Initial Intracerebral Hemorrhage Volume Research Articles

Correlation of Immune-Inflammatory Markers with Clinical Features and Novel Location-Specific Nomograms for Short-Term Outcomes in Patients with Intracerebral Hemorrhage.

(1) Background: We investigated the association of four immune-inflammatory markers with clinical features and established location-specific nomograms to predict mortality risk in patients with intracerebral hemorrhage (ICH). (2) Methods: We retrospectively enrolled 613 inpatients with acute ICH. (3) Results: Overall mortality was 22%, which was highest in pontine hemorrhage and lowest in thalamic hemorrhage. All four immune-inflammatory markers exhibited a positive linear correlation with glucose, ICH volume, ICH score, and discharge Modified Rankin Scale (mRS) score. Significant predictors of death due to lobar/putaminal hemorrhage were age, glucose and creatinine levels, initial Glasgow Coma Scale (GCS) score, ICH volume, and presence of intraventricular hemorrhage. None of the immune-inflammatory markers were significant predictors of unfavorable outcome or death. We selected significant factors to establish nomograms for predicting death due to lobar/putaminal, thalamic, pontine, and cerebellar hemorrhages. The C-statistic for predicting death in model I (comprising factors in the establishment of the nomogram) in each type of ICH was higher than that in model II (comprising ICH score alone), except for cerebellar hemorrhage. These nomograms for predicting death had good discrimination (C-index: 0.889 to 0.975) and prediction probabilities (C-index: 0.890 to 0.965). (4) Conclusions: Higher immune-inflammatory markers were associated with larger ICH volume, worse initial GCS, and unfavorable outcomes, but were not independent prognostic predictors. The location-specific nomograms provided novel and accurate models for predicting mortality risk.

National Institutes of Health Stroke Scale Correlates Well with Initial Intracerebral Hemorrhage Volume

The US Centers for Medicare and Medicaid Services (CMS) currently publicly reports hospital-quality, risk-adjusted mortality measure for ischemic stroke but not intracerebral hemorrhage (ICH). The NIHSS, which is captured in CMS administrative claims data, is a candidate metric for use in ICH risk adjustment and has been shown to predict clinical outcome with accuracy similar to the ICH Score. Correlation between early NIHSS and initial ICH volume would further support use of the NIHSS for ICH risk adjustment. Among 372 ICH patients enrolled in a large multicenter trial (FAST-MAG), the relation between early NIHSS and early ICH volume was assessed with correlation and linear trend analysis. Overall, there was strong correlation between NIHSS and ICH volume, r=0.77 (p<0.001), and for every 10cc increase in ICH the NIHSS increased by 4.5 points. Correlation coefficients were comparable in all subgroups, but magnitude of NIHSS increase with ICH unit volume increase was greater with left than right hemispheric ICH, with presence rather than absence of IVH, with imaging done within the first hour than second hour after last known well, with men than women, and with younger than older patients. Early NIHSS neurologic deficit severity values correlate strongly with initial ICH hematoma volume. As with ischemic stroke, lesion volume increases produce greater NIHSS change in the left than right hemisphere, reflecting greater NIHSS sensitivity to left hemisphere function. These findings provide further support for the use of NIHSS in risk-adjusted mortality measures for intracerebral hemorrhage.

Stereotactic IntraCerebral Underwater Blood Aspiration (SCUBA) Improves Survival Following Intracerebral Hemorrhage as Compared with Predicted Mortality

Recent publications on minimally invasive surgery (MIS) for hematoma evacuation have suggested survival benefits in select patients. Since 2015, our center has been performing an MIS technique using continuous irrigation with aspiration through an endoscope (stereotactic intracerebral underwater blood aspiration [SCUBA]). It is unknown how these patient outcomes compare with intracerebral hemorrhage (ICH) score predictions. Our aim is to determine if SCUBA patients had better 30-day mortality than predicted by their presenting ICH score. Retrospective review of consecutively admitted patients who underwent SCUBA between December 2015 and March 2019. Operative criteria for MIS evacuation included supratentorial hematoma volume ≥15 mL, age >18, National Institutes of Health Stroke Scale score ≥6, and modified Rankin Scale (mRS) score ≤3. Demographic, radiographic, and clinical data were collected prospectively. The prespecified primary outcome was observed 30-day mortality of SCUBA patients compared with predicted mortality by ICH score on presentation. One-hundred and fifteen patients underwent SCUBA for hematoma evacuation. Initial mean ICH volume was 51.4 mL (standard deviation 33.9 mL), with a median National Institutes of Health Stroke Scale score of 17 and ICH score of 2. At 1 month, 12 of the 115 SCUBA patients had passed away (30-day mortality rate 10.4%). This was significantly lower than the predicted mortality of 35.1% when calculated using the presenting ICH score (χ2 (1, N= 115)= 9.5, P < 0.0001), equating to an absolute risk reduction of 24.7%. This study suggests that minimally invasive hematoma evacuation with the SCUBA technique for ICH may reduce predicted 30-day mortality, with a number needed to treat of 4 to prevent 1 mortality.

