Severe Intracerebral Hemorrhage Research Articles

Intraclot recombinant tissue-type plasminogen activator reduces perihematomal edema and mortality in patients with spontaneous intracerebral hemorrhage

The study aimed to investigate the impact of intraclot recombinant tissue-type plasminogen activator (rt-PA) on perihematomal edema (PHE) development in patients with intracerebral hemorrhage (ICH) treated with minimally invasive surgery (MIS) and the effects of intraclot rt-PA on the 30-day survival. We reviewed the medical records of ICH patients undergoing MIS between October 2011 and July 2013. A volumetric analysis was done to assess the change in PHE and ICH volumes at pre-MIS (T1), post-MIS (T2) and day 10-16 (T3) following diagnostic computed tomographic scans (T0). Forty-three patients aged 52.8±11.1 years with (n=30) or without rt-PA (n=13) were enrolled from our institutional ICH database. The median rt-PA dose was 1.5 (1) mg, with a maximum dose of 4.0 mg. The ratio of clot evacuation was significantly increased by intraclot rt-PA as compared with controls (77.9%±20.4% vs. 64%±15%; P=0.046). From T1 to T2, reduction in PHE volume was strongly associated with the percentage of clot evacuation (ρ=0.34; P=0.027). In addition, PHE volume was positively correlated with residual ICH volume at the same day (ρ ranging from 0.39-0.56, P<0.01). There was no correlation between the cumulative dose of rt-PA and early (T2) PHE volume (ρ=0.24; P=0.12) or delayed (T3) PHE volume (ρ=0.19; P=0.16). The 30-day mortality was zero in this cohort. In the selected cohort of ICH patients treated with MIS, intraclot rt-PA accelerated clot removal and had no effects on PHE formation. MIS aspiration and low dose of rt-PA seemed to be feasible to reduce the 30-day mortality in patients with severe ICH. A large, randomized study addressing dose titration and long-term outcome is needed.

Intracranial pressure measured in freely moving rats for days after intracerebral hemorrhage

In some patients, intracerebral hemorrhage (ICH) causes life-threatening elevations in intracranial pressure (ICP) arising from mass effect of the hematoma and edema. Accordingly, edema is a common endpoint to gauge treatment efficacy in rodent ICH models. Despite widespread reliance on edema, its relationship with ICP and cerebral perfusion pressure (CPP) is unknown. Blood pressure (BP) and ICP were measured by telemetry devices in rats after collagenase (“severe” — 0.3U, and “moderate” — 0.15U doses) or blood infusion (100μL) into striatum (vs. saline infused shams). We compared epidural and intraparenchymal ICP readings (collagenase), evaluated CPP (collagenase), and compared models. Moderate (9.46mmHg±4.72 SD, 3day average) and severe collagenase ICHs (10.79±3.50) significantly increased ICP versus shams (4.02±2.09), whereas blood infusion did not (5.37±0.55). The two monitoring locations gave similar readings after severe collagenase ICH. Increased ICP reduced CPP by ~7.5mmHg for days after the larger collagenase infusion. CPP averaged from 103–112mmHg in shams. Edema occurred in all ICH models and predicted ICP. However, ICP and CPP were only modestly changed even after severe ICH and edema. Thus, small changes in edema typically reported in the literature, which often use smaller bleeds than presently used, likely minimally affects ICP and CPP. Further research into the face validity of these models, endpoints, and their ability to evaluate therapeutics is needed.

Determinants of External Ventricular Drain Placement and Associated Outcomes in Patients with Spontaneous Intraventricular Hemorrhage

External ventricular drain (EVD) usage in patients with intraventricular hemorrhage (IVH) is variable in current practice and in clinical trials, and its impact on outcome remains controversial. The objective of this study was to identify the clinical predictors of EVD utilization, and associated outcome in adults with spontaneous IVH with or without intracerebral hemorrhage (ICH). Retrospective review of 183 consecutive IVH patients admitted to a University Hospital between 2003 and 2010. Clinical and radiographic data were analyzed for associations between EVD placement and mortality, poor outcome, and improvement in Glasgow Coma Scale score (GCS) using multivariate logistic regression models. Average age was 62±15.6years, and average ICH and IVH volumes were 35.8±40.9cc and 19.7±25.3cc, respectively. Independent predictors of EVD placement within first 5days of admission were GCS≤8 (OR 11.5; P<0.001), Graeb score >5 (OR 4.6; P=0.001), and non-lobar ICH≤30cc (OR 9.7; P<0.001). Median GCS increased from 5 (IQR 3-7) 48h post-EVD (P<0.001). EVD placement was an independent predictor of reduced mortality (OR 0.31; P=0.04) and modified Rankin score 0-3 (OR 15.7; P=0.01) at hospital discharge. In patients with hydrocephalus on presentation, EVD was associated with reduced mortality for patients with GCS>3 after controlling for ICH and IVH severity (OR 0.02; P=0.01). Patients with lower GCS, higher IVH severity, and lower ICH volume are more likely to have an EVD placed. EVD placement is associated with reduced mortality and improved short-term outcomes in patients with IVH after adjusting for known severity factors. EVD use should be protocolized in clinical trials of ICH management where IVH is included.

