Acute Supratentorial Intracerebral Hemorrhage Research Articles

Usability of serum AIM2 as a predictive biomarker of stroke-associated pneumonia and poor prognosis after acute supratentorial intracerebral hemorrhage: A prospective longitudinal cohort study

BackgroundAbsent in melanoma 2 (AIM2) is implicated in inflammatory processes. We measured serum AIM2 with intent to unveil its predictive significance for stroke-associated pneumonia (SAP) and functional prognosis following acute intracerebral hemorrhage (ICH). MethodsIn this prospective cohort study, serum AIM2 concentrations of 163 ICH patients were gauged upon admission and 57 of them also consented for measurements at days 1, 3, 5, 7, 10 and 14. Coupled with 57 individuals without health conditions, dynamic change of serum AIM2 levels were uncovered. National Institutes of Health Stroke Scale (NIHSS) scores and hematoma volume were identified as the dual indicators of severity. Poststroke six-month modified Rankin Scale (mRS) scores ranging from 3 to 6 indicated an unfavorable outcome. SAP was observed during the first seven days after ICH. Sequential univariate and multivariate analyses were performed to discern predictors of SAP and adverse prognosis. ResultsThe serum levels of AIM2 in patients exhibited a marked elevation upon admission, reaching peak levels on the third and fifth days, and remained notably elevated until day 14 compared to those of the control group. Serum AIM2 levels showed independent correlations with both NIHSS scores and the volume of hematoma. Additionally, AIM2 concentrations were independently associated with a poor prognosis and SAP at the six-month mark. Within the framework of restricted cubic spline analysis, serum AIM2 concentrations exhibited a linear correlation with the likelihood of developing SAP and experiencing a poor prognosis. In the context of receiver operating characteristic (ROC) curve analysis, serum AIM2 concentrations effectively differentiated risks of SAP and poor prognosis. By employing segmented analysis, serum AIM2 concentrations showed negligible interactions with several traditional variables, such as age, gender, smoking habits, alcohol consumption, and more. The integrated model incorporating serum AIM2, NIHSS scores, and the volume of hematoma was depicted by employing a nomogram and demonstrated strong predictive performance for poor prognosis or SAP across various evaluation metrics, including ROC curve analysis, calibration curve analysis, and decision curve analysis. ConclusionSerum AIM2 levels show a marked increase shortly after intracerebral hemorrhage (ICH), which may accurately reflect stroke severity, and effectively predict SAP and poor neurological outcomes, and therefore serum AIM2 stands out as an encouraging predictive indicator for ICH.

Accuracy of automated segmentation and volumetry of acute intracerebral hemorrhage following minimally invasive surgery using a patch-based convolutional neural network in a small dataset

PurposeIn cases of acute intracerebral hemorrhage (ICH) volume estimation is of prognostic and therapeutic value following minimally invasive surgery (MIS). The ABC/2 method is widely used, but suffers from inaccuracies and is time consuming. Supervised machine learning using convolutional neural networks (CNN), trained on large datasets, is suitable for segmentation tasks in medical imaging. Our objective was to develop a CNN based machine learning model for the segmentation of ICH and of the drain and volumetry of ICH following MIS of acute supratentorial ICH on a relatively small dataset.MethodsNinety two scans were assigned to training (n = 29 scans), validation (n = 4 scans) and testing (n = 59 scans) datasets. The mean age (SD) was 70 (± 13.56) years. Male patients were 36. A hierarchical, patch-based CNN for segmentation of ICH and drain was trained. Volume of ICH was calculated from the segmentation mask.ResultsThe best performing model achieved a Dice similarity coefficient of 0.86 and 0.91 for the ICH and drain respectively. Automated ICH volumetry yielded high agreement with ground truth (Intraclass correlation coefficient = 0.94 [95% CI: 0.91, 0.97]). Average difference in the ICH volume was 1.33 mL.ConclusionUsing a relatively small dataset, originating from different CT-scanners and with heterogeneous voxel dimensions, we applied a patch-based CNN framework and successfully developed a machine learning model, which accurately segments the intracerebral hemorrhage (ICH) and the drains. This provides automated and accurate volumetry of the bleeding in acute ICH treated with minimally invasive surgery.