Abstract WP78: National Institutes Of Health Stroke Scale Correlates Well With Initial Intracerebral Hemorrhage Volume

Introduction: The US Centers for Medicare and Medicaid Services (CMS) currently publicly reports hospital-quality, risk-adjusted mortality measure for ischemic stroke but not intracerebral hemorrhage (ICH). The NIHSS, which is captured in CMS administrative claims data, is a candidate metric for use in ICH risk adjustment and has been shown to predict clinical outcome with accuracy similar to the ICH Score. Correlation between early NIHSS and initial ICH volume would further support use of the NIHSS for ICH risk adjustment. Methods: Among consecutive ICH patients enrolled in a large multicenter trial (FAST-MAG), the relation between early NIHSS and early ICH volume was assessed with correlation and linear trend analysis, in all patients and separately in; left vs right; IVH-positive vs IVH-negative, hyperacute (≤60min) vs acute (61-120min) imaging; men vs women; and younger (&lt;65y) vs older (≥65y). Results: Among 372 patients with ICH, age was 65y (SD 13), 67% were men, early NIHSS was 16 (IQR 9-25) and initial ICH volume was 14.9 cc (IQR 6.1-36.4). Overall, there was substantial correlation between NIHSS and ICH volume, r=0.77 (p&lt;0.001), and for every 10cc increase in ICH the NIHSS increased by 4.5 points. Correlations remained substantial and similar in all subgroups (Table), but magnitude of NIHSS change with ICH volume alteration varied, including greater NIHSS change with ICH unit volume increase in left than right hemisphere, absence of IVH, earlier (≤60min) than later presentation (61-120min), men than women, and younger than older patients (Table). Conclusion: Early NIHSS deficit severity values correlate strongly with initial ICH hematoma volume. As with ischemic stroke, lesion volume increases produce greater NIHSS changes in the left than right hemisphere, reflecting greater NIHSS sensitivity to left hemisphere function. These findings provide further support for the use of the NIHSS in risk-adjusted mortality measures for intracerebral hemorrhage.

Abstract 101: Predicting Hematoma Expansion Using An Artificial Neural Network: An Exploratory Analysis Of The Atach 2 Trial

Introduction: Hematoma expansion (HE) in patients with intracerebral hemorrhage (ICH) is a key predictor of poor prognosis and potentially amenable to treatment. Current clinical scoring models, radiological markers, and labs have limited ability to predict HE. This study aimed to create a more robust classification model to predict HE in patients with ICH using a deep learning algorithm, an artificial neural network (ANN). Methods: Data from the ATACH 2 trial (Antihypertensive Treatment of Acute Cerebral Hemorrhage) was utilized. Variables included in the models were chosen as per literature consensus on salient factors associated with HE and clinical expertise. HE was defined as increase in either &gt;33% or 6mL in hematoma volume in the first 24 hours. A multi-layer feedforward ANN was trained using the back-propagation method to minimize the loss function with 5-fold cross validation. 80% of patients were used for training and 20% for testing. The ANN was compared to a logistic regression model (GLM). Given the imbalance in patients with HE, AUPRC (area under the precision-recall curve), recall and precision were calculated for the respective models. Results: Of the 963 patients in the study (mean age 62±13.0, 38.5% female), 31% had hematoma expansion. The median [interquartile range (IQR)] initial hematoma volume was 10.5mm 3 [5.16 - 20.25], median admission SBP [IQR] was 200 [184-217], median platelet count [IQR] was 213 [178-256], median INR [IQR] was 1.0 [0.9-1.0], and median admission GCS [IQR] was 15 [13-15]. The GLM model had AUPRC of 0.38 with recall of 0.60 and precision of 0.38 in the testing cohort. The ANN training model demonstrated AUPRC of 0.92 with recall of 0.72 with precision of 0.39 during testing. Initial ICH volume, platelets, INR, and GCS had the highest feature importance. Conclusion: We developed an ANN to predict HE in ICH patients performing with improved sensitivity and similar positive predictive value when compared to GLM. We support that ANN can capture complex associations between variables not attainable in classic regression models. This model may help identify patients at risk for HE who warrant careful monitoring and aggressive treatment upfront including those suitable for clinical trials for treatments.

Individualized blood pressure targets in the postoperative care of patients with intracerebral hemorrhage.

