Frequency Of Intracerebral Hemorrhage Research Articles

Pharmaceutical management of hemorrhagic stroke: Optimizing outcomes following intracranial hemorrhage evacuation

Stroke can be mainly categorized into hemorrhagic and ischemic stroke. Intracerebral hemorrhage (ICH) is a subtype of hemorrhagic stroke that is caused due to unconstrained bleeding within the parenchyma of the brain. ICH is one of the major conditions that have a high rate of disease and a high rate of death in a given population. Risk factors for ICH emerged to be age, male gender, hypertension, and intake of alcohol in huge quantities. The frequency of ICH is increased where hypertension is mainly untreated. To improve the prognosis and outcomes of an ICH patient, we need to perform emergent evacuation of blood from the brain parenchyma and prevent edema formation while restricting further neuronal damage due to surgical intervention. Evidence-based guidelines exist for ICH and form the basis for a care framework. The pharmaceutical management of ICH from current literature includes an aggressive reduction in blood pressure, tranexamic acid use, and recombinant activated factor VII administration. In addition, advanced imaging, surgical evacuation of ICH, and minimally invasive surgery techniques for hematoma evacuation could provide great benefits to patients with a large ICH.

Chapter 13 - Hemorrhagic stroke

Hemorrhagic stroke comprises about 20% of all strokes, with intracerebral hemorrhage (ICH) being the most common type. Frequency of ICH is increased where hypertension is untreated. ICH in particularly has a disproportionately high risk of early mortality and long-term disability. Until recently, there has been a paucity of randomized controlled trials (RCTs) to provide evidence for the efficacy of various commonly considered interventions in ICH, including acute blood pressure management, coagulopathy reversal, and surgical hematoma evacuation. Evidence-based guidelines do exist for ICH and these form the basis for a framework of care. Current approaches emphasize control of extremely high blood pressure in the acute phase, rapid reversal of vitamin K antagonists, and surgical evacuation of cerebellar hemorrhage. Lingering questions, many of which are the topic of ongoing clinical research, include optimizing individual blood pressure targets, reversal strategies for newer anticoagulant medications, and the role of minimally invasive surgery. Risk stratification models exist, which derive from findings on clinical exam and neuroimaging, but care should be taken to avoid a self-fulfilling prophecy of poor outcome from limiting treatment due to a presumed poor prognosis. Cerebral venous thrombosis is an additional subtype of hemorrhagic stroke that has a unique set of causes, natural history, and treatment and is discussed as well.

Abstract WP30: Role of Solitaire in Endovascular treatment for Acute Serious Stroke Due to Intracranial In Situ Thrombosis (ROSE ASSIST study)

Background: Solitaire, a representative stent retriever, shows high performance in removing embolic clots; however, its reperfusion potential in intracranial atherosclerotic disease (ICAD)-related occlusions is rarely reported. In this ROSE ASSIST study, we hypothesized that Solitaire is as effective for removing in-situ thrombi in ICAD-related occlusions as much as its performance in cardiogenic or cryptogenic embolism. Methods: ASIAN KR, an observational multicenter registry (n=721) enrolling patients who underwent endovascular treatment for acute cervicocephalic artery occlusions, was retrospectively reviewed. Through blinded evaluations, ICAD-related (significant fixed focal stenosis observed at the occlusion site during endovascular treatment) and embolic (no or minimal stenosis observed) occlusions were classified. Among patients treated with Solitaire stent (n=373), exclusion criteria were as follows: onset to puncture time >720 min; occlusion etiology neither ICAD-related nor embolic; both ICAD-related occlusion and atrial fibrillation. Primary endpoint was successful reperfusion (modified Treatment In Cerebral Ischemia 2b-3) immediately after Solitaire stent retrieval. Comparative analyses were performed between embolic and ICAD-related occlusions (2:1 matched by propensity score; age, sex, onset to puncture time and primary endovascular method adjusted). Results: In total, 270 patients (embolic, 216; ICAD-related, 54) were included in the analyses. After propensity score matching, successful reperfusion rate following Solitaire stent treatment did not differ between etiologic groups (embolic, 77.8% vs. 68.5%, p=0.201). Although final successful reperfusion grade was similarly achieved between groups (83.3% vs. 75.9%, p=0.259), median number of endovascular methods was higher in ICAD-related occlusions (2 [interquartile range, 1-2] vs. 2 [2-3], p<0.001). The grade and frequency of intracerebral hemorrhagic transformation and subarachnoid hemorrhage did not differ between groups. Conclusions: The immediate reperfusion performance of Solitaire for ICAD-related occlusions was as substantial as for embolic occlusions although these occlusions more often needed other treatment methods.

