Outcome In Acute Intracerebral Hemorrhage Research Articles

Significance of serum sestrin2 as a biomarker of severity and functional outcome in acute intracerebral hemorrhage: a prospective observational longitudinal study

BackgroundSestrin2 is a highly conserved stress-inducible protein with neuroprotective properties. Herein, we investigated the prognostic significance of serum sestrin2 in human intracerebral hemorrhage (ICH).MethodsIn this prospective observational longitudinal study, we enrolled 126 patients with supratentorial ICH as cases together with 126 healthy individuals as controls. Severity indicators were National Institutes of Health Stroke Scale (NIHSS) and hematoma volume. Prognostic parameters were early neurologic deterioration (END) and post-stroke 6-month poor prognosis [modified Rankin Scale (mRS) scores of 3–6]. Multivariate analysis was performed to assess relations of serum sestrin2 levels to severity and prognosis.ResultsPatients had statistically significantly higher serum sestrin2 levels than controls. Serum sestrin2 levels of patients were independently correlated with NIHSS scores and hematoma volume, as well as were substantially elevated in order of mRS scores from 0 to 6. Serum sestrin2 was identified as an independent predictor of END and poor prognosis. Based on the receiver operating characteristic curve, serum sestrin2 had a similar predictive ability for END and poor prognosis, as compared to NIHSS scores and hematoma volume. Prediction models of END and poor prognosis, in which serum sestrin2, NIHSS scores and hematoma volume were integrated, were visually described via nomogram, were reliable and stable under calibration curve and were of clinical benefit using decision curve analysis. Also, prediction model of poor prognosis showed dramatically higher discriminatory efficiency than any of NIHSS scores, hematoma volume and serum sestrin2.ConclusionSerum sestrin2 levels, which are obviously increased following acute ICH, are independently related to illness severity and poor clinical outcomes, substantializing serum sestrin2 as a clinically valuable prognostic biomarker of ICH.

A Prospective Cohort Study of Inter-Alpha-Trypsin Inhibitor Heavy Chain 4 as a Serologic Marker in Relation to Severity and Functional Outcome of Acute Intracerebral Hemorrhage.

The inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4) may regulate immunity and inflammation. The current study was conducted to determine its role as a biomarker for reflecting the severity and predicting outcomes of intracerebral hemorrhage (ICH). In this prospective cohort study, 185 patients with supratentorial ICH were enrolled, among whom 62 had blood obtained not only at admission but also on days 1, 3, 5, 7, 10, and 14. In addition, 62 healthy controls underwent blood collection at the start of the study. The serum ITIH4 levels were then quantified. We recorded early neurological deterioration (END) and poor prognosis (modified Rankin Scale [mRS] scores of 3-6]) six months after ICH. Serum ITIH4 levels decreased prominently in the early phase after ICH, continued to decline until day 5, then gradually increased until day 14, and were significantly lower during 14 days in patients than in controls. Serum ITIH4 levels on admission were independently associated with serum C-reactive protein levels, National Institutes of Health Stroke Scale (NIHSS) scores and hematoma volume. Admission serum ITIH4 levels were independently associated with mRS scores, END, and poor prognosis. No substantial differences existed in the areas under the receiver operating characteristic curve of END and poor prognosis prediction between the serum ITIH4 levels, NIHSS scores, and hematoma volume. Prediction models, in which serum ITIH4 levels, NIHSS scores, and hematoma volume were integrated, were relatively reliable and stable using a series of statistical methods. In addition, the prediction model of poor prognosis had a higher discriminatory ability than the NIHSS scores and hematoma volume alone. A dramatic decline in serum ITIH4 levels during the early period following ICH is independently related to the inflammatory response, stroke severity, and poor neurologic outcomes, suggesting that serum ITIH4 may be a useful prognostic biomarker of ICH.

Serum β2-microglobulin is closely associated with 3-month outcome of acute intracerebral hemorrhage: a retrospective cohort study.