Recent guidelines recommend targeting a systolic blood pressure (SBP) < 140 mm Hg in the early management of patients with spontaneous intracerebral hemorrhage (ICH). The optimal SBP targets for ICH patients after hematoma evacuation (HE) remain unclear. Here, the authors aimed to define the optimal SBP range based on multimodal neuromonitoring data. Forty poor-grade ICH patients who had undergone HE and then monitoring of intracerebral pressure, brain tissue oxygen tension (PbtO2), and cerebral metabolism (via cerebral microdialysis [CMD]) were prospectively included. Episodes of brain tissue hypoxia (BTH) (1-hour averaged PbtO2 < 20 mm Hg) and metabolic distress (CMD-lactate/pyruvate ratio [LPR] ≥ 40) were identified and linked to corresponding parameters of hemodynamic monitoring (SBP and cerebral perfusion pressure [CPP]). Multivariable regression analysis was performed using generalized estimating equations to identify associations between SBP levels, PbtO2, and brain metabolism. The mean patient age was 60 (range 51-66) years and the median [IQR] initial ICH volume was 47 [29-60] ml. In multivariable models adjusted for Glasgow Coma Scale score, probe location, ICH volume, and age, lower SBP was independently associated with a higher risk of BTH (≤ 120 mm Hg: adjusted OR 2.9, p = 0.007; 120-130 mm Hg: adj OR 2.4, p = 0.002; 130-140 mm Hg: adj OR 1.6, p = 0.017) compared to a reference range of 140-150 mm Hg at the level of the foramen interventriculare Monroi, which corresponded to a CPP of 70-80 mm Hg and SBP levels between 150 and 160 mm Hg at the heart level. After exclusion of episodes with mitochondrial dysfunction, SBP targets < 140 mm Hg were associated with higher odds of cerebral metabolic distress (≤ 130 mm Hg: OR 2.5, p = 0.041; 130-140 mm Hg: OR 2.3, p = 0.033). Patients with a modified Rankin Scale score ≥ 5 at neurological ICU discharge more often exhibited BTH than patients with better outcomes (51% vs 10%, p = 0.003). These data suggest that lower SPB and CPP levels are associated with a higher risk for BTH. Further studies are needed to evaluate whether a higher SPB target may prevent BTH and improve outcomes.

Early Predictors of the Increase in Perihematomal Edema Volume After Intracerebral Hemorrhage: A Retrospective Analysis From the Risa-MIS-ICH Study.

Background and Purpose: Perihematomal edema (PHE) is associated with poor functional outcomes after intracerebral hemorrhage (ICH). Early identification of risk factors associated with PHE growth may allow for targeted therapeutic interventions.Methods: We used data contained in the risk stratification and minimally invasive surgery in acute intracerebral hemorrhage (Risa-MIS-ICH) patients: a prospective multicenter cohort study. Patients' clinical, laboratory, and radiological data within 24 h of admission were obtained from their medical records. The absolute increase in PHE volume from baseline to day 3 was defined as iPHE volume. Poor outcome was defined as modified Rankin Scale (mRS) of 4 to 6 at 90 days. Binary logistic regression was used to assess the relationship between iPHE volume and poor outcome. The receiver operating characteristic curve was used to find the best cutoff. Linear regression was used to identify variables associated with iPHE volume (ClinicalTrials.gov Identifier: NCT03862729).Results: One hundred ninety-seven patients were included in this study. iPHE volume was significantly associated with poor outcome [P = 0.003, odds ratio (OR) 1.049, 95% confidence interval (CI) 1.016–1.082] after adjustment for hematoma volume. The best cutoff point of iPHE volume was 7.98 mL with a specificity of 71.4% and a sensitivity of 47.5%. Diabetes mellitus (P = 0.043, β = 7.66 95% CI 0.26–15.07), black hole sign (P = 0.002, β = 18.93 95% CI 6.84–31.02), and initial ICH volume (P = 0.018, β = 0.20 95% CI 0.03–0.37) were significantly associated with iPHE volume. After adjusting for hematoma expansion, the black hole sign could still independently predict the increase of PHE (P < 0.001, β = 21.62 95% CI 10.10–33.15).Conclusions: An increase of PHE volume >7.98 mL from baseline to day 3 may lead to poor outcome. Patients with diabetes mellitus, black hole sign, and large initial hematoma volume result in more PHE growth, which should garner attention in the treatment.

Abstract TMP19: MRI Characteristics and Predictors of Diffusion Weighted Hyperintense Lesions After Spontaneous Intracerebral Hemorrhage: A Secondary Analysis of MISTIE-III