Abstract T MP76: Acute Kidney Injury in Acute Ischemic Strokes is Associated with Worse Outcomes

Background: Acute Kidney Injury (AKI) in setting of acute ischemic stroke (AIS) is associated with worse outcome. Objective: To determine the effect of AKI on outcomes of AIS patients treated in a large national cohort. In a sub-analysis we looked at the outcomes of AKI in AIS patients treated with and without thrombolytic. Methods: Data from all patients admitted to US hospitals between 2002 and 2010 with a primary discharge diagnosis of ischemic stroke and secondary diagnosis of AKI treated with or without IV thrombolysis were included. The effect of AKI on rates of intracerebral hemorrhage (ICH) and discharge outcomes was analyzed after adjusting for potential confounders using logistic regression analysis. Results: Of 7,068,334 patients with AIS, 372,223 (5.3%) had AKI. AIS patients with AKI had higher rates of moderate to severe disability (41.3% versus 30% p=&lt;0.0001), ICH (1.0% versus 0.5% p=&lt;0.0001) and In-hospital mortality (8.4% versus 2.9% p=&lt;0.0001) compared to those without AKI. After adjusting for potential confounders AIS patients with AKI had higher odds of moderate to severe disability [Odds ratio (OR) 1.4, 95% confidence interval (CI) (1.3-1.4, p=&lt;0.0001)], ICH [(OR) 1.6, 95% (CI) (1.5-1.8, p=&lt;0.0001)] and death [(OR) 2.6, 95% (CI) (2.5-2.8, p=&lt;0.0001)]. In a sub-analysis, AIS patients with AKI who were treated with thrombolytic had higher rates of moderate to severe disability (54.5% versus 41.1% p=&lt;0.0001), ICH (7.4% versus 0.8% p=&lt;0.0001) and In-hospital mortality (21.4% versus 8.2% p=&lt;0.0001) compared to those were not treated with thrombolytic. After adjusting for potential confounders AIS patients with AKI who were treated with thrombolytic had higher odds of moderate to severe disability [(OR) 1.7, 95% (CI) (1.5-2.0, p=&lt;0.0001)], ICH [(OR) 8.0, 95% (CI) (6.1-10.2, p=&lt;0.0001)] and death [(OR) 2.7, 95% (CI) (2.3-3.2, p=&lt;0.0001)] compared to those were not treated with thrombolytic. Conclusion: AKI in patients with AIS is associated with significantly higher rates of disability at discharge, ICH and in-hospital mortality. In such patients, administration of thrombolytic treatment further worsens the outcome.

Abstract W P248: Cerebral Tissue Iron Quantification on MRI Following Intracerebral Hemorrhage

Purpose: Intracerebral hemorrhage (ICH) is a fatal subtype of Hemorrhagic stroke. Tissue iron at the periphery of ICH has been demonstrated to be neurotoxic in animal models. No robust method to quantify tissue iron following ICH currently exists. Our aim is to determine a robust algorithm based on MRI to quantify tissue iron in the wake of ICH. Methods: Following Institutional review board approval we constructed an MRI phantom. Eight 4 cc vials with 50 % decreasing dilutions of Ferraheme (iron for IV therapy) were prepared starting from 0.6 mg/ml ending at 0.005 mg/ml. The vials were stuck to the undersurface of the lid of a water bath container and scanned in a 3T MRI with T2* sequences. The T2* signal magnitudes were calculated for each concentration. Subsequently a human control brain and two patients with left basal ganglia ICH were scanned with identical parameters. The T2* signal magnitude was calculated at 3 ROIs at the periphery of the ICH. Results: The R2* maps demonstrated a near linear correlation with the iron concentration in the phantom. The control T2* signal magnitude corresponded to 0.01 mg/ml iron concentration. The two patients on ICH day 7 had measurements of iron concentration of 0.04 mg/ml (4 x baseline) at the periphery of the hematoma. This corresponds favorably to a threefold increase in measured tissue iron levels in animal ICH model studies. Conclusion: Our experiment demonstrates that quantitative susceptibility measurements on MRI may be a robust technique to assess iron level in brain tissue following ICH. Encouraged by the results we have applied to the NIH (#GRANT11426089) for funding to be able to evaluate the validity of the algorithm. Tissue iron quantification by MRI may assist in judging severity of ICH and act as a surrogate marker for assessing treatment with iron chelator.