Intracerebral hemorrhage (ICH) is a frequent type of hemorrhagic stroke. Numerous studies have suggested that inflammation plays an important role in the injury and recovery of ICH. β2-microglobulin (β2M) is an inflammatory indicator with an unclear association with ICH development. This study aimed to explore the role of β2M in the outcome of patients with ICH after 3months of ICH onset. The β2M and other baseline information of 231 patients with ICH were assessed (83 females and 148 males). We followed up with all patients 3months after ICH onset, and severe disability or a worse outcome was our main focus. We collected the serum β2M levels, National Institutes of Health Stroke Scale (NIHSS) and modified Rankin scale (mRS) scores, and other relevant baseline information of each patient. We used multiple regression analysis to explore the association between β2M levels and follow-up outcomes. Our results indicated that the β2M level of the good outcome (2.35 ± 0.84mg/l) group was significantly lower than that of the poor outcome group (3.06 ± 1.71mg/l) (P < 0.001). Further multiple regression analysis showed that β2M was regarded as a risk factor that was closely associated with the poor outcome 3months after ICH onset (odds ratio = 2.26, 95% confidence interval = 1.22-4.19, P = 0.009). Further correlation analysis revealed that β2M was significantly correlated with NIHSS scores (r = 0.187, P = 0.004) and follow-up mRS scores (r = 0.25, P < 0.001). β2M was a risk factor for early outcome after ICH onset, and high β2M level was associated with short-time poor prognosis of ICH patients.

Added value of non-contrast CT and CT perfusion markers for prediction of intracerebral hemorrhage expansion and outcome.

To test the hypothesis that the combined analysis of non-contrast CT (NCCT) and CT perfusion (CTP) imaging markers improves prediction of hematoma expansion (HE) and outcome in intracerebral hemorrhage (ICH). Retrospective, single-center analysis of patients with primary ICH undergoing NCCT and CTP within 6 h from onset. NCCT images were assessed for the presence of intrahematomal hypodensity and shape irregularity. Perihematomal cerebral blood volume and spot sign were assessed on CTP. The main outcomes of the analysis were HE (growth > 6 mL and/or > 33%) and poor functional prognosis (90 days modified Rankin Scale 3-6). Predictors of HE and outcome were explored with logistic regression. A total of 150 subjects were included (median age 68, 47.1% males) of whom 54 (36%) had HE and 52 (34.7%) had poor outcome. The number of imaging markers on baseline imaging was independently associated with HE (odds ratio 2.66, 95% confidence interval 1.70-4.17, p < 0.001) and outcome (odds ratio 1.64, 95% CI 1.06-2.56, p = 0.027). Patients with the simultaneous presence of all the four markers had the highest risk of HE and unfavorable prognosis (mean predicted probability of 91% and 79% respectively). The combined-markers analysis outperformed the sensitivity of the single markers analyzed separately. In particular, the presence of at least one marker identified patients with HE and poor outcome with 91% and 87% sensitivity respectively. NCCT and CTP markers provide additional yield in the prediction of HE and ICH outcome. • Perihematomal hypoperfusion is associated with hematoma expansion and poor outcome in acute intracerebral hemorrhage. • Non-contrast CT and CT perfusion markers improve prediction of hematoma expansion and unfavorable prognosis. • A multimodal CT protocol including CT perfusion will help the identification of patients at high risk of clinical deterioration and poor outcome.

Temporal Trajectory of Systolic Blood Pressure and Outcomes in Acute Intracerebral Hemorrhage: ATACH-2 Trial Cohort.

Background:To highlight the heterogeneity of acute temporal blood pressure (BP) changes in the ATACH-2 trial (Antihypertensive Treatment of Acute Cerebral Hemorrhage-2) and associations with the outcomes of intracerebral hemorrhage.Methods:One thousand patients with acute intracerebral hemorrhage, who had been randomized to intensive (110–139 mm Hg) or standard (140–179 mm Hg) systolic BP (SBP) lowering with intravenous nicardipine in ATACH-2 from 2011 to 2015, were analyzed about temporal changes in hourly maximum SBP up to 24 hours after randomization using group-based trajectory modeling. Outcomes included death or disability (modified Rankin Scale score 4–6) at 3 months, neurological deterioration within 24 hours (≥2-point decrease in Glasgow Coma Scale score or ≥4-point increase in National Institutes of Health Stroke Scale score), and acute kidney injury (≥0.3 mg/dL within 48 hours or ≥1.5-fold increase in serum creatinine) within 7 days after onset.Results:Group-based trajectory modeling revealed 4 SBP trajectory groups: moderate SBP (from ≈190 mm Hg at hospital arrival to 150–160 mm Hg after randomization; n=298), moderate-to-low SBP (from ≈190 mm Hg to <140 mm Hg; n=395), high-to-low SBP (from >210 mm Hg to <140 mm Hg; n=134), and high SBP (from >210 mm Hg to 160–170 mm Hg; n=173). Patients with intensive treatment accounted for 11.1%, 88.6%, 85.1%, and 1.7% of each group, respectively. Compared with the moderate-to-low SBP group, the high-to-low SBP group showed increased risks of death or disability at 3 months (adjusted odds ratio, 2.29 [95% CI, 1.24–4.26]) and acute kidney injury (adjusted odds ratio, 3.50 [95% CI, 1.83–6.69]), while no increase in neurological deterioration was seen in this group (adjusted odds ratio, 0.48 [95% CI, 0.20–1.13]). The moderate SBP and high SBP groups showed no significant risk differences for such outcomes.Conclusions:Data-driven observation using a group-based trajectory modeling approach may be useful to clarify the relationship between antihypertensive treatment, temporal SBP changes, and outcomes in acute intracerebral hemorrhage.Registration:URL: https://www.clinicaltrials.gov; Unique identifier: NCT01176565.

