Perihematomal Edema and Clinical Outcome in Intracerebral Hemorrhage Related to Different Oral Anticoagulants.
Ontology highlight
ABSTRACT: Background
There is a need to examine the effects of different types of oral anticoagulant-associated intracerebral hemorrhage (OAC-ICH) on perihematomal edema (PHE), which is gaining considerable appeal as a biomarker for secondary brain injury and clinical outcome.Methods
In a large multicenter approach, computed tomography-derived imaging markers for PHE (absolute PHE, relative PHE (rPHE), edema expansion distance (EED)) were calculated for patients with OAC-ICH and NON-OAC-ICH. Exploratory analysis for non-vitamin-K-antagonist OAC (NOAC) and vitamin-K-antagonists (VKA) was performed. The predictive performance of logistic regression models, employing predictors of poor functional outcome (modified Rankin scale 4-6), was explored.Results
Of 811 retrospectively enrolled patients, 212 (26.14%) had an OAC-ICH. Mean rPHE and mean EED were significantly lower in patients with OAC-ICH compared to NON-OAC-ICH, p-value 0.001 and 0.007; whereas, mean absolute PHE did not differ, p-value 0.091. Mean EED was also significantly lower in NOAC compared to NON-OAC-ICH, p-value 0.05. Absolute PHE was an independent predictor of poor clinical outcome in NON-OAC-ICH (OR 1.02; 95%CI 1.002-1.028; p-value 0.027), but not in OAC-ICH (p-value 0.45).Conclusion
Quantitative markers of early PHE (rPHE and EED) were lower in patients with OAC-ICH compared to those with NON-OAC-ICH, with significantly lower levels of EED in NOAC compared to NON-OAC-ICH. Increase of early PHE volume did not increase the likelihood of poor outcome in OAC-ICH, but was independently associated with poor outcome in NON-OAC-ICH. The results underline the importance of etiology-specific treatment strategies. Further prospective studies are needed.
SUBMITTER: Nawabi J
PROVIDER: S-EPMC8196746 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Background and purposePerihematomal edema (PHE) is a marker of secondary injury in intracerebral hemorrhage (ICH). PHE measurement on computed tomography (CT) is challenging, and the principles used to detect PHE have not been described fully. We developed a systematic approach for CT-based measurement of PHE.MethodsTwo independent raters measured PHE volumes on baseline and 24-hour post-ICH CT scans of 20 primary supratentorial ICH subjects. Boundaries were outlined with an edge-detection tool and adjusted after inspection of the 3 orthogonal planes. PHE was delineated with the additional principle that it should be (a) more hypodense than the corresponding area in the contralateral hemisphere and (b) most hypodense immediately surrounding the hemorrhage. We examined intra- and interrater reliability using intraclass correlation coefficients and Bland-Altman plots for interrater consistency. CT-based PHE was also compared using magnetic resonance imaging-based PHE detection for 18 subjects.ResultsMedian PHE volumes were 22.7 cc at baseline and 20.4 cc at 24 hours post-ICH. There were no statistically significant differences in PHE measurements between raters. Interrater and intrarater reliability for PHE were excellent. At baseline and 24 hours, interrater intraclass correlation coefficients were 0.98 (0.96-1.00) and 0.98 (0.97-1.00); intrarater intraclass correlation coefficients were 0.99 (0.99-1.00) and 0.99 (0.98-1.00). Bland-Altman analysis showed the bias for PHE measurements at baseline and 24 hours, -0.5 cc (SD, 5.4) and -3.2 cc (SD, 5.0), was acceptably small. PHE volumes determined by CT and magnetic resonance imaging were similar (23.9±16.9 cc versus 23.9±16.0 cc, R(2) = 0.98, P<0.0001).ConclusionsOur method measures PHE with excellent reliability at baseline and 24 hours post-ICH.