Abstract W P300: Factors Affecting Functional Assessment Measures (FAM) Self-Completion Among Intracerebral Hemorrhage (ICH) Patients

Background: The Barthel Index (BI) and Stroke Impact Scale (SIS) are established functional assessments measuring (FAM) performance in daily living activities and overall quality of health and life in stroke patients, respectively. Purpose: To determine factors affecting FAM self-completion among intracerebral hemorrhage (ICH) patients at 3 months post-stroke. Methods: Sample size consisted of 84 patients enrolled in an ICH clinical trial. Three categories were created to account for FAM completion: 1) Patient (P), 2) Family/Surrogate (F), 3) Missing/Not Required (M), which also included expired patients. To compare the differences between groups, analysis of variance, Kruskal-Wallis test or extended Fisher’s exact test, as appropriate, were performed. Results: BI was performed at baseline [n(%): P = 29 (34.5%), F = 55 (65.5%), M = 0 (0%)] and 3 months post-stroke [P = 45 (53.6%), F = 11 (13.1%), M = 28 (33.3%)]. SIS was performed at 3 months post-stroke [P = 43 (51.2%), F = 12 (14.3%), M = 29 (34.5%)]. Several baseline factors were scrutinized for their effect on FAM self-completion at 3 months. BI was significantly affected by: Stroke Scale (NIHSS), Glasgow Coma Scale (GCS), Modified Ranking Scale (mRS) and Hyperlipidemia. SIS was significantly affected by: NIHSS, GCS and aphasia. Larger baseline hematoma volumes (≥ 20.1cc), although not significant, also appeared to affect the study outcome. Conclusion: Patients presenting at baseline with NIHSS score ≥ 16, larger hematoma volumes, lower GCS, aphasia and hyperlipidemia were less likely to complete their own functional assessments by 3 months. Further study is necessary to explore additional FAM for severe ICH patients.

Low-Density Lipoprotein and Intracerebral Hematoma Expansion in Daily Alcohol Users

Background: Epidemiological studies suggest that the intracerebral hemorrhage (ICH) rate correlates with alcohol consumption. Alcohol leads to elevated blood pressure (BP) and inhibition of platelet aggregation. These factors could promote excessive bleeding. To our knowledge, in the setting of normal liver function tests, there are no studies that have systematically evaluated the relationship between daily alcohol use and hematoma expansion. The aim of this study is to compare the baseline ICH characteristics, frequency of hematoma expansion, and outcomes in patients with ICH who are daily alcohol users with those who are not daily alcohol users. Methods: A retrospective chart review was performed on consecutive patients who presented from July 2008 to July 2013 to the Tulane University Hospital in New Orleans, La., USA, with a spontaneous ICH. Ninety-nine patients who met these criteria were admitted. Patients who underwent hematoma evacuation were excluded. Hemorrhage volumes were calculated based on the ABC/2 method. Low-density lipoprotein (LDL) was dichotomized into low (<100 mg/dl) and high (≥100 mg/dl) values. Comparisons were made using t tests, χ² and nonparametric equivalents where appropriate. ICH growth in 24 h and LDL were evaluated using linear regression. Results: Of the 226 patients who met inclusion criteria, 20.4% had a history of daily alcohol use. The average age was 61 years (range 19-94), 55.6% of the patients were males, and 67.1% were of African American origin. Daily alcohol use was associated with male gender, lower rate of home antihypertensive, higher presenting BP, and lower platelet counts, but there was no difference in ICH characteristics, ICH growth, or clinical outcome. Daily alcohol use in patients with a low LDL level was associated with supratentorial location and trends for lower baseline Glasgow Coma Scale score, higher ICH score, and follow-up ICH volume, but no significant difference in significant hematoma expansion or clinical outcome except for a trend for higher mortality was found (25 vs. 9.5%, p = 0.1311) compared to patients with high LDL values. Conclusions: Our data suggest that neither chronic daily alcohol use nor a low LDL level in combination with daily alcohol use can be used to predict ICH growth. Daily alcohol use was associated with untreated hypertension and higher BP on presentation. A low LDL level in combination with daily alcohol use may be linked with larger and more severe ICH, but we were unable to demonstrate a relationship with hematoma expansion or poor clinical outcome. The role of LDL in vessel fragility and clot stabilization needs to be further explored before concluding that a low LDL level confers risk of bleeding.

