Mean Intracerebral Hemorrhage Volume Research Articles

Activated Prothrombin Complex Concentrates for the Treatment of Factor Xa Inhibitor-Associated Spontaneous Intracerebral Hemorrhage

Background: Anticoagulant-associated intracerebral hemorrhage (ICH) is a significant cause of morbidity and mortality. Despite approval of a specific reversal agent for factor Xa inhibitors, there is still much interest in nonspecific reversal agents, such as activated prothrombin complex concentrates (aPCCs). Objective: The objective of this study was to describe ICH expansion in a cohort of patients with factor Xa inhibitor-associated ICH who were treated with aPCC. Methods: This was a retrospective cohort study conducted at an academic medical center designated as a comprehensive stroke center. Consecutive patients admitted for ICH who reported use of apixaban or rivaroxaban prior to admission were considered for inclusion in the study. Patients were treated with 25 to 50 units/kg of aPCC. Intracerebral hemorrhage volume was measured before administration of aPCC and then again within 36 hours of aPCC administration. Results: A total of 40 patients were included in the final analysis. Overall, the cohort was predominantly male (24 [60%]), white (27 [67.5%]), and the mean age was 75.3 ± 10.5 years. Most patients reported taking apixaban prior to admission (31 [77.5%]) and a large proportion were also taking aspirin (13 [32.5%]). The mean change in ICH volume was 1.12 ± 6.03 mL ( P = 0.2475). Conclusions and Relevance: There was a nonsignificant change in mean ICH volume and no reported cases of thromboembolism. Due to the relatively high proportion of patients with significant hematoma expansion, more studies are needed on which patient population would best benefit from treatment with aPCC.

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.

Noncontrast Computed Tomography Markers of Cerebral Hemorrhage Expansion: Diagnostic Accuracy Meta-Analysis.

Assess the diagnostic accuracy of noncontrast computed tomography (NCCT) markers of hematoma expansion in patients with primary intracerebral hemorrhage. We performed a meta-analysis of observational studies and randomized controlled trials with available data for calculation of sensitivity and specificity of NCCT markers for hematoma expansion (absolute growth >6 or 12.5 mL and/or relative growth >33%). The following NCCT markers were analyzed: irregular shape, island sign (shape-related features); hypodensity, heterogeneous density, blend sign, black hole sign, and swirl sign (density-related features). Pooled accuracy values for each marker were derived from hierarchical logistic regression models. A total of 10,363 subjects from 23 eligible studies were included. Significant risk of bias of included studies was noted. Hematoma expansion frequency ranged from 7% to 40%, mean intracerebral hemorrhage volume from 9 to 27.8 ml, presence of NCCT markers from 9% (island sign) to 82% (irregular shape). Among shape features, sensitivity ranged from 0.32 (95%CI = 0.20-0.47) for island sign to 0.68 (95%CI = 0.57-0.77) for irregular shape, specificity ranged from 0.47 (95%CI = 0.36-0.59) for irregular shape to 0.92 (95%CI = 0.85-0.96) for island sign; among density features sensitivity ranged from 0.28 (95%CI = 0.21-0.35) for black hole sign to 0.63 (95%CI = 0.44-0.78) for hypodensity, specificity ranged from 0.65 (95%CI = 0.56-0.73) for heterogeneous density to 0.89 (95%CI = 0.85-0.92) for blend sign. Diagnostic accuracy of NCCT markers remains suboptimal for implementation in clinical trials although density features performed better than shape-related features. This analysis may help in better tailoring patients' selection for hematoma expansion targeted trials.

Abstract P420: Predominant Juxtacortical White Matter Lesion Hallmarks NOTCH3 Mutation-Related Intracerebral Hemorrhage

Introduction: CADASIL caused by p.R544C point mutation at exon 11 of NOTCH3 gene is reported to account for 5% of spontaneous intracerebral hemorrhage (ICH) in East Asian patients. We aim to investigate whether computed tomography (CT) features can identify NOTCH3 -related ICH. Method: This study enrolled patients with spontaneous ICH from a single center during 2008 to 2017. All patients were screened for NOTCH3 p.R544C mutation by polymerase chain reaction. Neuroimaging features of noncontrast CT scans, including burden of white matter lesion (WML, total score 0-4), degree of brain atrophy, number of lacunes, presence of juxtacortical WML, and lobar lacunes, were analyzed by the neuroradiologists who were blinded to the mutation status. Results: Of 323 cases with spontaneous ICH, 299 patients (mean age, 61.4±14.7; male, 67.6%; mean ICH volume 14.1±17.8 ml; ICH score 1.14±1.04 ) had available CT scan at stroke onset. Thirteen patients (4.3%) carried p.R544C mutations. The clinical features, stroke severity, hematoma size, and hemorrhagic location were comparable between p.R544C mutation carriers and noncarriers. On CT scan, patient with p.R544C mutation had higher WML score (2.77±1.69 vs. 1.63±1.50, P = 0.018) and were more likely to have predominant juxtacortical WML (69.2% vs. 17.8%, P &lt; 0.001, Figure 1 ), which usually presented at the level of centrum semiovale ( Figure 2 ). In multivariable analysis, predominant juxtacortical WML was the only neuroimaging feature associated with p.R544C mutation (odds ratio 8.82, 95% CI, 2.74-28.4). Conclusion: In patients with spontaneous ICH, topographic distribution of WML can help in identifying potential NOTCH3 mutation-related ICH.

