scholarly journals Perihematomal Edema After Intracerebral Hemorrhage: An Update on Pathogenesis, Risk Factors, and Therapeutic Advances

2021 ◽  
Vol 12 ◽  
Author(s):  
Yihao Chen ◽  
Shengpan Chen ◽  
Jianbo Chang ◽  
Junji Wei ◽  
Ming Feng ◽  
...  
Keyword(s):  
Risk Factors ◽  
Intracerebral Hemorrhage ◽  
Mass Effect ◽  
Underlying Mechanism ◽  
Secondary Brain Injury ◽  
Surgical Measures ◽  
Promising Therapeutic Target ◽  
Potential Impact ◽  
Perihematomal Edema ◽  
Preclinical And Clinical Studies

Intracerebral hemorrhage (ICH) has one of the worst prognoses among patients with stroke. Surgical measures have been adopted to relieve the mass effect of the hematoma, and developing targeted therapy against secondary brain injury (SBI) after ICH is equally essential. Numerous preclinical and clinical studies have demonstrated that perihematomal edema (PHE) is a quantifiable marker of SBI after ICH and is associated with a poor prognosis. Thus, PHE has been considered a promising therapeutic target for ICH. However, the findings derived from existing studies on PHE are disparate and unclear. Therefore, it is necessary to classify, compare, and summarize the existing studies on PHE. In this review, we describe the growth characteristics and relevant underlying mechanism of PHE, analyze the contributions of different risk factors to PHE, present the potential impact of PHE on patient outcomes, and discuss the currently available therapeutic strategies.

Abstract P423: Race and Ethnicity Influence Perihematomal Edema Volume in Supratentorial Intracerebral Hemorrhage

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Julian N Acosta ◽  
Yasheng Chen ◽  
Cameron Both ◽  
Audrey C Leasure ◽  
Fernando Testai ◽  
...  
Keyword(s):  
Intracerebral Hemorrhage ◽  
Race And Ethnicity ◽  
Learning Algorithm ◽  
Multivariable Analysis ◽  
Secondary Brain Injury ◽  
Racial Groups ◽  
Deep Learning Algorithm ◽  
Perihematomal Edema ◽  
Study Participants ◽  
Racial Ethnic

Introduction: Perihematomal Edema (PHE) is a neuroimaging biomarker of secondary brain injury in patients with spontaneous, non-traumatic intracerebral hemorrhage (ICH). There are limited data on racial/ethnic differences in the development of PHE. This dearth of data is partially driven by the time-consuming process of manually segmenting PHE. Leveraging a validated automated pipeline for PHE segmentation, we evaluated whether race and ethnicity influence baseline PHE volume in patients with ICH. Methods: The Ethnic/Racial Variations in Intracerebral Hemorrhage (ERICH) study is a prospective, multicenter study of ICH that recruited 1,000 adult participants from each of three racial/ethnic groups (non-Hispanic White, non-Hispanic Black, and Hispanic). We applied a previously validated deep learning algorithm to automatically determine PHE volumes on baseline CTs in these study participants. Quality control procedures were used to include only sufficiently accurate PHE measurements. Linear regression was used to identify factors associated with log-transformed PHE volume and to identify differences across Ethnic/Racial groups. Results: Our imaging pipeline provided good quality baseline PHE measurements on 2,008 out of 3,000 ERICH study participants. After excluding infratentorial hemorrhages (273) and those with missing or null baseline ICH volume (49), 1,686 remained for analysis (median age 59 [IQR 51-71], 687 [41%] female sex). Median PHE volume was 12.0 (IQR 4.8-27.1) for whites, 11.9 (IQR 4.5-26.1) for Hispanics and 8.3 (IQR 3.0-19.2) for blacks. Compared to Blacks, Hispanics (beta 0.22; 95%CI 0.11-0.32; p<0.001) and Whites (beta 0.20; 95%CI 0.07-0.33; p=0.003) had higher baseline PHE volumes, in multivariable analysis adjusting for age, sex, ICH location, log-baseline ICH volume, log-baseline intraventricular volume, and systolic blood pressure on admission. Conclusion: Race and ethnicity influence the volume of baseline PHE. Further studies are needed to validate our results and investigate the biological underpinnings of this difference.