Abstract WMP82: Peri-Hematomal Edema (PHE) Shape Features as Independent Predictors of the 3-month Outcome in Acute Supratentorial Intracerebral Hemorrhage (ICH)

Background: Perihematomal edema (PHE) is a marker of post-ICH secondary brain injury and a potential treatment target. However, different studies have reported equivocal results regarding the optimal metrics of PHE volume in relation to clinical outcomes - such as absolute, and relative baseline PHE volume, or the rate of PHE volume growth over the first 24- and 72-hours post-ICH. In this study, we examined the association of different PHE shape features at baseline and 24-hour with outcome at 3-month follow-up. Methods: We used the data from ATACH-2 trial. We manually segmented ICH and PHE on baseline and follow-up CTs, and extracted 14 shape features. We explored the association of baseline, follow-up, difference (baseline subtracted from follow-up) and temporal rate (difference divided by time gap) of PHE shape changes with 3-month mRS. We applied Spearman correlation to assess univariate associations, and multivariate stepwise regression to evaluate if PHE shape features independently predict outcome adjusting for age, sex, NIHSS, GCS, baseline ICH volume, and treatment. Results: 796 patients were included. Baseline PHE maximum diameters across various planes, main axes, volume, surface and sphericity correlated with 3-month mRS after adjusting for multiple comparisons. The 24-hour difference and temporal change rates of these features also had significant association with outcome - but not the 24-hour absolute values. In multivariate regression, baseline PHE shape sphericity (p=0.029) and voxel volume (p=0.026), alongside admission NIHSS (p< 0.001), ICH volume (p=0.002), and age (p<0.001) were independent predictors of favorable outcomes. Conclusion: Aside from metrics of volume, PHE sphericity at baseline is an independent prognostic factor, with less spheric (more irregular) shape associated with worse outcome. In addition, baseline PHE shape features - compared to changes over the first 24 hours post-ICH - had stronger prognostic associations.

Serum Secreted Protein Acidic and Rich in Cysteine-Like 1 as a Biochemical Predictor for Prognosticating Clinical Outcomes After Acute Supratentorial Intracerebral Hemorrhage: A Prospective Cohort Study.

Secreted protein acidic and rich in cysteine-like 1 (SPARCL1) regulates synaptic stability and is up-regulated during axonal regeneration. Here, serum SPARCL1 was determined for estimating severity and prognosticating early neurological deterioration (END) and functional outcomes of acute intracerebral hemorrhage (ICH). In this prospective observational cohort study of 156 patients with supratentorial ICH, blood samples of 53 were acquired not only at admission but also ad days 1, 3, 5, 7 and 10. Another group of 53 healthy controls were recruited. The modified Rankin Scale (mRS) scores of 3-6 at poststroke six months were regarded as poor prognosis. As opposed to controls, serum SPARCL1 levels were markedly elevated during the early ten days after ICH, with the highest levels at days 1 and 3. Admission serum SPARCL1 levels were independently correlated with National Institutes of Health Stroke Scale scores and hematoma volume, were significantly increased in the order of six-month mRS scores from 0 to 6 and were independently correlated with six-month mRS scores. Serum SPARCL1 levels were linearly related to risks of poor six-month prognosis and END under restricted cubic spline, had significant efficiency under receiver operating characteristic (ROC) curve and were independently associated with END and poor prognosis. Subgroup analysis confirmed that no interactions existed for associations of serum SPARCL1 levels with other variables, such as age, gender and some specific vascular risk factors. END and poor prognosis prediction models integrating serum SPARCL1 were displayed using the two nomograms. The poor prognosis prediction model, but END prediction model not, performed well under calibration curve, decision curve and ROC curve. A substantial elevation of serum SPARCL1 levels during the early period after ICH is independently related to illness severity and poor neurological outcomes, thus signifying that serum SPARCL1 may appear as a prognostic biomarker of ICH.

Usability of Serum Stanniocalcin-1 as a Prognostic Biochemical Marker of Acute Supratentorial Intracerebral Hemorrhage: A Prospective Cohort Study.

