Matrix Metalloproteinases in Acute Intracerebral Hemorrhage.
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ABSTRACT:
SUBMITTER: Lattanzi S
PROVIDER: S-EPMC7283398 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Intracerebral hemorrhage is a devastating disease, and no specific therapy has been proven to reduce mortality in a randomized controlled trial. However, management in a neuroscience intensive care unit does appear to improve outcomes, suggesting that many available therapies do in fact provide benefit. In the acute phase of intracerebral hemorrhage care, strategies aimed at minimizing ongoing bleeding include reversal of anticoagulation and modest blood pressure reduction. In addition, the monitoring and regulation of glucose levels, temperature, and, in selected cases, intracranial pressure are recommended by many groups. Selected patients may benefit from hematoma evacuation or external ventricular drainage. Ongoing clinical trials are examining aggressive blood pressure management, hemostatic therapy, platelet transfusion, stereotactic hematoma evacuation, and intraventricular thrombolysis. Finally, preventing recurrence of intracerebral hemorrhage is of pivotal importance, and tight blood pressure management is paramount.
| S-EPMC3271150 | biostudies-literature
Project description:Intracerebral hemorrhage (ICH), the most devastating form of stroke, has no specific therapy proven to improve outcome by randomized controlled trial. Location and baseline hematoma volume are strong predictors of mortality, but are nonmodifiable by the time of diagnosis. Expansion of the initial hematoma is a further marker of poor prognosis that may be at least partly preventable. Several risk factors for hematoma expansion have been identified, including baseline ICH volume, early presentation after symptom onset, anticoagulation, and the CT angiography spot sign. Although the biological mechanisms of hematoma expansion remain unclear, accumulating evidence supports a model of ongoing secondary bleeding from ruptured adjacent vessels surrounding the initial bleeding site. Several large clinical trials testing therapies aimed at preventing hematoma expansion are in progress, including aggressive blood pressure reduction, treatment with recombinant factor VIIa guided by CT angiography findings, and surgical intervention for superficial hematomas without intraventricular extension. Hematoma expansion is so far the only marker of outcome that is amenable to treatment and thus a potentially important therapeutic target.
| S-EPMC3743539 | biostudies-literature
Project description:Intracerebral hemorrhage (ICH) is the most common hemorrhagic stroke subtype, and rates are increasing with an aging population. Despite an increase in research and trials of therapies for ICH, mortality remains high and no interventional therapy has been demonstrated to improve outcomes. We review known mechanisms of injury, recent clinical trial results, and newly discovered signaling pathways involved in hematoma clearance. Enthusiasm remains high for methods of minimally invasive clot removal as well as pharmacologic strategies to improve recovery after ICH, both of which are currently being evaluated in clinical trials. This article is part of the Special Issue entitled 'Cerebral Ischemia'.
| S-EPMC6027647 | biostudies-literature
Project description:Background and Purpose- Mechanisms contributing to acute hematoma growth in intracerebral hemorrhage are not well understood. Neuropathological studies suggest that the initial hematoma may create mass effect that can tear vessels in the vicinity by shearing, causing further bleeding and hematoma growth. Methods- To test this in mice, we simulated initial intracerebral hemorrhage by intrastriatal injection of a liquid polymer that coagulates upon contact with tissue and measured the presence and volume of bleeding secondary to the mass effect using Hemoglobin ELISA 15 minutes after injection. Results- Secondary hemorrhage occurred in a volume-dependent (4, 7.5, or 15 μL of polymer) and rate-dependent (0.05, 0.5, or 5 μL/s) manner. Anticoagulation (warfarin or dabigatran) exacerbated the secondary hemorrhage volume. In a second model of hematoma expansion, we confirmed that intrastriatal whole blood injection (15 μL, 0.5 μL/s) also caused secondary bleeding, using acute Evans blue extravasation as a surrogate. Anticoagulation once again exacerbated secondary hemorrhage after intrastriatal whole blood injection. Secondary hemorrhage directly and significantly correlated with arterial blood pressures in both nonanticoagulated and anticoagulated mice, when modulated by phenylephrine or labetalol. Conclusions- Our study provides the first proof of concept for secondary vessel rupture and bleeding as a potential mechanism for intracerebral hematoma growth.