J-shape relation of blood pressure reduction and outcome in acute intracerebral hemorrhage: A pooled analysis of INTERACT2 and ATACH-II individual participant data.

The aim of this study was to better define the shape of association between the degree ("magnitude") of early (< 1 h) reduction in systolic blood pressure (SBP) and outcomes in patients with acute intracerebral hemorrhage (ICH) through pooled analysis of the second Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT2) and second Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH-II) datasets. Association of the continuous magnitude of SBP reduction described using cubic splines and an ordinal measure of the functional outcome on the modified Rankin scale (mRS) scores at 90 days were analyzed in generalized linear mixed models. Models were adjusted for achieved (mean) and variability (standard deviation, SD) of SBP between 1 and 24 h, various baseline covariates, and trial as a random effect. Among 3796 patients (mean age 63.1 (SD = 13.0) years; female 37.4%), with a mean magnitude (< 1 h) of SBP reduction of 28.5 (22.8) mmHg, those with larger magnitude were more often non-Asian and female, had higher baseline SBP, received multiple blood pressure (BP) lowering agents, and achieved lower SBP levels in 1-24 h. Compared to those patients with no SBP reduction within 1 h (reference), the adjusted odds of unfavorable functional outcome, according to a shift in mRS scores, were lower for SBP reductions up to 60 mmHg with an inflection point between 32 and 46 mmHg, but significantly higher for SBP reductions > 70 mmHg. Similar J-shape associations were evident across various time epochs across 24 h and consistent according to baseline hematoma volume and SBP and history of hypertension. A moderate degree of rapid SBP lowering is associated with improved functional outcome after ICH, but large SBP reductions over 1 h (e.g. from > 200 to target < 140 mmHg) were associated with reduction, or reversal, of any such benefit.

Serum arachidonic acid levels is a predictor of poor functional outcome in acute intracerebral hemorrhage

Background and aimsCorrelations between serum levels of polyunsaturated fatty acids (PUFAs) such as eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arachidonic acid (AA) and dihomogammalinolenic acid (DHLA) and outcomes following cardiovascular disease have been reported. This study aimed to investigate the relationship between serum levels of PUFAs (including AA) and functional outcomes among intracerebral hemorrhage (ICH) patients. MethodsFrom November 2012 to July 2020, ICH patients within 24 h from onset were enrolled. Patients were divided into a good functional outcome group (modified Rankin Scale [mRS] score at 3 months, 0–3) and a poor functional outcome group (mRS score at 3 months, 4–6). We compared baseline variables between groups. ResultsParticipants comprised 133 patients (mean age, 60 years), with 106 patients (80%) in the good functional outcome group and 27 patients (20%) in the poor functional outcome group. Higher National Institutes of Health Stroke Scale (NIHSS) score and larger hematoma on admission were more frequent in the poor functional outcome group (median NIHSS score 6 vs. 14, p < 0.001; median hematoma volume, 7.5 ml vs. 13.5 ml, p = 0.07). In terms of serum PUFA levels, only median serum AA level was significantly lower in the poor functional outcome group (212 µg/ml vs. 179 µg/ml, p = 0.002). Multivariate logistic regression analysis showed lower serum AA level was independently associated with poor functional outcome (odds ratio 0.986, 95% confidence interval 0.976–0.996, p = 0.009). ConclusionLower serum AA level was associated with poor functional outcome in ICH patients. AA may represent an important biomarker of severity among ICH patients.

Effect of Heart Rate Variabilities on Outcome After Acute Intracerebral Hemorrhage: A Post Hoc Analysis of ATACH-2.