Stanniocalcin-1 (STC1) may be neuroprotective. This study aimed to evaluate the prognostic role of serum STC1 levels in intracerebral hemorrhage (ICH). This prospective observational study was assigned in two parts. In the first part, blood samples of 48 patients with ICH were acquired on admission and on days 1, 2, 3, 5, and 7 after ICH, and those of 48 controls were collected at their entry into the study. In the second part, blood samples of 141 patients with ICH were obtained upon admission. Serum STC1 levels were measured, and the National Institutes of Health Stroke Scale (NIHSS), hematoma volume, and poststroke 6-month modified Rankin Scale (mRS) scores were recorded. Dynamic changes in serum STC levels and their correlation with disease severity and prognosis were investigated. Serum STC1 levels were elevated after ICH, peaked on day 1, plateaued on day 2, declined gradually afterwards, and were significantly higher than those in controls. Serum STC1 levels were independently correlated with NIHSS scores, hematoma volume, and the 6-month post-injury mRS scores. Serum STC1 levels, NIHSS scores, and hematoma volume independently predicted a poor prognosis (mRS scores of 3-6). The model integrating serum STC1 levels, NIHSS scores, and hematoma volume was visually displayed using a nomogram and was relatively stable using the Hosmer-Lemeshow test and calibration curve analysis. Under the receiver operating characteristic curve, serum STC1 levels efficiently predicted a poor prognosis and showed similar prognostic ability to NIHSS scores and hematoma volume. The preceding model had significantly higher prognostic capability than NIHSS scores and hematoma volume alone and their combination. Substantial enhancement of serum STC1 levels after ICH, which is strongly correlated with severity, independently distinguished the risk of poor prognosis, assuming that serum STC1, as a prognostic parameter, may be clinically valuable in ICH.

Prognostic significance of serum resolvin D1 levels in patients with acute supratentorial intracerebral hemorrhage: A prospective longitudinal cohort study

ObjectiveResolvin D1 (RvD1) has anti-inflammatory properties and may be neuroprotective. This study was designed to assess usability of serum RvD1 as a prognostic biomarker after intracerebral hemorrhage (ICH). MethodsIn this prospective, observational study of 135 patients and 135 controls, serum RvD1 levels were measured. Its relations to severity, early neurologic deterioration (END) and poststroke 6-month worse outcome (modified Rankin Scale scores of 3–6) were determined via multivariate analysis. Predictive effectiveness was evaluated based on area under receiver operating characteristic curve (AUC). ResultsPatients had markedly lower serum RvD1 levels than controls (median, 0.69 ng/ml versus 2.15 ng/ml). Serum RvD1 levels were independently correlated with the National Institutes of Health Stroke Scale (NIHSS) [β, −0.036; 95 % confidence interval (CI), −0.060--0.013; VIF, 2.633; t = -3.025; P = 0.003] and hematoma volume (β, −0.019; 95 % CI, −0.056--0.009; VIF, 1.688; t = -2.703; P = 0.008). Serum RvD1 levels substantially discriminated risks of END and worse outcome with AUCs at 0.762 (95 % CI, 0.681–0.831) and 0.783 (95 % CI, 0.704–0.850) respectively. A RvD1 cut-off value of 0.85 ng/ml was effective in predicting END with a sensitivity of 95.0 % and specificity of 48.4 % and its levels <0.77 ng/ml distinguished patients at risk of worse outcome with a sensitivity of 84.5 % and specificity of 63.6 %. Under restricted cubic spline, serum RvD1 levels were linearly related to risk of END and worse outcome (both P > 0.05). Serum RvD1 levels and NIHSS scores independently predicted END with odds ratio (OR) values of 0.082 (95 % CI, 0.010–0.687) and 1.280 (95 % CI, 1.084–1.513) respectively. Serum RvD1 levels (OR, 0.075; 95 % CI, 0.011–0.521), hematoma volume (OR, 1.084; 95 % CI, 1.035–1.135) and NIHSS scores (OR, 1.240; 95 % CI, 1.060–1.452) were independently associated with worse outcome. END prediction model containing serum RvD1 levels and NIHSS scores, and prognostic prediction model containing serum RvD1 levels, hematoma volumes and NIHSS scores displayed efficient predictive ability with AUCs at 0.828 (95 % CI, 0.754–0.888) and 0.873 (95 % CI, 0.805–0.924) respectively. Such two models were visually shown via building two nomograms. Using Hosmer-Lemeshow test, calibration curve and decision curve, the models were comparatively stable and had clinical benefit. ConclusionThere is a dramatical declination of serum RvD1 levels after ICH, which is tightly related to stroke severity and is independently predictive of poor clinical outcome, implying that serum RvD1 may be of clinical significance as a prognostic marker of ICH.

Prognostic significance of serum NLRC4 in patients with acute supratentorial intracerebral hemorrhage: A prospective longitudinal cohort study.