Difference in de novo cerebral microbleed among direct oral anticoagulants

Background: Direct oral anticoagulants (DOACs) are widely applied to prevent stroke recurrence because of less frequency of intracerebral hemorrhage (ICH), but antithrombotic therapy can induce hemorrhagic adverse events, including cerebral microbleeds (CMBs). The relationship between DOACs and development of CMBs is unclear.

Low risk of ICH after reperfusion therapy in acute stroke patients treated with direct oral anti-coagulant

BackgroundThe safety of intravenous thrombolysis (IVT) and endovascular therapy (EVT) in patients treated with DOAC is unclear. We investigated whether recanalization therapy in patients treated with DOAC is safe. MethodsA nationwide, multicenter, retrospective cohort questionnaire survey was conducted to investigate the: (1) frequency of intracerebral hemorrhage (ICH) after recanalization therapy in patients treated with DOAC; (2) independent factors related to ICH; (3) relationship between last intake time of DOAC and ICH; and (4) comparison of ICH frequency between patients treated with DOAC, vitamin K antagonist (VKA), and no-anticoagulation (no-ACT) (control). ResultsOne hundred eighteen stroke centers returned the questionnaire and 100 patients (56 IVT alone, 29 EVT alone, and 15 both IVT and EVT) on DOAC were registered. The frequency of asymptomatic and symptomatic (≥4-point NIHSS score increase) ICH within 24h in DOAC patients were 18% and 2%, and were not different compared with the VKA and no-ACT groups (p=0.728; and p=0.626). On multivariate analysis, systolic blood pressure (OR, 1.04; p<0.001) and blood glucose (OR, 1.02; p=0.019) were independent factors for ICH. Among the 52 patients with a known last intake time of DOAC, the rate of ICH was higher in patients ≤4h from last intake than those >4h (38% vs. 10%, p=0.033). ConclusionsRisk of ICH after reperfusion therapy in patients treated with DOAC should be low. Systolic blood pressure, glucose level, and DOAC intake time appear to be factors for ICH.

Various meteorological conditions exhibit both immediate and delayed influences on the risk of stroke events: The HEWS-stroke study.

We hypothesized that meteorological conditions on the onset day and conditions on the former days may play important roles in the modulation of physical conditions. Associations of meteorological factors and their changes in former days with stroke onset are of interest. We conducted a multicenter retrospective study to evaluate the frequency of stroke events and their interaction with meteorological conditions and their daily changes. Acute stroke patients (n = 3935, 73.5±12.4 years, 1610 females) who were admitted to 7 stroke hospitals in three restricted areas were enrolled in this study. Poisson regression models involving time-lag variables was used to compare daily rates of stroke events with mean thermo-hydrological index (THI), atmospheric pressure, and their daily changes. We divided onset days into quintiles based on the THI, atmospheric pressure, and their daily changes for the last 7 days. The frequencies of ischemic stroke significantly increased when THI varied either cooler or warmer from a previous day (extremely cooler, risk ratio (RR) 1.19, 95% confidence interval (CI) 1.05 to 1.34; extremely warmer, RR 1.16, 95% CI 1.03 to 1.31; r2 = 0.001 for the best regression, p = 0.001). Intracerebral hemorrhage frequencies significantly decreased on high-THI days (extremely high, RR 0.72, 95% CI 0.54 to 0.95; r2 = 0.013 for the best regression, p<0.001) and increased in high atmospheric pressure days (high, RR 1.31, 95% CI 1.04 to 1.65; r2 = 0.009 for the best regression, p<0.001). Additionally, even after adjusting for the THI on the onset day and its changes for the other days, intracerebral hemorrhage increased when THI got extremely cooler in 4 days prior (RR 1.33, 95% CI 1.03 to 1.71, r2 = 0.006 for the best regression, p<0.001). Various meteorological conditions may exhibit influences on stroke onset. And, when temperature cooled, there may be a possibility to show delayed influence on the frequency of intracerebral hemorrhage 4 days later.

Clinical features of patients who died within 24 h after admission to a stroke care center.