BackgroundTo explore how the clinical impact of heart rate (HR) and heart rate variabilities (HRV) during the initial 24 hours after acute intracerebral hemorrhage (ICH) contribute to worse clinical outcomes.Methods and ResultsIn the ATACH‐2 (Antihypertensive Treatment in Intracerebral Hemorrhage 2) trial, the HR was recorded for every 15 minutes from baseline to 1 hour and hourly during the initial 24 hours post‐randomization. We calculated the following: mean, standard deviation, coefficient of variation, successive variation, and average real variability (ARV). Outcomes were hematoma expansion at 24 hours and unfavorable functional outcome, defined as modified Rankin Scale score 4 to 6 at 90 days. Of the 1000 subjects in ATACH‐2, 994 with available HR data were included in the analyses. Overall, 262 experienced hematoma expansion, and 362 had unfavorable outcomes. Increased mean HR was linearly associated with unfavorable outcome (per 10 bpm increase adjusted odds ratio [aOR], 1.31, 95% CI, 1.14–1.50) but not with hematoma expansion, while HR‐ARV was associated with hematoma expansion (aOR, 1.06, 95% CI, 1.01–1.12) and unfavorable outcome (aOR, 1.07, 95% CI, 1.01–1.3). Every 10‐bpm increase in mean HR increased the probability of unfavorable outcome by 4.3%, while every 1 increase in HR‐ARV increased the probability of hematoma expansion by 1.1% and unfavorable outcome by 1.3%.ConclusionsIncreased mean HR and HR‐ARV within the initial 24 hours were independently associated with unfavorable outcome in acute ICH. Moreover, HR‐ARV was associated with hematoma expansion at 24 hours. This may have future therapeutic implications to accommodate HR and HRV in acute ICH.RegistrationURL: https://www.clinicaltrials.gov; Unique Identifier: NCT01176565.

New Prediction Models of Functional Outcome in Acute Intracerebral Hemorrhage: The dICH Score and uICH Score.

Objectives: The original intracerebral hemorrhage (oICH) score is the severity score most commonly used in clinical intracerebral hemorrhage (ICH) research but may be influenced by hematoma expansion or intraventricular hemorrhage (IVH) growth in acute ICH. Here, we aimed to develop new clinical scores to improve the prediction of functional outcomes in patients with ICH.Methods: Patients admitted to the First Affiliated Hospital of Chongqing Medical University with primary ICH were prospectively enrolled in this study. Hematoma volume was measured using a semiautomated, computer-assisted technique. The dynamic ICH (dICH) score was developed by incorporating hematoma expansion and IVH growth into the oICH score. The ultra-early ICH (uICH) score was developed by adding the independent non-contrast CT markers to the oICH score. Receiver operating characteristic curve analysis was used to compare performance among the oICH score, dICH score, and uICH score.Results: There were 310 patients in this study which included 72 patients (23.2%) with hematoma expansion and 58 patients (18.7%) with IVH growth. Of 31 patients with two or more non-contrast computed tomography markers, 61.3% died, and 96.8% had poor outcomes at 90 days. After adjustment for potential confounding variables, we found that age, baseline Glasgow Coma Scale score, presence of IVH on initial CT, baseline ICH volume, infratentorial hemorrhage, hematoma expansion, IVH growth, blend sign, black hole sign, and island sign could independently predict poor outcomes in multivariate analysis. In comparison with the oICH score, the dICH score and uICH score exhibited better performance in the prediction of poor functional outcomes.Conclusions: The dICH score and uICH score were useful clinical assessment tools that could be used for risk stratification concerning functional outcomes and provide guidance in clinical decision-making in acute ICH.

Abstract P450: Serum Arachidonic Acid Levels in Relation With Outcome of Acute Intracerebral Hemorrhage

Introduction: The correlation between serum polyunsaturated fatty acids (PUFAs) such as Eicosapentaenoic Acid (EPA), Docosahexaenoic Acid (DHA), Arachidonic Acid (AA) and Dihomogammalinolenic Acid (DHLA) levels and clinical outcomes of cardiovascular disease are previously reported. The aim was to investigate serum PUFAs including AA levels to clinical outcome in intracerebral hemorrhage (ICH) patients. Method: From Nov 2012 to Nov 2019, ICH patients within 24 hours from the onset were enrolled. All patients underwent radiological investigations and laboratory examinations including measurement of serum PUFAs levels on admission. We divided patients into two groups, favorable outcome group (mRS at 3 months 0-3) and poor outcome group (mRS at 3 months 4-6). We compared baseline variables including serum PUFAs levels between two groups. Result: We enrolled 142patients (87 male, median age 60 years old, median NIHSS score 8). Of them, 113 patients (80%) were favorable outcome group and 29 patients (20%) were poor outcome group. Higher NIHSS score and larger size of hematoma on admission were found in poor outcome group (median NIHSS score 6 of favorable outcome vs. 14 of poor outcome, p&lt;0.001, and median hematoma size, 7.5ml vs. 13.5ml, p=0.048). In serum PUFAs levels, only serum AA levels was significantly lower in poor outcome group (median interval 213μg/ml vs. 179μg/ml, p=0.002) though there were no difference of DHLA, EPA and DHA levels between two groups. In multivariate logistic regression analysis, lower serum AA levels was independently associated with poor outcome (OR 0.987, 95%CI 0.978-0.996, p=0.007, Figure). Conclusion: Serum AA levels may play an important role in predicting the outcome in ICH.