Abstract P416: Remote Ischemic Conditioning Reduces Perihematomal Edema After Intracerebral Hemorrhage: First Proof-Of-Concept Randomized Controlled Trial

Introduction: The prognosis of intracerebral hemorrhage (ICH) is poor because of the mass effect arising from the hematoma and the associated perihematomal edema (PHE). Remote ischemic conditioning (RIC) has been shown to promote hematoma clearance and reduce PHE in animal models, however it remains unknown whether RIC is safe and effective in reducing PHE in ICH patients. Objective: To evaluate the safety and efficacy of RIC in reducing PHE after ICH. Methods: In this open-label, rater-blind, randomized control trial, 40 subjects with supratentorial ICH (hematoma volume:10-30 ml) diagnosed between 24 to 48 hours of onset were assigned to the RIC group or control group. All subjects received standard background medical therapy. Subjects in the RIC group underwent repeated daily RIC (4 cycles of 5 minutes inflation [200 mmHg] /deflation [0 mmHg] of cuff on one arm) for 7 consecutive days. The primary efficacy outcome was PHE volume at 7 days, and both absolute PHE volume and relative PHE volume (defined as absolute PHE volume divided by hematoma volume) were measured. Safety outcome included death, neurological deterioration, hematoma expansion, and any other severe adverse events. Results: All 40 subjects completed this study. Mean age was 59.3±11.7 years, and 57.5% were male. At baseline, the median National Institutes of Health Stroke Scale score was 9.5 (range 1-28), median Glasgow Come Score was 15 (range 10-15), and mean ICH volume was 13.9±4.5 ml. The mean relative PHE volume was 1.11±0.26 in the control group and 1.05±0.23 in the RIC group at baseline; and 1.49±0.30 vs. 1.33 ±0.32 at Day 3 (p&gt;0.05 each) respectively. After 7 days of treatment, RIC significantly reduced the relative PHE volume as compared to the control (1.77±0.39 vs. 2.02±0.27, p=0.02). The absolute PHE volume and hematoma volume at Day 3 and Day 7 had no significant difference between groups (p&gt;0.05 each). No subject died or suffered from neurological deterioration or hematoma expansion and no adverse event was associated with RIC. Conclusion: RIC seemed to be safe in patients with ICH and induced a significant reduction in the relative PHE volume after 7 day of treatment. These results warrant a further study with large sample to examine the effect of RIC on functional outcome after ICH.

Quantitative susceptibility mapping (QSM) as a means to monitor cerebral hematoma treatment.

Quantitative susceptibility mapping (QSM) offers a consistent hemorrhage volume measurement independent of imaging parameters. To investigate the magnetic susceptibility of intracerebral hemorrhage (ICH) as a quantitative measurement for monitoring treatment in hematoma patients. Prospective. Twenty-six patients with acute ICH were recruited and enrolled in treatment including surgery or medication (mannitol) for 1 week. A 3D gradient echo sequence at 3.0T. The hematoma volumes on computed tomography (CT) and QSM were calculated and used for correlation analysis. Magnetic susceptibility changes from pre- to posttreatment were calculated and compared to the National Institutes of Health stroke scale (NIHSS) measure of neurological deficit for each patient. Mean susceptibility values were calculated over each region of interest (ROI). A one-sample t-test was used to assess the changes of total volumes and mean magnetic susceptibility of ICH identified between pre- and posttreatment images (P < 0.05 was considered significant) and the Bland-Altman analysis with 95% limits of agreement (average difference, ±1.96 SD of the difference). Regression of volume measurements on QSM vs. CT and fitted linear regression of mean susceptibility vs. CT signal intensity for hematoma regions were conducted in all patients. Good correlation was found between hemorrhage volumes calculated from CT and QSM (CT volume = 0.94*QSM volume, r = 0.98). Comparison of QSM pre- and posttreatment showed that the mean ICH volume was reduced by a statistically insignificant amount from 5.74 cm3 to 5.45 cm3 (P = 0.21), while mean magnetic susceptibility was reduced significantly from 0.48 ppm to 0.38 ppm (P = 0.004). A significant positive association was found between changes in magnetic susceptibility values and NIHSS following hematoma treatment (P < 0.01). QSM in hematoma assessment, as compared with CT, offers a comparably accurate volume measurement; however, susceptibility measurements may enable improved monitoring of ICH treatment compared to volume measurements alone. 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;48:907-915.