Optimal cerebral perfusion pressure in patients with intracerebral hemorrhage: an observational case series

IntroductionCurrent guidelines for spontaneous intracerebral hemorrhage (ICH) recommend maintaining cerebral perfusion pressure (CPP) between 50 and 70 mmHg, depending on the state of autoregulation. We continuously assessed dynamic cerebral autoregulation and the possibility of determination of an optimal CPP (CPPopt) in ICH patients. Associations between autoregulation, CPPopt and functional outcome were explored.MethodsIntracranial pressure (ICP), mean arterial pressure (MAP) and CPP were continuously recorded in 55 patients, with 38 patients included in the analysis. The pressure reactivity index (PRx) was calculated as moving correlation between MAP and ICP. CPPopt was defined as the CPP associated with the lowest PRx values. CPPopt was calculated using hourly updated of 4 hour windows. The modified Rankin Scale (mRS) was assessed at 3 months and associations between PRx, CPPopt and outcomes were explored using Pearson correlation and Fisher’s exact test. Multivariate stepwise logistic regression models were calculated including standard outcome predictors along with percentage of time with PRx >0.2 and percentage of time within the CPPopt range.ResultsAn overall PRx indicating impairment of pressure reactivity was found in 47% of patients (n = 18). The mean PRx and the time spent with a PRx > 0.2 significantly correlated with mRS at 3 months (r = 0.50, P = 0.002; r = 0.46, P = 0.004). CPPopt was calculable during 57% of the monitoring time. The median CPP was 78 mmHg, the median CPPopt 83 mmHg. Mortality was lowest in the group of patients with a CPP close to their CPPopt. However, for none of the CPPopt variables a significant association to outcome was found. The percentage of time with impaired autoregulation and hemorrhage volume were independent predictors for acceptable outcome (mRS 1 to 4) at three months.ConclusionsFailure of pressure reactivity seems common following severe ICH and is associated with unfavorable outcome. Real-time assessment of CPPopt is feasible in ICH and might provide a tool for an autoregulation-oriented CPP management. A larger trial is needed to explore if a CPPopt management results in better functional outcomes.

Acute myocardial infarction and cocaine toxicity: One step closer

Sir, The article by Sarkar et al.,[1] is indeed interesting and timely as practitioners and emergency physicians have started seeing cases of cocaine intoxication in India. However, a few aspects of this paper require contemplation. The authors have administered thrombolytic agent initially for cocaine associated myocardial infraction (CAMI) which is not congruent with current evidence.[2] Current literature questions the routine use of thrombolytic therapy for patients with CAMI and there are reports of severe complications associated with thrombolytics in cocaine users.[3] The frequent presence of contraindications to thrombolysis, including severe hypertension, seizures, intracerebral hemorrhage, and aortic dissection in cocaine abusers precludes the liberal use of thrombolytic agents. Moreover, the standard electrocardiographic criteria (ST elevation) for thrombolytic therapy is hampered by the high rate of abnormal or nondiagnostic electrocardiogram (ECG)'s in patients presenting with cocaine associated chest pain. The guidelines issued by American College of Cardiology and American Heart Association[4] advocate the use of thrombolytic therapy in CAMI only if ST segments remain elevated despite nitroglycerin and calcium antagonists and coronary angiography is not possible. Secondly, the recent cocaine use can alter the specificity of cardiac biomarkers and making them difficult to interpret in CAMI, especially the serum creatinine kinase level is not a reliable indicator of myocardial injury and is increased in almost half of cocaine users irrespective of concurrent MI possibly because of cocaine-induced hyperthermia, increased skeletal muscle activity, and rhabdomyolysis.[5] The awareness of reliability of cardiac biomarkers in cocaine associated chest pain is warranted for effective management. The American Heart Association recommends nitroglycerin and benzodiazepines as first-line agents for cocaine associated chest pain. Benzodiazepines are administrated especially in cocaine-addicted patients with associated hypertension, tachycardia, or anxiety after the cocaine use. Intuitively, dexmedetomidine, a central sympatholytic agent is highly effective in reversing the cocaine's sympathomimetic actions.[6] Substance abuse remains one of the major public health issues across the globe, despite health education on prevention; the incidence of illicit substances is escalating. Since many patients with cocaine toxicity will present with chest pain to the emergency department, it is essential that these patients be recognized early and managed appropriately to prevent complications.

Cost of Spontaneous Intracerebral Hemorrhage in Canada During 1 Decade

Spontaneous intracerebral hemorrhage (ICH) is widely considered to be the most devastating form of stroke in North America. Currently there is no clear understanding of the cost of treatment in Canada and thus no way of understanding how to manage ICH spending in this country. We used a cohort study design to report and to examine the cost of ICH hospital care in a Canadian health center during 1 decade. Economic, treatment, and patients data were obtained from clinical and administrative sources. Analyses were performed using 987 consecutive patients with ICH from 1999 to 2008. The total inflation-adjusted cost of care was highly variable (median cost per discharge, $10,544.45 and $363.54 [min] to $265 470.43 [max] United States Dollars). Total cost did not change significantly during the decade. Patients age (cost change per year older, -$114.06 and -$189.01 to -$38.78) and in-hospital mortality (cost change for death, -$5092.84 and -$6270.65 to -$3697.09) were significantly associated with lower cost, whereas Charlson Comorbidity Index (cost change for ≥1, $5726.27 and $3965.36 to $7755.45), having surgery (cost change for surgery, $25,499.78 and $20,813.95 to $30,933.06), and admission National Institutes of Health Stroke Scale (cost change for ≥15 points, $7800.20 and $1637.78 to $17,026.38) were significantly associated with higher cost. To our knowledge, this is the most thorough published study to date to report and to examine predictors of ICH treatment costs in Canada. This study provides evidence that it may be reasonable to consider patients age, probability of death, level of comorbidity, need for surgery, and baseline ICH severity when forecasting health spending.

