The study of blood biomarkers can offer new possibilities in diagnostics, prognostication, determination of etiology, and management of spontaneous intracerebral hemorrhage. The aim of our study was to assess the relationship between a panel of selected blood biomarkers and clinical and radiodiagnostic parameters in patients with spontaneous intracerebral hemorrhage. Primarily, the aim was to find a prognostic biomarker which could help in deciding on the optimal categorization of treatment. A total of 70 patients were prospectively included in this study. As shown by our findings, higher levels of S100B protein are associated with larger hematoma volume. They predict hematoma progression and an unfavorable outcome. One other positive correlation was found between hematoma volume and interleukin 6, interleukin 10 and blood glucose. Lower levels of matrix metalloproteinase 9 are an independent prognostic factor for hematoma progression in patients with spontaneous intracerebral hemorrhage.

• Klíčová slova
• blood biomarkers, hematoma volume, prognostication, spontaneous intracerebral hemorrhage,
• MeSH
• biologické markery MeSH
• cerebrální krvácení * diagnostické zobrazování   MeSH
• hematom * MeSH
• lidé MeSH
• progrese nemoci MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• biologické markery MeSH

PURPOSE: Autonomic imbalance as measured by heart rate variability (HRV) has been associated with poor outcome after stroke. Observations on HRV changes in intracerebral hemorrhage (ICH) are scarce. Here, we aimed to investigate HRV in ICH as compared to a control group and to explore associations with stroke severity, hemorrhage volume and outcome after ICH. METHODS: We examined the autonomic modulation using frequency domain analysis of HRV during the acute phase of the ICH and in a healthy age- and hypertension-matched control group. Hematoma volume, intraventricular extension, initial stroke severity and baseline demographic, clinical parameters as well as mortality and functional outcome were included in the analysis. RESULTS: 47 patients with ICH and 47 age- and hypertension matched controls were analyzed. ICH patients showed significantly lower total high frequency band (HF) and low frequency band (LF) powers (p = 0.01, p < 0.001), higher normalized HF power (p = 0.03), and lower LF/HF ratio (p < 0.001) as compared to the controls. Autonomic parameters showed associations with stroke severity (p = 0.004) and intraventricular involvement (p = 0.01) and predicted poor outcome independently (p = 0.02). CONCLUSIONS: Autonomic changes seems to be present in acute ICH and are associated with poor outcome independently. This may have future monitoring and therapeutic implications.

• Klíčová slova
• Autonomic, Critical care, Heart rate variability, Intracerebral hemorrhage, Mortality, Outcome,
• MeSH
• autonomní nervový systém patofyziologie   MeSH
• cerebrální krvácení diagnóza   patofyziologie   MeSH
• cévní mozková příhoda patofyziologie   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• prognóza MeSH
• senioři MeSH
• srdeční frekvence fyziologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Clinical outcome after intracerebral hemorrhage (ICH) remains poor. Recent trials in ICH, focusing on hematoma reduction, have not yielded significant clinical improvement. The modulation of matrix metalloproteinase (MMP)-9 may represent a potential therapeutic target for reducing perihematomal edema (PHE) and improving clinical outcome. METHODS: We searched Cochrane Library, Ovid/Medline, and PubMed databases using combinations of the following MeSH search terms: "intracerebral hemorrhage," "matrix metalloproteinase," "minocycline," "inhibition," and "neuroprotection". RESULTS: MMP-9 levels in animal models have largely shown detrimental correlations with mortality, clinical outcome, hematoma volume, and PHE. Animal models and clinical studies have established a timeline for MMP-9 expression and corresponding PHE that include an initial peak on days 1-3 and a secondary peak on day 7. Clinical studies evaluating MMP-9 levels in the acute phase (days 1-3) and subacute phase (day 7) of ICH suggest that MMP-9 may be detrimental in the acute phase through destruction of basal lamina, activation of vascular endothelial growth factor, and activation of apoptosis but assist in recovery in the subacute phase through angiogenesis. CONCLUSIONS: MMP-9 inhibition represents a potentially effective target for neuroprotection in ICH. However, as a ubiquitous protein, the inhibition of pathologic processes must be balanced against the preservation of neuroprotective angiogenesis. As the opposing roles of MMP-9 may have similar mechanisms, the most important factor may be the timing of MMP-9 inhibition. Further studies are necessary to delineate these mechanisms and their temporal relationship.