Abstract TP349: Clinical Outcomes of Direct Oral Anticoagulants versus Warfarin in Patients With Atrial Fibrillation Who Have Had an Intracerebral Hemorrhage

Introduction: It has recently been demonstrated in a meta-analysis that patients with a history of intracerebral hemorrhage (ICH) and atrial fibrillation have a reduced risk of ischemic stroke (IS) with the initiation or resumption of oral anticoagulation (OAC). It remains uncertain if there is a difference in clinical outcomes between direct oral anticoagulants (DOAC) compared to warfarin (WF) in this patient population. We aimed to compare these two populations using data from the Southern California Kaiser Permanente (SCKP) health care system. Methods: Patient records with ICH and AF diagnosis were obtained from the SCKP Database, and divided into two cohorts: WF or DOAC. Subjects were included if the OAC was started after the index ICH. CT scans within 24 hours of symptom onset were examined for: ICH location, ICH size (Using the ABC/2 method), and leukoariosis. If available, an axial gradient echo sequence MRI scan taken within 180 days, either before or after the index ICH was examined for microbleeds. Differences in demographics, concurrent medications with an antithrombotic effect and statins, and traditional vascular risk factors were assessed using Kruskal-Wallis and Chi-Square tests. Results: Eighty-one subjects were identified (53 WF and 28 DOAC). In the DOAC group, 18 patients were on dabigatran, 9 on apixaban and 1 on rivaroxaban. There was no difference between WF and DOAC in baseline demographics, concurrent medications and location of ICH. The mean ICH volume was 15.4cc in DOAC and 5.6cc in WF (P=0.09). Time to start drug from ICH was 15.0 and 24.5 months for DOAC and WF respectively (P=0.26). More patients died in WF (28.3%) vs DOAC (10.7%) (P=0.0478). There was no difference in time to IS, ICH and major hemorrhage between the two groups. The composite outcome of IS, ICH, Major Hemorrhage and death was 35.8 % in WF vs 25% in DOAC group (P=0.32). Conclusion: Our results, while limited in size, suggest that patients with a previous ICH with AF, who are started on a DOAC have lower mortality compared to WF. There was a higher percentage of patients in the WF group who met the composite outcome of IS, ICH, major hemorrhage and death, but this did not reach statistical significance.

Abstract TP336: Acute Stroke in CADASIL: Emphasising on Intracerebral Haemorrhage

Introduction: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a common genetic cause of cerebral small vessel disease. In addition to ischemic stroke (IS), patients with CADASIL may also suffer from intracerebral hemorrhage (ICH). This study aimed to clarify the acute stroke presentation among CADASIL patients in Taiwan. Methods: We enrolled 106 genetically confirmed CADASIL patients (49 from a single university hospital; 57 from positive screening results of NOTCH3 R544C hotspot mutation in a national stroke registry). Acute stroke events with well-documented clinical and neuroimaging features of were included for further analysis. Results: There were 25 (38%) ICH among 66 patients with well-documented acute stroke events. The mean ICH volume was 12.4 ml, and 39% had intraventricular hemorrhage. The most common ICH location was thalamus (56%) and putamen (20%). Among ICH patients, those with past history of hypertension (88%) had larger ICH volume (13.7 ml vs 3.6 ml) and worse functional outcome at discharge (modified Rankin scale, mRS, 3.5 vs 1.0). While in 41 IS events, subcortical white matter was the most common location (49%), and small vessel occlusion type was the predominant pattern (68%). Patients with ICH had significantly higher stroke severity (mean NIHSS score, 14.0 vs 4.4, P &lt;0.01), worse function outcome at discharge (mRS 3.3 vs 2.1, P =0.02), and higher mortality rate (28% vs 2.4% P &lt;0.01) then IS. Higher age (OR 1.11, 95% CI 1.02 - 1.21) and NIHSS score at admission (OR 1.44, 1.12 - 1.83) were predictors of poor function outcome (mRS &gt;2) at discharge. Of 47 patients with available follow-up information, 22 (47%) of them had at least one recurrent stroke, and the recurrent events can be either ICH or IS in spite of the first stroke type. Conclusions: We found a high proportion of ICH among CADASIL patients with acute stroke events, and those with ICH had significant worse outcome than IS counterpart.