Associations of an Abnormal Physiological Score With Outcomes in Acute Intracerebral Hemorrhage: INTERACT2 Study.

We determined associations of physiological abnormalities (systolic blood pressure, glucose, and body temperature) and warfarin use with outcomes in spontaneous intracerebral hemorrhage. Post hoc analyses of INTERACT2 (Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial) comparing systolic blood pressure control (<140 versus <180 mm Hg) in 2839 hypertensive patients with intracerebral hemorrhage (onset <6 hours). Multivariable logistic regression defined associations of baseline scores assigned as 0 to 6 per 10 mm Hg systolic blood pressure increase (range, 150-220 mm Hg) and 0 or 1 for serum glucose (≤6.5 versus >6.5 mmol/L), body temperature (≤37.5 °C versus >37.5 °C), and warfarin use (no versus yes) and death or major disability (modified Rankin Scale scores 3-6 at 90 days). Baseline score distribution was 0 (7.7%), 1 (15.6%), 2 (19.0%), 3 (19.1%), 4 (15.2%), 5 (11.6%), 6 (8.9%), and 7 (2.9%). After adjustment for baseline neurological severity and potential confounders, significant linear associations were evident for increasing (per point) score and death or major disability (odds ratio, 1.12 [95% CI, 1.07-1.17]), death (odds ratio, 1.15 [95% CI, 1.07-1.23]), and major disability (odds ratio, 1.10 [95% CI, 1.05-1.15]). Combination of abnormal physiological parameters and warfarin use is associated with poor outcomes in intracerebral hemorrhage. Effects of their early control is under investigation in INTERACT3 (Intensive Care Bundle With Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial). Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00716079.

Hydrocephalus Growth: Definition, Prevalence, Association with Poor Outcome in Acute Intracerebral Hemorrhage.

To propose a novel definition for hydrocephalus growth and to further describe the association between hydrocephalus growth and poor outcome among patients with intracerebral hemorrhage (ICH). We analyzed consecutive patients who presented within 6h after ICH ictus between July 2011 and June 2017. Follow-up CT scans were performed within 36h after initial CT scans. The degree of hydrocephalus were evaluated by the hydrocephalus score of Diringer et al. The optimal increase of the hydrocephalus scores between initial and follow-up CT scan was estimated to define hydrocephalus growth. Poor long-term outcome was defined as a modified Rankin Scale of 4-6 at 3months. Multivariate logistic regression analysis was performed to investigate the hydrocephalus growth for predicting 30-day mortality, 90-day mortality, and poor long-term outcome. A total of 321 patients with ICH were included in the study. Of 64 patients with hydrocephalus growth, 34 (53.1%) patients presented with both concurrent hematoma expansion and intraventricular hemorrhage (IVH) growth. After adjusting for potential confounding factors, hydrocephalus growth independently predicted 30-day mortality, 90-day mortality, and 90-day poor long-term outcome in multivariate logistic regression analysis. Hydrocephalus growth showed higher accuracy for predicting 30-day mortality, 90-day mortality, and poor long-term outcome than IVH growth or hematoma expansion, respectively. Hydrocephalus growth is defined by strongly predictive of short- or long-term mortality and poor outcome at 90days, and might be a potential indicator for assisting clinicians for clinical decision-making.

Do Imaging Markers of Cerebral Small Vessel Disease Predict Hematoma Volume and Outcome in Acute Intracerebral Hemorrhage?