ObjectiveIn Japan, stroke care is provided through medical cooperation and standardized treatment. However, various factors affect mortality in the hyperacute phase. The present study investigated factors associated with death within 24 h after admission for acute stroke.MethodsAmong 2335 patients admitted within 24 h after stroke onset from 1 January 2007 to 31 December 2012, a total of 139 deaths occurred. Forty-eight deaths occurred within 24 h after admission. We retrospectively examined the clinical features of these 48 patients.ResultsThe overall mortality rate was 6.0%. When the initial 72-h period was divided into ≤24 h (Period I), >24 to 48 h (Period II), and >48 to 72 h (Period III), deaths were significantly more frequent in Period I than in the other two periods. The frequency of intracerebral haemorrhage (ICH) was also significantly higher in Period I than in the other two periods. Factors significantly associated with death from ICH were systolic blood pressure, hematoma volume, and surgery.ConclusionThe mortality rate was low among patients with stroke transported to the authors’ medical center within 24 h of onset. Blood pressure management and the timing of determining indications for surgery are important factors in acute haemorrhagic stroke care.

Thrombolysis in Ischemic Strokes with no Arterial Occlusion

Twelve million people develop ischemic stroke each year world over and 30-40% of them do not have arterial occlusions at presentation. Trials conducted to study the efficacy of thrombolytic drug reported better outcome with use of thrombolytic drug but none studied the subtypes of ischemic strokes specifically and adequately. The subgroups of patients with no arterial occlusion at presentation continue to receive thrombolytic therapy without proven benefit and with some risk. The aim of this article is to study whether intravenous thrombolysis with alteplase improves clinical outcome in ischemic stroke patients who do not have arterial occlusion at presentation. A retrospective medical record-based observational multicenter, multinational study. Primary outcome measure would be clinical outcome at three-months from stroke onset measured by modified Rankin Scale and National Institute of Health Stroke Scale. Secondary outcome measure will be frequency of intracerebral hemorrhage causing worsening of clinical deficit defined as increase in National Institute of Health Stroke Scale by >4.

Stroke Characteristics and Outcomes of Adult Patients Admitted to the University Teaching Hospital, Lusaka, Zambia

Objectives: Despite the high burden of strokes globally and among people of African origin in particular, there are few available data on stroke in most countries of sub-Saharan Africa (SSA), including Zambia. The aim of this study was to describe the characteristics and outcomes of stroke in adult Zambian patients admitted to the University Teaching Hospital (UTH) in Lusaka. Methods: The study was conducted at the UTH, which is the only tertiary hospital in the country, from July to December 2010. Stroke was confirmed by neurological examination and CT scan of the brain. Participants were assessed for risk factors and severity of stroke. Outcome measures included in-hospital stroke mortality and disability (modified Rankin score and Glasgow outcome scale on discharge). Results: A total of 250 consecutive stroke patients were included in the study. Of these 162 (65%) patients had ischemic and 88 (35%) hemorrhagic strokes. The mean age was 55 ±18years. Hypertension was most common risk factor for both strokes. Other risk factors included: alcohol intake (32.6%), previous stroke (23.6%), family history of stroke (23.2%), HIV infection (25.4%), hypercholesterolemia (14%) andtobacco smoking/sniffing (13.4%). In-hospital stroke mortality was 40%. Factors independently associated with mortality were female sex, pneumonia, Glasgow Coma Scale (GCS) � 8 and stroke severity at admission. Conclusions: Stroke in Zambian patients occurs at a relatively young age and frequency of intracerebral hemorrhage is higher than that reported in developed countries. Hypertension is common risk factor for both types of strokes. Family history of stroke is one of important risk factor. In-hospital stroke mortality is high at UTH. HIV infection is independently associated with ischemic stroke.

Abstract 3665: COL4A1 and COL4A2 Mutations cause Genetically Modifiable Cerebrovascular Diseases