• Klíčová slova
• Matrix metalloproteinase, blood brain barrier, gelatinase B, intracerebral hemorrhage, neuroprotection, perihematomal edema,
• MeSH
• apoptóza účinky léků   MeSH
• časové faktory MeSH
• cerebrální krvácení komplikace   farmakoterapie   metabolismus   mortalita   patologie   MeSH
• edém mozku farmakoterapie   metabolismus   mortalita   MeSH
• hematom farmakoterapie   metabolismus   mortalita   MeSH
• inhibitory matrixových metaloproteinas terapeutické užití   MeSH
• lidé MeSH
• matrixová metaloproteinasa 9 metabolismus   MeSH
• neuroprotektivní látky aplikace a dávkování   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• inhibitory matrixových metaloproteinas MeSH
• matrixová metaloproteinasa 9 MeSH
• neuroprotektivní látky MeSH

BACKGROUND AND OBJECTIVE: Intracerebral hemorrhage (ICH) is a serious medical condition with high mortality. However, factors leading to long-term mortality after ICH are largely unclear. The aim of this community-based study is to assess predictors of long-term mortality after spontaneous ICH. METHODS: We identified all patients admitted with spontaneous ICH to hospitals with a certified stroke unit in Brno, the second largest city in the Czech Republic (CR), in 2011, the year of the Czech Population and Housing Census. We reviewed their medical records for risk factors, radiographic parameters, and measures of post-stroke neurological deficit [National Institutes of Health Stroke Scale (NIHSS)]. Using the dates of death from the Czech National Mortality Register, we calculated mortality at 30 days, six months, one year, and three years after the ICH. Multivariate analysis with forward stepwise logistic regression was performed to determine independent predictors of mortality (p < 0.05). RESULTS: In 2011, 1086 patients with stroke were admitted to the four stroke-certified hospitals in Brno, CR. Of these, 134 had spontaneous ICH, with complete data available in 93 of them entering the final analysis. The mortality at 30 days, 6 months, 1 year, and 3 years post-ICH was 34%, 47%, 51%, and 63%, respectively. The mortality was highest in the first few days post-event, with 50% of patients dying in 255 days and average survival being 884 ± 90 days. Both NIHSS and modified ICH (MICH) score showed to be strong and reliable predictors of short- as well as long-term mortality; the risk of death post-ICH increased with older age and size of ICH. Other risk factors contributing to higher, primarily shorter-term mortality included history of cardiac failure, myocardial infarction, or atrial fibrillation. CONCLUSIONS: In our community-based study, we found that severity of neurological deficit at admission (NIHSS), combined with age and size of ICH, well predicted short- as well as long-term mortality after spontaneous ICH. A history of cardiac failure, myocardial infarction, or atrial fibrillation at presentation were also predictors of mortality, underscoring the need for optimal cardiac management in patients with ICH.

• Klíčová slova
• Community-based study, Czech Republic, Intracerebral hemorrhage, Mortality,
• MeSH
• cerebrální krvácení * mortalita   MeSH
• lidé středního věku MeSH
• lidé MeSH
• retrospektivní studie MeSH
• rizikové faktory MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH

OBJECTIVE: The aim of the present systematic review and meta-analysis was to evaluate the safety and efficacy of intensive blood pressure (BP) reduction in patients with acute-onset intracerebral hemorrhage (ICH) using data from randomized controlled trials. METHODS: We conducted a systematic review and meta-analysis according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines of all available randomized controlled trials that randomized patients with acute ICH to either intensive or guideline BP-reduction protocols. RESULTS: We identified 4 eligible studies, including a total of 3,315 patients (mean age 63.4 ± 1.4 years, 64% men). Death rates were similar between patients randomized to intensive BP-lowering treatment and those receiving guideline BP-lowering treatment (odds ratio = 1.01, 95% confidence interval: 0.83-1.23; p = 0.914). Intensive BP-lowering treatment tended to be associated with lower 3-month death or dependency (modified Rankin Scale grades 3-6) compared with guideline treatment (odds ratio = 0.87, 95% confidence interval: 0.76-1.01; p = 0.062). No evidence of heterogeneity between estimates (I(2) = 0%; p = 0.723), or publication bias in the funnel plots (p = 0.993, Egger statistical test), was detected. Intensive BP reduction was also associated with a greater attenuation of absolute hematoma growth at 24 hours (standardized mean difference ± SE: -0.110 ± 0.053; p = 0.038). CONCLUSIONS: Our findings indicate that intensive BP management in patients with acute ICH is safe. Fewer intensively treated patients had unfavorable 3-month functional outcome although this finding did not reach significance. Moreover, intensive BP reduction appears to be associated with a greater attenuation of absolute hematoma growth at 24 hours.

