ArticleLiterature Review

Spontaneous Intracerebral Hemorrhage

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Abstract

Nontraumatic intracerebral hemorrhage is bleeding into the parenchyma of the brain that may extend into the ventricles and, in rare cases, the subarachnoid space. Each year, approximately 37,000 to 52,400 people in the United States have an intracerebral hemorrhage.1,2 This rate is expected to double during the next 50 years as a result of the increasing age of the population and changes in racial demographics. Intracerebral hemorrhage accounts for 10 to 15 percent of all cases of stroke and is associated with the highest mortality rate, with only 38 percent of affected patients surviving the first year.3 Depending on . . .

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... ICH is characterized by bleeding within brain parenchyma due to rupture of blood vessels causing mass effect and cerebral damage (Qureshi et al., 2009). Hypertension is the main cause of ICH (Qureshi et al., 2001). The mechanism of ICH is complex. ...
... The mechanism of ICH is complex. The primary injury begins with the onset of bleeding and activation of inflammatory mechanisms which progressively leads to secondary brain injury that reach its peak in 3-7 days (Qureshi et al., 2001;Qureshi et al., 2009). Besides the inflammatory role of activated immune cells i-e., neutrophils, monocytes, astrocytes and dendritic cells; the blood derived components such as heme, iron and thrombin aggravate the ICH induced brain injury (Aronowski and Zhao, 2011). ...
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Background: Intracerebral hemorrhage (ICH) is a debilitating and fatal condition with continuously rising incidence globally, without effective treatment available. Zhilong Huoxue Tongyu (ZLHXTY) capsule is a traditional Chinese medicine that is used for ICH treatment in China. However, the evidence based mechanism is not clear. Purpose: To study the protective effects of ZLHXTY capsules against ICH pathogenesis via targetting nuclear factor kappa β (NFкβ) canonical signalling pathway. Methods: C57BL/6 J mice ICH models using autologous blood injection were used to study the effect of ZLHXTY (1.4 g/kg P.O.) after 24 and 72 hrs of ICH induction. The neurological scoring, corner turn test and balance beam with scoring was performed to assess neurological damage. Hematoxylin/eosin and nissl staining was used for histopathological evaluation. Levels of TNFα, NFкB, iNOS, COX2, IL1, IL6 were measured using real time qPCR and western blotting. Protein levels of IKKβ and IкBα were analyzed through western blotting. Immunofluorescence for co-expression of NeuN/TNFα, NeuN/NFкB, Iba1/TNFα, and Iba1/NFкB was also performed. Results: Treatment with ZLHXTY capsules after ICH ameliorated inflammatory brain injury after 24 and 72 h; revealed by neurological scoring, hematoxylin/eosin and nissl staining. The qPCR and western blot analyses demonstrated significant downregulation of TNFα, NFкB, iNOS, COX2, IL1β and IL6. Further, the IKKβ and IкBα revealed significant downregulation and upregulation respectively in western blot. Immunofluorescence also revealed attenuated expression of TNFα and NFкB in neurons and also low expression of Iba1. Conclusion: ZLHXTY capsules elicit its neuroprotective effect by targetting the NFкβ canonical signalling pathway, thereby ameliorating the ICH induced brain injury.
... Age-standardized non-traumatic SAH incidence rates continuously dropped during the 30-year span of the study. Lowered attributed DALYs rates can mediate this phenomenon to ambient particulate matter pollution, smoking, secondhand smoke, high SBP, and alcohol use in 2019 compared to 1990, all known as SAH and ICH risk factors [42][43][44][45][46][47][48]. Furthermore, better access to neurocritical care services secondary to economic development might have led to better management of these conditions, such as treating ruptured intracranial aneurysms and surgical hematoma evacuation, leading to lower death rates [43][44][45]47]. ...
... Lowered attributed DALYs rates can mediate this phenomenon to ambient particulate matter pollution, smoking, secondhand smoke, high SBP, and alcohol use in 2019 compared to 1990, all known as SAH and ICH risk factors [42][43][44][45][46][47][48]. Furthermore, better access to neurocritical care services secondary to economic development might have led to better management of these conditions, such as treating ruptured intracranial aneurysms and surgical hematoma evacuation, leading to lower death rates [43][44][45]47]. The agestandardized death rates of ischemic stroke are also considerably less in 2019 than in 1990, probably due to better access to specialized treatment such as thrombolysis therapy, mechanical thrombectomy, and decompressive craniectomy [49,50]. ...
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Background While several studies investigated the epidemiology and burden of stroke in the North Africa and Middle East region, no study has comprehensively evaluated the age-standardized attributable burden to all stroke subtypes and their risk factors yet. Objective The aim of the present study is to explore the regional distribution of the burden of stroke, including ischemic stroke, subarachnoid hemorrhage, and intracerebral hemorrhage, and the attributable burden to its risk factors in 2019 among the 21 countries of North Africa and Middle East super-region. Methods The data of the Global Burden of Disease Study (GBD) 2019 on stroke incidence, prevalence, death, disability-adjusted life years (DALYs), years of life lost (YLLs), years lived with disability (YLDs) rates, and attributed deaths, DALYs, YLLs, and YLDs to stroke risk factors were used for the present study. Results The age-standardized deaths, DALYs, and YLLs rates were diminished statistically significant by 27.8, 32.0, and 35.1% from 1990 to 2019, respectively. Attributed deaths, DALYs, and YLLs to stroke risk factors, including high systolic blood pressure, high body-mass index, and high fasting plasma glucose shrank statistically significant by 24.9, 25.8, and 28.8%, respectively. Conclusion While the age-standardized stroke burden has reduced during these 30 years, it is still a concerning issue due to its increased burden in all-age numbers. Well-developed primary prevention, timely diagnosis and management of the stroke and its risk factors might be appreciated for further decreasing the burden of stroke and its risk factors and reaching Sustainable Development Goal 3.4 target for reducing premature mortality from non-communicable diseases.
... Intracerebral hemorrhage (ICH), which is mainly caused by rupture of blood vessels in the brain, inflicts 10-30 per 100000 population each year [1]. In addition to surgical removal of the hematoma, limited medical treatments are effective at improving neurological functional recovery [2,3]. Brain injury caused by ICH includes primary injury and secondary injury. ...
... For in vitro experiments, after 24 hours of culture, 10 nM Omav dissolved in 0.1% DMSO/DMEM was applied with OxyHb to BV2 microglial cells and incubated for another 24 hours. 2 Oxidative Medicine and Cellular Longevity ...
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The polarization of microglia is recognized as a crucial factor in reducing neuroinflammation and promoting hematoma clearance after intracerebral hemorrhage (ICH). Previous studies have revealed that redox components participate in the regulation of microglial polarization. Recently, the novel Nrf2 activator omaveloxolone (Omav) has been validated to improve neurological function in patients with neurodegenerative disorders by regulating antioxidant responses. In this study, we examined the efficacy of Omav in ICH. Omav significantly promoted Nrf2 nuclear accumulation and the expression of HO-1 and NQO1 in BV2 cells. In addition, both in vitro and in vivo experiments showed that Omav treatment inhibited M1-like activation and promoted the activation of the M2-like microglial phenotype. Omav inhibited OxyHb-induced ROS generation and preserved the function of mitochondria in BV2 cells. Intraperitoneal administration of Omav improved sensorimotor function in the ICH mouse model. Importantly, these effects were blocked by pretreatment with ML385, a selective inhibitor of Nrf2. Collectively, Omav modulated microglial polarization by activating Nrf2 and inhibiting ROS generation in ICH models, suggesting that it might be a promising drug candidate for the treatment of ICH.
... ICH is diagnosed more frequently in the elderly (>55 years of age), and it is more common in men than in women with a predilection in the African and Asian populations [2][3][4]. Although the mortality rate related to ICH has decreased worldwide [5], its incidence in low/middle-income regions is doubled (50 per 100,000) compared to the rates in more economically developed countries [2]. ...
... ICH is diagnosed more frequently in the elderly (>55 years of age), and it is more common in men than in women with a predilection in the African and Asian populations [2][3][4]. Although the mortality rate related to ICH has decreased worldwide [5], its incidence in low/middle-income regions is doubled (50 per 100,000) compared to the rates in more economically developed countries [2]. The most important risk factors of ICH are increased age and chronic hypertension [3,4]. ...
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Significant advances in endovascular neurosurgery tools, devices, and techniques are changing the approach to the management of acute hemorrhagic stroke. The endovascular treatment of intracranial aneurysms emerged in the early 1990s with Guglielmi detachable coils, and since then, it gained rapid popularity that surpassed open surgery. Stent-assisted coiling and balloon remodeling techniques have made the treatment of wide-necked aneurysms more durable. With the introduction of flow diverters and flow disrupters, many aneurysms with complex geometrics can now be reliably managed. Arteriovenous malformations and fistulae can also benefit from endovascular therapy by embolization using n-butyl cyanoacrylate (NBCA), Onyx, polyvinyl alcohol (PVA), and coils. In this article, we describe the role of endovascular treatment for the most common causes of intracerebral and subarachnoid hemorrhages, particularly ruptured aneurysms and vascular malformations.
... Intracerebral hemorrhage (ICH), the most common form of hemorrhagic stroke, accounts for up to 15% of all strokes, with 67,000 Americans suffering an ICH annually (Brown et al., 1996;Mayo et al., 1996;Broderick et al., 1999;Qureshi et al., 2001;Rincon and Mayer, 2004). One-year mortality rates are >60% and fewer than 20% of ICH patients recover functional independence after 6 months (Dennis et al., 1993;Gebel et al., 2002;Broderick et al., 2007). ...
... ICH is predominantly caused by the rupture of small vessels damaged by chronic hypertension or cerebral amyloid angiopathy. The subsequent extravasation of blood creates a space-occupying hematoma that induces local microvascular compression, brain tissue loss, and cerebrovascular dysfunction (Nehls et al., 1988;Qureshi et al., 2001;Fewel et al., 2003). ...
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Spontaneous Intracerebral hemorrhage (ICH) is a devastating injury that accounts for 10–15% of all strokes. The rupture of cerebral blood vessels damaged by hypertension or cerebral amyloid angiopathy creates a space-occupying hematoma that contributes toward neurological deterioration and high patient morbidity and mortality. Numerous protocols have explored a role for surgical decompression of ICH via craniotomy, stereotactic guided endoscopy, and minimally invasive catheter/tube evacuation. Studies including, but not limited to, STICH, STICH-II, MISTIE, MISTIE-II, MISTIE-III, ENRICH, and ICES have all shown that, in certain limited patient populations, evacuation can be done safely and mortality can be decreased, but functional outcomes remain statistically no different compared to medical management alone. Only 10–15% of patients with ICH are surgical candidates based on clot location, medical comorbidities, and limitations regarding early surgical intervention. To date, no clearly effective treatment options are available to improve ICH outcomes, leaving medical and supportive management as the standard of care. We recently identified that remote ischemic conditioning (RIC), the non-invasive, repetitive inflation-deflation of a blood pressure cuff on a limb, non-invasively enhanced hematoma resolution and improved neurological outcomes via anti-inflammatory macrophage polarization in pre-clinical ICH models. Herein, we propose a pilot, placebo-controlled, open-label, randomized trial to test the hypothesis that RIC accelerates hematoma resorption and improves outcomes in ICH patients. Twenty ICH patients will be randomized to receive either mock conditioning or unilateral arm RIC (4 cycles × 5 min inflation/5 min deflation per cycle) beginning within 48 h of stroke onset and continuing twice daily for one week. All patients will receive standard medical care according to latest guidelines. The primary outcome will be the safety evaluation of unilateral RIC in ICH patients. Secondary outcomes will include hematoma volume/clot resorption rate and functional outcomes, as assessed by the modified Rankin Scale (mRS) at 1- and 3-months post-ICH. Additionally, blood will be collected for exploratory genomic analysis. This study will establish the feasibility and safety of RIC in acute ICH patients, providing a foundation for a larger, multi-center clinical trial.
... The proportion of nontraumatic intracerebral hemorrhage (ICH) in acute strokes is~10%-15%, and nontraumatic ICH has a much higher risk of mortality than ischemic strokes or subarachnoid hemorrhage (55,56). A recent research reported the NET infiltration in the brain of patients who died from spontaneous intracerebral hemorrhage (sICH), suggesting that NETs might interact with early hemostasis within the hematoma core and with the surrounding neuroinflammatory response (57). ...