Background and Purpose:Cerebral small vessel disease (CSVD) markers have not been widely studied in relation to hematoma volume and growth in hypertensive intracerebral hemorrhage (ICH). The objectives to assess the relationship of white matter hyperintense lesions (WMHL), microbleeds (MBs), and cortical siderosis (CSS) with hematoma volume, hematoma expansion (HE), and 3 months outcome in patients with hypertensive ICH.Methods:All consecutive acute hypertensive supratentorial ICH presenting to the emergency were prospectively recruited. Baseline and 24 hours computed tomography (CT) to assess hematoma volume and magnetic resonance imaging (MRI) for CSVD markers were performed in all subjects. WMHL (graded using Fazekas's scale), MBs, and CSS were assessed and compared with baseline variables and outcomes. All the images were assessed by an experienced stroke neurologist/neuroradiologist.Results:One hundred and fifty-seven patients were screened and 60 were included. Mean age was 54.08 ± 11.57 years and 47 (78%) were males. Of 60, 19 (28.1%) had HE, 31 (51.6%) had major bleed (>30 ml), and 28 (47.46%) had poor 3 month outcome (mRS 4-6). On univariate analysis, high grade WMHL was associated with greater HE [odds ratio (OR): 2.65, confidence interval (CI) 1.48–4.72, P = 0.001), greater proportion with volume >30 ml (OR: 7.16, CI: 1.09–47.13, P = 0.001) and poor outcome (OR: 2.1, CI: 0.05–3.27, P = 0.001). MBs were associated with poor outcome (P = 0.029) but not with HE/volume. CSS was related to HE (P = 0.031), a large volume bleed (P = 0.023), and poor outcome (P = 0.021). On multivariate model, only WMHL independently predicted HE (P = 0.034), greater proportion with bleed volume >30 ml (P = 0.041), and poor outcome (P = 0.042).Conclusions:WMHL in MRI serves as a predictor of hematoma expansion, a large volume bleed, and poor outcome in hypertensive ICH and may be incorporated into existing prediction models.

Potential role of serum substance P as a favorable biomarker of functional outcome in acute spontaneous intracerebral hemorrhage

BackgroundSubstance P (SP) is implicated in brain inflammation. We clarified relationship between serum SP concentrations and functional outcome of acute intracerebral hemorrhage (ICH). MethodsWe quantified admission serum SP concentrations in 106 ICH patients. The primary outcome measure was a poor outcome at 90 days (modified Rankin Scale score ≥ 3) after onset. ResultsPatients with a poor outcome compared with the rest had substantially higher serum SP concentrations. The area under the curve for serum SP concentrations with regard to discriminating a poor outcome was 0.795 (95% CI, 0.706 to 0.867). Serum SP concentrations >449 pg/ml predicted the risk of a poor outcome with 63.0% sensitivity and 78.9% specificity, and were independently associated with a poor outcome (odds ratio, 5.437; 95% CI, 2.156 to 13.715). There were the positive associations between serum SP concentrations, National Institutes of Health Stroke Scale score (r = 0.480), hematoma volume (r = 0.464) and serum C-reactive protein concentrations (r = 0.398). ConclusionsHigher serum SP concentrations in the acute phase of ICH were intimately associated with aggravated inflammation response, rising severity and increased risk of a poor functional outcome, suggesting that serum SP could be an inflammatory prognostic factor for ICH.

The Magnitude of Blood Pressure Reduction Predicts Poor In-Hospital Outcome in Acute Intracerebral Hemorrhage

Early systolic blood pressure (SBP) reduction is believed to improve outcome after spontaneous intracerebral hemorrhage (ICH), but there has been a limited assessment of SBP trajectories in individual patients. We aimed to determine the prognostic significance of SBP trajectories in ICH. We collected routine data on spontaneous ICH patients from two healthcaresystems over 10years. Unsupervised functional principal components analysis (FPCA) was used to characterize SBP trajectories over first 24h and their relationship to the primary outcome of unfavorable shift on modified Rankin scale (mRS) at hospital discharge, categorized as an ordinal trichotomous variable (mRS 0-2, 3-4, and 5-6 defined as good, poor, and severe, respectively). Ordinal logistic regression models adjusted for baseline SBP and ICH volume were used to determine the prognostic significance of SBP trajectories. The 757 patients included in the study were 65 ± 23years old, 56% were men, with a median (IQR) Glasgow come scale of 14 (8). FPCA revealed that mean SBP over 24h and SBP reduction within the first 6h accounted for 76.8% of the variation in SBP trajectories. An increase in SBP reduction (per 10mmHg) was significantly associated with unfavorable outcomes defined as mRS > 2 (adjusted-OR = 1.134; 95% CI 1.044-1.233, P = 0.003). Compared with SBP reduction < 20mmHg, worse outcomes were observed for SBP reduction = 40-60mmHg (adjusted-OR = 1.940, 95% CI 1.129-3.353, P = 0.017) and > 60mmHg, (adjusted-OR = 1.965, 95% CI 1.011, 3.846, P = 0.047). Furthermore, the association of SBP reduction and outcome varied according to initial hematoma volume. Smaller SBP reduction was associated with good outcome (mRS 0-2) in small (< 7.42mL) and medium-size (≥ 7.42 and < 30.47mL) hematomas. Furthermore, while the likelihood of good outcome was low in those with large hematomas (≥ 30.47mL), smaller SBP reduction was associated with decreasing probability of severe outcome (mRS 5-6). Our analyses suggest that in the first 6h SBP reduction is significantly associated with the in-hospital outcome that varies with initial hematoma volume, and early SBP reduction > 40mmHg may be harmful in ICH patients. For early SBP reduction to have an effective therapeutic effect, both target levels and optimum SBP reduction goals vis-à-vis hematoma volume should be considered.