Caspase activation and recruitment domain-containing protein 4 (NLRC4) is implicated in neuroinflammation. The aim of the study was to discern the potential ability of serum NLRC4 in assessment of prognosis after intracerebral hemorrhage (ICH). In this prospective, observational study, serum NLRC4 levels were quantified in 148 acute supratentorial ICH patients and 148 controls. Severity was evaluated using the National Institutes of Health Stroke Scale (NIHSS) and hematoma volume, and poststroke 6-month functional outcome was estimated according to the modified Rankin Scale (mRS). Early neurologic deterioration (END) and 6-month poor outcome (mRS 3-6) were deemed as the two prognostic parameters. Multivariate models were established for investigating associations, and receiver operating characteristic (ROC) curves were configured to indicate predictive capability. Patients had substantially higher serum NLRC4 levels than controls (median, 363.2 pg/ml vs. 74.7 pg/ml). Serum NLRC4 levels had independent correlation with NIHSS scores [β, 0.308; 95% confidence interval (CI), 0.088-0.520], hematoma volume (β, 0.527; 95% CI, 0.385-0.675), serum C-reactive protein levels (β, 0.288; 95% CI, 0.109-0.341) and 6-month mRS scores (β, 0.239; 95% CI, 0.100-0.474). Serum NLRC4 levels above 363.2 pg/ml were independently predictive of END (odds ratio, 3.148; 95% CI, 1.278-7.752) and 6-month poor outcome (odds ratio, 2.468; 95% CI, 1.036-5.878). Serum NLRC4 levels significantly distinguished END risk [area under ROC curve (AUC), 0.765; 95% CI, 0.685-0.846] and 6-month poor outcome (AUC, 0.795; 95% CI, 0.721-0.870). In terms of predictive ability for 6-month poor outcome, serum NLRC4 levels combined with NIHSS scores and hematoma volume was superior to NIHSS scores combined with hematoma volume, NIHSS scores and hematoma volume (AUC, 0.913 vs. 0.870, 0.864 and 0.835; all P < 0.05). Nomograms were built to reflect prognosis and END risk of combination models, where serum NLRC4, NIHSS scores and hematoma volume were enforced. Calibration curves confirmed stability of combination models. Markedly raised serum NLRC4 levels following ICH, in close relation to illness severity, are independently associated with poor prognosis. Such results are indicative of the notion that determination of serum NLRC4 may aid in severity assessment and prediction of functional outcome of ICH patients.

Increased serum pannexin-1 concentrations reflect illness severity and predict a poor prognosis after acute supratentorial intracerebral hemorrhage: A prospective longitudinal cohort study

BackgroundPannexin-1 is a nonselective, large pore and voltage gated channel protein, whose activation may aggravate acute brain injury. We ascertained the clinical significance of serum pannexin-1 as a prognostic biomarker of acute intracerebral hemorrhage (ICH). MethodsIn this prospective, observational study of 124 acute supratentorial ICH patients and 124 healthy controls, serum pannexin-1 concentrations were determined. Admission National Institutes of Health Stroke Scale (NIHSS) score and hematoma volume were used for assessment of hemorrhagic severity, post-stroke 6-month modified Rankin scale (mRS) score was registered to reflect clinical outcome and early neurologic deterioration (END) and 6-month poor outcome (mRS score of 3–6) were regarded as the 2 prognostic parameters. Their associations with serum pannexin-1 concentrations were investigated using multivariate analysis. The predictive performance was evaluated in terms of area under receiver operating characteristic curve (AUC). ResultsIn comparison to controls, significantly increased serum pannexin-1 concentrations after ICH (median, 6.8 vs. 2.7 mg/ml) were independently correlative with NIHSS score (β, 0.193; 95% CI: 0.086–0.300), hematoma volume (β, 0.641; 95% CI: 0.423–0.859) and mRS score (β, 0.199; 95% CI: 0.065–0.174), were independently predictive of END (OR, 1.176; 95% CI: 1.081–1.280) and poor outcome (odds ratio, 1.218; 95% CI: 1.059–1.400), as well as were efficiently discriminative of END (AUC, 0.764; 95% CI: 0.663–0.864) and poor 6-month outcome (AUC, 0.790; 95% CI: 0.711–0.870). Serum pannexin-1 combined with NIHSS score and hematoma volume (AUC, 0.908; 95% CI: 0.857–0.960) displayed significantly higher predictive ability for poor 6-month outcome than NIHSS score and hematoma volume alone (both P < 0.05). ConclusionRising serum pannexin-1 concentrations following ICH, in strong correlation with hemorrhagic severity, independently distinguish the risk of END and 90-day poor outcome. Assumably, serum pannexin-1 may represent a valuable prognostic biomarker of ICH.

Elevated serum nuclear factor erythroid 2-related factor 2 levels contribute to a poor prognosis after acute supratentorial intracerebral hemorrhage: A prospective cohort study.

Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key transcriptional factor for antioxidant response element-regulated genes. The purpose of this study was to assess the prognostic role of serum Nrf2 in intracerebral hemorrhage (ICH). In this prospective observational study, serum Nrf2 levels of 115 acute supratentorial ICH patients and 115 controls were gaged. Early neurologic deterioration (END) was defined as an increase of four or greater points in National Institutes of Health Stroke Scale (NIHSS) score or death at post-stroke 24 h. A poor outcome was referred to as the post-stroke 90-day modified Rankin scale (mRS) score of 3-6. END and a poor outcome were considered as the two prognostic parameters. As compared to controls, serum Nrf2 levels of patients were substantially elevated (P < 0.001), with its levels increasing during the 6-h period immediately, peaking in 12-18 h, plateauing at 18-24 h, and decreasing gradually thereafter (P < 0.05). Serum Nrf2 levels of patients were independently correlated with NIHSS score (t = 3.033; P = 0.003) and hematoma volume (t = 3.210; P = 0.002), independently predicted END (odds ratio 1.125; 95% confidence interval 1.027-1.232; P = 0.011) and poor outcome (odds ratio 1.217; 95% confidence interval 1.067-1.387; P = 0.013), as well as efficiently distinguished END (area under curve 0.771; 95% confidence interval 0.666-0.877; P < 0.001) and poor outcome (area under curve 0.803; 95% confidence interval 0.725-0.882; P < 0.001). Its predictive ability was equivalent to those of NIHSS score and hematoma volume (both P > 0.05), and it also significantly improved their predictive abilities under receiver operating characteristic (ROC) curve (all P < 0.05). Elevated serum Nrf2 levels are closely correlated with severity, END, and 90-day poor outcome following ICH. Hence, Nrf2 may play an important role in acute brain injury after ICH, and serum Nrf2 may have the potential to serve as a prognostic biomarker of ICH.

An Exploratory Analysis of Biomarkers of Perihematomal Edema in the CN-105 in Participants with Acute Supratentorial Intracerebral Hemorrhage (CATCH) Trial

ObjectiveTo identify biomarkers with potential to indicate severity of perihematomal edema and secondary tissue injury after intracerebral hemorrhage (ICH), and which could be used as surrogate markers in future clinical trials for novel ICH therapeutics. Materials and MethodsThis exploratory cohort study compared trends in neuroinflammatory biomarker levels in 18 consecutively enrolled patients with acute supratentorial ICH and 16 patients treated with the investigational neuroprotective therapy CN-105 to identify a panel of 10 biomarkers. Biomarker levels over five days post-hemorrhage were then compared with edema volumes in a larger sample of patients treated with CN-105. ResultsMean normalized edema volumes increased over time; higher CRP levels were associated with increased edema volumes (p = 0.006, r = 0.56). Higher IL8, IL10, MCP, and MMP-9 levels were associated with decreased edema volumes (p = 0.005, r =-0.57; p = 0.02, r =-0.51; p = 0.02, r =-0.52; p = .002, r =-0.63, respectively). IL1-RA, IL1-B, IL23, vWF, and IL17 levels were not significantly associated with edema volumes (p > 0.05). ConclusionsThis exploratory study provides some of the first insights into the longitudinal associations between markers of neuroinflammation and development of perihematomal edema and secondary tissue injury in human ICH. We hypothesize that these biomarkers could be used as surrogates for treatment effect in novel therapies intended to limit neuroinflammation after ICH.

Soluble triggering receptor expressed on myeloid cells-1 as a serum biomarker of early neurologic deterioration and prognosis in acute supratentorial intracerebral hemorrhage

BackgroundTriggering receptor expressed on myeloid cells-1 (TREM-1) participates in neuroinflammation. We intended to ascertain whether serum soluble TREM-1 (sTREM-1) could be utilized as a biomarker of inflammation, severity, early neurologic deterioration (END) and outcome after primary intracerebral hemorrhage (ICH). MethodsSerum sTREM-1 levels were gauged in 104 ICH patients and 104 healthy controls. END was diagnosed when the National Institutes of Health Stroke Scale (NIHSS) score increased ≥ 4 points or death between admission and 24 h after admission. Patients with a modified Rankin scale score of > 2 at 3 months were considered to have poor outcome. ResultsAs compared to controls, patients exhibited significantly elevated serum sTREM-1 levels (median: 309.0 vs 67.9 pg/ml). Serum sTREM-1 concentrations were intimately correlated with NIHSS score (r = 0.574), hematoma volume (r = 0.554), blood leukocyte count (r = 0.529) and serum C-reactive protein concentrations (r = 0.509). Serum sTREM-1 concentrations > 309.0 pg/ml independently predicted END and poor outcome with odds ratio values of 4.054 and 4.721 respectively. Serum sTREM-1 concentrations distinguished END and poor outcome with areas under receiver operating characteristic curve of 0.789 and 0.813 respectively. ConclusionSerum sTREM-1 may represent a promising inflammatory biomarker for assessment of severity and prediction of END and poor outcome after ICH.