Factors Associated with Fever in Intracerebral Hemorrhage

Fever is common in patients with intracerebral hemorrhage (ICH). We sought to identify predictors of fever in patients hospitalized with ICH, and compare infectious fever with noninfectious fever. A retrospective review on consecutive spontaneous ICH patients from April 2009 to March 2010 was performed. Fever was defined as temperature 100.9°F or higher and attributed to infectious versus noninfectious etiology, based upon the National Healthcare Safety Network criteria. Univariate analysis and multivariable logistic regression model were used to determine factors associated with fever and with infection. Among the 351 ICH patients, 136 (39%) developed fever. Factors associated with fever included mean ICH volume, intraventricular hemorrhage (IVH), external ventricular drain (EVD) placement or surgical evacuation, positive microbial cultures, longer length of stay (LOS), and higher in-hospital mortality. Among patients with fever, 96 (71%) were noninfectious and 40 (29%) were infectious. Infectious fever was associated with higher LOS. Noninfectious fever was associated with higher in-hospital mortality. In multivariable analysis, ICH volume (OR = 1.01, P = .04), IVH (OR = 2.0, P = .03), EVD (OR = 3.7, P < .0001), and surgical evacuation (OR = 6.78, P < .0001) were significant predictors of fever. Infectious fever (OR = 5.26, P = .004), EVD (OR = 4.86, P = .01), and surgical evacuation (OR = 4.77, P = .04) correlated with prolonged LOS when dichotomized using a median of 15 days. Fever is common in ICH patients and is not associated with a clear infectious etiology in the majority of patients. Patients with noninfectious fever have higher in-hospital mortality, but survivors have shorter LOS. Further studies are warranted to better understand fevers in ICH.

Abstract WP366: Quantitative Diffusion Tensor Tractography of the Corticospinal Tract as a Predictive Outcome Parameter in Patients With Intracerebral Hemorrhage

Introduction: Intracerebral hemorrhage (ICH) is a devastating disease with poor outcome. Established predictive markers include initial hematoma size, clinical status, intraventricular bleeding and age. However, prognostic assessment is often difficult which additionally burdens patients and caregivers and complicates rehabilitation. Functional outcome especially relies on motor function which is correlated with the integrity of the Corticospinal Tract (CST). Diffusion Tensor (DT) Tractography allows visualization of the CST. However, sufficient data about the prognostic impact of quantitative CST assessment is lacking. Methods: We prospectively enrolled patients with spontaneous supratentorial ICH admitted between 08/2012 und 08/2015. Informed consent and ethical approval was obtained. MRI scan was performed on day 5±1. DT data was normalized to MNI Space and Q-Space diffeomorphic reconstruction was performed using DSI-studio. CST was reconstructed based on quantitative anisotropy (QA) using the CST region (JHU white matter atlas) as seeding region and cerebral peduncle as region of interest (ROI). Fractional Anisotropy (FA) and QA were analyzed in the seeding and ROI region and in the posterior limb of the internal capsule (PLIC). Dichotomized modified Rankin Scale on day 90 (favorable outcome = mRS 0-2) was assessed as primary outcome variable. Results: 33 patients, mean age 70.7 y (standard deviation (SD) 12.9), 12 male, 21 with lobar hemorrhage, mean ICH volume on admission 16.5 (SD 11.3) cm 3 were included. 16 patients had a favorable outcome on day 90 (median mRS 3 (IQR 1-3.5). Mean number of reconstructed CST fiber pathways ipsilateral to ICH was higher in patients with favorable outcome (11343 (SD 8201)) than in patients with unfavorable outcome (4868 (SD 3221), p=0.008). Median QA and FA values in the PLIC ipsilateral to ICH were also higher in patients with favorable outcome (QA: 18.9 (IQR 16.2-23.3) vs. 14.6 (IQR 11.7 - 17.7), p=0.016, FA: 0.49 (IQR 0.45-0.53) vs. 0.41 (IQR 0.38-0.49), p=0.026). Conclusion: Higher FA- and QA-values in the PLIC and higher numbers of CST fiber pathways ipsilateral to ICH seem to be associated with a favorable outcome. DT Imaging may turn out as a useful quantitative predictive marker in the acute phase of ICH.

Effects of Mannitol 20% on Outcomes in Nontraumatic Intracerebral Hemorrhage.

Background:A large number of stroke patients are not the perfect candidate for craniotomy and invasive procedures, so providing an alternative and noninvasive method, which is applicable in terms of costs and facilities, is necessary. Thus, the present study aimed to determine the effects of mannitol 20% on outcome of the patients with nontraumatic intracerebral hemorrhage (ICH) in patients admitted to Isfahan's Al-Zahra Hospital during 2012 and 2013.Materials and Methods:This is a clinical trial study which is conducted during 2012–2013 in Isfahan's Al-Zahra Hospital. In this study, 41 patients suffering from ICH received mannitol 20% for 3 days, and volume of hemorrhage and Glasgow Coma Scale (GCS) of patients were controlled every 12 h. The collected data were analyzed via SPSS software.Results:The mean ICH volume was 22.1 ± 6.3 ml in pre intervention and 38.4 ± 19.3 ml in post intervention, and according to the t-paired test, before and after treatment the difference was significant (P < 0.001). Hemorrhage volume was stable in nine patients (22%), it increased in 25 patients (61%), and decreased in seven patients (17.1%). The mean index of GCS before and after treatment was 11.85 ± 1.6 and 9.37 ± 2.65, respectively. Moreover according to t-paired test, the difference was significant before and after treatment (P < 0.001). During using mannitol, the GCS index was stable in eight patients (19.5%), it increased in eight patients (19.5%) and decreased in 25 patients (61%).Conclusions:Mannitol injection was not effective in reducing hemorrhage size, and its use is not recommended, also, further studies in this field have been proposed.