• MeSH
• antihypertenziva terapeutické užití   MeSH
• cerebrální krvácení komplikace   farmakoterapie   MeSH
• hypertenzní intrakraniální krvácení farmakoterapie   etiologie   MeSH
• krevní tlak účinky léků   fyziologie   MeSH
• lidé MeSH
• MEDLINE statistika a číselné údaje   MeSH
• randomizované kontrolované studie jako téma statistika a číselné údaje   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• systematický přehled MeSH
• Názvy látek
• antihypertenziva MeSH

BACKGROUND: Providing the correct level of care for patients with intracerebral hemorrhage (ICH) is crucial, but the level of care needed at initial presentation may not be clear. This study evaluated factors associated with admission to intensive care unit (ICU) level of care. METHODS: This is an observational study of all adult patients admitted to our institution with non-traumatic supratentorial ICH presenting within 72 h of symptom onset between 2009-2012 (derivation cohort) and 2005-2008 (validation cohort). Factors associated with neuroscience ICU admission were identified via logistic regression analysis, from which a triage model was derived, refined, and retrospectively validated. RESULTS: For the derivation cohort, 229 patients were included, of whom 70 patients (31 %) required ICU care. Predictors of neuroscience ICU admission were: younger age [odds ratio (OR) 0.94, 95 % CI 0.91-0.97; p = 0.0004], lower Full Outline of UnResponsiveness (FOUR) score (0.39, 0.28-0.54; p < 0.0001) or Glasgow Coma Scale (GCS) score (0.55, 0.45-0.67; p < 0.0001), and larger ICH volume (1.04, 1.03-1.06; p < 0.0001). The model was further refined with clinician input and the addition of intraventricular hemorrhage (IVH). GCS was chosen for the model rather than the FOUR score as it is more widely used. The proposed triage ICH model utilizes three variables: ICH volume ≥30 cc, GCS score <13, and IVH. The triage ICH model predicted the need for ICU admission with a sensitivity of 94.3 % in the derivation cohort [area under the curve (AUC) = 0.88; p < 0.001] and 97.8 % (AUC = 0.88) in the validation cohort. CONCLUSIONS: Presented are the derivation, refinement, and validation of the triage ICH model. This model requires prospective validation, but may be a useful tool to aid clinicians in determining the appropriate level of care at the time of initial presentation for a patient with a supratentorial ICH.

• Klíčová slova
• Intensive care, Intracerebral hemorrhage, Triage,
• MeSH
• cerebrální krvácení diagnóza   diagnostické zobrazování   terapie   MeSH
• Glasgowská stupnice následků * MeSH
• intraventrikulární krvácení do mozku diagnóza   terapie   MeSH
• jednotky intenzivní péče statistika a číselné údaje   MeSH
• lidé středního věku MeSH
• lidé MeSH
• modely neurologické MeSH
• příjem pacientů statistika a číselné údaje   MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• třídění pacientů metody   normy   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH

BACKGROUND AND PURPOSE: Spontaneous intracerebral hemorrhage is a major cause of death and disability, yet there is no convincing evidence of the benefit of any medical treatment and the role of surgery remains controversial. The international randomized Surgical Trial in Intracerebral Hemorrhage (STICH) provided an opportunity to assess the role of surgery within the centers taking part. METHODS: Screening logs were completed to record details of all patients assessed by the department, whether they were included in the trial, the reasons if they were not included, and whether they underwent surgery. RESULTS: Logs were returned by 42 centers and cover 704 months. They include details on 1578 patients with characteristics comparable to STICH inclusion criteria. Neurosurgeons were more likely to express clinical certainty about treatment for older patients, patients with a higher Glasgow Coma Score scale, and patients in whom the hematoma was located on the right or in the basal ganglia or thalamus. Patients for whom the neurosurgeon was certain about treatment were more likely to have the hematoma removed if they were younger (62 versus 68 years of age), had a lower Glasgow Coma Scale score (10 versus 13), and had a lobar hematoma (49% versus 40%). The operation rate varied between 74% in Lithuania and 2% in Hungary. CONCLUSIONS: The difference in operation rates could not be explained by differences in patient characteristics alone. This finding demonstrates the need for further evidence to ensure that treatment for intracerebral hemorrhage is not governed by local custom.