Mutations in the type IV collagen alpha 1 gene (COL4A1) cause Cerebrovascular Diseases (CVDs) in mice and human patients. Patients with COL4A1 mutations suffer from a broad range of CVDs, from infantile porencephaly to debilitating or fatal intracerebral hemorrhage (ICH), to subclinical cerebral microbleeds, suggesting that environmental and other genetic factors may influence their phenotypes. COL4A1 is one of the most abundant proteins in basement membranes and forms heterotrimers with COL4A2. Among possible pathogenic mechanisms are cellular stress due to the toxic intracellular aggregation of the COL4A1 and COL4A2 proteins and/or their absence in the basement membrane. Our first goal is to identify the relative contributions of COL4A1 and COL4A2 mutations to sporadic ICH and to understand the cellular mechanisms and genetic complexity underlying the disease. We identified novel COL4A1 mutations and for the first time, we discovered COL4A2 mutations in a cohort of 96 patients with sporadic ICH. Using a cell-based assay we determined that the mutations impair COL4A1 and COL4A2 secretion. We showed that mutant COL4A1 or COL4A2 proteins accumulate within the cell where they titrate normal COL4A1 and COL4A2 proteins. Interestingly, we found that some of the mutations can ultimately result in endoplasmic reticulum (ER) stress and activation of the Unfolded Protein Response. Our second goal was to test the hypothesis that differences in genetic context could contribute to phenotypic variability in human patients. Thus, we characterized CVD in Col4a1 mutant mice with two different genetic backgrounds. Using cerebral magnetic resonance imaging and histological analysis, we show that one or more genetic modifiers from the CAST/EiJ strain significantly reduce the size and frequency of ICHs detected in Col4a1 mutant mice on a C57BL/6J background. In conclusion, we found that both COL4A1 and COL4A2 mutations cause ICH in human patients, our results support that ER stress could be involved in the pathogenesis and we showed that genetic context is crucial for expressivity and severity of the CVD. We predict that ongoing experiments to better understand the cell biology of COL4A1 and COL4A2 mutations and the mechanisms of genetic modification could lead to targeted therapeutics to reduce the risk of CVD in patients with COL4A1 or COL4A2 mutations.

Variation in the Frequency of Intracerebral Haemorrhage and Ischaemic Stroke in China: A National, Multicentre, Hospital Register Study

Background: Intracerebral haemorrhage (ICH) accounts for about one third of all strokes in China, a proportion that is three times higher than in Western populations. We aimed to determine the frequency distribution of ICH in China. Methods: Using the ChinaQUEST hospital register database, the proportional frequency of ICH was determined by region and city location. Linear regression analysis was then performed to evaluate associations between the frequency of ICH and distribution of risk factors by city. Results: Proportional frequency of ICH was 25% overall, but varied markedly across major geographical regions ranging from 11 to 36%. The differences between cities were even more profound, with the age- and sex-standardised proportional frequencies ranging from 5% in Guangzhou to 55% in Baoji. Significant associations were found between the proportional frequency of ICH and history of diabetes, hyperlipidaemia, and a high body mass index. Notably, cities with higher frequencies of diabetic, hyperlipidaemic or overweight individuals tended to have lower frequencies of ICH. Conclusions: Considerable interregional variation in the distribution of ICH in China can be partially explained by differences in distribution of risk factors in the population.

Reliable Estimation of the Proportion of Minor Stroke Due to Intracerebral Haemorrhage

A previous hospital clinic-based study estimated that 3.5% of minor strokes are due to primary intracerebral haemorrhage, but the confidence intervals were wide. Moreover this figure may be an underestimate in older patients, who are less likely to be referred to secondary care, and who may have higher rates of intracerebral haemorrhage. Further studies are required to validate and increase the precision of this estimate and to determine any association with age, in order to plan appropriate services for minor stroke. We determined the frequency of intracerebral haemorrhage and haemorrhagic transformation of infarction in consecutive patients presenting with minor stroke (National Institute of Health Stroke Scale<or=3) in two separate cohorts: a population-based study (Oxford Vascular Study) scanned early with computed tomography, and a hospital-based stroke clinic cohort, scanned with magnetic resonance imaging. We then pooled these data in a meta-analysis with published data from similar studies identified from a systematic literature review. In the Oxford Vascular Study, of 334 cases with minor stroke (58% men, median age 75 years), 17 had intracerebral haemorrhage (5.1%, 95% confidence interval 3.2-8.0%) and four had haemorrhagic transformation of infarction (1.2%, 0.5-3.0%). In the hospital-clinic cohort, of 280 patients with minor stroke (59% men, median age 73 years), 15 had intracerebral haemorrhage (5.4%, 3.3-8.7%) and six had haemorrhagic transformation of infarction (2.1%, 1.0-4.6%). There was no trend for an increase in the frequency of intracerebral haemorrhage with age, with the lowest frequency in patients aged >or=85 years (0-3%). We identified only one previous study with a reliable estimate of the proportion of minor stroke due to intracerebral haemorrhage, and in a pooled analysis including 842 patients, the overall frequency of intracerebral haemorrhage was 4.8% (4.5-5.0%). We have shown that the proportion of minor stroke due to intracerebral haemorrhage was very similar in a population-based cohort and a hospital clinic-based cohort using different imaging strategies, and that the frequency is independent of age. A frequency of between 4.5 and 5.0% appears to be a reliable estimate at all ages.