CN-105 in Participants with Acute Supratentorial Intracerebral Hemorrhage (CATCH) Trial.

Endogenous apolipoprotein (apo) E mediates neuroinflammatory responses and recovery after brain injury. Exogenously administered apoE-mimetic peptides effectively penetrate the central nervous system compartment and downregulate acute inflammation. CN-105 is a novel apoE-mimetic pentapeptide with excellent evidence of functional and histological improvement in preclinical models of intracerebral hemorrhage (ICH). The CN-105 in participants with Acute supraTentorial intraCerebral Hemorrhage (CATCH) trial is a first-in-disease-state multicenter open-label trial evaluating safety and feasability of CN-105 administration in patients with acute primary supratentorial ICH. Eligible patients were aged 30-80years, had confirmed primary supratentorial ICH, and were able to intiate CN-105 administration (1.0mg/kg every 6h for 72h) within 12h of symptom onset. A priori defined safety end points, including hematoma volume, pharmacokinetics, and 30-day neurological outcomes, were analyzed. For clinical outcomes, CATCH participants were compared 1:1 with a closely matched contemporary ICH cohort through random selection. Hematoma volumes determined from computed tomography images on days 0, 1, 2, and 5 and ordinal modified Rankin Scale score at 30days after ICH were compared. In 38 participants enrolled across six study sites in the United States, adverse events occurred at an expected rate without increase in hematoma expansion or neurological deterioration. CN-105 treatment had an odds ratio (95% confidence interval) of 2.69 (1.31-5.51) for lower 30-day modified Rankin Scale score, after adjustment for ICH score, sex, and race/ethnicity, as compared with a matched contemporary cohort. CN-105 administration represents an excellent translational candidate for treatment of acute ICH because of its safety, dosing feasibility, favorable pharmacokinetics, and possible improvement in neurological recovery.

Letter to the Editor Regarding “Relationship of Serum Uric Acid to Hematoma Volume and Prognosis in Patients with Acute Supratentorial Intracerebral Hemorrhage”

Letter to the Editor Regarding “Relationship of Serum Uric Acid to Hematoma Volume and Prognosis in Patients with Acute Supratentorial Intracerebral Hemorrhage”

In Reply to the Letter to the Editor Regarding “Relationship of Serum Uric Acid to Hematoma Volume and Prognosis in Patients with Acute Supratentorial Intracerebral Hemorrhage”

In Reply to the Letter to the Editor Regarding “Relationship of Serum Uric Acid to Hematoma Volume and Prognosis in Patients with Acute Supratentorial Intracerebral Hemorrhage”

Relationship of Serum Uric Acid to Hematoma Volume and Prognosis in Patients with Acute Supratentorial Intracerebral Hemorrhage

Oxidative stress and inflammation play important roles in the neuronal injury caused by intracerebral hemorrhage (ICH). Uric acid (UA), an important natural antioxidant, might reduce the neuronal injury caused by ICH. Delineating the relationship between UA and ICH will enhance our understanding of antioxidative mechanisms in recovery from ICH. We conducted a retrospective study of 325 patients with acute supratentorial ICH to investigate the relationship between serum UA levels and hematoma volumes and prognosis. A hematoma volume of ≥30 mL was defined as a large hematoma. An unfavorable outcome was defined as a modified Rankin scale score of 4-6 on day30. The serum UA level was significantly lower in the patients with a large hematoma volume (median, 306 μmol/L; 25th to 75th percentile, 243-411 μmol/L) than in those with a small hematoma volume (median, 357 μmol/L; 25th to 75th percentile, 271-442 μmol/L; P= 0.012). Similarly, the unfavorable outcome group had had lower serum UA levels (median, 309 vs. 363 μmol/L; P= 0.009) compared with the favorable outcome group. The results of the multivariate logistic analysis indicated that a lower serum UA level was associated with a larger hematoma volume (odds ratio, 0.996; P= 0.006) and an unfavorable outcome (odds ratio, 0.997; P= 0.030). The results from the present study have indicated that in patients with acute supratentorial ICH, a low serum UA level might indicate that the patient has a large hematoma volume and might be a risk factor for a poor day 30 functional prognosis.