Predictors of Supratentorial Deep Intracerebral Hemorrhage Volume and Their Effect on Short-Term Mortality in Asians

Background: The volume of intracerebral hemorrhage (ICH) measured at hospital admission is the strongest predictor of clinical outcomes in patients with ICH. Despite the high incidence rate of ICH in Asians, there is lack of data regarding predictors of ICH volume in this ethnic group. The purpose of this study was to determine predictors of deep ICH volume and examine their effect on short-term mortality in Asians. Methods: Hematoma volume was measured using the ABC/2 method. ICH volume was transformed to the natural log scale to normalize distributions for all analyses. We estimated the coefficients of ICH volume based on relevant predictors using multivariable linear regression. We also determined the association between body mass index (BMI) and ICH volume using a regression line and a line determined by a locally weighted scatter plot smoothing. Results: A total of 1,039 patients from 2 twin hospitals in Korea who were admitted with primary spontaneous supratentorial deep ICH over a 12-year period were enrolled in this study. The median ICH volume was 19.7 ml. The average patient age was 59.2, and 62.4% of patients were men. The mean ICH volume showed a gradual, approximately 2% decrease per 1 BMI increase in the current study, after adjusting for all relevant variables (β = -0.024; SE 0.004; p < 0.001). In addition, patients with frequent alcohol consumption showed a 10% increase in mean ICH volume (β = 0.098; SE 0.041; p = 0.016), and patients undergoing warfarin treatment showed a 30% increase in mean ICH volume after full adjustment of all relevant variables (β = 0.296; SE 0.050; p < 0.001). Relative to overweight patients, there was a 47, 11, and 18% increase in admission mean ICH volume in underweight, normal weight and obese patients, respectively. Patients in the first quartile and underweight BMI groups had 1.45-fold (hazard ratio (HR) 1.45; 95% CI 1.03-2.03; p = 0.035) and 1.77-fold (HR 1.77; 95% CI 1.10-2.84; p = 0.019) higher increased risk of death during the first 3 months after ICH, retrospectively. In addition, patients in groups with frequent alcohol consumption and warfarin use both showed a significant association with mortality 90 days after ICH. Conclusions: We demonstrated the association between various predictors and admission ICH volume with short-term mortality in Asians. Further studies are needed to account for these observations and determine their underlying mechanisms.

Initial Single-Center Technical Experience With the BrainPath System for Acute Intracerebral Hemorrhage Evacuation.

Surgical intervention has been proposed as a means of reducing the high morbidity and mortality associated with acute intracerebral hemorrhage (ICH), but many previously reported studies have failed to show a clinically significant benefit. Newer, minimally invasive approaches have shown some promise. We report our early single-center technical experience with minimally invasive clot evacuation using the BrainPath system. Prospective data were collected on patients who underwent ICH evacuation with BrainPath at the Cleveland Clinic from August 2013 to May 2015. Eighteen patients underwent BrainPath evacuation of ICH at our center. Mean ICH volume was 52.7mL ± 22.9mL, which decreased to 2.2mL ± 3.6mL postevacuation, resulting in a mean volume reduction of 95.7% ± 5.8% (range 0-14mL, P < .001). In 65% of patients, a bleeding source was identified and treated. There were no hemorrhagic recurrences during the hospital stay. In this cohort, only 1 patient (5.6%) died in the first 30days of follow-up. Median Glasgow Coma Score improved from 10 (interquartile range 5.75-12) preoperation to 14 (interquartile range 9-14.25) postoperation. Clinical follow-up in this cohort is ongoing. Evacuation of ICH using the BrainPath system is safe and technically effective. The volume of clot removed compares favorably with other published studies. Early improved clinical outcomes are suggested by improvement in Glasgow Coma Score and reduced 30-day mortality. Ongoing analysis is necessary to elucidate long-term clinical outcomes and the subsets of patients who are most likely to benefit from surgery.