Introduction: Mechanisms of diffusion weighted hyperintense lesions (DWIHL) after spontaneous intracerebral hemorrhage (ICH) are controversial. We evaluated mechanism and outcome of DWIHL. Methods: Protocolized MRI scans within 7 days from ICH were reviewed from MISTIE-III trial. Imaging analysis included DWIHL, leukoariosis (Fazekas score), enlarged perivascular space (EPVS), and cerebral microbleeds. Multivariable logistic regression analysis was performed to assess predictors and outcomes of having DWIHLs. Favorable outcome was defined as modified Rankin Score 0-3 at 12 months. Results: Of 499 patients, 300 underwent DWI studies (62% lobar ICH; 38% deep ICH) and 178 (59%) had acute DWIHLs (66% lobar; 34% deep). DWIHL locations were perihematomal in 140 (79%); and remote in 96 (54%). In multivariable regression analysis, DWIHLs were associated with initial mean arterial pressure [MAP] (odds ratio [OR]: 1.004; 95% confidence interval [CI]: 1.002-1.01), initial ICH volume (OR: 1.004; 95%CI: 1.001-1.01), NIHSS at randomization (OR: 1.01; 95%CI: 1.01-1.02), hypertension history (OR: 1.41; 95%CI: 1.04-1.93), and Fazekas score (OR: 1.04; 95%CI: 1.01-1.08). Patients with DWIHLs were less likely to have favorable outcome (66% vs. 50%; OR: 0.89; 95%CI: 0.81-0.99) after adjusting for ICH severity; however, the presence of DWIHLs did not confer an independent mortality risk at 12 months. In addition, perihematomal DWIHLs were associated with ICH volume (OR: 1.003; 95%CI: 1.00-1.01), NIHSS (OR: 1.01; 95%CI: 1.00-1.02), deep location (OR: 1.25; 95%CI: 1.10-1.42), and centrum semiovale EPVS score (OR: 0.99; 95% CI: 0.99-1.00). Remote DWIHLs were associated with Fazekas score (OR: 1.17; 95%CI: 1.06-1.29), centrum semiovale EPVS score (OR: 1.01; 95%CI: 1.00-1.01), atrial fibrillation (OR: 1.40; 95%CI: 1.04-1.90), and maximal ΔMAP on first 24 hours (OR: 1.004; 95%CI: 1.001-1.006). Conclusions: DWIHLs were common (59%) in patients after spontaneous ICH, predominantly in lobar locations and were associated with unfavorable neurologic outcome. While perihematomal DWIHLs were associated with ICH severity, remote DWIHLs suggested different mechanisms including acute blood pressure reduction, cardiac emboli, and white matter disease severity.

Similar outcomes between vitamin K and non-vitamin K antagonist oral anticoagulants associated intracerebral hemorrhage

The application of non-vitamin K antagonist oral anticoagulant (NOAC) reduces the risk of intracerebral hemorrhage (ICH) in comparison with vitamin K antagonist (VKA). However, the features and outcomes of NOAC-associated ICH are still unclear, especially for Asian populations. We retrospectively analyzed 49 consecutive patients who had spontaneous ICH while using NOAC or VKA. We compared the clinical characteristics, ICH volume, 7-day and 3-month mortality, and functional outcomes at discharge and 3 months post-stroke using the modified Rankin Scale (mRS) between NOAC- and VKA-associated ICH. The clinical features, ICH volume, ICH location, and/or treatment methods were statistically adjusted. Among the 49 ICH patients, 15 (30.6%) were using NOAC and 34 (69.4%) were taking VKA. There were no significant differences in the initial ICH volume between groups (mean volume 34.2±43.8 vs. 59.4±46.5mL, p=0.061). The percentage of early mortality (within 7 days post-ICH) was significantly lower in the NOAC group (13.3% vs. 44.1%; p=0.047), but the 3-month mortality was similar (33.3% vs. 47.1%; p=0.294). The functional outcome was equally poor in both groups at discharge (p=0.670) and 3 months post-ICH (mean mRS score 4.7±1.3 vs. 4.6±1.7, p=0.766). There were no significant differences in initial ICH volume, 90-day mortality, or functional outcomes between NOAC and VKA-associated ICH in Asians.

Early thrombosis prophylaxis with enoxaparin is not associated with hematoma expansion in patients with spontaneous intracerebral hemorrhage.

Early pharmacological deep vein thrombosis (DVT) prophylaxis is recommended by guidelines, but rarely started within 48h. We aimed to analyze the effect of early (within 48h) versus late (>48h) DVT prophylaxis on hematoma expansion (HE) and outcome in patients with spontaneous intracerebral hemorrhage (ICH). We analyzed 134 consecutive patients admitted to a tertiary neurointensive care unit with diagnosed spontaneous ICH, without previous anticoagulation, severe coagulopathy, hematoma evacuation, early withdrawal of therapy or ineligibility for DVT prophylaxis according to our institutional protocol. Significant late HE was defined as ≥6mL increase of hematoma volume between neuroimaging within 48h and day 3-6. Multivariate analysis was performed to identify risk factors for late HE, poor 3-month outcome (modified Rankin Scale score≥4) and mortality. Patients had a median Glasgow Coma Scale score of 14 [interquartile range (IQR), 10-15], ICH volume of 11 (IQR, 5-24)mL and were 71 (IQR, 61-76)years old. A total of 56% (n=76) received early DVT prophylaxis, 37% (n=50) received late DVT prophylaxis and 8 (6%) had unknown bleeding onset. Patients with early DVT prophylaxis had smaller ICH volume [9.5 (IQR, 4-18.5) vs. 17.5 (IQR, 8-29)mL, P=0.038] and were more often comatose (26% vs. 10%, P=0.025). Significant late HE [n=5/134 (3.7%)] was associated with larger initial ICH volume (P=0.02) and lower thrombocyte count (P=0.03) but not with early DVT prophylaxis (P=0.36). Early DVT prophylaxis was not associated with worse outcome. Significant late HE is uncommon and DVT prophylaxis within 48h of symptom onset may be safe in selected patients with ICH.