Comparison of the effect of edoxaban, a direct factor Xa inhibitor, with a direct thrombin inhibitor, melagatran, and heparin on intracerebral hemorrhage induced by collagenase in rats

Intracerebral hemorrhage (ICH) is a major clinical concern with anticoagulation therapy. The effect of a new oral direct FXa inhibitor, edoxaban, was determined in a rat model of ICH and compared with a direct thrombin inhibitor, melagatran, and heparin. To induce ICH, 0.1 U collagenase type VII was injected into the striatum of male Wistar rats under anesthesia with thiopental or halothane. Immediately after ICH induction, edoxaban, melagatran, or heparin were infused intravenously. Five hours after ICH induction, the brain was removed and ICH size was measured. To estimate the margin of safety, antithrombotic effects were evaluated in a rat venous thrombosis model. Edoxaban at 6mg/kg/h significantly increased ICH volume (1.8-fold) and prolonged prothrombin time (PT) 2.8-fold compared to the vehicle group. No deaths were observed with edoxaban. Melagatran at 1mg/kg/h increased ICH volume at 1mg/kg/h (2.8-fold) with 6.1-fold PT prolongation. At 3mg/kg/h, all rats died due to severe ICH (3.9-fold). Heparin at both 100 and 500U/kg/h significantly increased ICH. At 500U/kg/h, 5 out of 8 rats died. The doses required for 50% inhibition of thrombosis of edoxaban, melagatran, and heparin were 0.045mg/kg/h, 0.14mg/kg/h, and 55U/kg/h, respectively. The safety margins between antithrombotic and ICH exacerbation effects of these anticoagulants were 133, 7.1, and 1.8, respectively. The safety margin of edoxaban was wider than that of melagatran or heparin. These results suggest that edoxaban may be preferable from the perspective of ICH exacerbation risk.

Heritability Estimates Identify a Substantial Genetic Contribution to Risk and Outcome of Intracerebral Hemorrhage

Previous studies suggest that genetic variation plays a substantial role in occurrence and evolution of intracerebral hemorrhage (ICH). Genetic contribution to disease can be determined by calculating heritability using family-based data, but such an approach is impractical for ICH because of lack of large pedigree-based studies. However, a novel analytic tool based on genome-wide data allows heritability estimation from unrelated subjects. We sought to apply this method to provide heritability estimates for ICH risk, severity, and outcome. We analyzed genome-wide genotype data for 791 ICH cases and 876 controls, and determined heritability as the proportion of variation in phenotype attributable to captured genetic variants. Contribution to heritability was separately estimated for the APOE (encoding apolipoprotein E) gene, an established genetic risk factor, and for the rest of the genome. Analyzed phenotypes included ICH risk, admission hematoma volume, and 90-day mortality. ICH risk heritability was estimated at 29% (SE, 11%) for non-APOE loci and at 15% (SE, 10%) for APOE. Heritability for 90-day ICH mortality was 41% for non-APOE loci and 10% (SE, 9%) for APOE. Genetic influence on hematoma volume was also substantial: admission volume heritability was estimated at 60% (SE, 70%) for non-APOEloci and at 12% (SE, 4%) for APOE. Genetic variation plays a substantial role in ICH risk, outcome, and hematoma volume. Previously reported risk variants account for only a portion of inherited genetic influence on ICH pathophysiology, pointing to additional loci yet to be identified.

Anaemia on Admission is Associated with More Severe Intracerebral Haemorrhage and Worse Outcomes