Abstract WP355: Intracerebral Hemorrhage Care in a Stroke Unit is Safe and Associated With Lower Costs

Background: There is little data to support level of care decisions for lower risk intracerebral hemorrhage (ICH) patients. The addition of a dedicated stroke unit (SU) at our institution allowed for a comparison of such patients cared for in the intensive care unit (ICU) or SU. We hypothesized that SU care of select ICH patients would not change functional outcome, and result in reduced costs. Methods: Two retrospective cohorts of consecutive patients with small (&lt;20 cc) supratentorial ICH and the absence of anticoagulation were enrolled. In the first study period from August 1, 2008 to February 1, 2011, patients were admitted to the neurological or medical ICU (historical control). In the second study period from August 1, 2012 to January 30, 2014, patients were admitted to a dedicated SU. Intubated patients, those requiring vasopressors, osmotic therapy, or ventriculostomy were excluded. Primary outcomes were discharge modified Rankin Score (mRS) and total hospital charges. Multivariate analyses were used for predicting mRS and early complications. Results: There were 104 patients included in the analysis (41 ICU, 63 SU). Mean age, gender and race did not differ significantly between groups. Mean ICH volume was 6cc in the SU group and 8cc in the ICU group (P&gt;.05). Prior antiplatelet use, ICH location, and ICH score did not differ between groups. Intraventricular hemorrhage and hydrocephalus were more common in the ICU group (P&lt;.001). Two SU patients transferred to the ICU for pneumonia and acute myocardial infarction. There were no significant differences in complications such as ICH expansion, use of osmotic therapy, seizures, or pneumonia. There was no difference in discharge mRS between groups (P&gt;.05). Median hospital length of stay was 6 days in the ICU group and 3 days in SU group (P&lt;.001). Median direct costs for the ICU group were $5,859 (IQR 4,782-9,733) and were $4,078 (IQR 2,861-6,865) for the SU group (P&lt;.001). Unit of admission was not a significant predictor of early complication (P=.73) or discharge mRS (P=.43) in multivariate analysis. Conclusions: This preliminary retrospective study provides support for select low-risk ICH patients to be safely cared for in a lower intensity setting with potential for reducing costs.

Predictors of 30-day mortality in patients with spontaneous primary intracerebral hemorrhage.

Background:Intracerebral hemorrhage (ICH) is a life threatening entity, and an early outcome assessment is mandatory for optimizing therapeutic efforts.Methods:We retrospectively analyzed data from 342 patients with spontaneous primary ICH to evaluate possible predictors of 30-day mortality considering clinical, radiological, and therapeutical parameters. We also applied three widely accepted outcome grading scoring systems [(ICH score, FUNC score and intracerebral hemorrhage grading scale (ICH-GS)] on our population to evaluate the correlation of these scores with the 30-day mortality in our study. We also applied three widely accepted outcome grading scoring systems [(ICH score, FUNC score and intracerebral hemorrhage grading scale (ICH-GS)] on our population to evaluate the correlation of these scores with the 30-day mortality in our study.Results:From 342 patients (mean age: 67 years, mean Glasgow Coma Scale [GCS] on admission: 9, mean ICH volume: 62.19 ml, most common hematoma location: basal ganglia [43.9%]), 102 received surgical and 240 conservative treatment. The 30-day mortality was 25.15%. In a multivariate analysis, GCS (Odds ratio [OR] =0.726, 95% confidence interval [CI] =0.661–0.796, P < 0.001), bleeding volume (OR = 1.012 per ml, 95% CI = 1.007 – 1.017, P < 0.001), and infratentorial hematoma location (OR = 5.381, 95% CI = 2.166-13.356, P = 0.009) were significant predictors for the 30-day mortality. After receiver operating characteristics analysis, we defined a “high-risk group” for an unfavorable short-term outcome with GCS <11 and ICH volume >32 ml supratentorially or 21 ml infratentorially. Using Pearson correlation, we found a correlation of 0.986 between ICH score and 30-day mortality (P < 0.001), 0.853 between FUNC score and 30-day mortality (P = 0.001), and 0.924 between ICH-GS and 30-day mortality (P = 0.001).Conclusions:GCS score on admission together with the baseline volume and localization of the hemorrhage are strong predictors for 30-day mortality in patients with spontaneous primary intracerebral hemorrhage, and by relying on them it is possible to identify high-risk patients with poor short-term outcome. The ICH score and the ICH-GS accurately predict the 30-day mortality.

CT Evolution of Hematoma and Surrounding Hypodensity in a Cadaveric Model of Intracerebral Hemorrhage.