Left ventricular ejection fraction as an independent predictor of poor outcome in acute intracerebral hemorrhage.

IntroductionFew studies of the effect of cardiac abnormalities on acute intracerebral hemorrhage (ICH) outcomes have been published. We sought to determine whether the left ventricular ejection fraction (LVEF) is associated with the functional outcome and mortality of acute ICH patients.MethodsWe conducted a retrospective study on 364 acute ICH patients from January to December 2016. The primary outcome was defined by the modified Rankin Scale and mortality at 3 months. The associations between LVEF and outcome were investigated using univariable and multivariable logistic regression models.ResultsDepressed LVEF was significantly associated with a poor functional outcome with an odds ratio [OR] of 0.966, 95% confidence interval (CI) 0.942–0.991, p = .008, and high mortality (OR 0.968 [95% CI 0.943–0.994], p = .015) at 3 months for acute ICH patients by univariate analysis. Multivariable logistic regression analysis indicated that LVEF was an independent predictor of a poor functional outcome (OR 0.961 [95% CI 0.935–0.988], p = .005) and mortality (OR 0.949 [95% CI 0.918–0.981], p = .002). The percentage of acute ICH patients with poor functional outcome (p = .005) and mortality (p = .002) was obviously higher in the group of patients with a LVEF of <50%.ConclusionsLVEF is an independent predictor of functional outcome and mortality at 3 months for acute ICH patients. These findings could provide the evidence needed for prognosis prediction in acute ICH patients.

Serum netrin-1 concentrations are associated with clinical outcome in acute intracerebral hemorrhage

BackgroundNetrin-1 is an axon guidance protein, which can inhibit inflammatory reaction and stabilize the blood-brain barrier to protect against experimental brain injury. We evaluated the concentration of netrin-1 in acute intracerebral hemorrhage (ICH) patients and explored whether netrin-1 is a potential prognostic biomarker for ICH. MethodsThis study recruited a total of 126 ICH patients and 126 healthy controls. Netrin-1 concentration was determined using a commercially available human enzyme-linked immune sorbent assay kit. National Institutes of Health Stroke Scale (NIHSS) score and hematoma volume were used to assess hemorrhagic severity. An unfavorable outcome was defined as modified Rankin Scale >2 at 90 days. ResultsICH patients showed significantly lower serum netrin-1 concentrations than controls. Serum netrin-1 concentrations were strongly and inversely correlated with serum C-reactive protein concentrations, NIHSS score and hematoma volume. Multivariate analyses revealed that low netrin-1 concentration was associated with 90-day death, unfavorable outcome and overall survival after adjustment for other confounding variables. Under the receiver operating characteristic curve, serum netrin-1 remarkably discriminated patients at risk of 90-day death and unfavorable outcome. ConclusionsSerum netrin-1 concentrations are decreased in patients with ICH, and the concentrations of netrin-1 were intimately associated with inflammation, hemorrhagic severity and clinical outcome of ICH.

Abstract WP399: Delayed Response to Intensive Blood Pressure Lowering and Poor Clinical Outcomes in Acute Intracerebral Hemorrhage

Background and purpose: We aimed to highlight temporal trajectories of systolic blood pressure (SBP) in patients with acute intracerebral hemorrhage (ICH) to investigate the clinical relevance of heterogeneity in responses to blood pressure lowering therapy. Methods: A post-hoc analysis of ATACH-2 trial, in which ICH patients were randomly assigned to intensive or standard SBP lowering with intravenous administration of nicardipine. Using data for all 1000 patients enrolled from 110 clinical sites, temporal changes of hourly maximum SBP up to 24 hours after randomization were analyzed with the group-based trajectory modeling (GBTM). Model selection was mainly based on the Bayesian Information Criteria. The primary outcome was death or disability (modified Rankin Scale score 4-6) at 3 months. Secondary outcomes included hematoma expansion within 24 hours and acute kidney injury (AKI). AKI was defined as an increase in serum creatinine by ≥0.3 mg/dl or to ≥1.5 times baseline within 48 hours. The outcomes were compared between the trajectory groups using multivariable logistic models with random-effects by clinical sites. Results: Of the analyzed 1000 patients, death or disability, hematoma expansion, and AKI were encountered in 367, 161, and 101 patients, respectively. GBTM revealed 4 SBP trajectory groups: early response-low SBP (38.2%), moderate SBP (16.8%), delayed response-low SBP (14.2%), and high SBP (30.8%). Nicardipine dosage was highest in the delayed response-low SBP group, 81.7% of which were from the intensive SBP lowering group. The risk of death or disability was higher only in the delayed response-low SBP group (adjusted odds ratio [aOR] 2.86; 95% confidence interval [CI] 1.66-4.93) than in the early response-low SBP group. The risk of hematoma expansion was not significantly different among the groups. The delayed response-low SBP group had higher risk of AKI (aOR 2.78; 95% CI 1.46-5.31; reference, the early response-low SBP group). Conclusions: An SBP trajectory group with delayed SBP lowering despite intensive treatment was associated with increased risk of death or disability at 3 months. Resistance to intensive SBP lowering may predict poor clinical outcomes, and intensive SBP control in these cases will increase the risk of AKI.