Modeling prognostic factors for poor neurological outcome in conservatively treated patients with intracerebral hemorrhage: A focus on TNF-α

ObjectivePrognostic models for Intracerebral hemorrhage (ICH), mainly based on clinical evaluation, have remained inherently confounded by subjective scoring assessments and limited accuracy. In this study, we aimed at assessing the risk for poor outcome after ICH based on peripheral biochemical markers (TNF-α, glutamate and glucose) and radiological variables (both at admission and five days after patient’s care), for modeling purposes of prognostication. Patients and MethodsThe defined initial variables of fifty non-comatose conservatively treated ICH patients without severe complications during the hospitalization process (as intraventricular bleeding, or hematoma expansion) were aligned with the evaluated parameters during re-evaluation (3 months later). A comprehensive statistical approach has been applied by using different modeling strategies for prediction of their functional status and outcome. ResultsHigher blood plasma glutamate, TNF-α and initial ICH volume at admission, as well as higher volumes of ICH and perihematomal edema after five days of care were significantly more likely associated with the poor outcome. Nevertheless, in all of the constructed models, TNF-α was estimated as the only significant predictive risk factor, thus outperforming the capacity of the initial ICH volume and the radiological variables after 5 days, both in terms of prognostication of the functional status and the 3-month neurological outcome. The constructed canonical variable that has fairly marked off the different outcomes was also mainly weighed by the admission TNF-α levels. For the first time, we have carefully developed probability functions for the neurological outcome as a response to the admission TNF-α levels; TNF-α levels >110.35 pg/mL were assessed as an optimal cutoff point fairly identifying patients who will fall into the group with poor outcome. ConclusionsTNF-α based models and admission TNF-α screening might be appropriate as a key component that assists more objective prognostication and management of patient’s care in clinical decision making, as rapid initial diagnosis and concentrated management are crucial for secondary prevention of further devastating neurological impairments after ICH.

Effect of Hyperosmolar Therapy on Outcome Following Spontaneous Intracerebral Hemorrhage: Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) Study

We aimed to identify the effect of hyperosmolar therapy (mannitol and hypertonic saline) on outcomes after intracerebral hemorrhage (ICH) in the Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) study. Comparison of ICH cases treated with hyperosmolar therapy versus untreated cases was performed using a propensity score based on age, initial Glasgow Coma Scale, location of ICH (lobar, deep, brainstem, and cerebellar), log-transformed initial ICH volume, presence of intraventricular hemorrhage, and surgical interventions. ERICH subjects with a pre-ICH modified Rankin Scale (mRS) score of 3 or lower were included. Treated cases were matched 1:1 to untreated cases by the closest propensity score (difference ≤.15), gender, and race and ethnicity (non-Hispanic white, non-Hispanic black, or Hispanic). The McNemar and the Wilcoxon signed-rank tests were used to compare 3-month mRS outcomes between the 2 groups. Good outcome was defined as a 3-month mRS score of 3 or lower. As of December 31, 2013, the ERICH study enrolled 2279 cases, of which 304 hyperosmolar-treated cases were matched to 304 untreated cases. Treated cases had worse outcome at 3 months compared with untreated cases (McNemar, P = .0326), and the mean 3-month mRS score was lower in the untreated group (Wilcoxon, P = .0174). Post hoc analysis revealed more brain edema, herniation, and death at discharge for treated cases. Hyperosmolar therapy was not associated with better 3-month mRS outcomes for ICH cases in the ERICH study. This finding likely resulted from greater hyperosmolar therapy use in patients with edema and herniation rather than those agents leading to worse outcomes. Further studies should be performed to determine if hyperosmolar agents are effective in preventing poor outcomes.

Retrospective Validation of a Computer-Assisted Quantification Model of Intracerebral Hemorrhage Volume on Accuracy, Precision, and Acquisition Time, Compared with Standard ABC/2 Manual Volume Calculation.