| S-EPMC6478448 | biostudies-literature
Project description:Opinion statementIntracerebral hemorrhage is a medical emergency. It is the most deadly and disabling form of stroke, and no individual therapy has been demonstrated to improve outcome. However, it appears that aggressive medical care in general, and management by neuroscience specialists in particular, offers substantial benefit. Therefore, providing the best supportive care based on currently available evidence may well improve outcomes. Airway management and management of blood pressure aimed at maximizing cerebral perfusion while minimizing ongoing bleeding, as well as rapid reversal of anticoagulation, are likely to be important in the early phase. Additionally, efforts should be undertaken to provide careful glucose management and temperature management and to maximize cerebral perfusion pressure. Selected patients are likely to benefit from external ventricular drainage or even hematoma evacuation. Except in rare circumstances, most patients should be managed in a neuroscience intensive care unit during the acute phase. Some patients appear to have no reasonable likelihood of recovery and can be considered for limitations of care such as Do Not Resuscitate orders or Comfort Measures Only orders. However, it can be difficult to accurately predict long-term outcome in the acute phase; formal prognostic tools should be used to offer information to patients and their families. After the hemorrhage has stabilized, efforts to minimize complications include thromboembolism prophylaxis, physical therapy, and acute rehabilitation.
| S-EPMC3100105 | biostudies-literature
Project description:Intracerebral hemorrhage (ICH) is the deadliest type of stroke and up to half of patients die in hospital. Blood pressure management, coagulopathy reversal, and intracranial pressure control are the mainstays of acute ICH treatment. Prevention of hematoma expansion and minimally invasive hematoma evacuation are promising therapeutic strategies under investigation. This article provides an updated review on ICH diagnosis and management in the emergency department.
| S-EPMC5089075 | biostudies-literature
Project description:Intracerebral hemorrhage remains a challenging worldwide clinical problem with no proven treatments. In the acute phase of the illness, there has been some controversy regarding the appropriate management of elevated blood pressure. Recently published and ongoing clinical trials are beginning to shed some light on appropriate blood pressure management in acute intracerebral hemorrhage. This brief review focuses on these trials. In the next few years, it is hoped that clinical uncertainty regarding this issue will be obviated after completion of these trials.
| S-EPMC2981178 | biostudies-other
Project description:Seizures are believed to be common presenting symptoms in neonates and children with spontaneous intracerebral hemorrhage (ICH). However, few data are available on the epidemiology of acute symptomatic seizures or the risk for later epilepsy.To define the incidence of and explore risk factors for seizures and epilepsy in children with spontaneous ICH. Our a priori hypotheses were that younger age at presentation, cortical involvement of ICH, acute symptomatic seizures after presentation, ICH due to vascular malformation, and elevated intracranial pressure requiring urgent intervention would predict remote symptomatic seizures and epilepsy.Prospective cohort study conducted between March 1, 2007, and January 1, 2012.Three tertiary care pediatric hospitals.Seventy-three pediatric subjects with spontaneous ICH including 20 perinatal (?37 weeks' gestation to 28 days) and 53 childhood subjects (>28 days to <18 years at presentation).Acute symptomatic seizures (clinically evident and electrographic-only seizures within 7 days), remote symptomatic seizures, and epilepsy.Acute symptomatic seizures occurred in 35 subjects (48%). Acute symptomatic seizures as a presenting symptom of ICH occurred in 12 perinatal (60%) and 19 childhood (36%) subjects (P = .07). Acute symptomatic seizures after presentation occurred in 7 children. Electrographic-only seizures were present in 9 of 32 subjects (28%) with continuous electroencephalogram monitoring. One-year and 2-year remote symptomatic seizure-free survival rates were 82% (95% CI, 68-90) and 67% (95% CI, 46-82), respectively. One-year and 2-year epilepsy-free survival rates were 96% (95% CI, 83-99) and 87% (95% CI, 65-95), respectively. Elevated intracranial pressure requiring acute intervention was a risk factor for seizures after presentation (P = .01; Fisher exact test), remote symptomatic seizures, and epilepsy (P = .03, and P = .04, respectively; log-rank test).Presenting seizures are common in perinatal and childhood ICH. Continuous electroencephalography may detect electrographic seizures in some subjects. Single remote symptomatic seizures occur in many, and development of epilepsy is estimated to occur in 13% of patients at 2 years. Elevated intracranial pressure requiring acute intervention is a risk factor for acute seizures after presentation, remote symptomatic seizures, and epilepsy.