Lower haemoglobin levels may impair cerebral oxygen delivery and threaten tissue viability in the setting of acute brain injury. Few studies have examined the association between haemoglobin levels and outcomes after spontaneous intracerebral haemorrhage. We evaluated whether anaemia on admission was associated with greater intracerebral haemorrhage severity and worse outcome. Consecutive patients with spontaneous intracerebral haemorrhage were analyzed from the Registry of the Canadian Stroke Network. Admission haemoglobin was related to stroke severity (using the Canadian Neurological Scale), modified Rankin score at discharge, and one-year mortality. Adjustment was made for potential confounders including age, gender, medical history, warfarin use, glucose, creatinine, blood pressure, and intraventricular haemorrhage. Two thousand four hundred six patients with intracerebral haemorrhage were studied of whom 23% had anaemia (haemoglobin <120 g/l) on admission, including 4% with haemoglobin <100 g/l. Patients with anaemia were more likely to have severe neurological deficits at presentation [haemoglobin ≤ 100 g/l, adjusted odds ratio 4.04 (95% confidence interval 2.39, 6.84); haemoglobin 101-120 g/l, adjusted odds ratio 1.93 (95% confidence interval 1.43, 2.59), both P < 0.0001]. In nonanticoagulated patients, severe anaemia was also associated with poor outcome (modified Rankin score 4-6) at discharge [haemoglobin ≤ 100 g/l, adjusted odds ratio 2.42 (95% confidence interval 1.07-5.47), P = 0.034] and increased mortality at one-year [haemoglobin ≤ 100 g/l, adjusted hazard ratio 1.73 (95% confidence interval 1.22-2.45), P = 0.002]. Anaemia on admission is associated with greater intracerebral haemorrhage severity and worse outcomes. The utility of transfusion remains unclear in this setting.

Diagnostic impact of baseline cerebral blood flow in patients with acute ischemic stroke prior to intravenous recombinant tissue plasminogen activator therapy

To determine whether severe cerebral perfusion defects measured by SPECT prior to rt-PA therapy attribute to severe intracerebral hemorrhage (SICH). We measured baseline cerebral blood flow (CBF) using technetium-99m-labeled hexamethylpropyleneamine oxime (99mTc-HMPAO) SPECT qualitatively prior to rt-PA therapy, in 52 consecutive patients (range 38-93 years). The degree and extent of the asymmetry of local CBF were analyzed semi-quantitatively. We did not administrate rt-PA in patients with severe perfusion defects. Clinical outcome and the incidence of SICH were studied. Three (5.8%) patients had severe perfusion defects that were undetected by CT and/or DWI. The other 49 (94.2%) patients had mild perfusion defects. The asymmetry of local CBF was 0.08±0.08 (n=3) and 0.3±0.15 (n=49) in the two groups, respectively. The percentages of the ipsilateral hemisphere in which perfusion was impaired severely were 17.5±9.5% (n=3) and 0.43±0.87% (n=49). Two patients were found petechial hemorrhage, but there was no patient who developed SICH in the former group following conventional antithrombotic therapy. In the latter group, SICH occurred in 1/49 (2.0%) patient following rt-PA therapy. These results suggest that rt-PA therapy for patients with severe cerebral perfusion defects may cause SICH and baseline CBF may contribute to identify patients at high risk for SICH after intravenous rt-PA therapy.

Subarachnoid Extension of Primary Intracerebral Hemorrhage is Associated With Poor Outcomes

Extension of hemorrhage into the subarachnoid space is observed in primary intracerebral hemorrhage (ICH), yet the phenomenon has undergone limited study and is of unknown significance. The objective of this study is to evaluate the incidence, characteristics, and clinical consequences of subarachnoid hemorrhage extension (SAHE) in ICH on functional outcomes. Patients with primary ICH were enrolled into a prospective registry between December 2006 and June 2012. Patients were managed and serial neuroimaging was obtained per a structured protocol. Presence of any subarachnoid blood on imaging was identified as SAHE by expert reviewers blinded to outcomes. Regression models were developed to test whether the occurrence of SAHE was an independent predictor of functional outcomes as measured with the modified Rankin Scale. Of 234 patients with ICH, 93 (39.7%) had SAHE. Interrater agreement for SAHE was excellent (kappa=0.991). SAHE was associated with lobar hemorrhage location (65% of SAHE vs 19% of non-SAHE cases; P<0.001) and larger hematoma volumes (median 23.8 vs 6.7; P<0.001). Fever (69.9% vs 51.1%; P=0.005) and seizures (8.6% vs 2.8%; P=0.07) were more common in patients with SAHE. SAHE was a predictor of death by day 14 (odds ratio, 4.45; 95% confidence interval, 1.88-10.53; P=0.001) and of higher (worse) modified Rankin Scale scores at 28 days (odds ratio, 1.76 per mRS point; 95% confidence interval, 1.01-3.05; P=0.012) after adjustment for ICH score. SAHE is associated with worse modified Rankin Scale independent of traditional ICH severity measures. Underlying mechanisms and potential treatments of SAHE require further study.