Comparison of ABC Methods with Computerized Estimates of Intracerebral Hemorrhage Volume: The INTERACT2 Study

Background and Purpose: Hematoma volume is a key determinant of outcome in acute intracerebral hemorrhage (ICH). We aimed to compare estimates of ICH volume between simple (ABC/2, length, width, and height) and gold standard planimetric software approaches. Methods: Data are from the second Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT2). Multivariable linear regression was used to compare ICH volumes on baseline CT scans using the ABC/2, modified ABC/2 (mABC/2), and MIStar software. Other aspects of ICH morphology examined included location, irregularity, heterogeneity, intraventricular and subarachnoid hemorrhage extension (SAH) of hematoma, and associated white matter lesions and brain atrophy. Results: In 2,084 patients with manual and semiautomated measurements, median (IQR) ICH volumes for each approach were: ABC/2 11.1 (5.11–20.88 mL), mABC/2 7.8 (3.88–14.11 mL), and MIStar 10.7 (5.59–18.66 mL). Median differences between ABC/2 and MIStar, and mABC/2 and MIStar were 0.34 (–1.01 to 2.96) and –2.4 (–4.95 to –0.7416), respectively. Hematoma volumes differed significantly with irregular shape (ABC/2 and MIStar, p < 0.001; mABC/2 and MIStar, p = 0.007) and larger volumes (mABC/2 and MIStar, p < 0.001; ABC/2 and MIStar, p = 0.07). ICH with SAH showed a significant discrepancy between ABC/2 and MIStar (p < 0.001). Conclusions: Overall, ABC/2 performs better than mABC/2 in estimating ICH volume. The largest discrepancies were evidenced against automated software for irregular-shaped and large ICH with SAH, but the clinical significance of this is uncertain.

Higher Hemoglobin A1c Level Is Associated With Poor Outcome of Intracerebral Hemorrhage.

Background: Pre-morbid chronic hyperglycemia is associated with the poor outcome of ischemic stroke, but the association between chronic hyperglycemia, and the long-term outcome of acute intracerebral hemorrhage is still poor understood.Methods: Data on patients with acute intracerebral hemorrhage in the ACROSS-China registry (Abnormal Glucose Regulation in Patients With Acute Stroke Across China) were reviewed. Elevated hemoglobin A1c (HbA1c) level on admission was indicative of chronic hyperglycemia. According to the clinical categories of HbA1c, patients were divided into three groups. Multivariable logistic regression or Cox method was performed to analyze the association of HbA1c and the prognosis of patients with acute intracerebral hemorrhage (poor functional outcome [modified Rankin scale score 3–6] and mortality) at 1 year.Results: A total of 416 patients were included in this study. Fifty-two (12.5%) patients died and 130 (31.8%) had poor functional outcome at 1-year follow-up. The higher levels of HbA1c (≥6.5%) was associated with a poor functional outcome (OR 2.35, 95% CI, 1.28–4.29) and increased mortality (OR 2.63, 95% CI 1.34–5.15), compared with the lowest category. When further stratified by diabetic or non-diabetic medical history, higher HbA1c (≥6.5%) still increased the risk of poor functional outcome (OR 3.42, 95% CI 1.39–8.44) and mortality (OR 4.48, 95% CI 1.64–12.24) in patients with non-diabetic medical history. However, higher HbA1c didn't have the association with the increased risk of poor functional outcome (OR 1.06, 95% CI 0.37–3.03) and mortality (OR 1.20, 95% CI 0.39–3.72) in patients with diabetic medical history.Conclusions: Higher HbA1c was associated with a higher risk of death and poor functional outcome 1 year after intracerebral hemorrhage, especially in patients without a diabetic history.