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It has been reported that several immune cells can release chromatin and granular proteins into extracellular space in response to the stimulation, forming extracellular traps (ETs). The cells involved in the extracellular trap formation are recognized including neutropils, macrophages, basophils, eosinophils, and mast cells. With the development of research related to central nervous system, the role of ETs has been valued in neuroinflammation, blood–brain barrier, and other fields. Meanwhile, it has been found that microglial cells as the resident immune cells of the central nervous system can also release ETs, updating the original understanding. This review aims to clarify the role of the ETs in the central nervous system, especially in neuroinflammation and blood–brain barrier.
... Intracerebral hemorrhage (ICH) is a leading cause of morbidity and mortality (approximately 40% at 1 month and 54% at 1 year) among stroke patients, accounting for 10-20% of all stroke cases [1][2][3]. The lack of understanding of the ICH pathomechanism, and thus its effective treatment strategies remain as the major roadblock in minimizing the high mortality and disability rates in ICH. ...
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Extracellular matrix metalloproteinase inducer (EMMPRIN) has been shown to be a vital inflammatory mediator in several neurological and neurodegenerative diseases. However, the role of EMMPRIN in intracerebral hemorrhage (ICH) remains unexplored. In this study, we aimed to exploit a highly selective monoclonal anti-EMMPRIN antibody to functionally inhibit EMMPRIN activity and thus that of MMPs as the downstream effector. To induce ICH pathology, adult C57BL/6 male mice were injected with collagenase type VII or saline as control into the right basal ganglia and were euthanized at different time points. The anti-EMMPRIN monoclonal antibody was intravenously injected once daily for 3 days to block the expression of EMMPRIN initiating at 4 h post-ICH. Western blot and immunofluorescence analysis results revealed that EMMPRIN expression was significantly increased surrounding the hematoma at 3 and 7 d time points after ICH when compared to the saline treated control group. EMMPRIN expression was co-localized with GFAP (astrocytes) and Iba1 (microglia) at 3 d time point post-ICH, but not in the control group mice. The co-localization of EMMPRIN with CD31 in endothelial cells occurred in both groups and was higher in the ICH brain. However, EMMPRIN expression was not detected in neurons from either group. The inhibition of EMMPRIN reduced the expression of MMP-9, the number of infiltrated neutrophils, the degree of brain injury and promoted neurological recovery after ICH. In conclusion, EMMPRIN could mediate the upregulation of MMP-9 and exacerbate neurological dysfunction in a mouse model of experimental ICH. Furthermore, blocking EMMPRIN reduced brain injury and subsequently promoted neurological recovery in ICH mice brains. These outcomes highlight that inhibition of EMMPRIN can be a potential therapeutic intervention strategy to regulate MMP-9’s pathological roles during ICH.
... Currently, the scope of cranial CT scans basically depends on empirical judgment; such predicaments make it difficult for clinicians to compare and analyze the progress of intracranial lesions. Although emerging intracranial hematoma measurement tools have been developed (8), these volumebased software cannot widely be used in ischemic stroke (9). If the standardization, accuracy and reproducibility of images acquired during follow-up can be ensured, patients (especially children) will be protected due to reduced radiation exposure, and it might be beneficial for neurologists and radiologists to evaluate the condition of stroke patients during follow-up imaging examinations. ...
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Background Computed tomography (CT) plays an essential role in classifying stroke, quantifying penumbra size and supporting stroke-relevant radiomics studies. However, it is difficult to acquire standard, accurate and repeatable images during follow-up. Therefore, we invented an intelligent CT to evaluate stroke during the entire follow-up. Methods We deployed a region proposal network (RPN) and V-Net to endow traditional CT with intelligence. Specifically, facial detection was accomplished by identifying adjacent jaw positions through training and testing an RPN on 76,382 human faces using a preinstalled 2-dimensional camera; two regions of interest (ROIs) were segmented by V-Net on another training set with 295 subjects, and the moving distance of scanning couch was calculated based on a pre-generated calibration table. Multiple cohorts including 1,124 patients were used for performance validation under three clinical scenarios. Results Cranial Automatic Planbox Imaging Towards AmeLiorating neuroscience (CAPITAL)-CT was invented. RPN model had an error distance of 4.46 ± 0.02 pixels with a success rate of 98.7% in the training set and 100% with 2.23 ± 0.10 pixels in the testing set. V-Net-derived segmentation maintained a clinically tolerable distance error, within 3 mm on average, and all lines presented with a tolerable angle error, within 3° on average in all boundaries. Real-time, accurate, and repeatable automatic scanning was accomplished with and a lower radiation exposure dose (all P < 0.001). Conclusions CAPITAL-CT generated standard and reproducible images that could simplify the work of radiologists, which would be of great help in the follow-up of stroke patients and in multifield research in neuroscience.
... Another study reported similar results; CAA patients with HTN had better clinical outcomes after ICH events . Treating with anti-hypertensive therapies was shown to reduce incidence of ICH and stroke in HTN patients (Qureshi et al., 2001) and was also found to decrease ICH incidence in CAA patients (Arima et al., 2010). Overall, clinical data suggests that HTN and CAA as comorbidities could provide a protective effect against characteristic ICH events of CAA but further investigation is required. ...
Article
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Cerebral amyloid angiopathy (CAA), a common comorbidity of Alzheimer’s disease (AD), is a cerebral small vessel disease (CSVD) characterized by deposition of fibrillar amyloid β (Aβ) in blood vessels of the brain and promotes neuroinflammation and vascular cognitive impairment and dementia (VCID). Hypertension, a prominent non-amyloidal CSVD, has been found to increase risk of dementia, but clinical data regarding its effects in CAA patients is controversial. To understand the effects of hypertension on CAA, we bred rTg-DI transgenic rats, a model of CAA, with spontaneously hypertensive, stroke prone (SHR-SP) rats producing bigenic rTg-DI/SHR-SP and non-transgenic SHR-SP littermates. At 7 months (M) of age, cohorts of both rTg-DI/SHR-SP and SHR-SP littermates exhibit elevated systolic blood pressures. However, transgene human amyloid β-protein (Aβ) precursor and Aβ peptide levels, as well as behavioral testing showed no changes between bigenic rTg-DI/SHR-SP and rTg-DI rats. Subsequent cohorts of rats were aged further to 10 M where bigenic rTg-DI/SHR-SP and SHR-SP littermates exhibit elevated systolic and diastolic blood pressures. Vascular amyloid load in hippocampus and thalamus was significantly decreased, whereas pial surface vessel amyloid increased, in bigenic rTg-DI/SHR-SP rats compared to rTg-DI rats suggesting a redistribution of vascular amyloid in bigenic animals. There was activation of both astrocytes and microglia in rTg-DI rats and bigenic rTg-DI/SHR-SP rats not observed in SHR-SP rats indicating that glial activation was likely in response to the presence of vascular amyloid. Thalamic microbleeds were present in both rTg-DI rats and bigenic rTg-DI/SHR-SP rats. Although the number of thalamic small vessel occlusions were not different between rTg-DI and bigenic rTg-DI/SHR-SP rats, a significant difference in occlusion size and distribution in the thalamus was found. Proteomic analysis of cortical tissue indicated that bigenic rTg-DI/SHR-SP rats largely adopt features of the rTg-DI rats with enhancement of certain changes. Our findings indicate that at 10 M of age non-pharmacological hypertension in rTg-DI rats causes a redistribution of vascular amyloid and significantly alters the size and distribution of thalamic occluded vessels. In addition, our findings indicate that bigenic rTg-DI/SHR-SP rats provide a non-pharmacological model to further study hypertension and CAA as co-morbidities for CSVD and VCID.
... Spontaneous intracerebral hemorrhage (ICH) is a kind of nontraumatic hemorrhage in the brain parenchyma (Qureshi et al., 2001). It is a common emergency in neurosurgery with high morbidity, disability, and mortality (Broderick et al., 2007). ...
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The main purpose of the study was to explore a reliable way to automatically handle emergency cases, such as intracerebral hemorrhage (ICH). Therefore, an artificial intelligence (AI) system, named, H-system, was designed to automatically recognize medical text data of ICH patients and output the treatment plan. Furthermore, the efficiency and reliability of the H-system were tested and analyzed. The H-system, which is mainly based on a pretrained language model Bidirectional Encoder Representations from Transformers (BERT) and an expert module for logical judgment of extracted entities, was designed and founded by the neurosurgeon and AI experts together. All emergency medical text data were from the neurosurgery emergency electronic medical record database (N-eEMRD) of the First Affiliated Hospital of Chongqing Medical University, Chongqing Emergency Medical Center, and Chongqing First People’s Hospital, and the treatment plans of these ICH cases were divided into two types. A total of 1,000 simulated ICH cases were randomly selected as training and validation sets. After training and validating on simulated cases, real cases from three medical centers were provided to test the efficiency of the H-system. Doctors with 1 and 5 years of working experience in neurosurgery (Doctor-1Y and Doctor-5Y) were included to compare with H-system. Furthermore, the data of the H-system, for instance, sensitivity, specificity, accuracy, positive predictive value (PPV), negative predictive value (NPV), and the area under the receiver operating characteristics curve (AUC), were calculated and compared with Doctor-1Y and Doctor-5Y. In the testing set, the time H-system spent on ICH cases was significantly shorter than that of doctors with Doctor-1Y and Doctor-5Y. In the testing set, the accuracy of the H-system’s treatment plan was 88.55 (88.16–88.94)%, the specificity was 85.71 (84.99–86.43)%, and the sensitivity was 91.83 (91.01–92.65)%. The AUC value of the H-system in the testing set was 0.887 (0.884–0.891). Furthermore, the time H-system spent on ICH cases was significantly shorter than that of doctors with Doctor-1Y and Doctor-5Y. The accuracy and AUC of the H-system were significantly higher than that of Doctor-1Y. In addition, the accuracy of the H-system was more closed to that of Doctor-5Y. The H-system designed in the study can automatically recognize and analyze medical text data of patients with ICH and rapidly output accurate treatment plans with high efficiency. It may provide a reliable and novel way to automatically and rapidly handle emergency cases, such as ICH.
... Hypertensive arteriopathy (HA) and cerebral amyloid angiopathy (CAA) are two common forms of cerebral small vessel diseases (CSVD), which are responsible for the major causes of primary intracerebral hemorrhage (ICH) [1,2]. Despite the devastating consequences of primary ICH, the mechanisms underlying ICH are poorly understood. ...
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We aimed to study the distribution of Circle of Willis (CoW) morphology and its association with intracerebral hemorrhage (ICH) etiology and cerebral small vessel disease (CSVD) burden. Patients with primary ICH who had brain MRIs were consecutively enrolled between March 2012 and January 2021. CoW morphology, CSVD features and the combined CSVD burden (including global CSVD burden, total hypertensive arteriopathy [HA] burden, and total cerebral amyloid angiopathy [CAA] burden) were assessed. CoW morphology included poor CoW (defined as CoW score 0–2), incomplete CoW, and complete fetal-variant of the posterior communicating artery (CFPcoA). Among 296 patients enrolled, 215 were included in the analysis. There was no significant difference among HA-, CAA-, and mixed-ICH in each CoW morphology. Exploratory subgroup analyses suggested that poor CoW was associated with a greater incidence of HA-ICH and low incidence of mixed ICH in patients aged < 60 years, while mixed ICH occurred more frequently in patients with CFPcoA, especially in those without hypertension history (all p < 0.050). Additionally, incomplete CoW was correlated with a larger incidence of lacunes (adjusted OR [adOR] 2.114, 95% CI 1.062–4.207), microbleeds ≥ 5 (adOR 2.437, 95% CI 1.187–5.002), and therefore the combined CSVD burden (adOR 1.194, 95% CI 1.004–1.419 for global CSVD burden, adOR 1.343, 95% CI 1.056–1.707 for total CAA burden), independent of modifiable vascular risk factors, but not age and sex. The CoW might therefore have a potential impact on ICH etiology and is associated with a greater CSVD burden. Our findings are novel, and need to be verified in future studies.
... Previous studies have indicated that CAA is characterized by vascular occlusion and local ischemia (Olichney et al., 1995;Cadavid et al., 2000;Thal et al., 2009). Besides, the local fragility of the vessels can result in singular or chronic intracerebral or subarachnoid bleeding (Vinters, 1987;Itoh et al., 1993;Qureshi et al., 2001Qureshi et al., , 2009Nakata-Kudo et al., 2006;Charidimou et al., 2012). The typical CAA finding of linear cortical superficial siderosis (cSS) winds around the gyri and sulci of the brain and the blood component hemosiderin, in particular, can be measured in gradient-echo-T2 * -weighted-imaging (GRE-T2 * -WI), a sequence of MRI (Linn et al., 2008(Linn et al., , 2010Kumar, 2010). ...