| S-EPMC3640376 | biostudies-literature
Project description:ObjectiveSpontaneous intracerebral hemorrhage (ICH) is the commonest form of hemorrhagic stroke and is associated with a poor prognosis. Neurosurgical removal of intracerebral hematoma has limited benefit and no pharmacotherapies are available. In acute ICH, primary tissue damage is followed by secondary pathology, where the cellular and neuroinflammatory changes are poorly understood.MethodsWe studied histological changes in postmortem tissue from a cohort of spontaneous supra-tentorial primary ICH cases (n = 27) with survival of 1-12 days, compared to a matched control group (n = 16) examined in corresponding regions. Hematoxylin-eosin and microglial (Iba1) immunolabelled sections were assessed at 0-2, 3-5, and 7-12 days post-ICH.ResultsPeri-hematoma, the observed ICH-related changes include edema, tissue neutrophils and macrophages from day 1. Ischemic neurons and swollen endothelial cells were common at day 1 and universal after day 5, as were intramural erythrocytes within small vessel walls. Activated microglia were evident at day 1 post-ICH. There was a significant increase in Iba1 positive area fraction at 0-2 (threefold), 3-5 (fourfold), and 7-12 days post ICH (ninefold) relative to controls. Giant microglia were detected peri-hematoma from day 5 and consistently 7-12 days post-ICH.InterpretationOur data indicate that neuroinflammatory processes commence from day 1 post-ICH with changing microglial size and morphology following ICH and up to day 12. From day 5 some microglia exhibit a novel multiply nucleated morphology, which may be related to changing phagocytic function. Understanding the time course of neuroinflammatory changes, post-ICH may reveal novel targets for therapy and brain restoration.
| S-EPMC6689697 | biostudies-literature
Project description:We hypothesized that imaging-only-based machine learning algorithms can analyze non-enhanced CT scans of patients with acute intracerebral hemorrhage (ICH). This retrospective multicenter cohort study analyzed 520 non-enhanced CT scans and clinical data of patients with acute spontaneous ICH. Clinical outcome at hospital discharge was dichotomized into good outcome and poor outcome using different modified Rankin Scale (mRS) cut-off values. Predictive performance of a random forest machine learning approach based on filter- and texture-derived high-end image features was evaluated for differentiation of functional outcome at mRS 2, 3, and 4. Prediction of survival (mRS ≤ 5) was compared to results of the ICH Score. All models were tuned, validated, and tested in a nested 5-fold cross-validation approach. Receiver-operating-characteristic area under the curve (ROC AUC) of the machine learning classifier using image features only was 0.80 (95% CI [0.77; 0.82]) for predicting mRS ≤ 2, 0.80 (95% CI [0.78; 0.81]) for mRS ≤ 3, and 0.79 (95% CI [0.77; 0.80]) for mRS ≤ 4. Trained on survival prediction (mRS ≤ 5), the classifier reached an AUC of 0.80 (95% CI [0.78; 0.82]) which was equivalent to results of the ICH Score. If combined, the integrated model showed a significantly higher AUC of 0.84 (95% CI [0.83; 0.86], P value <0.05). Accordingly, sensitivities were significantly higher at Youden Index maximum cut-offs (77% vs. 74% sensitivity at 76% specificity, P value <0.05). Machine learning-based evaluation of quantitative high-end image features provided the same discriminatory power in predicting functional outcome as multidimensional clinical scoring systems. The integration of conventional scores and image features had synergistic effects with a statistically significant increase in AUC.
| S-EPMC8557152 | biostudies-literature