Abstract TP432: Dilated Optic Nerve Sheath Diameter by Trans-Orbital Ultrasound Predicts Mortality Among Patients With Acute Intracerebral Hemorrhage

Introduction: Supratentorial Intracerebral hemorrhage (ICH) main prognostic factors on admission are age, Glasgow coma scale (GCS), ICH volume and ventricular hemorrhage. Subsequent ICH expansion and associated elevated intracranial pressure (ICP) have also been linked to poorer outcomes. Dilatation of optic nerve sheath diameter (ONSD) by trans-orbital ultrasound examination is an increasingly recognized marker of elevated ICP. We sought to evaluate whether increased ONSD at hospital admission could be associated with mortality among patients with supratentorial ICH. Methods: Prospective cohort of consecutive acute supratentorial ICH patients admitted to a tertiary stroke center. Exclusion criteria: 1) last well seen &gt; 24 hours; 2) immediate surgical intervention indicated by neurosurgery team; 3) Secondary ICH (anticoagulants and antiplatelets were allowed); 4) previous optic nerve pathology precluding accurate ONSD measurements. Ultrasound assessment and CT performed within the first hour after admission. Primary outcome was 90-days mortality. Multivariate logistic regression, ROC curve and c-statistics was used to identify independent predictors of mortality. Results: Between July 2014 and July 2017, 57 patients were evaluated. Among those, 13 were excluded and 44 were recruited into the trial. Their mean age was 62.3± 13.1 years and 32 (72.7%) were male. On univariate analysis, ICH volume on admission CT scan, ICH ipsilateral ONSD measurement on admission TCCD, diabetes and current smoking were predictors of mortality. After multivariate analysis, ipsilateral ONSD (OR:6.24;95CI%1.18-33.1;p=0.031) was an independent predictor of mortality, even after adjustment for ICH volume, age, GCS and intraventricular hemorrhage. The ONSD had an area under the curve (AUC) of 0.71 (p=0.021) for mortality at 3 months. Conclusion: ONSD is a non-invasively, bedside, low cost technique that could be used to estimate increased ICP in patients with acute supratentorial ICH. Among these patients, increased ONSD is an independent predictor of mortality at 3 months.

Acute ischaemic lesions are associated with cortical superficial siderosis in spontaneous intracerebral hemorrhage.

Diffusion-weighted imaging (DWI) commonly detects acute ischaemic lesions in patients with acute intracerebral hemorrhage (ICH), especially with cerebral amyloid angiopathy (CAA). We investigated the relationship between cortical superficial siderosis (cSS), a neuroimaging marker of CAA, and DWI lesions in patients with acute ICH. We conducted a retrospective analysis of prospectively collected data from consecutive patients with acute supratentorial ICH who underwent brain magnetic resonance imaging within 10days after symptom onset. Magnetic resonance imaging scans were analyzed for DWI lesions, cSS and other markers for small-vessel disease. Univariate and multivariate analyses were performed to assess the association between cSS and DWI lesions. Among 246 ICH survivors (mean age 71.4±12.6years) who were enrolled, 126 had lobar ICH and 120 had deep ICH. Overall, DWI lesions were observed in 38 (15.4%) patients and were more common in patients with lobar ICH than deep ICH (22.2% vs. 8.3%; P=0.003). In multivariate logistic regression analysis, the extent of white matter hyperintensities [odds ratio (OR), 1.29; 95% confidence interval (CI), 1.05-1.58; P=0.02] and cSS severity (focal cSS: OR, 3.54; 95% CI, 1.28-9.84; disseminated cSS: OR, 4.41; 95% CI, 1.78-10.97; P=0.001) were independently associated with the presence of DWI lesions. Diffusion-weighted imaging lesions are more frequently observed in patients with acute lobar ICH than in those with deep ICH. cSS severity and white matter hyperintensity extent are independent predictors for the presence of DWI lesions, suggesting that CAA may be involved in the pathogenesis of DWI lesions associated with acute ICH.