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Objective This is a cross-sectional study to evaluate whether β-amyloid-(Aβ)-PET positivity and cortical superficial siderosis (cSS) in patients with cerebral amyloid angiopathy (CAA) are regionally colocalized. Methods Ten patients with probable or possible CAA (73.3 ± 10.9 years, 40% women) underwent MRI examination with a gradient-echo-T2*-weighted-imaging sequence to detect cSS and ¹⁸ F-florbetaben PET examination to detect fibrillar Aβ. In all cortical regions of the Hammers Atlas, cSS positivity (MRI: ITK-SNAP segmentation) and Aβ-PET positivity (PET: ≥ mean value + 2 standard deviations of 14 healthy controls) were defined. Regional agreement of cSS- and Aβ-PET positivity was evaluated. Aβ-PET quantification was compared between cSS-positive and corresponding contralateral cSS-negative atlas regions. Furthermore, the Aβ-PET quantification of cSS-positive regions was evaluated in voxels close to cSS and in direct cSS voxels. Results cSS- and Aβ-PET positivity did not indicate similarity of their regional patterns, despite a minor association between the frequency of Aβ-positive patients and the frequency of cSS-positive patients within individual regions ( r s = 0.277, p = 0.032). However, this association was driven by temporal regions lacking cSS- and Aβ-PET positivity. When analyzing all composite brain regions, Aβ-PET values in regions close to cSS were significantly higher than in regions directly affected with cSS ( p < 0.0001). However, Aβ-PET values in regions close to cSS were not different when compared to corresponding contralateral cSS-negative regions ( p = 0.603). Conclusion In this cross-sectional study, cSS and Aβ-PET positivity did not show regional association in patients with CAA and deserve further exploitation in longitudinal designs. In clinical routine, a specific cross-sectional evaluation of Aβ-PET in cSS-positive regions is probably not useful for visual reading of Aβ-PETs in patients with CAA.
... Apart from heart transplant donors, ICB is a major health problem, accounting for 10-15% of all strokes worldwide each year, with the highest mortality rate among all strokes with 38% of 1 year survival. 19,20 From a pathophysiological perspective, different pathways delivering primary and secondary damage in ICB patients were described, including mechanical compression caused by hematoma as well as inflammation, oxidative stress, cytotoxicity, and the neurotoxicity of thrombin. 21 Some of those mechanisms, including inflammation and oxidative stress, could potentially influence other organs including the heart. ...
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Aim: The quality of the donor heart is known to have a crucial effect on outcome after heart transplantation (HTx). Although leading to brain death in the end, the initial cause of death of the donor and its potential influences on organ quality are heterogeneous. However, it is still controversial to which extent the donor cause of death is associated with outcome or survival post-HTx. Methods and results: We included all patients undergoing HTx in our centre between September 2010 and June 2021 (n = 218). Recipients were divided in five groups related to their donor cause of death: intracerebral bleeding ('ICB', n = 95, 44%), traumatic brain injury ('trauma', n = 54, 25%), hypoxic brain damage ('hypoxic', n = 34, 16%), cerebrovascular ('vascular', n = 15, 7%), or other cause (n = 20, 9%). Baseline characteristics, perioperative parameters, and survival after 30 and 90 days as well as 5 years after transplantation were collected. Results: Intracerebral bleeding in donors compared with traumatic brain injury is associated with higher probability of need for ECLS post-HTx (35% vs. 19%, P = 0.04) and significantly reduced survival up to 5 years post-HTx (i.e. 1 year survival: 61% vs. 95%, P < 0.0001). Although other conditions also show significant changes in outcome and survival, the effect is strongest for ICB, where survival is also reduced compared with all other causes (1 year: 61% vs. 89%, P < 0.0001). Conclusions: In this retrospective analysis, donor cause of death is associated with differing outcome and survival after HTx. Intracerebral bleeding hereby shows strongest decline in outcome and survival in comparison with all other causes.
... Studies showed that the incidence of ICH today is as high as 3 in 10,000, which already accounts for 10-15% of all strokes [1][2][3]. In patients with hypertension, cerebral blood vessels rupture due to a sudden increase in blood pressure, such as intracranial hemorrhage and subarachnoid hemorrhage. ...
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Patients with hypertensive intracerebral hemorrhage (ICH) have a high hematoma expansion (HE) incidence. Noninvasive prediction HE helps doctors take effective measures to prevent accidents. This study retrospectively analyzed 253 cases of hypertensive intraparenchymal hematoma. Baseline non-contrast-enhanced CT scans (NECTs) were collected at admission and compared with subsequent CTs to determine the presence of HE. An end-to-end deep learning method based on CT was proposed to automatically segment the hematoma region, region of interest (ROI) feature extraction, and HE prediction. A variety of algorithms were employed for comparison. U-Net with attention performs best in the task of segmenting hematomas, with the mean Intersection overUnion (mIoU) of 0.9025. ResNet-34 achieves the most robust generalization capability in HE prediction, with an area under the receiver operating characteristic curve (AUC) of 0.9267, an accuracy of 0.8827, and an F1 score of 0.8644. The proposed method is superior to other mainstream models, which will facilitate accurate, efficient, and automated HE prediction.
... After ICH occurs, the rapid accumulation of blood in the surrounding brain causes high pressure in the local brain tissue (Qureshi et al., 2009;Wang et al., 2015). Brain edema and neuroinflammation after ICH induce a series of secondary injuries, resulting in severe neurological impairment (Qureshi et al., 2001). At present, there is still a lack of effective treatment strategies for ICH and secondary brain injury caused by ICH. ...
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Background: The differentiation of microglia from M1 to M2 exerts a pivotal role in the aggression of intracerebral hemorrhage (ICH), and long non-coding RNAs (lncRNAs) are associated with the differentiation of microglia. However, the underlying mechanism had not been fully clarified. Methods: The expression profile of lncRNAs in thrombin-induced primary microglia was analyzed by RNA sequencing. Under thrombin treatment, the effect of lncRNA TCONS_00145741 on the differentiation of microglia was determined by immunofluorescence staining, quantitative real-time PCR, and Western blot. The potential mechanism and related signaling pathways of TCONS_00145741 in the M1 and M2 differentiation of microglia in ICH were assessed by Gene Ontology analysis, flow cytometry, RNA pull-down, RNA Immunoprecipitation, and RNA fluorescence in situ hybridization followed by immunofluorescence analysis. Results: LncRNA TCONS_00145741 expression was elevated in the thrombin-induced primary microglia, and the interference with TCONS_00145741 restrained the M1 differentiation of microglia and facilitated the M2 differentiation under thrombin treatment. The interference with TCONS_00145741 restrained the activation of the JNK pathway in microglia under thrombin treatment and repressed the JNK phosphorylation levels by enhancing the interaction between DUSP6 and JNK. In vivo experiments further illustrated that the interference with TCONS_00145741 alleviated ICH. Conclusion: LncRNA TCONS_00145741 knockdown prevented thrombin-induced M1 differentiation of microglia in ICH by enhancing the interaction between DUSP6 and JNK. This study might provide a promising target for the clinical treatment of ICH.
... The mortality of ICH at the early stage is very high, and most survivors have severe sequelae such as motor cognitive and language impairment (Chen et al., 2018;Wilkinson et al., 2018;Marques et al., 2019). The etiology of ICH mainly includes cerebrovascular dysfunctions during pathological conditions such as hypertension, hyperlipidemia, diabetes, aging, smoking and drinking, etc. ICH induces a huge economic and social burden due to the increased incidence in young patients (Qureshi et al., 2001;Whiteley et al., 2012). However, there is no effective treatment for ICH with high mortality and disability (Murthy et al., 2017;Imai et al., 2021). ...
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Objective Intracerebral hemorrhage (ICH) is a common cerebrovascular disease with high incidence, disability, and mortality. Casein kinase 2 (CK2) is a serine/threonine kinase with hundreds of identified substrates and plays an important role in many diseases. This study aimed to explore whether CK2 plays protective roles in ICH-induced neuronal apoptosis, inflammation, and oxidative stress through regulation NR2B phosphorylation. Methods CK2 expression level of brain tissues taken from ICH patients was determined by immunoblotting. Neurons from embryonic rat and astrocytes from newborn rats were cultured and treated by Hemoglobin chloride (Hemin). The proliferation of astrocytes, the apoptosis and oxidative stress of neurons and the inflammatory factors of astrocytes were detected. CK2 expression was determined in ICH model rats. The effects of CK2 overexpression plasmid (pc-CK2) on neurobehavioral defects and brain water content in ICH rats were observed. Results CK2 expression in ICH patients was down-regulated. Overexpression of CK2 promoted the astrocyte proliferation, inhibited neuronal apoptosis, and reduced astrocyte-mediated inflammation. N -methyl- D -aspartate receptor 2B (NR2B) reversed the effects of pc-CK2 on neurons and astrocytes. CK2 phosphorylated NR2B at the S1480 site, down-regulated the expression of NR2B and interfered with the interaction between NR2B and postsynaptic density protein 95 (PSD95). In vivo experiments showed that the expression of CK2 decreased and the expression of NR2B increased in ICH rats. Furthermore, pc-CK2 attenuated neurobehavioral defects, brain water content and neuronal damage in ICH rats. Conclusion CK2 phosphorylated NR2B, down-regulated the expression of NR2B, interfered with the interaction between NR2B and PSD95, alleviated inflammatory reactions, inhibited neuronal apoptosis and oxidative stress after ICH. CK2 and NR2B may be new potential therapeutic targets for the treatment of ICH. However, the limitation of this study is that we only investigated the regulation of NR2B by CK2.
... In Globally, ICH is one of the most deleterious types of all strokes; it has an incidence of 10-30 per 100,000 patients annually, with a morbidity rate of 75% and a mortality rate of 30-50% January 1980, and November 2008 (3). ICH is diagnosed more frequently in the elderly (>55 years old) and in males, with predilection observed in patients of African and Asian ethnicity (4,5). Hematoma following ICH destroys the surrounding vascular system, which induces hemorrhage and potentiates growth of hematoma, which leads to neuronal deficit (6). ...
Article
microRNAs (miRNAs or miRs) have been reported to regulate the pathology of intracerebral hemorrhage (ICH). Therefore, the present study aimed to investigate the function of miR-30e-5p in rats with ICH with specific focus on Toll-like receptor (TLR)4. In the present study, collagenase type IV was used for the establishment of the ICH model in rats, prior to which the rats were injected with miR-30e-5p mimic or miR-30e-5p mimic + pcDNA3.1-TLR4 plasmid. The expression levels of miR-30e-5p and TLR4 were then measured using reverse transcription-quantitative PCR and western blotting. The potential interaction between miR-30e-5p and TLR4 was tested using the MicroRNA Target Prediction Database and dual-luciferase reporter and RNA immunoprecipitation assay. In addition, the concentration of TNF-α, IL-6 and IL-1β was measured using ELISA. The protein expression levels of TLR4/myeloid differentiation factor 88 (MyD88)/TIR-domain-containing adapter-inducing interferon-β (TRIF) signaling-associated molecules were measured by western blotting. Following induction of ICH, miR-30e-5p expression was downregulated, while TLR4 expression was upregulated. By contrast, injection with miR-30e-5p mimic rescued neuronal function while suppressing neuronal inflammation in rats following ICH; these effects were reversed by co-overexpression of TLR4. Furthermore, overexpression of miR-30e-5p inactivated TLR4/MyD88/TRIF signaling in rats with ICH; this was also reversed by overexpression of TLR4. Taken together, these results suggested that overexpression of miR-30e-5p exerted a protective role against neuronal deficit and inflammation caused by ICH in rats by targeting TLR4 and inactivating TLR4/MyD88/TRIF signaling.
... Compared to bAVM, which represent only 2% of intracerebral hemorrhages, epileptic seizures after spontaneous intracerebral hematomas (ICH) and ruptured aneurysms have been more widely studied in the literature. Indeed, the former are the leading cause of hemorrhagic stroke, accounting for 10-15% of all strokes [26][27][28], whereas the latter account for 5% of all strokes [29]. The incidence of seizures after spontaneous ICH varies from 4 to 16% [30][31][32][33] and can reach 42% in case of electroencephalographic monitoring [34,35]. ...