scholarly journals Spreading depolarizations in patients with spontaneous intracerebral hemorrhage: Association with perihematomal edema progression

2016 ◽  
Vol 37 (5) ◽  
pp. 1871-1882 ◽  
Author(s):  
Raimund Helbok ◽  
Alois Josef Schiefecker ◽  
Christian Friberg ◽  
Ronny Beer ◽  
Mario Kofler ◽  
...  
Keyword(s):  
Brain Injury ◽  
Intracerebral Hemorrhage ◽  
Electrode Placement ◽  
Secondary Brain Injury ◽  
Spontaneous Intracerebral Hemorrhage ◽  
Strip Electrode ◽  
Hematoma Evacuation ◽  
Perihematomal Edema ◽  
Pathophysiologic Mechanisms

Pathophysiologic mechanisms of secondary brain injury after intracerebral hemorrhage and in particular mechanisms of perihematomal-edema progression remain incompletely understood. Recently, the role of spreading depolarizations in secondary brain injury was established in ischemic stroke, subarachnoid hemorrhage and traumatic brain injury patients. Its role in intracerebral hemorrhage patients and in particular the association with perihematomal-edema is not known. A total of 27 comatose intracerebral hemorrhage patients in whom hematoma evacuation and subdural electrocorticography was performed were studied prospectively. Hematoma evacuation and subdural strip electrode placement was performed within the first 24 h in 18 patients (67%). Electrocorticography recordings started 3 h after surgery (IQR, 3–5 h) and lasted 157 h (median) per patient and 4876 h in all 27 patients. In 18 patients (67%), a total of 650 spreading depolarizations were observed. Spreading depolarizations were more common in the initial days with a peak incidence on day 2. Median electrocorticography depression time was longer than previously reported (14.7 min, IQR, 9–22 min). Postoperative perihematomal-edema progression (85% of patients) was significantly associated with occurrence of isolated and clustered spreading depolarizations. Monitoring of spreading depolarizations may help to better understand pathophysiologic mechanisms of secondary insults after intracerebral hemorrhage. Whether they may serve as target in the treatment of intracerebral hemorrhage deserves further research.

scholarly journals The risk factors and prognosis of delayed perihematomal edema in patients with spontaneous intracerebral hemorrhage

2019 ◽  
Vol 25 (10) ◽  
pp. 1189-1194 ◽  
Author(s):  
Wen‐jie Peng ◽  
Qian Li ◽  
Jin‐hua Tang ◽  
Cesar Reis ◽  
Camila Araujo ◽  
...  
Keyword(s):  
Risk Factors ◽  
Intracerebral Hemorrhage ◽  
Spontaneous Intracerebral Hemorrhage ◽  
Perihematomal Edema

scholarly journals Emerging experimental therapies for intracerebral hemorrhage: targeting mechanisms of secondary brain injury

2013 ◽  
Vol 34 (5) ◽  
pp. E9 ◽  
Author(s):  
Praveen K. Belur ◽  
Jason J. Chang ◽  
Shuhan He ◽  
Benjamin A. Emanuel ◽  
William J. Mack
Keyword(s):  
Brain Injury ◽  
Intracerebral Hemorrhage ◽  
Mass Effect ◽  
Therapeutic Strategies ◽  
Experimental Models ◽  
Thrombin Inhibitors ◽  
Hematoma Expansion ◽  
Secondary Brain Injury ◽  
Limited Efficacy ◽  
Experimental Therapies