| S-EPMC5340416 | biostudies-literature
Project description:Acute intracerebral hemorrhage (ICH) is a devastating type of stroke worldwide. Neuronal destruction involved in the brain damage process caused by ICH includes a primary injury formed by the mass effect of the hematoma and a secondary injury induced by the degradation products of a blood clot. Additionally, factors in the coagulation cascade and complement activation process also contribute to secondary brain injury by promoting the disruption of the blood-brain barrier and neuronal cell degeneration by enhancing the inflammatory response, oxidative stress, etc. Although treatment options for direct damage are limited, various strategies have been proposed to treat secondary injury post-ICH. Perihematomal edema (PHE) is a potential surrogate marker for secondary injury and may contribute to poor outcomes after ICH. Therefore, it is essential to investigate the underlying pathological mechanism, evolution, and potential therapeutic strategies to treat PHE. Here, we review the pathophysiology and imaging characteristics of PHE at different stages after acute ICH. As illustrated in preclinical and clinical studies, we discussed the merits and limitations of varying PHE quantification protocols, including absolute PHE volume, relative PHE volume, and extension distance calculated with images and other techniques. Importantly, this review summarizes the factors that affect PHE by focusing on traditional variables, the cerebral venous drainage system, and the brain lymphatic drainage system. Finally, to facilitate translational research, we analyze why the relationship between PHE and the functional outcome of ICH is currently controversial. We also emphasize promising therapeutic approaches that modulate multiple targets to alleviate PHE and promote neurologic recovery after acute ICH.
| S-EPMC9509250 | biostudies-literature
Project description:We attempt to generate a definition of delayed perihematomal edema expansion (DPE) and analyze its time course, risk factors, and clinical outcomes. A multi-cohort data was derived from the Chinese Intracranial Hemorrhage Image Database (CICHID). A non-contrast computed tomography (NCCT) -based deep learning model was constructed for fully automated segmentation hematoma and perihematomal edema (PHE). Time course of hematoma and PHE evolution correlated to initial hematoma volume was volumetrically assessed. Predictive values for DPE were calculated through receiver operating characteristic curve analysis and were tested in an independent cohort. Logistic regression analysis was utilized to identify risk factors for DPE formation and poor outcomes. The test cohort's Dice scores of lesion segmentation were 0.877 and 0.642 for hematoma and PHE, respectively. Overall, 1201 patients were enrolled for time-course analysis of ICH evolution. A total of 312 patients were further selected for DPE analysis. Time course analysis showed the growth peak of PHE approximately concentrates in 14 days after onset. The best cutoff for DPE to predict poor outcome was 3.34 mL of absolute PHE expansion from 4-7 days to 8-14 days (AUC=0.784, sensitivity=72.2%, specificity=81.2%), and 3.78 mL of absolute PHE expansion from 8-14 days to 15-21 days (AUC=0.682, sensitivity=59.3%, specificity=92.1%) in the derivation sample. Patients with DPE was associated with worse outcome (OR: 12.340, 95%CI: 6.378-23.873, P<0.01), and the larger initial hematoma volume (OR: 1.021, 95%CI: 1.000-1.043, P=0.049) was the significant risk factor for DPE formation. This study constructed a well-performance deep learning model for automatic segmentations of hematoma and PHE. A new definition of DPE was generated and is confirmed to be related to poor outcomes in ICH. Patients with larger initial hematoma volume have a higher risk of developing DPE formation.