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Background Little is known about incidence, time of onset, clinical presentation, and risk factors of epileptic seizure following brain arteriovenous malformation (bAVM) rupture. Methods We performed a monocentric retrospective cohort study from January 2003 to March 2021. The main objective of this study was to determine the incidence of seizures after spontaneous bAVM rupture in nonepileptic adult patients and describe the corresponding clinical features. The secondary objective was to identify clinical, radiological, or biological predictors for the occurrence of de novo seizures after bAVM rupture. Results Of the 296 cases of bAVM rupture registered during the study period, 247 nonepileptic patients (male 53%, median age 40) were included in the study. Fifty-nine patients (23.9%) had at least one seizure after bAVM rupture. The use of preventive antiepileptic drugs (10.3 [1.5–74.1]; P = 0.02) and decompressive craniectomy (15.4 [2.0–125]; P < 0.009) were independently associated with the occurrence of epilepsy after the bAVM rupture. The factors independently associated with the absence of any seizure after the rupture were isolated intraventricular hemorrhage (0.3 [0.1–0.99]; P = 0.04) and infratentorial location of the bAVM (0.2 [0.1–0.5]; P = 0.09). The first seizure occurred within the first year or within 5 years in, respectively, 83.1% and 98.3% of the patients. Conclusions Epilepsy affects nearly a quarter of patients after bAVM rupture. Decompressive craniectomy represents an independent risk factor significantly associated with the occurrence of epilepsy after bAVM rupture. The introduction of preventive AEDs after rupture could be considered in these most severe patients who have a decompressive craniectomy.
... They correspond to a bleeding in the cerebral parenchyma that can extend to the cerebral ventricles. 1 They represent 10 to 15% of all strokes 2 and are often related to the spontaneous rupture of small vessels Nepal Journal of Neuroscience, Volume 18, Number 4, 2021 weakened by chronic arterial hypertension or amyloid angiopathy. 3 More rarely, hemorrhage is secondary to rupture of a vascular malformation, tumor, venous thrombosis, hemorrhagic transformation of an arterial infarct, cavernoma, cerebral phlebitis, coagulopathy, or anticoagulant medication. ...
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Context and Objective: Hemorrhagic Cerebrovascular Accidents represent 10 to 15% of all strokes and are often related to the spontaneous rupture of small vessels weakened by chronic arterial hypertension or amyloid angiopathy. The aim of this work was to study the prognostic determinants of intracerebral haematomas at the neurology department of Conakry University Hospital. Patients and Method: This was a retrospective analytical study conducted on all patients who were hospitalized with intracerebral hematoma over the 24-month period. Only the records of patients in whom intracerebral hematoma was confirmed by brain imaging were included in this study. Logistic regression (uni-variate and multi-variate) identified prognostic determinants of intracerebral hematoma at p < 0.05. The data were entered using Epi Info software version 7.1.4.0 then analysed using STATA / SE software version 11.2. Results: This study found 21% of cases of intracerebral hematomas during the study period, with a male predominance of 60% and a sex ratio of 1.50. The study was conducted in the presence of a male patient. Hypertension was the cause found in 89.52% of patients; followed by arteriovenous malformations in 6.67% of patients, 2.86% of cases of amyloid angiopathy and 0.95% of unknown cause. Nevertheless, we still recorded 20% of deaths during hospitalization. Conclusion: Previous quality of life and co-morbidities also modify the prognosis and should be taken into account in the prediction of disability and future quality of life of patients with intracerebral haematoma.
... Spontaneous intracerebral hemorrhage (ICH), defined as nontraumatic bleeding into the parenchyma of the brain [1], is the second most common subtype of stroke [1][2][3] and is associated with the highest mortality rate [4], with 5.3 million cases and over 3.0 million deaths secondary to ICH worldwide in 2010 reported by the "Global Burden of Diseases, Injuries, and Risk Factors" [5,6]. The 30-day mortality for ICH has been reported to be 30-55% [7][8][9][10], with half of fatal cases occurring in the acute phase, especially in the first 48 h after presentation [10][11][12]. ...
Article
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Intracerebral hemorrhage (ICH) is a common subtype of stroke and places a great burden on the family and society with a high mortality and disability rate and a poor prognosis. Many findings from imaging and pathologic studies have suggested that cerebral ischemic lesions visualized on diffusion-weighted imaging (DWI) in patients with ICH are not rare and are generally considered to be associated with poor outcome, increased risk of recurrent (ischemic and hemorrhagic) stroke, cognitive impairment, and death. In this review, we describe the changes in cerebral blood flow (CBF) and DWI lesions after ICH and discuss the risk factors and possible mechanisms related to the occurrence of DWI lesions, such as cerebral microangiopathy, cerebral atherosclerosis, aggressive early blood pressure lowering, hyperglycemia, and inflammatory response. We also point out that a better understanding of cerebral DWI lesions will be a key step toward potential therapeutic interventions to improve long-term recovery for patients with ICH.
Article
Background: Seizures are a harmful complication of acute intracerebral hemorrhage (ICH). "Early" seizures in the first week after ICH are a risk factor for deterioration, later seizures, and herniation. Ideally, seizure medications after ICH would only be administered to patients with a high likelihood to have seizures. We developed and validated machine learning (ML) models to predict early seizures after ICH. Methods: We used two large datasets to train and then validate our models in an entirely independent test set. The first model ("CAV") predicted early seizures from a subset of variables of the CAVE score (a prediction rule for later seizures)-cortical hematoma location, age less than 65 years, and hematoma volume greater than 10 mL-whereas early seizure was the dependent variable. We attempted to improve on the "CAV" model by adding anticoagulant use, antiplatelet use, Glasgow Coma Scale, international normalized ratio, and systolic blood pressure ("CAV + "). For each model we used logistic regression, lasso regression, support vector machines, boosted trees (Xgboost), and random forest models. Final model performance was reported as the area under the receiver operating characteristic curve (AUC) using receiver operating characteristic models for the test data. The setting of the study was two large academic institutions: institution 1, 634 patients; institution 2, 230 patients. There were no interventions. Results: Early seizures were predicted across the ML models by the CAV score in test data, (AUC 0.72, 95% confidence interval 0.62-0.82). The ML model that predicted early seizure better in the test data was Xgboost (AUC 0.79, 95% confidence interval 0.71-0.87, p = 0.04) compared with the CAV model AUC. Conclusions: Early seizures after ICH are predictable. Models using cortical hematoma location, age less than 65 years, and hematoma volume greater than 10 mL had a good accuracy rate, and performance improved with more independent variables. Additional methods to predict seizures could improve patient selection for monitoring and prophylactic seizure medications.
Article
Objectives Spontaneous intracerebral hemorrhage (SICH) is a subtype of stroke associated with high mortality and devastating disabilities. Therefore, identifying non-invasive biomarkers for SICH would have a tremendous clinical impact. MicroRNAs (miRNAs) are non-coding single-stranded RNAs containing 21 to 23 nucleotides that control the activity of various protein-coding genes through post-transcriptional repression. In this systematic review, we report the recent clinical evidence on the role of miRNAs as biomarkers for the prediction, prognosis, early detection, and risk stratification of SICH. Methods We conducted a systematic search of PubMed, PubMed Central, MEDLINE, and Embase databases and included only full-text peer-reviewed articles published in English. Results We included 10 studies comprising seven case-control studies, two cohort studies, and one cross-sectional study, among which we found 27 altered miRNAs, suggesting their role as biomarkers for the early detection of ICH. Additionally, the expression of 34 miRNAs was associated with poor prognosis of ICH; miR-126 and miR-23a-3p expression correlated with relative perihematomal edema (PHE) volume, and using a subset of 10 miRNA signatures had an accuracy of 100% in predicting hematoma in patients with ICH. Moreover, miR-4317 and miR-4325 profiling predicted the development of late seizures. Thirty-nine miRNAs were associated with the incidence of all types of strokes, while 10 miRNAs correlated with the predicted risk of stroke but were not specific to a stroke subtype. The altered miRNA signatures contributed to endothelial dysfunction, hematoma, and PHE through leukocyte activation, oxidative stress response, programmed cell death, smooth muscle cell proliferation, and apoptosis of cerebrovascular endothelial cells. The current data had limitations and gaps, especially the human studies, and there may have been selection bias in the prospective studies. There were also some limitations regarding the methods for obtaining miRNAs and identifying target RNAs specific to SICH pathology. Additionally, there may have been correlations between the outcomes and other factors, such as therapeutic interventions and ICH severity, the circulating miRNA profiles and gene expression profiles, and other pathological conditions and patients’ age. Finally, the prediction and risk stratification of SICH could not be calculated separately from ischemic stroke. Conclusions Following our literature retrieval, we noted alterations in various miRNA signatures, suggesting their potential role as biomarkers for the early detection and differentiation of SICH. Indeed, miRNA expression was associated with a poor prognosis of SICH and correlated with the predicted risk of stroke but was not specific to a stroke subtype. Further studies are needed, especially on the therapeutic potential of miRNAs and their target RNAs in SICH.
Article
Background: We compare the effect of urokinase (urokinase-type plasminogen activator [uPA]) versus alteplase (recombinant tissue plasminogen activator [rt-PA]) for intraventricular fibrinolysis (IVF) in patients with intraventricular hemorrhage (IVH) on ventriculoperitoneal shunt (VPS) dependence, functional outcome, and complications in the management of IVH. Methods: We retrospectively reviewed the patients admitted with IVH or intracerebral hemorrhage (ICH) with IVH within 7 years in three different departments and found 102 patients who met the inclusion criteria. The primary end points were VPS dependence and Glasgow outcome score (GOS) at 3 months. Secondary end points were rate of rebleeding under IVF and incidence of treatment-related complications. Patients were divided into three groups: group I comprised patients treated with external ventricular drain (EVD) and IVF with uPA; group II comprised patients treated with EVD and IVF with rt-PA; and group III comprised patients treated with EVD alone. Results: In all, 9.8% patients needed VPS: 12.2% in group I and 15.0% in group II, with no statistically significant difference. VPS patients had higher values of the modified Graeb score (mGS), IVH score, and IVH volume. We saw a trend for a better outcome in group II, with six patients achieving a GOS of 4 or 5 after 3 months. The mortality rate was higher in groups I and III. We found no statistical difference in the complication rate between groups I and II. Logistic regression analysis revealed that higher mGS and age predicted worse prognosis concerning mortality. The risk for death rose by 7.8% for each year of age. Any additional mGS point increased the chances of death by 9.7%. Conclusion: Our data suggest that both uPA and rt-PA are safe and comparable regarding incidence of communicating hydrocephalus, and age and mGS are predictive for mortality.
Chapter
Intracerebral hemorrhage remains one of the most deadly and disabling forms of neurologic disease. The evaluation and management are focused on rapid stabilization and diagnostic testing to rule out the presence of an underlying lesion such as an aneurysm, vascular malformation, or tumor that would require additional testing or treatment in the acute phase. Treatment strategies are limited to control of blood pressure, reversal of anticoagulation, control of intracranial pressure, and supportive care. Surgery is often reserved for the emergent management of increased intracranial pressure or mass effect from the hematoma. Minimally invasive intracerebral hemorrhage evacuation has demonstrated benefit in some settings and is under active investigation in multiple clinical trials. Prognosis overall is poor and is negatively impacted by advanced age, larger hematoma, hematoma located in subcortical locations, the presence of intraventricular hemorrhage, and poor neurologic examination at presentation. Fortunately, significant scientific and translational efforts are underway to develop novel pharmaceutical, device, and data-driven innovations which are likely to lead to novel treatments for this devastating disease process in the near future.
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The management of ischemic stroke has been marked by three major advances that transformed the approach to its diagnosis and treatment: (1) creation of stroke units, (2) IV thrombolytic (IVT) use, and (3) mechanical thrombectomy.
Article
Background Intracranial hemorrhage is seen more frequently in acute leukemia patients compared to the general population. Besides leukemia related risk factors, also risk factors that are present in the general population might contribute to hemorrhagic complications in leukemia patients. Of those, cardiovascular risk factors leading to chronic vascular damage could modulate the occurrence of intracranial hemorrhage in these patients, as during their disease and treatment acute endothelial damage occurs due to factors like thrombocytopenia and inflammation. Objectives Our aim was to explore if cardiovascular risk factors can predict intracranial hemorrhage in acute leukemia patients. Methods In a case control study nested in a cohort of acute leukemia patients, including 17 cases with intracranial hemorrhage and 55 matched control patients without intracranial hemorrhage, data on cardiovascular risk factors was collected for all patients. Analyses were performed via conditional logistic regression. Results Pre-existing hypertension and ischemic heart disease in the medical history were associated with intracranial hemorrhage, with an incidence rate ratio of 12.9 (95% confidence interval (CI) 1.5 to 109.2) and 12.1 (95% CI 1.3 to110.7), respectively. Conclusion Both pre-existing hypertension and ischemic heart disease seem to be strong predictors of an increased risk for intracranial hemorrhage in leukemia patients.