Vessel ultrastructure in APP23 transgenic mice after passive anti-Aβ immunotherapy and subsequent intracerebral hemorrhage

Passive immunization of amyloid precursor protein (APP) transgenic mice with anti-amyloid beta (Aβ) antibodies was shown to reduce Aβ-deposition in brain and to improve cognition. However, immunotherapy may also be accompanied by a significant increase in the frequency of intracerebral hemorrhages. Because hemorrhages are associated with amyloid-laden vessels, this raises the question whether high concentrations of anti-Aβ antibodies may directly or indirectly lead to a structural destabilization of the vessel wall. To address this point, transmission electron microscopy was performed and the ultrastructure of bleeding and non-bleeding vessels in immunized and non-immunized APP23 transgenic animals was analyzed. To localize bleeding vessels, hemosiderin-positive macrophages were visualized by pre-embedding Perl's Berlin Blue histochemistry. Vessels were analyzed morphologically, anomalies evaluated and quantified. Bleeding vessels were, furthermore, reconstructed in three dimensions to analyze the spatial distribution of amyloid deposits and other pathological changes of the vessel wall. This in-depth morphological analysis revealed that bleeding vessels in immunized as well as in non-immunized APP23 mice were surrounded by a higher number of macrophages compared to non-bleeding vessels in the same animals. However, no differences in the number of macrophages or other structural parameters, such as amyloid deposition, were observed between bleeding vessels of immunized and non-immunized mice. No pathologies which may indicate impending bleeding were observed in the vascular wall of non-bleeding vessels. We conclude, that the increased hemorrhage frequency observed after passive immunization with anti-Aβ antibodies does not lead to overt structural changes in the vessel wall of APP23 transgenic mice. Minor structural alterations of the vessel wall, however, cannot be excluded due to the sample size of our study and the high complexity of the three-dimensional vessel wall ultrastructure.

Intracerebral hemorrhage in young people: analysis of risk factors, location, causes, and prognosis.

The frequency of intracerebral hemorrhages (ICHs) in people aged </=40 years has been poorly studied. We investigated the incidence, causes, locations, and prognosis of ICH in young patients. We evaluated all consecutive patients with neuroimaging evidence or pathological confirmation of symptomatic ICH. We excluded patients with primary subarachnoid or traumatic hemorrhage, past evidence of vascular malformation, or brain tumor. We analyzed the risk factors, number, locations, and causes of ICH, and final outcome measured by the modified Glasgow Outcome Scale. We retrospectively evaluated 200 patients (mean age, 27 years; range, 15 to 40 years). The most frequent risk factors were tobacco use (20%), hypocholesterolemia (35%), hypertension, (13%), and alcohol use (10%). The locations of ICH were lobar (55%), basal ganglia/internal capsule (22%), and others (24%). The most common causes of ICH were vascular malformations (49%), including cavernous angioma, and hypertension (11%). Cryptogenic ICH was considered in 15%. Other causes included cerebral venous thrombosis (5%) and sympathomimetic drug use (4%). The majority of patients with ICH that resulted from hypertension were aged >31 years (odds ratio, 3.48), and those with ICH that resulted from arteriovenous malformations were aged <20 years (odds ratio, 2.80). The final outcome was considered favorable in 60%. ICHs in young people are mainly lobar in location and result from vascular malformation. Hypertension causes most cases in which the ICH is located in the basal ganglia. Mortality and morbidity in the acute phase are low and are related to hypertension as the cause of ICH.

Intracerebral Haemorrhage in AIDS

We report 8 patients with the acquired immunodeficiency syndrome (AIDS) and intracerebral haemorrhage. There were 7 men and 1 woman (mean age 37.2 years) with a mean CD4 count of 81.2/mm³. Alcohol abuse was recorded in 7 patients, intravenous drug use in 4, homosexual activity in 2, thrombocytopaenia in 1 and severe hypertension in 1. There were 5 lobar and 3 deep haemorrhages. Potential aetiologies of intracerebral haemorrhage included cerebral toxoplasmosis (n = 2), thrombocytopenia (n = 2), hypertension (n = 1) and cerebral tuberculosis (n = 1). Data of these patients were compared with those of 30 AIDS inpatients without brain haemorrhage matched by age and sex and no statistically significant differences in risk factors for AIDS except for alcohol abuse (>80 g/day) (p = 0.045) were found. Causes of brain haemorrhage in AIDS patients are heterogeneous. The relationship between both conditions may be explained by the effect of several predisposing factors to stroke in association with AIDS-related complications. Intracerebral haemorrhage is a late and serious complication of AIDS (mortality 62.5%). The frequency of intracerebral haemorrhage in AIDS (1.0%) is higher than that expected in a general population of young adults.