Intracerebral hemorrhage accounts for 6.5%-19.6% of all acute strokes. Initial intracerebral hemorrhage volume and expansion are both independent predictors of clinical outcomes and mortality. Therefore, a rapid, unbiased, and precise measurement of intracerebral hemorrhage volume is a key component of clinical management. The most commonly used method, ABC/2, results in overestimation. We developed an interactive segmentation program, SegTool, using a novel graphic processing unit, level set algorithm. Until now, the speed, bias, and precision of SegTool had not been validated. In a single stroke academic center, 2 vascular neurologists and 2 neuroradiologists independently performed a test-retest experiment that involved repeat measurements of static, unchanging intracerebral hemorrhage volumes on CT from 76 intracerebral hemorrhage cases. Measurements were made with SegTool and ABC/2. True intracerebral hemorrhage volumes were estimated from a consensus of repeat manual tracings by 2 operators. These data allowed us to estimate measurement bias, precision, and speed. The measurements with SegTool were not significantly different from the true intracerebral hemorrhage volumes, while ABC/2 overestimated volume by 45%. The interrater measurement variability with SegTool was 50% less than that with ABC/2. The average measurement times for ABC/2 and SegTool were 35.7 and 44.6 seconds, respectively. SegTool appears to have attributes superior to ABC/2 in terms of accuracy and interrater reliability with a 9-second delay in measurement time (on average); hence, it could be useful in clinical trials and practice.

Incontinence and gait disturbance after intraventricular extension of intracerebral hemorrhage.

We tested the hypothesis that intraventricular hemorrhage (IVH) is associated with incontinence and gait disturbance among survivors of intracerebral hemorrhage (ICH) at 3-month follow-ups. The Genetic and Environmental Risk Factors for Hemorrhagic Stroke study was used as the discovery set. The Ethnic/Racial Variations of Intracerebral Hemorrhage study served as a replication set. Both studies performed prospective hot-pursuit recruitment of ICH cases with 3-month follow-up. Multivariable logistic regression analyses were computed to identify risk factors for incontinence and gait dysmobility at 3 months after ICH. The study population consisted of 307 ICH cases in the discovery set and 1,374 cases in the replication set. In the discovery set, we found that increasing IVH volume was associated with incontinence (odds ratio [OR] 1.50; 95% confidence interval [CI] 1.10-2.06) and dysmobility (OR 1.58; 95% CI 1.17-2.15) after controlling for ICH location, initial ICH volume, age, baseline modified Rankin Scale score, sex, and admission Glasgow Coma Scale score. In the replication set, increasing IVH volume was also associated with both incontinence (OR 1.42; 95% CI 1.27-1.60) and dysmobility (OR 1.40; 95% CI 1.24-1.57) after controlling for the same variables. ICH subjects with IVH extension are at an increased risk for developing incontinence and dysmobility after controlling for factors associated with severity and disability. This finding suggests a potential target to prevent or treat long-term disability after ICH with IVH.

Enlarged perivascular spaces and small diffusion-weighted lesions in intracerebral hemorrhage.

To examine the association between enlarged perivascular spaces (EPVS) and the prevalence and extent of small acute diffusion-weighted imaging (DWI) lesions (SA-DWIL) in patients with spontaneous supratentorial intracerebral hemorrhage (ICH). We conducted a retrospective review of a consecutive cohort of 201 patients with spontaneous supratentorial ICH who had brain MRI with DWI within 1 month of ICH onset. We compared the clinical and imaging characteristics, including EPVS, of patients with and without SA-DWIL. We used univariate and multivariate logistic regression analyses to determine the variables associated with SA-DWIL. Small acute DWI lesions were detected in 27.9% (n = 56) of patients. Intraventricular and subarachnoid extension of ICH (p ≤ 0.001), high centrum semiovale (CSO)-EPVS (p < 0.001), high basal ganglia-EPVS (p = 0.007), overall extent of white matter hyperintensity (p = 0.018), initial ICH volume (p < 0.001), and mean change in mean arterial blood pressure (δ MAP = MAP at admission - the lowest MAP before MRI scan) (p = 0.027) were associated with SA-DWIL on univariate analyses. On multivariate logistic regression analyses, larger ICH volume (odds ratio [OR] 1.03; 95% confidence interval [CI] 1.01-1.06; p = 0.006) and high CSO-EPVS (OR 12.56; 95% CI 4.40-35.85; p < 0.001) were independently associated with the presence of SA-DWIL. In our cohort, high EPVS, in particular CSO-EPVS, and larger hematoma volume emerged as independent predictors for SA-DWIL after ICH. Our findings might provide a new explanation for the pathophysiologic mechanisms predisposing to SA-DWIL after ICH.