The evolution of intracerebral hematoma and perihematoma edema in the ultra-early period on computed tomographic (CT) scans in patients with intracerebral hemorrhage (ICH) is not well understood. We aimed to investigate hematoma and perihematoma changes in "neutral brain" models of ICH. One human and five goat cadaveric heads were used as "neutral brains" to provide physical properties of brain without any biological activity or new bleeding. ICH was induced by slow injection of 4 ml of fresh human blood into the right basal ganglia of the goat brains. Similarly, 20 ml of fresh blood was injected deep into the white matter of the human cadaver head in each hemisphere. Serial CT scans of the heads were obtained immediately after hematoma induction and then 1, 3, and 5 hours afterward. Analyze software (AnalyzeDirect, Overland Park, KS, USA) was used to measure hematoma and perihematoma hypodensity volumes in the baseline and follow-up CT scans. The initial hematoma volumes of 11.6 ml and 10.5 ml in the right and left hemispheres of the cadaver brains gradually decreased to 6.6 ml and 5.4 ml at 5 hours, showing 43% and 48% retraction of hematoma, respectively. The volume of the perihematoma hypodensity in the right and left hemisphere increased from 2.6 ml and 2.2 ml in the 1-hour follow-up CT scans to 4.9 ml and 4.4 ml in the 5-hour CT scan, respectively. Hematoma retraction was also observed in all five goat brains ICH models with the mean ICH volume decreasing from 1.49 ml at baseline scan to 1.01 ml at the 5-hour follow-up CT scan (29.6% hematoma retraction). Perihematoma hypodensity was visualized in 70% of ICH in goat brains, with an increasing mean hypodensity volume of 0.4 ml in the baseline CT scan to 0.8 ml in the 5-hour follow-up CT scan. Our study demonstrated that substantial hematoma retraction and perihematoma hypodensity occurs in ICH in the absence of any new bleeding or biological activity of surrounding brain. Such observations suggest that active bleeding is underestimated in patients with no or small hematoma expansion and our understanding of perihematoma hypodensity needs to be reconsidered.

Impact of Perihemorrhagic Edema on Short-Term Outcome After Intracerebral Hemorrhage.

Intracerebral hemorrhage (ICH) is a devastating disease with ICH volume being the main predictor of poor outcome. The prognostic role of perihemorrhagic edema (PHE) is still unclear; however, available data are mainly derived from analyses during the first days after symptom onset. As PHE growth may continue up to 14days after ICH, we evaluated PHE over a longer period of time and investigated its impact on short-term clinical outcome. In this monocentric retrospective cohort study, patients with spontaneous supratentorial ICH were identified from our institutional data base. Different time points of CT scans were merged to time clusters for better comparison (day 1, 2-3, 4-6, 7-9, 10-12). Absolute volumes of ICH and PHE were obtained using a validated semiautomatic volumetric algorithm. Clinical outcome at discharge was assessed using the modified Rankin Scale (0-3=favorable, 4-6=poor). 220 patients (83 with favorable, 137 with poor outcome) were included in the final analysis. Mean ICH volume on admission was 22.8 [standard deviation (SD) 24.6] cm(3). Mean absolute PHE volume on admission was 22.5 (SD 20.8) cm(3) and increased to a mean peak volume of 38.1 (SD 31.4) cm(3) during 6.7 (SD 4.1) days on average. Besides GCS on admission, functional status before ICH, peak hematoma volume, lobar localization and fever burden, and high peak PHE volume predicted poor outcome at discharge [OR 0.977 (95% CI 0.957-0.998)] in the multivariable analysis. PHE may have a negative impact on short-term functional outcome after ICH and therefore represent a possible treatment target.

Abstract 97: Ischemic Lesions in Intracerebral Hemorrhage Associated with Drop in Blood Pressure and Poor Outcomes in the ERICH Study

Background: Up to 1/3 of patients with primary intracerebral hemorrhage (ICH) have acute ischemic lesions remote from the hematoma visualized on diffusion-weighted MRI (DWI). Prior reports associated these lesions with large blood pressure fluctuations in the acute hospital setting. Here, the Ethnic/Racial variations of Intracerebral Hemorrhage (ERICH) study explored predictors of ischemic lesions in primary ICH and their impact on long-term outcomes. Methods: ERICH is a multi-center, prospective study of ICH among white, black, and Hispanic patients. At least every 5th patient undergoes a study MRI interpreted by a central core blinded to clinical data. We calculated change in mean arterial pressure (delta MAP) by taking the difference in highest and lowest blood pressure prior to MRI. Results: For the 601 cases with a DWI MRI, mean±SD age was 61±14 years, mean ICH volume was 16±18 cc, 55% were male, 79% had hypertension and 26% had ≥1 DWI lesions. The frequency of DWI lesions differed by ethnicity (blacks 33%, Hispanics 24%, whites 20%, overall p=0.005). The multivariable logistic regression analysis identified lower age (10 year OR=0.68, p&lt;0.001), higher delta MAP (10 unit OR=1.16, p&lt;0.001), higher WMD score (1 unit OR=1.164, p&lt;0.001) and presence of microbleeds (OR=2.122, p=0.001) as predictors of DWI lesions. After controlling for age, ICH volume, IVH and admission GCS, presence of DWI lesions was associated with 6 month poor outcome (MRS 4-6, OR=1.25, p=0.02; Figure). Conclusions: The ERICH study confirms that large fluctuations in blood pressure during the acute hospitalization period predict DWI lesions, and that DWI lesions predict poor outcomes. We hypothesize that substantial reductions in blood pressure precipitate acute small vessel ischemia in those ICH patients with a more severe underlying diseased vasculature. Further studies are needed to determine whether there is a level of acute blood pressure reduction at which the risks outweigh the benefits.