Thesis
Hintergrund und Ziele: Subarachnoidalblutungen (SAB) gehen nicht selten mit intrazerebralen Blutanteilen (ICB) einher, welche den klinischen Zustand und Krankheitsverlauf zusätzlich beeinträchtigen können. Die Bedeutung begleitender ICB für das langfristige Outcome ebenso wie ihre Behandlung blieben bislang jedoch im Wesentlichen ungeklärt. Zwar empfehlen die aktuellen Leitlinien bei massenwirksamen Blutungen eine chirurgische Hämatomevakuation (CHE), die Evidenz für dieses Vorgehen ist allerdings limitiert. Methoden: Retrospektiv ausgewertet wurden die Daten von allen konsekutiven Patienten, welche in einem Zeitraum von 5 Jahren (2008–2012) aufgrund einer atraumatischen SAB in der Neurologischen und Neurochirurgischen Klinik des Universitätsklinikums Erlangen behandelt worden sind. Neben klinischen Parametern und dem Ausmaß der SAB wurden die Häufigkeit und Lokalisation von ICB erfasst und ihr Volumen anhand der ABC/2-Formel abgeschätzt. Die Beurteilung des Outcomes nach 12 Monaten umfasste funktionelle Einschränkungen (modified Rankin Scale (mRS)), die gesundheitsbezogene Lebensqualität (EQ-5D-VAS) sowie Langzeitkomplikationen (u.a. Epilepsie). Zur besseren Vergleichbarkeit von Patienten mit und ohne ICB wurde ein Propensity Score Matching (PSM; Ratio 1:1, Caliper 0,1) durchgeführt. Ferner erfolgten Subanalysen, um den Einfluss verschiedener Behandlungsverfahren (chirurgische Hämatomevakuation versus konservative Behandlung) auf das Outcome zu überprüfen. Ergebnisse und Beobachtungen: Von insgesamt 494 Patienten mit atraumatischer SAB wiesen initial 85 (17,2 %) Patienten intrazerebrale Blutanteile auf. Diese hatten zum Zeitpunkt der Aufnahme einen schlechteren klinischen Zustand und ein größeres Ausmaß subarachnoidaler und intraventrikulärer Blutanteile (IVB) (mFisher, Median (IQR): ICB 3 (2–4) vs. ØICB 2 (1– 3); p = 0,001; IVB: ICB 74,1 % vs. ØICB 57,0 %; p = 0,004; Graeb Score, Median (IQR): ICB 4 (2–8) vs. ØICB 2,5 (2–4); p < 0,001)). Das mediane intrazerebrale Blutvolumen betrug 11,0 (5,4–31,8) ml, wobei die größten ICB-Volumina mit rupturierten Aneurysmen der Arteria cerebri media (MCA) verbunden waren (31,6 ml (16,3–43,2)). Nach Adjustierung mittels PSM erlangten ICB-Patienten nicht nur seltener ein günstiges funktionelles Outcome (mRS 0–2: ICB 31,8 % vs. ØICB 57,7 %; p < 0,001), sie litten auch häufiger an einer Epilepsie (ICB 23,4 % vs. ØICB 7,3 %; p = 0,03), konnten seltener beruflich wiedereingegliedert werden (ICB 12,7 % vs. ØICB 32,1 %; p = 0,008) und schätzten ihre eigene Gesundheit schlechter ein (EQ-5D-VAS: ICB 50 (30–70) vs. ØICB 80 (65–95); p < 0,001). Die Behandlung mit einer chirurgischen Hämatomevakuation, ungeachtet des Alters oder der Aneurysmalokalisation, war häufiger mit einem günstigen Outcome nach 12 Monaten assoziiert als eine konservative Behandlung (CHE 14/28 (50,0 %) vs. konservativ 14/57 (24,6 %); adjustierte Odds Ratio (OR, 95 % KI): 1,34 (1,08–1,66); p = 0,001). Dieser Vorteil zeigte sich den Subgruppen- Analysen nach insbesondere für Patienten mit frontal lokalisierten ICB (OR 1,59 (1,14– 2,23)), großen ICB-Volumina (> 10 ml; OR 1,39 (1,09–1,79)) und bei Patienten, die frühzeitig einer CHE unterzogen wurden (≤ 600 min nach Blutungsbeginn; OR 1,42 (1,03–1,94)). Schlussfolgerungen: Intrazerebrale Blutanteile sind häufige Komplikationen einer SAB, die gravierende funktionelle sowie subjektive Einschränkungen nach sich ziehen. Möglicherweise könnten diese Patienten von einer frühzeitigen chirurgischen Hämatomevakuation profitieren.
Article
Objective. To explore the convolutional neural network (CNN) method in measuring hematoma volume-assisted microsurgery for spontaneous cerebral hemorrhage. Methods. A total of 120 patients with spontaneous cerebral hemorrhage were selected and randomly divided into control and CNN groups with 60 patients in each group. Patients in the control group received traditional Tada formula to calculate hematoma volume and microsurgery. Convolutional neural network algorithm segmentation was used to measure hematoma volume, and microsurgery was performed in the CNN group. This article assessed neurological function, ability to live daily, complication rate, and prognosis. Results. The incidence of postoperative complications in the CNN group (13.33%) was lower than the control group (43.33%). The neurological function and daily living ability in the CNN groups were recovered better. The incidence of poor prognosis in the CNN group (16.67%) was lower than the control group (30.00%). Conclusion. Convolutional neural network measurement of hematoma volume to assist microsurgical treatment of spontaneous intracerebral hemorrhage patients is conducive to early recovery, reducing the damage to the patients’ cerebral nerves.
Article
MicroRNAs (miRNAs) participate in the diagnosis and treatment of intracerebral hemorrhage (ICH). miR-141-3p has been widely reported to regulate neurological disorders and cerebropathy. However, the specific role of miR-141-3p in ICH has not yet been revealed. The aim of this study was exploration of the biological functions and mechanism of miR-141-3p in ICH by establishing a collagenase-induced ICH mouse model. After ICH induction, miR-141-3p mimics or miR-NC were administered into the right striatum of the model mice followed by the performance of neurological tests. After euthanasia of the mice, the injury volume, brain water content, and injury to the blood–brain barrier (BBB) were evaluated. Evans blue (EB) was used to stain the brain slices, and EB extravasation was detected to evaluate the injury to BBB. miR-141-3p expression in perihematomal edema and hematoma areas after ICH was assessed by RT–qPCR. The levels of tight junction proteins in brain tissues and human brain microvascular endothelial cells (BMECs) were evaluated by western blotting. The FITC-dextran 20 method was used to assess BMEC permeability. The binding between miR-141-3p and zinc finger E-box-binding homeobox 2 (ZEB2) was verified with a luciferase reporter assay. In this study, miR-141-3p overexpression alleviated ICH-induced brain injury and protected BBB integrity in vivo. ZEB2 was a target gene of miR-141-3p. ZEB2 overexpression promoted BBB disruption, and miR-141-3p overexpression attenuated the promoting effect exerted by ZEB2. Overall, miR-141-3p protects against BBB disruption and attenuates brain injuries induced by ICH by targeting ZEB2.
Chapter
The minimally invasive procedures used by interventional neuroradiologists accomplish a wide variety of treatments designed to provide correct life-threatening conditions, such as haemorrhagic or ischemic stroke. Endovascular treatment strategies of haemorrhagic intracranial aneurysms include coiling, balloon-assisted coiling, intrasaccular flow-disruptors, stent-assisted coiling, and flow-diverter devices. Interventional neuroradiology allows also minimally invasive treatments of haemorrhagic stroke, which are due to an underlying vascular lesion such as arteriovenous malformations or dural arterio-venous fistulas. Embolization with acrylic glues or with non-adhesive embolic materials may be used for “target” embolization in the setting of intracerebral haemorrhage. Finally, endovascular treatment of acute ischemic stroke is now the younger field of interventional neuroradiology. It is important to recognize that modern endovascular stroke therapy focuses on direct clot removal with mechanical devices and it represents the standard of care in cases of proximal large vessel occlusion of the anterior circulation. In this chapter, we review the current practice on neuroendovascular therapy in acute phase and we discuss the main techniques used by interventional neuroradiologists.
Article
Intracerebral hemorrhage (ICH), which is a form of hemorrhagic stroke, is an extremely serious disease. This pathology is characterized by very high levels of disability and mortality. Despite the improvement in the treatment of those diseases that can lead to ICH, its frequency is currently increasing, which is largely due to the use of drugs, in which case the term «drug-induced intracerebral hemorrhage» (DI ICH) is used. One of the main reasons for drug-induced ICH is an increase in the frequency of prescribing anticoagulant therapy for the prevention of ischemic stroke in atrial fibrillation, as well as dual antithrombotic therapy. In addition to anticoagulants, thrombolytic drugs can lead to the development of this pathology. According to the literature, an increase in the risk of developing ICH is also associated with therapy with antidepressants from the group of selective serotonin reuptake inhibitors, as well as high doses of statins. Risk factors for this adverse reaction are age, smoking, hypertension, and thrombocytopenia. Treatment of DI ICH is an extremely difficult task and includes the withdrawal of the culprit medication, antihypertensive therapy, correction of intracranial hypertension, and, in some cases, the administration of antidotes. The main method of prevention is the use of antiplatelet drugs and other drugs, the use of which is associated with an increased risk of developing DI ICH, in strict accordance with modern protocols and recommendations.
Article
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Objective Spontaneous intracerebral hemorrhage (sICH) is a frequently encountered neurosurgical disease. The purpose of this study was to evaluate the relationship between modified Graeb Score (mGS) at admission and clinical outcomes of sICH and to investigate whether the combination of ICH score could improve the accuracy of outcome prediction. Methods We retrospectively reviewed the medical records of 511 patients who underwent surgery for sICH between January 2017 and June 2021. Patient outcome was evaluated by the Glasgow Outcome Scale (GOS) score at 3 months following sICH, where a GOS score of 1–3 was defined as a poor prognosis. Univariate and multivariate logistic regression analyses were conducted to determine risk factors for unfavorable clinical outcomes. Receiver operating characteristic (ROC) curve analysis was performed to detect the optimal cutoff value of mGS for predicting clinical outcomes. An ICH score combining mGS was created, and the performance of the ICH score combining mGS was assessed for discriminative ability. Results Multivariate analysis demonstrated that a higher mGS score was an independent predictor for poor prognosis (odds ratio [OR] 1.207, 95% confidence interval [CI], 1.130–1.290, p < 0.001). In ROC analysis, an optimal cutoff value of mGS to predict the clinical outcome at 3 months after sICH was 11 ( p < 0.001). An increasing ICH-mGS score was associated with increased poor functional outcome. Combining ICH score with mGS resulted in an area under the curve (AUC) of 0.790, p < 0.001. Conclusion mGS was an independent risk factor for poor outcome and it had an additive predictive value for outcome in patients with sICH. Compared with the ICH score and mGS alone, the ICH score combined with mGS revealed a significantly higher discriminative ability for predicting postoperative outcome.