Sepsis Associated Encephalopathy Predicts Poor Outcome among Acute Supratentorial Intracerebral Hemorrhage with Coma

Background: Both sepsis associated encephalopathy (SAE) and supratentorial intracerebral hemorrhage (SICH) are a significant cause of coma and death throughout the world. The aim of this study was to investigate whether the presence of SAE among acute SICH with coma would predict a poor outcome. Methods: A retrospective of consecutive patients was selected for study. All registered an adult intensive care unit (ICU) of university teaching hospital between June, 2013 and July, 2015. Brain computed tomography (CT) scans were analyzed on admission and at coma onset or after coma onset. Univariate and Cox regression analyses were performed. Results: A total of 379 SICH with coma was studied. Among these, 245 (64.6%) SICH patients with coma due to SAE and 134 (35.4%) SICH with coma no SAE was compared. Our data showed that the frequency of the SAE in SICH patients increased at about double the proportion over the four SIRS criteria. The SICH patients with SAE were more likely to present with infection (100% vs 35.8%) and multiple organ failure (1.2 ± 0.9 vs 0.1 ± 0.3), especially nosocomal brain failure (60.4%). The 30 days mortality was significantly higher in the SAE group than those who did not (60.8% vs 11.2%). In Cox multivariate logistic analysis, the SAE (RR, 4.4; 95% CI, 2.296 - 8.422; P = 0.000) was more likely to related to risk on death in SICH patient with coma. Conclusions: SAE is a frequent complication of SICH, which greatly increased risk of death among SICH patients with coma.

Ultra-early hematoma growth in antithrombotic pretreated patients with intracerebral hemorrhage.

Patients with acute intracerebral hemorrhage (ICH) pretreated with antithrombotic drugs may have increased early hematoma growth, which would increase mortality risk. The effect of antiplatelet (AP) and vitamin K antagonist (VKA) pretreatment on ultra-early hematoma growth (uHG) and its relationship with mortality in patients with acute supratentorial ICH was analyzed. This is an observational retrospective study of a prospective register of 197 ICH patients with first computed tomography (CT) scan taken <6 h from ICH symptom onset. ICH volume was calculated by the ABC/2 formula and uHG by the baseline ICH volume/onset-to-CT time (ml/h) formula. The uHG analysis took into account the patient's pretreatment (none, AP or VKA) and the relationship between uHG and very-early (first 24 h) and 3-month mortality. In the pretreatment group, 50 (25.4%) patients were treated with AP and 37 (18.8%) with VKA. The median (interquartile range 25-75) uHG was 19.7 ml/h (2.9-44.8) for AP pretreated patients, 16.2 ml/h (5.1-42.5) for VKA pretreated patients and 8.4 ml/h (2.4-21.8) for non-pretreated patients, P = 0.019. The uHG was higher in patients with very-early [42.1 ml/h (20.1-79.6)] and total 3-month mortality [28.0 ml/h (15.8-52.5)] compared with survivors [3.9 ml/h (1.5-10.4)], P < 0.0001. Adjusted by ICH severity and previous functional status, uHG was an independent factor related to very-early (P = 0.028) and total 3-month mortality (P = 0.014). Patients pretreated with antithrombotics have much higher uHG, which would explain the increased mortality in these patients compared to untreated patients.

No Awakening in Supratentorial Intracerebral Hemorrhage Is Potentially Caused by Sepsis-Associated Encephalopathy.

BackgroundAcute supratentorial intracerebral hemorrhage (sICH) with secondary sepsis is increasing in frequency. We investigated whether no awakening (NA) after sICH with coma is potentially caused by sepsis-associated encephalopathy (SAE).Material/MethodsA case-control study of 147 recruited sICH cases with NA and 198 sICH controls with subsequent awakening (SA) was performed at 2 centers in China. All patients underwent brain computed tomography (CT) scans on admission. The odds ratio (OR) of NA was calculated using logistic regression.ResultsDuring the study period, 56.5% (83/147) of the patients with sICH with coma and NA had SAE, and 10% (20/198) with sICH with coma and SA had SAE; this difference between the 2 groups was significant (p<0.000). The sICH patients with coma and NA exhibited a longer median time from onset to coma (2.0 days vs. 0.5 days), more frequent confirmed infection (98.0% vs. 24.2%), and a higher Sequential Organ Failure Assessment (SOFA) score (6.3±1.5 vs. 3.4±0.8). These patients also exhibited lower hematoma volume (28.0±18.8 vs. 38.3±24), a lower initial National Institutes of Health Stroke Scale score (19.5±6.6 vs. 30.3±6.8), more frequent brain midline shift (59.2% vs. 27.8%), more frequent diffuse cerebral swelling (64.6% vs. 16.0%), and higher 30-day mortality (54.4% vs. 0.0%) than the patients who did awaken. Logistic multivariable regression analyses revealed that only a higher SOFA score (OR, 1.4; 95% CI, 1.079–1.767; p=0.010) and SAE (OR, 4.0; 95% CI, 1.359–6.775; p=0.001) were associated with NA events in patients with sICH.ConclusionsNA in sICH patients with coma is potentially caused by secondary SAE.