Abstract TP291: Hematoma Retraction and Perihematoma Hypodensity in Neutral Brain Model of Intracerebral Hemorrhage

Background: The temporal evolution of intracerebral hematomas and perihematoma edema in the ultra-early period on computed tomographic (CT) scans in patients with intracerebral hemorrhage (ICH) is not well understood. We aimed to investigate hematoma and perihematoma changes in “neutral brain” models of ICH. Methods: One human and 6 goat cadaveric heads were used as “neutral brains” to provide physical properties of the brain without any biological activity or new bleeding. ICH was induced by slow injection of 4 ml of fresh blood into the right basal ganglia of the goat brains. Similarly, 20 ml of fresh blood was injected deep into the white matter of the human cadaver head in each hemisphere. Serial CT scans of the heads were performed at 0, 1, 3, and 5 hours after inducing ICH. Analyze software (AnalyzeDirect, Overland Park, KS) was used to measure hematoma and perihematoma hypodensity volumes in the baseline and follow up CT scans. Results: The initial hematoma volumes of 11.6 ml and 10.5 ml in the right and the left hemispheres of the human cadaver brain gradually decreased to 6.6 ml and 5.4 ml at 5 hours, showing 43% and 48% retraction of hematoma, respectively. The volume of the perihematoma hypodensity in the right and left hemisphere increased from 2.6 ml and 2.2 ml in the 1 hour follow up CT scans to 4.9 ml and 4.4 ml in the 5 hour CT scan, respectively. Hematoma retraction was also observed in all six ICH models in the goat brains. The mean ICH volume in the goat heads was decreased from 1.49 ml in the baseline CT scan to 1.01 ml in the 5 hour follow up CT scan showing 29.6% hematoma retraction. Perihematoma hypodensity was visualized in 70% of ICH in goat brains, with an increasing mean hypodensity volume of 0.4 ml in the baseline CT scan to 0.8 ml in the 5 hour follow up CT scan. Conclusion: Our study demonstrated that substantial hematoma retraction and perihematoma hypodensity occurs in intracerebral hematomas in the absence of any new bleeding or biological activity of the surrounding brain. Such observations suggest that active bleeding is underestimated in patients with no or small hematoma expansion and our understanding of perihematoma hypodesity needs to be reconsidered.

Abstract 99: Impact of Acute Perihematomal Edema on Long Term Outcomes Following Primary Intracerebral Hemorrhage

Introduction: The impact of acute perihematomal edema (PHE) as an independent predictor of clinical outcomes following an intracerebral hemorrhage (ICH) has been controversial. To date, some studies have reported that PHE is associated with poorer outcomes, while others have found an association with good outcomes. The goals of the current analysis were to 1) identify predictors of acute PHE, and 2) determine impact of PHE on clinical outcomes in a predominantly African American hypertensive ICH population. Methods: Subjects with spontaneous non-traumatic ICH who were prospectively enrolled in the DiffErenCes in the Imaging of Primary Hemorrhage based on Ethnicity or Race (DECIPHER) Project were included in the analysis. Baseline MRIs were performed in subjects at median of 2 days from onset. Hematoma volume as well as PHE were calculated from GRE and FLAIR sequences, respectively, employing a semiautomated volumetric analysis. PHE volume was expressed as a percent of the hematoma volume (PHEv/ICHv x 100). Outcome measures included year 1 NIHSS score using a log-linear model and dichotomized (0-2 vs. 3-6) modified Rankin Scale (mRS) using a logistic regression model. Results: A total of 140 subjects were included in the analysis. Mean age was 59, 58% were male, 75% were black, and 85% had a history of hypertension. Baseline NIHSS score was mean 9 (median 6), mean ICH volume was 25 cc (range 0.5-136 cc), and mean relative PHE percent was 115% (range 0-559%). Independent predictors of PHE on multivariate analysis included ICH volume (p=0.004) and antiplatelet use on admission (p=0.02). At the year 1 timepoint, there was no significant association between the severity of PHE percent and good or poor outcome based on dichotomized mRS (p=0.67); however there was a modest trend towards an association between increased edema and lower NIHSS scores (p=0.15). Conclusions: In this large MRI-based cohort of patients with primary ICH, acute perihematomal edema measured on FLAIR sequences was not an independent predictor of poor functional outcome at year 1 employing the mRS. However, there was a modest trend towards an association between increased relative edema volume and lower year 1 NIHSS scores, which may suggest a protective effect of edema on outcome. Further studies in a larger cohort are needed to clarify the impact of both acute and peak perihematomal edema on outcome following primary ICH.