Abstract 31: Ultraearly Hematoma Growth: Multicenter External Validation of the Adjustment of Intracerebral Hemorrhage Volume by Onset-to-imaging Time

Background: The impact of baseline intracerebral hemorrhage (ICH) volume on hematoma growth (HG) and clinical outcome may vary widely depending on the onset-to-imaging time (OIT). We previously reported that the adjustment of initial ICH volume by OIT (coined as ultraearly HG, uHG) is a powerful tool for outcome prediction in acute ICH. We aimed to validate our previous findings in a multicenter external cohort and to assess the relationship between uHG and the CTA spot-sign. Methods: The PREDICT study was a prospective, observational cohort study of consecutive ICH patients &lt;6 hours. Patients underwent baseline and 24-hour CT scans, and CTA for the blinded detection of spot sign. uHG was defined as the relation between baseline ICH volume/OIT, HG as hematoma expansion &gt;33% or &gt;6 mL, early neurologic deterioration (END) as increase ≥4 points in the NIHSS score or death at 24 hours, and poor outcome as mRS score &gt;2 at 3 months. Results: Two hundred and thirty-seven patients were included in this study. Median baseline ICH volume was 14.5 (6[[Unable to Display Character: &amp;#8211;]]30.4) mL, median OIT 135 (85.5[[Unable to Display Character: &amp;#8211;]]199) minutes, and median uHG 6.5 (2.5-14.3) mL/h. The spot sign was present in 31.2% of patients. uHG was 2.7-fold higher in spot sign-positive patients (11.1 [5.7-17.7] mL/h vs. 4.1 [1.9-12.3] mL/h, P&lt;0.001). uHG &gt;4.7 mL/h improved the sensitivity-specificity of both baseline ICH volume &gt;10 mL and spot sign in the prediction of HG (73.9%-57.5% vs. 68.1%-54.3% and 48.9%-73.9%), 90-day mortality (82%-56.3% vs. 78%-53.5% and 45.8%-70.8%), and poor outcome (72.9%-80.4% vs. 69.8%-70.6% and 38%-75%), respectively. The median hematoma expansion at 24 hours among spot-positive patients was 3.2 mL in uHG &lt;5 mL/h group, 4.1 mL in uHG 5-10 mL/h group, and 4.8 mL in uHG &gt;10 mL/h group (P&lt;0.001). In adjusted multivariate analyses uHG independently predicted HG (OR 1.08, 95% CI 1.04-1.12), END (OR 1.06, 95% CI 1.02-1.10), 90-day mortality (OR 1.07, 95% CI 1.02-1.11), and poor outcome (OR 1.12, 95% CI 1.02-1.23). Conclusions: These results validate uHG as a powerful predictor of outcome in acute ICH. uHG is significantly higher in spot sign patients, improves the accuracy of baseline ICH volume and spot sign in the prediction of HG and clinical outcome, and independently predicts HG, END, 90-day mortality, and poor outcome.

Warfarin associated intracerebral hemorrhage in Hong Kong Chinese

Objectives: Warfarin-associated intracerebral hemorrhage (WICH) is a serious neurological condition associated with significant mortality and morbidity. We aimed to study the clinical features and factors that predict clinical outcome of Chinese patients with WICH.Methods: Medical records of patients with spontaneous intracerebral hemorrhage (ICH) admitted to our hospital between July 2001 and June 2010 were reviewed and those with WICH were studied in detail retrospectively.Results: Fifty-one patients with WICH were studied. The mean age was 74·3 ± 10·5 years and 52·9% of the patients were female. The mean international normalized ratio (INR) on presentation was 2·9 ± 1·0. The median ICH volume was 23·3 (10·4–59·3) ml. The mortality rate at 3–6 months for WICH was 62·0%. Multivariate logistic analysis revealed that an initial ICH volume of > 20 ml (OR 34·4, P = 0·037) and presence of intraventricular hemorrhage (OR 22·9, P = 0·046) were independently associated with poor outcome. Supratherapeutic INR (INR > 3·0) on admission (P = 0·724) and complete correction of INR within 24 hours after admission (P = 0·486) were not independent predictors of poor outcome. The median ICH volumes did not differ between INR groups (18·2 (9·4–61·1) ml for INR ≤ 3 vs 27·3 (13·7–58·5) ml for INR > 3, P = 0·718). Neurological deterioration (ND) was documented in 19 (63·3%) of the 30 patients included in a smaller sub-cohort, and was associated with poor neurological outcome (OR 20·7, P = 0·027). Warfarin was resumed in 7 of the 20 survivors. There were two episodes of recurrent WICH and one episode of ischemic stroke during a mean follow-up duration of 5·4 years. In survivors who were not resumed on warfarin, there were two episodes of recurrent ICH and 12 episodes of ischemic vascular events (nine ischemic strokes) during a mean follow-up duration of 2·6 years.Conclusion: Warfarin-associated intracerebral hemorrhage is a very serious complication of warfarin therapy with high mortality and morbidity. Initial ICH volume, presence of intraventricular hemorrhage, and ND are independent predictors of clinical outcome.