Article
BACKGROUND: Spontaneous intra-cerebral haemorrhage (ICH) is a major public health problem with an annual incidence of 10–30 cases per 100 000 population, accounting for 2 million (10–15%) of approximately 15 million strokes, which occur worldwide each year. AIMS AND OBJECTIVE: The main objective of this study is (i) to correlate volume and location of lesion (hemorrhage) with clinical picture and prognosis, (ii) to determine clinical and CT parameters or ndings that could predict prognosis. METHODS AND MATERIAL: The study was conducted on 100 Patients with diagnosis of spontaneous ICH and who were diagnosed and admitted to MGM Medical College and LSK Hospital, Kishanganj, Bihar, India from 01/08/19 to 30/07/2021, age ranged between 18 and 75 years. The inclusion criteria were as follows: (1) spontaneous ICHs on the basis of C.T scan and (2) No antecedent disease such as arterio venous malformations, tumour, anticoagulation therapy, cerebral aneurysms, or traumatic events. RESULT: The haemorrhagic stroke on the basis of site, putamen is 44, frontal and parietal is 5 and temporal is 3 in numbers with weakness of limbs or focal neurological decit was commonest presentation associated with hypertension and diabetes as risk factors was 50% and 07% respectively. The lobar and deep haemorrhages constitute 18% and 75% respectively but the mean volume of haemorrhage 28.44cm3 and 36.52cm3. CONCLUSION: In present study the location of ICH was lobar in 18% deep ganglionic (+ventricle) in 75%, cerebellar in 3% and pontine or midbrain in 4% of the patients. The location of the hematoma in 13 (72.7%) of the LH patients was conned to a single cerebral lobe, while in 5 (27.2%) of LH patients, hematoma was located in two lobes
Article
Hemorrhagic stroke (HS) is a disastrous occurrence with high mortality rates, however, there are no established treatments for this pathology. Given recent advances in stem cell therapies, concerted research efforts have elucidated the therapeutic potential of stem cells in treating HS. In 2020, our group reviewed the use of SCs in regulating the neuroinflammatory reactions which occur after HS.¹ This review will build on that work, highlighting more recent advancements in the field of SC treatments for HS. Ultimately, with greater focus in this area of research, innovative SC therapies can be optimized in preclinical studies and soon be transferred to clinical applications for HS therapeutics.
Article
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Non-traumatic intracerebral hemorrhage is a highly destructive intracranial disease with high mortality and morbidity rates. The main risk factors for cerebral hemorrhage include hypertension, amyloidosis, vasculitis, drug abuse, coagulation dysfunction, and genetic factors. Clinically, surviving patients with intracerebral hemorrhage exhibit different degrees of neurological deficits after discharge. In recent years, with the development of regenerative medicine, an increasing number of researchers have begun to pay attention to stem cell and exosome therapy as a new method for the treatment of intracerebral hemorrhage, owing to their intrinsic potential in neuroprotection and neurorestoration. Many animal studies have shown that stem cells can directly or indirectly participate in the treatment of intracerebral hemorrhage through regeneration, differentiation, or secretion. However, considering the uncertainty of its safety and efficacy, clinical studies are still lacking. This article reviews the treatment of intracerebral hemorrhage using stem cells and exosomes from both preclinical and clinical studies and summarizes the possible mechanisms of stem cell therapy. This review aims to provide a reference for future research and new strategies for clinical treatment.
Article
Background: Spontaneous intracerebral hemorrhage (ICH) is the second most prevalent subtype of stroke and has high mortality and morbidity. The utility of radiographic features to predict secondary brain injury related to hematoma expansion (HE) or increased intracranial pressure has been highlighted in patients with ICH, including the computed tomographic angiography (CTA) spot sign and intraventricular hemorrhage (IVH). Understanding the pathophysiology of spot sign and IVH may help identify optimal therapeutic strategies. We examined factors related to the spot sign and IVH, including coagulation status, hematoma size, and location, and evaluated their prognostic value in patients with ICH. Methods: Prospectively collected data from a single center between 2012 and 2015 were analyzed. Patients who underwent thromboelastography within 24 h of symptom onset and completed follow-up brain imaging and CTA within 48 h after onset were included for analysis. Multivariate logistic regression analyses were performed to identify determinants of the spot sign and IVH and their predictive value for HE, early neurological deterioration (END), in-hospital mortality, and functional outcome at discharge. Results: Of 161 patients, 50 (31.1%) had a spot sign and 93 (57.8%) had IVH. In multivariable analysis, the spot sign was associated with greater hematoma volume (odds ratio [OR] 1.02; 95% confidence interval [CI] 1.00-1.03), decreased white blood cell count (OR 0.88; 95% CI 0.79-0.98), and prolonged activated partial thromboplastin time (OR 1.14; 95% CI 1.06-1.23). IVH was associated with greater hematoma volume (OR 1.02; 95% CI 1.01-1.04) and nonlobar location of hematoma (OR 0.23; 95% CI 0.09-0.61). The spot sign was associated with greater risk of all adverse outcomes. IVH was associated with an increased risk of END and reduced HE, without significant impact on mortality or functional outcome. Conclusions: The spot sign and IVH are associated with specific hematoma characteristics, such as size and location, but are related differently to coagulation status and clinical course. A combined analysis of the spot sign and IVH can improve the understanding of pathophysiology and risk stratification after ICH.
Article
Spontaneous intracerebral hemorrhage (ICH) constitutes 10–15% of all strokes, and is a significant cause of mortality and morbidity. Survivors of ICH, especially those with atrial fibrillation (AF), are at risk for both recurrent hemorrhagic and ischemic cerebrovascular events. A conundrum in the field of vascular neurology, neurosurgery, and cardiology has been the decision to initiate or resume versus withhold anticoagulation in survivors of ICH with AF. To initiate anticoagulation would decrease the risk of ischemic stroke but may increase the risk of hemorrhage. To withhold anticoagulation maintains a lower risk of hemorrhage but does not decrease the risk of ischemic stroke. In this narrative review, we discuss the evidence for and against the use of antithrombotics in ICH survivors with AF, focusing on recently completed and ongoing clinical trials.
Article
Background and purpose: Intracranial hemorrhage (ICH) is a common finding in patients presenting to the emergency department with acute neurological symptoms. Noncontrast head computed tomography (NCCT) is the primary modality for assessment and detection of ICH in the acute setting. RAPID ICH software aims to automatically detect ICH on NCCT and was previously shown to have high accuracy when applied to a curated test data set. Here, we measured the test performance characteristics of RAPID ICH software in detecting ICH on NCCT performed in patients undergoing emergency stroke evaluation at a tertiary academic comprehensive stroke center. Materials and methods: This retrospective study assessed consecutive patients over a 6-month period who presented with acute neurological symptoms suspicious for stroke and underwent NCCT with RAPID ICH postprocessing. RAPID ICH detection was compared with the interpretation of a reference standard comprising a board-certified or board-eligible neuroradiologist, or in cases of discrepancy, adjudicated by a consensus panel of 3 neuroradiologists. Accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of RAPID ICH for ICH detection were determined. Results: Three hundred seven NCCT scans were included in the study. RAPID ICH correctly identified 34 of 37 cases with ICH and 228 of 270 without ICH. RAPID ICH had a sensitivity of 91.9% (78.1%-98.3%), specificity of 84.4% (79.6%-88.6%), NPV of 98.7% (96.3%-99.6%), PPV of 44.7% (37.6%-52.1%), and overall accuracy of 85.3% (80.9%-89.1%). Conclusions: In a real-world scenario, RAPID ICH software demonstrated high NPV but low PPV for the presence of ICH when evaluating possible stroke patients.
Article
Background: Perihematomal edema (PHE) has been proposed as a radiological marker of secondary injury and therapeutic target in intracerebral hemorrhage (ICH). We conducted a systematic review and meta-analysis to assess the prognostic impact of PHE on functional outcome and mortality in patients with ICH. Methods: We searched major databases through December 2020 using predefined keywords. Any study using logistic regression to examine the association between PHE or its growth and functional outcome was included. We examined the overall pooled effect and conducted secondary analyses to explore the impact of individual PHE measures on various outcomes separately. Study quality was assessed by three independent raters using the Newcastle-Ottawa Scale. Odds ratios (per 1-unit increase in PHE) and their confidence intervals (CIs) were log transformed and entered into a DerSimonian-Laird random-effects meta-analysis to obtain pooled estimates of the effect. Results: Twenty studies (n = 6633 patients) were included in the analysis. The pooled effect size for overall outcome was 1.05 (95% CI 1.02-1.08; p < 0.00). For the following secondary analyses, the effect size was weak: mortality (1.01; 95% CI 0.90-1.14), functional outcome (1.04; 95% CI 1.02-1.07), both 90-day (1.06; 95% CI 1.02-1.11), and in-hospital assessments (1.04; 95% CI 1.00-1.08). The effect sizes for PHE volume and PHE growth were 1.04 (95% CI 1.01-1.07) and 1.14 (95% CI 1.04-1.25), respectively. Heterogeneity across studies was substantial except for PHE growth. Conclusions: This meta-analysis demonstrates that PHE volume within the first 72 h after ictus has a weak effect on functional outcome and mortality after ICH, whereas PHE growth might have a slightly larger impact during this time frame. Definitive conclusions are limited by the large variability of PHE measures, heterogeneity, and different evaluation time points between studies.
Article
Background: While clinical guidelines provide a framework for hospital management of spontaneous intracerebral hemorrhage (ICH), variation in the resource utilization and costs of these services exist. Objectives: Perform a systematic literature review to assess the evidence on hospital resource utilization and costs associated with management of adult ICH patients, as well as identify factors that impact variation in such hospital resource utilization and costs, regarding clinical characteristics and delivery of services. Methods: A systematic literature review was performed using PubMed, Cochrane Central Register of Controlled Trials, and Ovid MEDLINE(R) 1946 to Present. Articles were assessed against inclusion and exclusion criteria. Study design, ICH sample size, population, setting, objective, hospital characteristics, hospital resource utilization and cost data, and main study findings were abstracted. Results: 43 studies met the inclusion criteria. Pertinent clinical characteristics that increased hospital resource use included presence of comorbidities and baseline ICH severity. Aspects of service delivery that greatly impacted hospital resource consumption included ICU length of stay and performance of surgical procedures and intensive care procedures. Conclusion: Hospital resource utilization and costs for ICH patients were high and differed widely across studies. Making concrete conclusions on hospital resources and costs for ICH care was constrained given methodological and patient variation in the studies. Future research should evaluate the long-term cost-effectiveness of ICH treatment interventions and use specific economic evaluation guidelines and common data elements to mitigate study variation.
Thesis
L'angiopathie amyloïde cérébrale (AAC) sporadique est une microangiopathie cérébrale, dont l'intérêt auprès des cliniciens et des chercheurs est grandissant. L'AAC est fréquente chez les sujets âgés et constitue une cause majeure et croissante d'hémorragie intracérébrale et de démence. Des avancées importantes ont été réalisées ces dernières années dans ce champ de recherche, permettant d'identifier de nouveaux biomarqueurs de la maladie, grâce aux progrès réalisés en neuroimagerie structurelle, fonctionnelle et moléculaire. Des thérapies anti-amyloïdes sont en cours de développement et des essais cliniques évaluant la meilleure stratégie vis à vis des traitements anticoagulants chez ces patients ont débuté, laissant entrevoir des possibilités thérapeutiques. Ainsi, l'évaluation de ces nouveaux biomarqueurs d'AAC semble particulièrement importante. L'objectif principal de cette thèse était d'apporter de nouvelles connaissances sur les biomarqueurs de neuroimagerie les plus récents et leurs applications potentielles en pratique clinique chez les patients avec AAC. Nous avons pour cela conduit 6 études de recherche clinique explorant des nouveaux biomarqueurs hémorragiques (hémosidérose corticale, hémorragie sous arachnoïdienne de la convexité) et non hémorragiques (espaces périvasculaires dilatés, TEP amyloïde et réseau de connectivité cérébrale) de la maladie. Nous évaluons ces biomarqueurs comme outils diagnostiques et leur pertinence clinique comme facteur pronostique.
Chapter
Asia is home to a community of diverse ethnicities and races which contributes to more than half of the world’s population. Asia also shares a significant number in the statistics of worldwide mortality and morbidity, in particular, cerebrovascular disease. Cerebrovascular disease or stroke is a leading cause of mortality and long-term disability worldwide. Globally, there was a downward trend of stroke statistics since the 1990s, however, the collective stroke burden in terms of absolute number of people affected still increases. Stroke is an important health concern as about 60% of the world’s population is in Asia and with many countries regarded as developing economies. Notably, Asia has a higher burden related to stroke compared to coronary artery disease, while the opposite is observed in Western countries. Also, Asia has a higher burden of cerebrovascular risk factors with hypertension as the most prevalent cause of both ischemic and hemorrhagic strokes. Compared to Western countries, Asia has a higher incidence of hemorrhagic strokes and ischemic strokes related to cerebral small vessel disease such as lacunar infarcts, silent strokes, white matter hyperintensities, and cerebral microbleeds. Cases of large vessel occlusion and subarachnoid hemorrhages are variable. Unique to Asia is the higher incidence of hemorrhagic strokes and AIS related to CSVD. Among the many known and established risk factors for stroke, HTN remains to be the most significant, though modifiable and preventable. Through time, chronic HTN leads to degeneration of the intracranial blood vessel wall leading to occlusion in cerebral ischemia or rupture in cerebral hemorrhages. This chapter highlights cerebrovascular disease in Asia and its causative factors by exploring different stroke subtypes and impact of hypertension. A discussion on blood pressure variability is provided as it is currently an emerging factor contributing to the development of strokes including the Asian population.