| S-EPMC9125313 | biostudies-literature
Project description:Although preclinical studies have shown inflammation to mediate perihematomal edema (PHE) after intracerebral hemorrhage, clinical data are lacking. Leukocyte count, often used to gauge serum inflammation, has been correlated with poor outcome but its relationship with PHE remains unknown. Our aim was to test the hypothesis that leukocyte count is associated with PHE growth.We included patients with intracerebral hemorrhage admitted to a tertiary-care stroke center between 2011 and 2015. The primary outcome was absolute PHE growth during 24 hours, calculated using semiautomated planimetry. Linear regression models were constructed to study the relationship between absolute and differential leukocyte counts (monocyte count and neutrophil-lymphocyte ratio) and 24-hour PHE growth.A total of 153 patients were included. Median hematoma and PHE volumes at baseline were 14.4 (interquartile range, 6.3-36.3) and 14.0 (interquartile range, 5.9-27.8), respectively. In linear regression analysis adjusted for demographics and intracerebral hemorrhage characteristics, absolute leukocyte count was not associated with PHE growth (?, 0.07; standard error, 0.15; P=0.09). In secondary analyses, neutrophil-lymphocyte ratio was correlated with PHE growth (?, 0.22; standard error, 0.08; P=0.005).Higher neutrophil-lymphocyte ratio is independently associated with PHE growth. This suggests that PHE growth can be predicted using differential leukocyte counts on admission.
| S-EPMC5810930 | biostudies-literature
Project description:Background and Purpose- Patients with active malignancy are at risk for intracerebral hemorrhage (ICH). We aimed to characterize perihematomal edema (PHE) and hematoma volumes after spontaneous nontraumatic ICH in patients with cancer without central nervous system involvement. Methods- Patients with active malignancy who developed ICH were retrospectively identified through automated searches of institutional databases. Control patients were identified with ICH and without active cancer. Demographic and cancer-specific data were obtained by chart review. Hematoma and PHE volumes were determined using semiautomated methodology. Univariate and multivariate linear regression models were created to assess which variables were associated with hematoma and PHE expansion. Results- Patients with cancer (N=80) and controls (N=136) had similar demographics (all P>0.20), although hypertension was more prevalent among controls (P=0.004). Most patients with cancer had received recent chemotherapy (n=45, 56%) and had recurrence of malignancy (n=43, 54%). Patients with cancer were thrombocytopenic (median platelet count 90 000 [interquartile range, 17 500-211 500]), and most had undergone blood product transfusion (n=41, 51%), predominantly platelets (n=38, 48%). Thirty-day mortality was 36% (n=29). Patients with cancer had significantly increased PHE volumes (23.67 versus 8.61 mL; P=1.88×10-9) and PHE-to-ICH volume ratios (2.26 versus 0.99; P=2.20×10-16). In multivariate analyses, variables associated with PHE growth among patients with cancer were ICH volume (β=1.29 [95% CI, 1.58-1.30] P=1.30×10-5) and platelet transfusion (β=15.67 [95% CI, 3.61-27.74] P=0.014). Variables associated with 30-day mortality were ICH volume (odds ratio, 1.06 [95% CI, 1.03-1.10] P=6.76×10-5), PHE volume (odds ratio, 1.07 [95% CI, 1.04-1.09] P=7.40×10-6), PHE growth (odds ratio, 1.05 [95% CI, 1.01-1.10] P=0.01), and platelet transfusion (odds ratio, 1.48 [95% CI, 1.22-1.79] P=0.0001). Conclusions- Patients with active cancer who develop ICH have increased PHE volumes. PHE growth was independent of thrombocytopenia but associated with blood product transfusion. Thirty-day mortality was associated with PHE and ICH volumes and blood product transfusion.
| S-EPMC7048624 | biostudies-literature
Project description:BackgroundUncertainty surrounds the effects of cerebral edema on outcomes in intracerebral hemorrhage (ICH).MethodsWe used data from the INTERACT trial to determine the predictors and prognostic significance of "perihematomal" edema over 72 hours after ICH. INTERACT included 404 patients with CT-confirmed ICH and elevated systolic blood pressure (BP) (150-220 mm Hg) who had the capacity to commence BP lowering treatment within 6 hours of ICH. Baseline and repeat CT (24 and 72 hours) were performed using standardized techniques, with digital images analyzed centrally. Predictors of growth in edema were determined using generalized estimating equations, and its effects on clinical outcomes were estimated using a logistic regression model.ResultsOverall, 270 patients had 3 sequential CT scans available for analyses. At baseline, there was a highly significant correlation between hematoma and perihematomal edema volumes (r(2) = 0.45). Lower systolic BP and baseline hematoma volume were independently associated with absolute increase in perihematomal edema volume. History of hypertension, baseline hematoma volume, and earlier time from onset to CT were independently associated with relative increase in edema volume. Both absolute and relative increases in perihematomal edema growth were significantly associated with death or dependency at 90 days after adjustment for age, gender, and randomized treatment, but not when additionally adjusted for baseline hematoma volume.ConclusionsThe degree of, and growth in, perihematomal edema are strongly related to the size of the underlying hematoma of acute intracerebral hemorrhage, and do not appear to have a major independent effect in determining the outcome from this condition.