Intracerebral hemorrhage (ICH) is associated with a higher degree of morbidity and mortality than other stroke subtypes. Despite this burden, currently approved treatments have demonstrated limited efficacy. To date, therapeutic strategies have principally targeted hematoma expansion and resultant mass effect. However, secondary mechanisms of brain injury are believed to be critical effectors of cell death and neurological outcome following ICH. This article reviews the pathophysiology of secondary brain injury relevant to ICH, examines pertinent experimental models, and highlights emerging therapeutic strategies. Treatment paradigms discussed include thrombin inhibitors, deferoxamine, minocycline, statins, granulocyte-colony stimulating factors, and therapeutic hypothermia. Despite promising experimental and preliminary human data, further studies are warranted prior to effective clinical translation.

scholarly journals Intracerebral Hemorrhage, Oxidative Stress, and Antioxidant Therapy

2016 ◽  
Vol 2016 ◽  
pp. 1-17 ◽  
Author(s):  
Xiaochun Duan ◽  
Zunjia Wen ◽  
Haitao Shen ◽  
Meifen Shen ◽  
Gang Chen
Keyword(s):  
Oxidative Stress ◽  
Intracerebral Hemorrhage ◽  
Stress Responses ◽  
Secondary Brain Injury ◽  
Mortality And Morbidity ◽  
Systemic Oxidative Stress ◽  
Preclinical And Clinical Studies ◽  
Apoptosis And Necrosis ◽  
Oxidative Stress Responses

Hemorrhagic stroke is a common and severe neurological disorder and is associated with high rates of mortality and morbidity, especially for intracerebral hemorrhage (ICH). Increasing evidence demonstrates that oxidative stress responses participate in the pathophysiological processes of secondary brain injury (SBI) following ICH. The mechanisms involved in interoperable systems include endoplasmic reticulum (ER) stress, neuronal apoptosis and necrosis, inflammation, and autophagy. In this review, we summarized some promising advances in the field of oxidative stress and ICH, including contained animal and human investigations. We also discussed the role of oxidative stress, systemic oxidative stress responses, and some research of potential therapeutic options aimed at reducing oxidative stress to protect the neuronal function after ICH, focusing on the challenges of translation between preclinical and clinical studies, and potential post-ICH antioxidative therapeutic approaches.

Thrombin and hemin as central factors in the mechanisms of intracerebral hemorrhage–induced secondary brain injury and as potential targets for intervention

2012 ◽  
Vol 32 (4) ◽  
pp. E8 ◽  
Author(s):  
Ranjith Babu ◽  
Jacob H. Bagley ◽  
Chunhui Di ◽  
Allan H. Friedman ◽  
Cory Adamson
Keyword(s):  
Brain Injury ◽  
Intracerebral Hemorrhage ◽  
Molecular Mechanisms ◽  
Treatment Strategies ◽  
Mass Effect ◽  
Thrombin Inhibitors ◽  
Hematoma Expansion ◽  
Secondary Brain Injury ◽  
Antiinflammatory Drugs ◽  
Primary Hemorrhage

Intracerebral hemorrhage (ICH) is a subtype of stoke that may cause significant morbidity and mortality. Brain injury due to ICH initially occurs within the first few hours as a result of mass effect due to hematoma formation. However, there is increasing interest in the mechanisms of secondary brain injury as many patients continue to deteriorate clinically despite no signs of rehemorrhage or hematoma expansion. This continued insult after primary hemorrhage is believed to be mediated by the cytotoxic, excitotoxic, oxidative, and inflammatory effects of intraparenchymal blood. The main factors responsible for this injury are thrombin and erythrocyte contents such as hemoglobin. Therapies including thrombin inhibitors, N-methyl-D-aspartate antagonists, chelators to bind free iron, and antiinflammatory drugs are currently under investigation for reducing this secondary brain injury. This review will discuss the molecular mechanisms of brain injury as a result of intraparenchymal blood, potential targets for therapeutic intervention, and treatment strategies currently in development.