Article
The morbidity and mortality associated with spontaneous intracerebral haemorrhage high, with 40% reported mortality at 1 month and fewer than 40% of patients regaining functional independence. Despite advances made in the treatment of ischemic stroke, similar improvements have not been seen with intracerebral hemorrhage. Medical control of blood pressure and intracranial pressure, among other factors, are key to management. The impact of surgical intervention is less clear. This article reviews the data surrounding the surgical management of intracerebral hemorrhage, including open and minimally invasive techniques and discusses the controversies and future directions surrounding surgical management.
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The oedema which forms around an intracerebral haemorrhage has a complex aetiology. The immune response may have a role in its formation. There is clinical and experimental evidence that circulating leucocytes and platelets may mediate oedema formation. Global depletion of circulating leucocytes and platelets by whole body irradiation in a rodent model of intracerebral haemorrhage was found to confer protection against both ischaemia and oedema formation. This was not a direct effect of irradiation of the brain. The possible mechanisms for this protection are discussed.
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The National Institute of Neurological and Communicative Disorders and Stroke initiated the Stroke Data Bank, which is a multicenter project to prospectively collect data on the clinical course and sequelae of stroke. Additional objectives were to provide information that would enable a standard diagnostic clinical evaluation, to identify prognostic factors, and to provide planning data for future studies. A brief description of the structure and methods precede the baseline characterization of 1,805 patients enrolled in the Stroke Data Bank between July 1983 and June 1986. Two thirds of these patients were admitted within 24 hours after stroke onset. Medical history, neurologic history, and hospitalization summaries are presented separately for the following stroke subtypes: infarction, unknown cause; embolism from cardiac source; infarction due to atherosclerosis; lacune; parenchymatous or intracerebral hemorrhage; subarachnoid hemorrhage; and other. The utility and limitations of these data are discussed.
Article
The Hypertension Detection and Follow-up Program (HDFP) previously reported a 16.9% reduction in all-cause mortality among its Stepped Care (SC) group, relative to the community-treated Referred Care (RC) group. The current report compares cerebrovascular disease (CV) morbidity and mortality in the SC and RC populations. The SC five-year stroke incidence (1.9 per 100 persons) is significantly lower than that found among the RC (2.9 per 100 persons). Reductions in stroke rates among SC were experienced for all race-sex groups, all diastolic blood pressure strata, all ages, and among those with or without evidence of long-standing hypertension. Comparisons of the CV death rates for SC (1.06 per 1,000 persons) and RC (1.91 per 1,000 persons) with those obtained for the general US population (0.83 per 1,000 persons) indicate that the CV death rate decreased in the SC hypertensive population to a level approaching that of the general US population.
Article
We studied 17 consecutive patients with nonaneurysmal cerebral hemorrhages larger than 55 cm3 to determine the computerized tomographic correlates of stupor and coma. Coma was associated with 8 mm or greater pineal displacement in 8 of 14 comatose patients. An extension of the clot that occupied or displaced the lower diencephalic region explained coma in the remaining 6 patients with less than 8 mm horizontal pineal displacement. All patients with diencephalic clot were comatose. Three initially drowsy or stuporous patients had 3 mm mean pineal displacement. Massive hydrocephalus occurred in 5 patients, always associated with diencephalic clot, and therefore never independently accounting for coma. Clot volume could be estimated from: volume (cm3) = [largest clot diameter (cm) X 14] – 14. We incidentally found that at least 6 of the 17 massive hemorrhages had progressed from smaller clots.
Article
To determine the effect of continuous hypertonic (3%) saline/acetate infusion on intracranial pressure (ICP) and lateral displacement of the brain in patients with cerebral edema. Retrospective chart review. Neurocritical care unit of a university hospital. Twenty-seven consecutive patients with cerebral edema (30 episodes), including patients with head trauma (n = 8), postoperative edema (n = 5), nontraumatic intracranial hemorrhage (n = 8), and cerebral infarction (n = 6). Intravenous infusion of 3% saline/acetate to increase serum sodium concentrations to 145 to 155 mmol/L. A reduction in mean ICP within the first 12 hrs correlating with an increase in the serum sodium concentration was observed in patients with head trauma (r2 = .91, p = .03), and postoperative edema (r2 = .82, p = .06), but not in patients with nontraumatic intracranial hemorrhage or cerebral infarction. In patients with head trauma, the beneficial effect of hypertonic saline on ICP was short-lasting, and after 72 hrs of infusion, four patients required intravenous pentobarbital due to poor ICP control. Among the 21 patients who had a repeat computed tomographic scan within 72 hrs of initiating hypertonic saline, lateral displacement of the brain was reduced in patients with head trauma (2.8 +/- 1.4 to 1.1 +/- 0.9 [SEM]) and in patients with postoperative edema (3.1 +/- 1.6 to 1.1 +/- 0.7). This effect was not observed in patients with nontraumatic intracranial bleeding or cerebral infarction. The treatment was terminated in three patients due to the development of pulmonary edema, and was terminated in another three patients due to development of diabetes insipidus. Hypertonic saline administration as a 3% infusion appears to be a promising therapy for cerebral edema in patients with head trauma or postoperative edema. Further studies are required to determine the optimal duration of benefit and the specific patient population that is most likely to benefit from this treatment.
Article
This population study describes the experience with primary intracerebral hemorrhage (PIH) in residents of Rochester, MN, for the 32-year period from 1945 through 1976. The average annual age-adjusted incidence rate for PIH was 12.1 per 100,000 population, and the incidence for all cases of spontaneous intracerebral hemorrhage was 15.2 per 100,000. The PIH rates were higher for males than for females, and they increased steadily with age. When patients on long-term anticoagulant therapy were excluded, there was a steady decrease in the average annual age-adjusted incidence rate for PIH in each succeeding 8-year interval since 1945. Prehemorrhage hypertension, present overall in 89% of patients, was much more frequent and severe in the earlier years of the study. The frequency and severity of prehemorrhage hypertension also varied inversely with age in the population with PIH. The median age at the onset of PIH increased from 65 years for the period 1945 through 1952 to 71 years for 1969 through 1976.
Article
The course of intracranial pressure (ICP) over time was studied in 66 hypertensive and/or altherosclerotic patients harboring intracerebral hematomas. Patients with no disturbance of consciousness showed normal or only slightly elevated pressure. Conversely, most patients in deep coma exhibited high pressure with a tendency to rise further no matter what treatment was used. In the remaining patients with intermediate disturbances of consciousness, no definite correlation was found between ICP, clinical condition, and outcome. In all of the patients who underwent operation, the postoperative course of ICP over time was also studied and seemed to depend to a certain extent on the timing of the operation.
Article
Data from 694 patients hospitalized with stroke were entered in a prospective, computer-based registry. Three hundred and sixty-four patients (53 percent) were diagnosed as having thrombosis, 215 (31 percent)as having cerebral embolism 70 (10 percent) as having intracerebral hematoma, and 45 (6 percent) as having subarachnoid hemorrhage from aneurysm or arteriovenous malformations. The 364 patients diagnosed as having thrombosis were divided into 233 (34 percent of all 694 patients) whose thrombosis was thought to involve a large artery and 131 (19 percent) with lacunar infarction. Many of the findings in this study were comparable to those in previous registries based on postmortem data. New observations include the high incidence of lacunes and cerebral emboli, the absence of an identifiable cardiac origin in 37 percent of all emboli, a nonsudden onset in 21 percent of emboli, and the occurrence of vomiting at onset in 51 percent and the absence of headache at onset in 67 percent of hematomas.
Article
Stroke is an important cause of death among blacks, and intracerebral and subarachnoid hemorrhages account for nearly half of all early deaths from stroke. The present study investigates whether blacks and whites differ in their risk of having either intracerebral or subarachnoid hemorrhage. We reviewed the medical records, autopsy reports, and CT scans of all patients suspected of having had an intracerebral or subarachnoid hemorrhage during 1988 among the nearly 1.3 million people in the Greater Cincinnati metropolitan area. There were 221 cases of first spontaneous intracranial hemorrhage among 1,086,462 whites (159 intracerebral and 62 subarachnoid hemorrhages), and 45 cases among 171,718 blacks (27 intracerebral and 18 subarachnoid hemorrhages). Blacks had 2.1 times the risk of subarachnoid hemorrhage of whites (95 percent confidence interval, 1.3 to 3.6) and 1.4 times the risk of intracerebral hemorrhage (95 percent confidence interval, 0.9 to 2.1). In those under the age of 75, the risk of intracerebral hemorrhage among blacks was 2.3 times that of whites (95 percent confidence interval, 1.5 to 3.6), whereas the risk among blacks 75 or older was one fourth that of whites (95 percent confidence interval, 0.1 to 0.8). Deaths within 30 days of intracerebral or subarachnoid hemorrhage accounted for 1.9 years of life lost per 1000 blacks under 65 years of age, as compared with 0.5 year per 1000 whites. Young and middle-aged blacks have a substantially higher risk of subarachnoid or intracerebral hemorrhage than whites of similar age. These types of stroke are important causes of excess mortality among young and middle-aged blacks.
Article
The incidence of cerebral haemorrhage was studied from a population-based stroke registry. The incidence was 12.3 per 100,000 per year in women and 13.9 per 100,000 per year in men, with a peak in the eighth decade and a male preponderance. Haemorrhages were deep seated and mostly due to hypertension. Recognised clinical characteristics of haemorrhage are acute onset, convulsion, vomiting, and disturbed consciousness. This study showed that cerebral haemorrhage may present with pure motor deficit or transient deficit preceding the stroke. The mortality was 51% in the first month, and 61% by two years.
Article
A lesion simulating intracerebral haemorrhage was produced in the right caudate nucleus of rats immunosuppressed with whole body or regional irradiation. Whole body irradiation produced significant leucopaenia and thrombocytopaenia and conferred protection against cerebral ischaemia and oedema when compared to nonirradiated control animals. Local radiation to the head or torso did not confer protection.
Article
The authors evaluate eight patients with intracerebral hemorrhage (ICH) who underwent computerized tomography (CT) within 2 1/2 hours after symptom onset and then again several hours later. The second CT scan was performed within 12 hours after onset for seven of the patients and 100 hours after onset for the eighth patient. In four patients, the second CT scan was obtained prospectively. The mean percentage of increase in the volume of hemorrhage between the first and second CT scans was 107% (range 1% to 338%). In each of the six patients with a greater than 40% increase in hemorrhage volume, neurological deterioration occurred soon after the first CT. A systolic blood pressure of 195 mm Hg or greater was recorded during the first 6 hours in five of the same six patients. The data from this study indicate that, in ICH, bleeding may continue after the 1st hour post-hemorrhage, particularly in patients with early clinical deterioration.
Article
We examined the relation between the serum total cholesterol level and the risk of death from stroke during six years of follow-up in 350,977 men, 35 to 57 years of age, who had no history of heart attack and were not currently being treated for diabetes mellitus. The diagnosis of stroke and the type of stroke were obtained from death certificates. Using proportional-hazards regression to control for age, cigarette smoking, diastolic blood pressure, and race or ethnic group, we found that the six-year risk of death from intracranial hemorrhage (International Classification of Diseases, ninth edition [ICD-9], categories 431 and 432) was three times higher in men with serum cholesterol levels under 4.14 mmol per liter (160 mg per deciliter) than in those with higher cholesterol levels (P = 0.05 by omnibus test across five cholesterol levels). On the other hand, a positive association was observed between the serum cholesterol level and death from nonhemorrhagic stroke (P = 0.007). The inverse association of the serum cholesterol level with the risk of death from intracranial hemorrhage was confined to men with diastolic blood pressure greater than or equal to 90 mm Hg, in whom death from intracranial hemorrhage is relatively common. We conclude that there is an inverse relation between the serum cholesterol level and the risk of death from hemorrhagic stroke in middle-aged American men, but that its public health impact is overwhelmed by the positive association of higher serum cholesterol levels with death from nonhemorrhagic stroke and total cardiovascular disease (ICD-9 categories 390 through 459).