| S-EPMC2796457 | biostudies-literature
Project description:The purpose of this study was to determine whether jugular venous reflux (JVR) is associated with perihematomal edema (PHE) in individuals with intracerebral hemorrhage (ICH). Patients with spontaneous supratentorial ICH within 72 h of symptom onset were enrolled. Baseline brain computed tomography (CT) scan was performed, with a follow-up CT examination at 12 ± 3 days after onset. Jugular venous color Doppler ultrasound was performed at 12 ± 3 days after onset to examine the JVR status. A total of 65 patients with ICH were enrolled. In logistic regression analysis, absolute PHE volume was significantly associated with JVR (OR, 5.46; 95% CI, 1.04-28.63; p = 0.044) and baseline hematoma volume (OR, 1.14; 95% CI, 1.03-1.26; p = 0.009) within 72 h of onset. It was also correlated with JVR (OR, 15.32; 95% CI, 2.52-92.99; p = 0.003) and baseline hematoma volume (OR, 1.14; 95% CI, 1.04-1.24; p = 0.006) at 12 ± 3 days after onset. In a similar manner, relative PHE volume was significantly associated with JVR (OR, 14.85; 95% CI, 3.28-67.17; p < 0.001) within 72 h of onset and at 12 ± 3 days after onset (OR, 5.87; 95% CI, 1.94-17.77; p = 0.002). JVR is associated with both absolute and relative PHE volumes after ICH.
| S-EPMC5485297 | biostudies-other
Project description:Background and Purpose- Volumes of hemorrhage and perihematomal edema (PHE) are well-established biomarkers of primary and secondary injury, respectively, in spontaneous intracerebral hemorrhage. An automated imaging pipeline capable of accurately and rapidly quantifying these biomarkers would facilitate large cohort studies evaluating underlying mechanisms of injury. Methods- Regions of hemorrhage and PHE were manually delineated on computed tomography scans of patients enrolled in 2 intracerebral hemorrhage studies. Manual ground-truth masks from the first cohort were used to train a fully convolutional neural network to segment images into hemorrhage and PHE. The primary outcome was automated-versus-human concordance in hemorrhage and PHE volumes. The secondary outcome was voxel-by-voxel overlap of segmentations, quantified by the Dice similarity coefficient (DSC). Algorithm performance was validated on 84 scans from the second study. Results- Two hundred twenty-four scans from 124 patients with supratentorial intracerebral hemorrhage were used for algorithm derivation. Median volumes were 18 mL (interquartile range, 8-43) for hemorrhage and 12 mL (interquartile range, 5-30) for PHE. Concordance was excellent (0.96) for automated quantification of hemorrhage and good (0.81) for PHE, with DSC of 0.90 (interquartile range, 0.85-0.93) and 0.54 (0.39-0.65), respectively. External validation confirmed algorithm accuracy for hemorrhage (concordance 0.98, DSC 0.90) and PHE (concordance 0.90, DSC 0.55). This was comparable with the consistency observed between 2 human raters (DSC 0.90 for hemorrhage, 0.57 for PHE). Conclusions- We have developed a deep learning-based imaging algorithm capable of accurately measuring hemorrhage and PHE volumes. Rapid and consistent automated biomarker quantification may accelerate powerful and precise studies of disease biology in large cohorts of intracerebral hemorrhage patients.