Intracerebral hemorrhage during anticoagulation with vitamin K antagonists: a consecutive observational study

Intracerebral hemorrhage (ICH) is the most devastating complication of oral anticoagulation (OAC). As the number of patients on long-term OAC is expected to rise, the proportion of intracerebral hemorrhage related to OAC (OAC-ICH) in relation to spontaneous ICH (spont-ICH) is expected to increase as well. We determined the proportion of OAC-ICH in consecutive stroke patients and explored differences between OAC-ICH and spont-ICH regarding initial volume, hematoma expansion and outcome. Our prospective study consecutively enrolled patients with supra- and infratentorial ICH. The National Institute of Health Stroke Scale Score and the modified Rankin Scale (mRS) score at baseline and after 3 months, medical history and demographic variables were recorded. All admission and follow-up CTs/MRIs were analysed regarding ICH volume using the ABC/2-method. Intraventricular hemorrhage (IVH) was quantified using the Graeb score. Within 19 months, 2,282 patients were admitted to our ER. 206 ICH patients were included. Overall, 24.8 % of all ICH were related to OAC. Compared to patients with spont-ICH, OAC-ICH patients were older (p = 0.001), more frequently had initial extension of ICH into the ventricles (p = 0.05) or isolated primary IVH (p = 0.03) and a higher Graeb score upon admission (p = 0.01). In contrast, initial ICH volume (p = 0.16) and ICH expansion (p = 0.9) in those receiving follow-up imaging (n = 152) did not differ between the two groups. After correction for age, there was a trend towards poorer outcome in OAC-ICH (p = 0.08). One-fourth of all ICH are related to OAC. Initial extension of ICH into the ventricles and primary IVH are more frequent in OAC-ICH. The rate of hematoma expansion in OAC-ICH patients is similar to non-anticoagulated ICH patients.

Intraventricular Fibrinolysis Does Not Increase Perihemorrhagic Edema After Intracerebral Hemorrhage

Additional intraventricular hemorrhage leads to higher mortality and worse functional outcome after intracerebral hemorrhage (ICH). Intraventricular fibrinolysis (IVF) with recombinant tissue plasminogen activator (rtPA) is an emerging treatment strategy for such patients. However, experimental studies suggest that rtPA may exert proedematous effects and lead to increased perihemorrhagic edema (PHE) after ICH. We aimed to compare the course of PHE after ICH between patients who received IVF with rtPA and controls matched for ICH volume. Patients were identified retrospectively from our institutional ICH database. Sixty-four patients with ICH and intraventricular hemorrhage who were treated with IVF were compared with 64 controls, who did not receive IVF, matched for ICH volume. The course of PHE was assessed on computed tomography scans (day 1, days 2 and 3, days 4-6, 7-9, and 10-12) using a threshold-based semiautomatic volumetric algorithm. Relative PHE was calculated as a ratio of PHE volume and initial ICH volume. The matching algorithm resulted in similar mean ICH volumes in both groups (20.01 ± 17.5 mL, IVF vs 20.08 ± 17.1 mL, control). Intraventricular hemorrhage volume was larger in the IVF group (26.8 ± 19.2 mL vs 9.2 ± 13.4 mL). The mean total rtPA dose used for IVF was 8 ± 6 mg. PHE increased over time in both groups until day 12. At all investigated time points, there was no significant difference in relative PHE between the IVF group and controls (F=0.39; P=0.844). IVF with rtPA did not lead to a relevant increase in PHE after ICH. rtPA doses used in the current study seem to be safe regarding PHE.

Ultraearly hematoma growth predicts poor outcome after acute intracerebral hemorrhage

To investigate the impact of the adjustment of initial intracerebral hemorrhage (ICH) volume by onset-to-imaging time (ultraearly hematoma growth [uHG]) on further hematoma enlargement and outcome in patients with acute ICH. We studied 133 patients with acute (<6 hours) supratentorial ICH. Patients underwent baseline and 24-hour CT scans for ICH volume measurement, and a CT angiography (CTA) for the detection of the spot sign. We defined uHG as the relation between baseline ICH volume/onset-to-imaging time, hematoma growth (HG) as hematoma enlargement >33% or >6 mL at 24 hours, early neurologic deterioration (END) as increase ≥4 points in the NIH Stroke Scale score or death at 24 hours, and poor long-term outcome as modified Rankin Scale score >2 at 3 months. The uHG was significantly faster in spot sign patients (p < 0.001), as well as in patients who experienced HG (p = 0.021), END (p < 0.001), 3-month mortality (p < 0.001), and poor long-term outcome (p < 0.001). The uHG improved the accuracy of baseline ICH volume in the prediction of END (sensitivity 93.1% vs 82.8%, specificity 85.3% vs 82.4%) and 3-month mortality (sensitivity 77.5% vs 70%, specificity 87.9% vs 84.6%). A uHG >10.2 mL/hour emerged as the most powerful predictor of HG (odds ratio [OR] 3.55, 95% confidence interval [CI] 1.39-9.07, p = 0.008), END (OR 70.22, 95% CI 14.63-337.03, p < 0.001), 3-month mortality (OR 16.96, 95% CI 5.32-54.03, p < 0.001), and poor long-term outcome (OR 6.19, 95% CI 1.32-28.98, p = 0.021). The uHG represents a powerful and easy-to-use tool for improving the prediction of HG and outcome in patients with acute ICH.