Abstract 49: Withdrawal of Care in the Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) Study

Introduction: Withdrawal of care (WOC) during hospitalization is the most common cause of death after intracerebral hemorrhage (ICH). Prior work suggests minority groups are less likely to choose WOC. Our goal was to evaluate for differences in rates of WOC among racial/ethnic groups from the ERICH cohort. Methods: ERICH is an ongoing multicenter study of genetic and environmental risk factors for spontaneous ICH. We analyzed data from the first 725 individuals. Baseline characteristics,do not resuscitate (DNR) status, intensive care procedures, and WOC were prospectively recorded. A central core analyzed all imaging. We compared characteristics among patients with and without eventual WOC and by race/ethnicity. Logistic regression was used to identify variables independently associated with WOC and associations are presented as the odds ratio (95% confidence interval). Results: 9.9% (72/725) of patients underwent WOC. After controlling for age, ICH volume, initial Glasgow Coma Scale (GCS) score, and presence of intraventricular hemorrhage (IVH), there were no significant differences in WOC between non-Hispanic white, non-Hispanic black (OR 1.82; CI 0.78-4.25), and Hispanic (OR 2.16; CI 0.93-5.00) patients. There were also no differences in rates of DNR/DNI status across racial/ethnic groups. In multivariate analysis, patients who underwent WOC had larger ICH volume (1.75; 1.13-2.73); were older (1.43; 1.27-1.61), more likely to have IVH (3.21; 1.53-6.73), and had lower GCS (2.41; 1.63-3.56). While patients who underwent WOC were more likely to have a DNR/DNI order (12.7; 4.69-34.7), intubated patients were more likely to undergo WOC (4.09; 1.08-9.25), even after adjusting for ICH severity. Conclusions: In our cohort, we were able to model ICH severity and factors predictive of WOC. There were not significant racial/ethnic differences in WOC rates. Intubated patients are more likely to undergo care limitations, independent of ICH severity.

Abstract TP305: Lower Serum Total Cholesterol Levels Are Associated With Increased Severity of Intracerebral Hemorrhage: Results from the Taiwan Stroke Registry

Background and Purpose: Evidence of a causal relationship between serum cholesterol level and hemorrhagic stroke is inconclusive. We hypothesized that lower total serum cholesterol (TC) levels are associated with severe intracerebral hemorrhage (ICH). Methods: During May, 2006 and April, 2009, patients registered in the Taiwan Stroke Registry, a prospective registry engaging 38 academic and community hospitals across Taiwan (Hsie FI et al, Circulation, 2010), and who had first-ever spontaneous ICH were included. Patients who did not have measure of TC at baseline were excluded. Lower TC was defined as the serum level of TC &lt;160 mg/dl. Stroke severity measured by the National Institutes of Health Stroke Scale (NIHSS) was dichotomized (score &gt;15 versus ≤15). Mortality and poor functional outcome (modified Rankin Scale score &gt;2) at 1 month were collected. Multivariable logistic regression analysis was used to determine the association between lower TC and initial severity of ICH. Results: A total of 2239 ICH patients (mean age 62±14 years, 64% men) were included in this analysis. There were 774 (34.6%) patients presented with lower TC on admission. Lower TC levels at baseline was significantly associated with higher baseline NIHSS &gt;15 (odds ratio, 1.78; 95% CI, 1.44 to 2.19). One-month case-fatality was higher in patients with low TC than those without (9.2% vs. 5.1%, P=0.0002). Prior use of lipid-lowering drugs was not associated with low TC or not. Conclusion: A lower total cholesterol level was associated with increased severity of ICH at presentation.

Abstract TP378: Statin Use among Patients with Intracerebral Hemorrhage in the Paul Coverdell National Acute Stroke Registry

Background: Various studies have produced conflicting results on whether statins increase the risk of intracerebral hemorrhage (ICH) yet many studies show a protective effect for those on statins at the time of acute ischemic stroke (AIS). This study assesses the characteristics and outcomes of patients having intracerebral hemorrhage and statin use in the Paul Coverdell National Acute Stroke Registry (PCNASR). Methods: There were 103,491patients with AIS and 16,319 with ICH enrolled in the PCNASR during 2009-2011. Chi-square tests were used to test for association of clinical characteristics with ICH and ICH with statin use. Logistic regression analysis was used to assess factors associated with odds of ICH vs. AIS and mortality among ICH patients. Results: Of 16,319 patients with ICH, 5,522 were on statins at the time of ICH (33.8%). Among ICH patients, mean age was 72.8 for statin users (S) and 65.3 for non-statin users (NS) (p&lt;0.0001). Median NIHSS score was 7 for ICH on S and 9 for ICH among NS (p=0.002). Mean LDL cholesterol was 101 among ICH and 102 among AIS (p=0.28). Statin use was associated with less ICH (AOR 0.82, CI 0.79, 0.85). Statin users with ICH had higher prevalence of hypertension, atrial fibrillation, ischemic heart disease, heart failure, diabetes, carotid stenosis, cardiac valve prosthesis, taking antithrombotics, antihypertensives, or prior stroke compared to NS with ICH (p&lt;0.0001 for all). Among ICH patients, adjusted analyses showed males, older age, NIHSS score, cardiac valve prosthesis (CVP) and antithrombotic use were associated with increased in-hospital mortality, while statin use was not associated with in-hospital mortality (AOR 0.97, CI 0.80,1.16) (Table). Conclusions: Mortality among patients with ICH was greatest among those with CVP or on antithrombotics. Statin use was associated with less severe ICH, but not with ICH in-hospital mortality.