| S-EPMC6993878 | biostudies-literature
Project description:BackgroundPerihematomal edema contributes to secondary brain injury in the course of intracerebral hemorrhage. The effect of decompressive surgery on perihematomal edema after intracerebral hemorrhage is unknown. This study analyzed the course of PHE in patients who were or were not treated with decompressive craniectomy.MethodsMore than 100 computed tomography images from our published cohort of 25 patients were evaluated retrospectively at two university hospitals in Switzerland. Computed tomography scans covered the time from admission until day 100. Eleven patients were treated by decompressive craniectomy and 14 were treated conservatively. Absolute edema and hematoma volumes were assessed using 3-dimensional volumetric measurements. Relative edema volumes were calculated based on maximal hematoma volume.ResultsAbsolute perihematomal edema increased from 42.9 ml to 125.6 ml (192.8%) after 21 days in the decompressive craniectomy group, versus 50.4 ml to 67.2 ml (33.3%) in the control group (? at day 21 = 58.4 ml, p = 0.031). Peak edema developed on days 25 and 35 in patients with decompressive craniectomy and controls respectively, and it took about 60 days for the edema to decline to baseline in both groups. Eight patients (73%) in the decompressive craniectomy group and 6 patients (43%) in the control group had a good outcome (modified Rankin Scale score 0 to 4) at 6 months (P = 0.23).ConclusionsDecompressive craniectomy is associated with a significant increase in perihematomal edema compared to patients who have been treated conservatively. Perihematomal edema itself lasts about 60 days if it is not treated, but decompressive craniectomy ameliorates the mass effect exerted by the intracerebral hemorrhage plus the perihematomal edema, as reflected by the reduced midline shift.
| S-EPMC4752325 | biostudies-literature
Project description:Background and Purpose- It is unknown whether blood pressure (BP) reduction influences secondary brain injury in spontaneous intracerebral hemorrhage (ICH). We tested the hypothesis that intensive BP reduction is associated with decreased perihematomal edema expansion rate (PHER) in deep ICH. Methods- We performed an exploratory analysis of the ATACH-2 randomized trial (Antihypertensive Treatment of Acute Cerebral Hemorrhage-2). Patients with deep, supratentorial ICH were included. PHER was calculated as the difference in perihematomal edema volume between baseline and 24-hour computed tomography scans divided by hours between scans. We used regression analyses to determine whether intensive BP reduction was associated with PHER and if PHER was associated with poor outcome (3-month modified Rankin Scale score 4-6). We then used interaction analyses to test whether specific deep location (basal ganglia versus thalamus) modified these associations. Results- Among 1000 patients enrolled in ATACH-2, 870 (87%) had supratentorial, deep ICH. Of these, 780 (90%) had neuroimaging data (336 thalamic and 444 basal ganglia hemorrhages). Baseline characteristics of the treatment groups remained balanced (P>0.2). Intensive BP reduction was associated with a decrease in PHER in univariable (β= -0.15; 95% CI, -0.26 to -0.05; P=0.007) and multivariable (β=-0.12; 95% CI, -0.21 to -0.02; P=0.03) analyses. PHER was not independently associated with outcome in all deep ICH (odds ratio, 1.14; 95% CI, 0.93-1.41; P=0.20), but this association was modified by the specific deep location involved (multivariable interaction P=0.02); in adjusted analyses, PHER was associated with poor outcome in basal ganglia (odds ratio, 1.42; 1.05-1.97; P=0.03) but not thalamic (odds ratio, 1.02; 95% CI, 0.74-1.40; P=0.89) ICH. Conclusions- Intensive BP reduction was associated with decreased 24-hour PHER in deep ICH. PHER was not independently associated with outcome in all deep ICH but was associated with poor outcome in basal ganglia ICH. PHER may be a clinically relevant end point for clinical trials in basal ganglia ICH.
| S-EPMC6646091 | biostudies-literature