Article
We studied the relations between reported alcohol use and the incidence of hospitalization for several types of cerebrovascular disease. Daily consumption of three or more drinks, but not lighter drinking, was related to higher hospitalization rates for hemorrhagic cerebrovascular disease, especially intracerebral hemorrhage. Age, blood pressure, and black race were other independent predictors of hemorrhagic events; higher blood pressure appeared to be a partial mediator of the relation between alcohol use and hemorrhagic events. Alcohol use was associated with lower hospitalization rates for occlusive cerebrovascular disease; an inverse relation was present in both sexes, whites and blacks, and for extracranial and intracerebral occlusive lesions. Other predictors of hospitalization for occlusive disease included age, blood pressure, smoking, blood glucose and total cholesterol concentrations, and baseline disease. Our data suggest that heavier drinking increases the risk of hemorrhagic cerebrovascular events, but that alcohol use may lessen the risk of occlusive lesions.
Article
A controlled randomized study of endoscopic evacuation versus medical treatment was performed in 100 patients with spontaneous supratentorial intracerebral (subcortical, putaminal, and thalamic) hematomas. Patients with aneurysms, arteriovenous malformations, brain tumors, or head injuries were excluded. Criteria for inclusion were as follows: patients' age between 30 and 80 years; a hematoma volume of more than 10 cu cm; the presence of neurological or consciousness impairment; the appropriateness of surgery from a medical and anesthesiological point of view; and the initiation of treatment within 48 hours after hemorrhage. The criteria of randomization were the location, size, and side of the hematoma as well as the patient's age, state of consciousness, and history of hypertension. Evaluation of outcome was performed 6 months after hemorrhage. Surgical patients with subcortical hematomas showed a significantly lower mortality rate (30%) than their medically treated counterparts (70%, p less than 0.05). Moreover, 40% of these patients had a good outcome with no or only a minimal deficit versus 25% in the medically treated group; the difference was statistically significant for operated patients with no postoperative deficit (p less than 0.01). Surgical patients with hematomas smaller than 50 cu cm made a significantly better functional recovery than did patients of the medically treated group, but had a comparable mortality rate. By contrast, patients with larger hematomas showed significantly lower mortality rates after operation but had no better functional recovery than the medically treated group. This effect from surgery was limited to patients in a preoperatively alert or somnolent state; stuporous or comatose patients had no better outcome after surgery. The outcome of surgical patients with putaminal or thalamic hemorrhage was no better than for those with medical treatment; however, there was a trend toward better quality of survival and chance of survival in the operated group.
Article
The dynamic changes in regional cerebral blood flow (rCBF), induced by a developing intracerebral hematoma, were studied in eight anesthetized monkeys. Hematomas were generated by allowing femoral arterial blood to enter the caudate nucleus via a stereotactically implanted needle. Intracranial pressure peaked at 51 +/- 8 mmHg at 3 minutes after the ictus, and remained high throughout the 3-hour procedure. Cerebral blood flow was significantly reduced in all brain regions for 1 hour after the ictus. The lowest rCBF values were recorded in the immediate clot penumbra and were below threshold levels for ischemic neuronal damage for 90 minutes after the hemorrhage.
Article
Seizures occurred in 19 of 112 patients (17%) with nontraumatic, supratentorial intracerebral hemorrhage (ICH). All seizures occurred at ICH onset; patients without seizures at hemorrhage onset remained seizure-free until the last recorded follow-up. Seizures were significantly associated with extension of blood into the cerebral cortex. We found no association between seizures and hemorrhage size or the presence of subarachnoid or intraventricular blood. These data suggest that (1) seizures, in ICH, occur at hemorrhage onset, (2) patients without seizures at hemorrhage onset are at very low risk for subsequent seizures during their hospitalization, (3) hemorrhage involving the cerebral cortex, regardless of site of origin, predisposes to seizures, and (4) the prophylactic use of anticonvulsants in the acute management of these patients appears unwarranted, especially in patients without cortical extension.
Article
The clinical findings and computerized tomography (CT) brain scans of 45 patients with supratentorial intracerebral hematomas were evaluated to determine the effect of hematoma location on the clinical course and outcome of the disease. The lesions were frontal in 18 patients, temporal or temporoparietal in 17, and parieto-occipital in 10. No patient with a frontal or parieto-occipital hematoma had clinical signs of transtentorial herniation at admission or subsequently, whereas seven (41%) of those with temporal or temporoparietal lesions had signs of herniation (p less than 0.05); three of these seven patients had an abnormal mental status, ipsilateral anisocoria, and lateralizing motor findings at admission, and four developed these signs within 12 hours after admission, necessitating urgent surgical intervention. The mean volume of the lesions estimated from the CT scans was similar in the three groups (frontal 47 +/- 28 cc; parieto-occipital 53 +/- 26 cc; temporal/temporoparietal 41 +/- 21 cc). None of the six patients with temporal or temporoparietal hematomas smaller than 30 cc had signs of tentorial herniation, compared with seven (64%) of 11 patients with larger hematomas (p less than 0.05); in six of these seven cases, the hematoma was caused by head injury. Patients with a temporal or temporoparietal hematoma had a worse outcome than those in the other two groups, and no patient with signs of tentorial herniation had a good outcome. Patients with temporal or temporoparietal hematomas appear to be at greater risk of brain-stem compression, especially if the lesion is larger than 30 cc and caused by head injury, than are those with hematomas in other sites. In such cases, prompt surgical intervention should be considered.
Article
An analysis was performed of 2,168 consecutive stroke patients who were examined by computed tomography and entered into a hospital-based stroke registry in Akita Prefecture, Japan. The occurrence of cerebral hemorrhage, cerebral infarction, and subarachnoid hemorrhage was 30, 55, and 14%, respectively. Age-specific rates of subarachnoid hemorrhage were higher in women than men; other types of stroke showed a preponderance in men. Total strokes increased in the winter; this seasonal difference was confined to cerebral hemorrhage. Putaminal hemorrhages predominated in the younger age groups; thalamic hemorrhage and cerebellar hemorrhage were predominant in the older age groups. The increased accuracy of the diagnosis of stroke subtypes by the use of computed tomography in this study is in contrast to other community-based epidemiologic studies that have relied solely on clinical diagnosis. This increased accuracy is seen to be the reason that new ratios of stroke subtype incidence have been identified.
Article
To evaluate the efficacy of dexamethasone for treatment of primary supratentorial intracerebral hemorrhage, we studied 93 patients 40 to 80 years old, using a double-blind randomized block design. After the subjects were stratified according to their level of consciousness (Glasgow Coma Scale), those with objectively documented primary supratentorial intracerebral hemorrhage were randomly assigned to either dexamethasone or placebo. For ethical reasons, three interim analyses were planned, to permit early termination of the trial if one study group did better than the other. During the third interim analysis, the death rate at the 21st day was identical in the two groups (dexamethasone vs. placebo, 21 of 46 vs. 21 of 47; chi-square = 0.01, P = 0.93). In contrast, the rate of complications (mostly infections and complications of diabetes) was much higher in the dexamethasone group (chi-square = 10.89, P less than 0.001), leading to early termination of the study. In the light of the absence of a demonstrable beneficial effect and the presence of a significant harmful effect, current practices of using dexamethasone for treatment of primary supratentorial hemorrhage should be reconsidered.
Article
A model of experimental intracerebral hemorrhage is described in which carefully controlled volumes of autologous blood were injected at arterial pressure into the caudate nucleus of the rat. A comparison of intracranial pressure changes and local cerebral blood flow (CBF) was made between three groups of rats, each receiving different injection volumes, and sham-operated control rats by monitoring intraventricular pressure and by obtaining quantitative autoradiographic measurements of CBF within 1 minute of the experimental hemorrhage. Cerebral blood flow was reduced both around the hematoma and in the surrounding brain. This change was strongly volume-dependent and was not accompanied by significant alterations in cerebral perfusion pressure. This finding suggests that the degree of ischemia at the time of an intracerebral bleed depends on the size of the lesion, and implicates local squeezing of the microcirculation by the hematoma, rather than a generalized alteration in perfusion pressure, as the cause of ischemia.
Article
Alcohol might contribute to stroke in several ways: induction of cardiac arrhythmias and cardiac wall motion abnormalities which predispose to cerebral embolism, induction of hypertension, enhancement of platelet aggregation and activation of the clotting cascade, and reduction of cerebral blood flow by stimulation of cerebral vascular smooth muscle contraction or by altering cerebral metabolism. While these pathophysiological mechanisms have gained enthusiastic experimental and theoretical support, the findings are preliminary and will require further large-scale clinical and epidemiological analyses to substantiate their roles as causal factors or potentiators of stroke. Documentation of measurable platelet and coagulation cascade abnormalities reported in healthy volunteers who have ingested alcohol will need to be confirmed on a broader scale in stroke patients with recent ethanol consumption. The risk of stroke in those with alcohol-induced atrial fibrillation and cardiomyopathy must be ascertained for the general population. While the experimental evidence is exciting and provocative, epidemiological evidence also suggests a link between alcohol consumption and stroke. Regular alcohol ingestion is associated with hypertension, fatal and nonfatal intracranial hemorrhage, cerebral infarction, and increased risk of death from stroke. Recent, less stringently controlled studies suggest that alcohol consumption is a risk factor for cerebral infarction in young adults with occasional ethanol intoxication and middle-aged women and young men with occasional alcohol intoxication and regular heavy drinking. Alcohol may also be a risk factor for subarachnoid hemorrhage.
Article
To better define the etiologic importance of hypertension for spontaneous intracerebral hemorrhage, hospital records were studied for all patients sustaining intracerebral hemorrhage during 1982 in the Cincinnati metropolitan area. Hypertension pre-dating the hemorrhage was present in 45% (69 of 154), as determined by history. A more inclusive definition of hypertension, combining those with a positive history with those found to have left ventricular hypertrophy by electrocardiogram or cardiomegaly by chest radiography, applied in 56% (87 of 154). The cases were compared to controls with and without hypertension derived from the NHANES II study of blood pressure (n = 16,204) to determine relative risk. For the presence of hypertension by history, the relative risk of intracerebral hemorrhage was 3.9 (95% confidence interval, 2.7 to 5.7). For the inclusive definition of hypertension, the relative risk was 5.4 (3.7 to 7.9). Relative risk was also determined for hypertension in blacks (= 4.4), age greater than 70 (= 7), prior cerebral infarction (= 22), and diabetes (= 3). We conclude that the term "hypertensive hemorrhage" should be used very selectively, particularly in whites, and propose that hypertension be viewed as one of several important risk factors for spontaneous intracerebral hemorrhage.
Article
The authors describe a new device for removal of intracerebral hematomas, based on the principle of stereotaxic evacuation of these lesions proposed in 1978 by Backlund and von Holst. The optimum parameters of stereotaxic aspiration, including speed of screw rotation and amount of suction, have been determined experimentally. Computerized tomography scanning was used to locate the hematoma site, to assess its volume, and to determine stereotaxic coordinates. A new method of preventing rebleeding is also described. This procedure was used to aspirate hematomas in 32 patients with spontaneous intracerebral hemorrhage, including one case caused by aneurysmal rupture and one secondary to rupture of an arteriovenous malformation. All patients were operated on in a severely comatose or semicomatose state. In all but four cases, the hematomas were almost totally removed. Three patients were operated on twice because of recurrent bleeding. The mortality rate for the series was 22%. A preliminary conclusion is made that this new method is safer and less traumatic than open surgery in most cases of severe intracerebral hematoma.
Article
The authors summarize the findings of previous studies relating to the natural history of aneurysms and arteriovenous malformations (AVM's). Ruptured aneurysms have their highest rate of rebleeding on Day 1, and at least 50% will rebleed during the 6 months after the first hemorrhage. Thereafter, the rate drops to at least 3% a year. This is the same rate as seen in anterior and posterior communicating artery aneurysms treated by anterior cerebral artery clipping and carotid ligation; these operations provide immediate protection but do not result in long-term diminution of the risk of rebleeding. Patients with unruptured incidental and unruptured multiple aneurysms rebleed at a rate of 1% per year, as do patients with subarachnoid hemorrhage of unknown etiology. The risk of rebleeding for AVM's is 3% a year.
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Two thirds of 56 patients suffering spontaneous cerebellar hemorrhage were responsive on admission. The diagnosis was made solely on clinical bases in the majority of cases. Timing and rate of clinical deterioration were unpredictable in individual cases, especially in the initial hours and days after onset. Fifty % of patients became comatose by 24 hr, and 75%, within one wk after onset. The results of surgical decompression were strongly influenced by preoperative mental status: 17% mortality for responsive and 75% for unresponsive patients. However, nine patients survived without undergoing surgical decompression. The results suggest that substantial improvement in the overall mortality could be made by immediate craniectomy and evacuation of hematoma in all patients encountered within 48 hr of onset, and in most within a wk after onset.