Abstract WP309: Association of Molecular Markers with Perihematomal Edema and Clinical Outcome in Intracerebral Hemorrhage

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Na Li ◽  
Yan Fang Liu ◽  
Li Ma ◽  
Hans Worthmann ◽  
Peter Raab ◽  
...  
Keyword(s):  
Molecular Markers ◽  
Brain Injury ◽  
Clinical Outcome ◽  
Intracerebral Hemorrhage ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Stroke Severity ◽  
Secondary Brain Injury ◽  
Hematoma Volume ◽  
Perihematomal Edema

Background and Purpose: Perihematomal edema (PHE) contributes to secondary brain injury in intracerebral hemorrhage (ICH). Increase of matrix metalloproteinases (MMPs) and growth factors (GFs) is considerably involved in blood-brain barrier disruption and neuronal cell death in ICH models. We therefore hypothesized that increased levels of these molecular markers are associated with PHE and clinical outcome in ICH patients. Methods: Fifty-nine patients with spontaneous ICH admitted within 24 hours of symptom onset were prospectively investigated. Noncontrast CT was performed on admission for diagnosis of ICH and quantification of initial hematoma volume. MRI was performed on day 3 in order to evaluate PHE. Concentrations of MMP-3, MMP-9, as well as vascular endothelial growth factor (VEGF) and Angiopoietin-1(Ang-1) on admission were determined by enzyme-linked immunosorbent assays. Clinical outcome was assessed by modified Rankin Scale (mRS) at 90days. Results: Increased MMP-3 levels were independently associated with PHE volume (P<0.05). Cytotoxic edema (CE) surrounding the hematoma was seen in 36 (61%) cases on 3-day MRI. CE did not correlate with the level of any of the biomarkers studied. Levels of MMP-3 ≥12.4 ng/ml and MMP-9 ≥192.4 ng/ml but not VEGF and Ang-1 predicted poor clinical outcome at 90 days (mRS>3) independent of stroke severity and hematoma volume at baseline (OR 25.3, P=0.035; OR 68.9, P=0.023; respectively). Conclusion: Metalloproteinases 3 and 9 seem to be significantly involved in secondary brain injury and outcome after primary ICH in humans and thus should be further evaluated as targets for therapeutic strategies in this devastating disorder.

Ultra-early clot aspiration after lysis with tissue plasminogen activator in a porcine model of intracerebral hemorrhage: edema reduction and blood-brain barrier protection

1999 ◽  
Vol 90 (3) ◽  
pp. 491-498 ◽  
Author(s):  
Kenneth R. Wagner ◽  
Guohua Xi ◽  
Ya Hua ◽  
Mario Zuccarello ◽  
Gabrielle M. de Courten-Myers ◽  
...  
Keyword(s):  
White Matter ◽  
Intracerebral Hemorrhage ◽  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Mass Effect ◽  
Content Type ◽  
Tissue Plasminogen ◽  
Clot Aspiration ◽  
Perihematomal Edema ◽  
Fine Print

Object. Ultra-early hematoma evacuation (< 4 hours) after intracerebral hemorrhage (ICH) may reduce mass effect and edema development and improve outcome. To test this hypothesis, the authors induced lobar hematomas in pigs.Methods. The authors infused 2.5 ml of blood into the frontal cerebral white matter in pigs weighing 8 to 10 kg. In the treatment group, clots were lysed with tissue plasminogen activator ([tPA], 0.3 mg) and aspirated at 3.5 hours after hematoma induction. Brains were frozen in situ at 24 hours post-ICH and hematomal and perihematomal edema volumes were determined on coronal sections by using computer-assisted morphometry.Hematoma evacuation rapidly reduced elevated cerebral tissue pressure from 12.2 ± 1.3 to 2.8 ± 0.8 mm Hg. At 24 hours, prior clot removal markedly reduced hematoma volumes (0.40 ± 0.10 compared with 1.26 ± 0.13 cm3, p < 0.005) and perihematomal edema volumes (0.28 ± 0.05 compared with 1.46 ± 0.24 cm3, p < 0.005), compared with unevacuated control lesions. Furthermore, no Evans blue dye staining of perihematomal edematous white matter was present in brains in which the hematomas had been evacuated, compared with untreated controls.Conclusions. Hematomas were quickly and easily aspirated after treatment with tPA, resulting in significant reductions in mass effect. Hematoma aspiration after fibrinolysis with tPA enabled removal of the bulk of the hematoma (> 70%), markedly reduced perihematomal edema, and prevented the development of vasogenic edema. These findings in a large-animal model of ICH provide support for clinical trials that include the use of fibrinolytic agents and ultra-early stereotactically guided clot aspiration for treating ICH.