Abstract TMP83: Propensity Score Matching to Estimate Supported Outcomes in Intracerebral Hemorrhage Patients with Withdrawal of Life Support

Background: Observational reports suggest that a self-fulfilling prognostic pessimism may lead to withdrawal of life support (WOLS) in patients with more severe intracerebral hemorrhages (ICHs) who might otherwise have acceptable clinical outcomes. Our objective was to estimate what outcomes in a cohort of ICH patients might have been if they did not have WOLS. Methods: Multivariate modeling was used to create a propensity score (PS) for WOLS in a Seattle single center cohort of ICH patients with hospital discharge modified Rankin Scale (mRS) as the primary outcome. Using nearest neighbor matching, individual ICH patients with WOLS were matched to individual ICH patients without WOLS and baseline variables and outcome were compared. Results: The cohort comprised 590 ICH patients with mean age of 67 years, 42% women, 76% white and 18% WOLS. Factors used to create the PS for WOLS included age, pre-ICH mRS, GCS, ICH volume, intraventricular hemorrhage, pre-existing hypertension, diabetes and atrial fibrillation, first temperature and intubation. Matches were possible for 78 WOLS/non-WOLS pairs. Groups were well matched on all PS factors, mean age (67 years), GCS (6.4), ICH volume (59cc) and % intubation (59). Discharge mRS in the both groups varied from 3-6 and was for the WOLS group 1.3%, 2.6%, 6.4% and 90% respectively; in the matched non-WOLS group discharge mRS was 6.4%, 32%, 24% and 37% respectively (difference p&lt;0.0005). Using mRS &lt;= 4 at discharge as an acceptable outcome, % in WOLS/non-WOLS were 4%/38% (difference p&lt;0.0005). Conclusions: The proportion of ICH patients with WOLS that might have had an acceptable outcome without WOLS was ~38%. This discharge “acceptable outcome” of mRS &lt;= 4 assumes eventual recovery to better function in many. The 34% absolute difference in WOLS/non-WOLS outcomes suggests that for every 3 fewer ICH patients with WOLS, one more patient might have an acceptable clinical outcome. This proportion would vary depending on an individual patient’s interpretation of what constitutes an acceptable outcome.

Abstract WP311: Estimating Supported Outcomes in Intracerebral Hemorrhage Patients with Withdrawal of Life Support through Propensity Score Matching

Background: Observational reports have suggested that a self-fulfilling prognostic pessimism may lead to withdrawal of life support (WOLS) in more severe intracerebral hemorrhage patients (ICHs) who might otherwise have acceptable clinical outcomes. Our objective was to estimate outcomes in a cohort of ICHs who had WOLS, if instead they had life support continued. Methods: Multivariable modeling was used to create a propensity score (PS) for WOLS in a Boston single center cohort of ICHs with follow up modified Rankin Scale (mRS) or known death at 6 months. Individual ICHs with WOLS were then matched to individual ICHs without WOLS and baseline variables and outcomes compared. Results: There were 576 ICHs with all variables available for analysis; mean age was 72 years, 44% women, 83% white and WOLS in 45%. Factors used to create the PS for WOLS included age, GCS, ICH and IVH volume, diabetes, ICH location, SBP, sex, race, history of HTN, DM, CAD, atrial fibrillation, warfarin, intubation, and EVD. WOLS/non-WOLS matches were possible for 81 pairs (N=162 total), and the groups were well matched on all PS variables; key values included mean age (73 years), GCS (9.5), ICH volume (37cc) and % intubation (57) and EVD use (23); more patients had dementia in the WOLS group than non-WOLS (24 vs. 11%, p=0.03). Follow up mRS in the WOLS group was 3 in 1.2%, 5 in 2.5% and 6 (death) in 96%; in the matched non-WOLS group, % in mRS scores 0-6 were 4.9, 8.6, 3.7, 24.7, 25.9, 16.0 and 16.0 respectively (p&lt;0.0001 for difference in distribution). Using mRS &lt;= 3 as an acceptable outcome, % in WOLS/non-WOLS were 1.2%/42% (difference p&lt;0.0001). Conclusions: The proportion of ICHs with WOLS that, without WOLS, might have had an acceptable clinical outcome was estimated to be 42%, suggesting that for every 2-3 less ICHs with WOLS, one more patient might have an acceptable clinical outcome. This proportion might vary depending on an individual patient’s interpretation of what constitutes an acceptable outcome.