface of a nomogram, and the points were summed up to determine the predicted probability of SHE for a specific ICH patient. Results: SHE occurred in 74 patients (31.2%). The final model to predict SHE, presented as a nomogram, included: time from onset to baseline CT scan (&lt; 3h vs 3-12h), dementia, current smoking, antiplatelet use, serum creatinine level, Glasgow Comma Scale score, and presence of subarachnoid hemorrhage on baseline CT. The model had satisfactory discrimination ability with a bootstrap corrected c index of 0.77 (95% CI, 0.75-0.82) and good calibration. The in-hospital mortality was higher in patients with SHE (42% vs. 15%; p &lt;0.001). Conclusion: We developed and internally validated a novel nomogram model which accurately predicts the possibility of SHE based on seven easily obtainable parameters. This could be useful for treatment decision and stratification. External validation of our nomogram is warranted before its application to other populations.

The relationship of hematoma growth to rdw in patients with hypertensive intracerebral hemorrhage

Hypertension is a primary risk factor for intracerebral hemorrhage (ICH) and is thought to be responsible for about 55% of all ICH cases. Thus, the primary goal of the study was to examine whether the status of vascular rheological factors upon admission to the hospital was associated with hypertensive ICH growth and early outcomes. Over a 2-year period, the present study evaluated 60 ICH patients who were admitted within the first 12 hours of symptom onset. Brain computed tomography scans were performed at admission and then 24 hours later as a control. Hematoma growth was classified as an volume increase more than 6.5 ml or > 33%, and good outcome was defined using the modified Rankin Scale (mRS) score (? 2 at 3 months). The mean age of the study population was 65.07 ± 11.659 years, with 34 men and 26 women. The leading vascular risk factor was hypertension (86.7%). There were significant associations between the initial red blood cell distribution width (RDW) and hematoma growth (p=0.038). Therefore, hematoma growth in the first 24 hours after symptom onset was significantly related to a poor clinical outcome at 3 months (p = 0.050). The study identified significant relationships between the initial RDW and poor outcome as well as the initial RDW and hypertensive hematoma growth. Additionally, this study demonstrated that these parameters are easily obtainable and could be used to effectively evaluate outcomes in ICH patients.

Clinical Prediction Algorithm (BRAIN) to Determine Risk of Hematoma Growth in Acute Intracerebral Hemorrhage

We developed and validated a simple algorithm to predict the risk of hematoma growth in acute spontaneous intracerebral hemorrhage (ICH) to better inform clinicians and researchers in their efforts to improve outcomes for patients. We analyzed data from the computed tomography substudies of the pilot and main phases of the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trials (INTERACT1 and 2, respectively). The study group was divided into a derivation cohort (INTERACT2, n=964) and a validation cohort (INTERACT1, n=346). Multivariable logistic regression was used to identify factors associated with clinically significant (≥6 mL) increase in hematoma volume at 24 hours after symptom onset. A parsimonious risk score was developed on the basis of regression coefficients derived from the logistic model. A 24-point BRAIN score was derived from INTERACT2 (C-statistic, 0.73) based on baseline ICH volume (mL per score, ≤10=0, 10-20=5, >20=7), recurrent ICH (yes=4), anticoagulation with warfarin at symptom onset (yes=6), intraventricular extension (yes=2), and number of hours to baseline computed tomography from symptom onset (≤1=5, 1-2=4, 2-3=3, 3-4=2, 4-5=1, >5=0) predicted the probability of ICH growth (ranging from 3.4% for 0 point to 85.8% for 24 points) with good discrimination (C-statistic, 0.73) and calibration (Hosmer-Lemeshow P=0.82) in INTERACT1. The simple BRAIN score predicts the probability of hematoma growth in ICH. This could be used to improve risk stratification for research and clinical practice. http://www.clinicaltrials.gov. Unique identifier: NCT00226096 and NCT00716079.

Modeling the pattern of contrast extravasation in acute intracerebral hemorrhage using dynamic contrast-enhanced MR.

Contrast extravasation (CE) in spontaneous intracerebral hemorrhage (ICH), coined the spot sign, predicts hematoma expansion (HE) and poor clinical outcome. The dynamic relationship between CE and the mode of ICH growth are poorly understood. We characterized the in vivo pattern and rate of HE using a novel animal model of acute ICH. Basal ganglia ICH was created in 14 Yorkshire swine utilizing a novel MRI integrated model, permitting real-time CE observation using dynamic contrast-enhanced (DCE) MRI. Computerized planimetry measured CE volume at each time point. Spatial vector analysis along three orthogonal axes determined distance vectors. Maximizing and minimizing the coefficient of determination defined the temporal phases of growth and stability, respectively. CE rate was calculated using a Patlak model. Asymmetric growth and variable rates of expansion characterized HE defining three distinct growth phases and patterns. A primary growth phase (duration 160 s; IQR 50-130) demonstrated rapid linear growth (0.04 mm/s IQR 0.01-0.10) accounting for 85 ± 15 % of total HE. The stationary phase demonstrated stability (duration 145 s; IQR 0-655). A secondary growth phase (duration 300; 130-600 s) accounted for 23 ± 8 % of total HE. In the primary and secondary growth phase, asymmetric growth occurred in the anterior-posterior (AP) planes (0.056 mm/s; p = 0.026 and 0.0112 mm/s; p = 0.03). Monophasic 2 (14 %), biphasic 4 (35 %) (primary followed by secondary growth), and triphasic 8 (56 %) patterns (primary, stationary, and secondary growth phase) were observed. A novel model of ICH provides real-time study of the dynamics and rate of CE. This data facilitates the understanding of pattern and rate of ICH formation.

Factors associated with early deterioration after spontaneous intracerebral hemorrhage: a systematic review and meta-analysis.

Background and PurposeSpontaneous intracerebral hemorrhage (ICH) is a devastating form of stroke with a poor prognosis overall. We conducted a systematic review and meta-analysis to identify and describe factors associated with early neurologic deterioration (END) after ICH.MethodsWe sought to identify any factor which could be prognostic in the absence of an intervention. The Cochrane Library, EMBASE, the Global Health Library, and PubMed were searched for primary studies from the years 1966 to 2012 with no restrictions on language or study design. Studies of patients who received a surgical intervention or specific experimental therapies were excluded. END was defined as death, or worsening on a reliable outcome scale within seven days after onset.Results7,172 abstracts were reviewed, 1,579 full-text papers were obtained and screened. 14 studies were identified; including 2088 patients. Indices of ICH severity such as ICH volume (univariate combined OR per ml:1.37, 95%CI: 1.12–1.68), presence of intraventricular hemorrhage (2.95, 95%CI: 1.57–5.55), glucose concentration (per mmol/l: 2.14, 95%CI: 1.03–4.47), fibrinogen concentration (per g/l: 1.83, 95%CI: 1.03–3.25), and d-dimer concentration at hospital admission (per mg/l: 4.19, 95%CI: 1.88–9.34) were significantly associated with END after random-effects analyses. Whereas commonly described risk factors for ICH progression such as blood pressure, history of hypertension, and ICH growth were not.ConclusionsThis study summarizes the evidence to date on early ICH prognosis and highlights that the amount and distribution of the initial bleed at hospital admission may be the most important factors to consider when predicting early clinical outcomes.