Abstract 216: Neuroimaging Profile and Outcomes in Vitamin K Antagonist and Direct Oral Anticoagulant Related Non-traumatic Intracerebral Hemorrhage

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Georgios Tsivgoulis ◽  
Nitin Goyal ◽  
Christos Krogias ◽  
Aristeidis H Katsanos ◽  
Vijay K Sharma ◽  
...  
Keyword(s):  
Risk Factors ◽  
Intracerebral Hemorrhage ◽  
Functional Outcome ◽  
Vitamin K ◽  
Vitamin K Antagonists ◽  
Stroke Severity ◽  
Regression Analyses ◽  
Median Baseline ◽  
Ich Score ◽  
Perihematomal Edema

Background & Purpose: The safety and efficacy of direct oral anticoagulants (DOAC) for the prevention of thromboembolism in patients with non-valvular atrial fibrillation (NVAF) have been compared to vitamin-k antagonists (VKA) in randomized-controlled clinical trials. There are limited data regarding neuroimaging profile and outcomes in intracerebral hemorrhage (ICH) occurring during DOAC treatment. We sought to compare neuroimaging findings and outcomes in VKA- and DOAC-related ICH. Methods: We prospectively evaluated consecutive NVAF patients with non-traumatic, anticoagulant-related ICH that were admitted during a 1-year period in 9 stroke centers. Baseline hematoma volume was calculated by ABC/2 formula. Baseline stroke severity and 3-month functional outcome (FO) were assessed using NIHSS- and mRS-scores. The ICH severity was determined using ICH-score (severe ICH: ICH-score of 3-5). Results: We evaluated 91 patients with ICH due to DOAC (n=30) or VKA (n=61). The two groups did not differ in demographic, vascular risk factors, HAS-BLED & CHA2DS2-VASc scores, antithrombotic medications with the exception of higher renal failure prevalence in VKA (28% vs. 4%). DOAC group had significantly (p<0.05) lower median baseline NIHSS-score (5 vs. 12 points) and median baseline ICH volume (11 vs. 25 cm 3 ). The rates of severe ICH (13% vs. 34%), perihematomal edema (44% vs.74%), midline shift (20% vs. 49%), 3-month disability (mRS-score: 3-6; 37% vs. 64%) and 3-month mortality (10% vs. 35%) were significantly (p>0.05) higher in VKA group. DOAC-related ICH was independently (p<0.05) associated with lower likelihood of severe ICH (OR=0.14;95%CI:0.03-0.75), perihematomal edema (OR=0.27;95%CI:0.09-0.81) and adverse 3-month FO (common OR= 0.27;95%CI:0.11-0.68) In multivariable logistic regression analyses adjusting for potential confounders. DOAC-related ICH was independently (p=0.028) related to reduced log-trasformed baseline ICH volume in multiple linear regression analyses adjsuting for demographics, risk factors, HAS-BLED & CHA2DS2-VASc scores, ICH location and concomittant medications. Conclusion: DOAC-related ICHs appear to have more favorable neuroimaging profile and functional outcome compared to VKA-related ICHs.

Sign in / Sign up

Export Citation Format

Share Document