• MeSH
• akutní nemoc MeSH
• cerebrální krvácení diagnóza   chirurgie   MeSH
• chorobopisy statistika a číselné údaje   MeSH
• Glasgowská stupnice kómat MeSH
• lékařská praxe - způsoby provádění * MeSH
• lidé MeSH
• logistické modely MeSH
• neurochirurgické výkony statistika a číselné údaje   trendy   MeSH
• prospektivní studie MeSH
• randomizované kontrolované studie jako téma * statistika a číselné údaje   MeSH
• věkové faktory MeSH
• výběr pacientů * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Belgie MeSH
• Česká republika MeSH
• Japonsko MeSH
• Litva MeSH
• Maďarsko MeSH
• Německo MeSH
• Polsko MeSH
• Řecko MeSH
• Rusko MeSH
• Španělsko MeSH
• Spojené království MeSH
• Švédsko MeSH

BACKGROUND: Patients with acute intracerebral hemorrhage who are receiving factor Xa inhibitors have a risk of hematoma expansion. The effect of andexanet alfa, an agent that reverses the effects of factor Xa inhibitors, on hematoma volume expansion has not been well studied. METHODS: We randomly assigned, in a 1:1 ratio, patients who had taken factor Xa inhibitors within 15 hours before having an acute intracerebral hemorrhage to receive andexanet or usual care. The primary end point was hemostatic efficacy, defined by expansion of the hematoma volume by 35% or less at 12 hours after baseline, an increase in the score on the National Institutes of Health Stroke Scale of less than 7 points (scores range from 0 to 42, with higher scores indicating worse neurologic deficit) at 12 hours, and no receipt of rescue therapy between 3 hours and 12 hours. Safety end points were thrombotic events and death. RESULTS: A total of 263 patients were assigned to receive andexanet, and 267 to receive usual care. Efficacy was assessed in an interim analysis that included 452 patients, and safety was analyzed in all 530 enrolled patients. Atrial fibrillation was the most common indication for factor Xa inhibitors. Of the patients receiving usual care, 85.5% received prothrombin complex concentrate. Hemostatic efficacy was achieved in 150 of 224 patients (67.0%) receiving andexanet and in 121 of 228 (53.1%) receiving usual care (adjusted difference, 13.4 percentage points; 95% confidence interval [CI], 4.6 to 22.2; P = 0.003). The median reduction from baseline to the 1-to-2-hour nadir in anti-factor Xa activity was 94.5% with andexanet and 26.9% with usual care (P<0.001). Thrombotic events occurred in 27 of 263 patients (10.3%) receiving andexanet and in 15 of 267 (5.6%) receiving usual care (difference, 4.6 percentage points; 95% CI, 0.1 to 9.2; P = 0.048); ischemic stroke occurred in 17 patients (6.5%) and 4 patients (1.5%), respectively. There were no appreciable differences between the groups in the score on the modified Rankin scale or in death within 30 days. CONCLUSIONS: Among patients with intracerebral hemorrhage who were receiving factor Xa inhibitors, andexanet resulted in better control of hematoma expansion than usual care but was associated with thrombotic events, including ischemic stroke. (Funded by Alexion AstraZeneca Rare Disease and others; ANNEXA-I ClinicalTrials.gov number, NCT03661528.).

• MeSH
• akutní nemoc MeSH
• cerebrální krvácení * farmakoterapie   chemicky indukované   MeSH
• faktor Xa * terapeutické užití   škodlivé účinky   MeSH
• fibrilace síní farmakoterapie   komplikace   MeSH
• hematom * chemicky indukované   farmakoterapie   MeSH
• inhibitory faktoru Xa * škodlivé účinky   terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• rekombinantní proteiny * terapeutické užití   škodlivé účinky   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH

Α limited number of genetic variants have been linked to the development of intracerebral hemorrhage (ICH). Ιntegrin AV and/or B8-deficient mice were found to develop ICH. The present candidate gene association study was designed to investigate possible influence of integrin AV (ITGAV) and integrin B8 (ITGB8) gene region polymorphisms on the risk of ICH. 1015 participants (250 Greek and 193 Polish patients with primary ICH and 250 Greek and 322 Polish controls) were included in the study. Using logistic regression analyses, 11 tag single nucleotide polymorphisms (SNPs) for ITGAV and 11 for ITGB8 gene were tested for associations with ICH risk, lobar ICH risk and non-lobar ICH after adjustment for age, gender, history of hypertension and country of origin. Linear regression models were used to test the effect of tag SNPs on the ICH age of onset. Correction for multiple comparisons was carried out. The rs7565633 tag SNP of the ITGAV gene was independently associated with the risk of lobar ICH in the codominant model of inheritance [odds ratio (95 % confidence interval (CI)) 0.56 (0.36-0.86), p = 0.0013]. Furthermore, heterozygous individuals of the rs10251386 and the rs10239099 of the ITGB8 gene had significantly lower age of ICH onset compared to the wild-type genotypes [regression coefficient (b) -3.884 (95 % CI -6.519, -1.249), p = 0.0039 and b = -4.502 (95 % CI -7.159, -1.845), p = 0.0009, respectively]. The present study provides preliminary indication for an influence of ITGAV gene tag SNP in the development of lobar ICH and of ITGB8 gene variants in the age of ICH onset.

• Klíčová slova
• ITGAV, ITGB8, Integrins, Intracerebral hemorrhage, Polymorphism, Tag SNPs,
• MeSH
• beta řetězce integrinu genetika   MeSH
• cerebrální krvácení etnologie   genetika   MeSH
• frekvence genu MeSH
• genetická predispozice k nemoci MeSH
• genotyp MeSH
• integrin alfaV genetika   MeSH
• jednonukleotidový polymorfismus * MeSH
• lidé středního věku MeSH
• lidé MeSH
• mozková kůra krevní zásobení   MeSH
• rizikové faktory MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• věk při počátku nemoci MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Polsko epidemiologie   MeSH
• Řecko epidemiologie   MeSH
• Názvy látek
• beta řetězce integrinu MeSH
• integrin alfaV MeSH
• integrin beta8 MeSH Prohlížeč

OBJECTIVE: Whether intracerebral hemorrhage (ICH) associated with non-vitamin K antagonist oral anticoagulants (NOAC-ICH) has a better outcome compared to ICH associated with vitamin K antagonists (VKA-ICH) is uncertain. METHODS: We performed a systematic review and individual patient data meta-analysis of cohort studies comparing clinical and radiological outcomes between NOAC-ICH and VKA-ICH patients. The primary outcome measure was 30-day all-cause mortality. All outcomes were assessed in multivariate regression analyses adjusted for age, sex, ICH location, and intraventricular hemorrhage extension. RESULTS: We included 7 eligible studies comprising 219 NOAC-ICH and 831 VKA-ICH patients (mean age = 77 years, 52.5% females). The 30-day mortality was similar between NOAC-ICH and VKA-ICH (24.3% vs 26.5%; hazard ratio = 0.94, 95% confidence interval [CI] = 0.67-1.31). However, in multivariate analyses adjusting for potential confounders, NOAC-ICH was associated with lower admission National Institutes of Health Stroke Scale (NIHSS) score (linear regression coefficient = -2.83, 95% CI = -5.28 to -0.38), lower likelihood of severe stroke (NIHSS > 10 points) on admission (odds ratio [OR] = 0.50, 95% CI = 0.30-0.84), and smaller baseline hematoma volume (linear regression coefficient = -0.24, 95% CI = -0.47 to -0.16). The two groups did not differ in the likelihood of baseline hematoma volume < 30cm3 (OR = 1.14, 95% CI = 0.81-1.62), hematoma expansion (OR = 0.97, 95% CI = 0.63-1.48), in-hospital mortality (OR = 0.73, 95% CI = 0.49-1.11), functional status at discharge (common OR = 0.78, 95% CI = 0.57-1.07), or functional status at 3 months (common OR = 1.03, 95% CI = 0.75-1.43). INTERPRETATION: Although functional outcome at discharge, 1 month, or 3 months was comparable after NOAC-ICH and VKA-ICH, patients with NOAC-ICH had smaller baseline hematoma volumes and less severe acute stroke syndromes. Ann Neurol 2018;84:702-712.

• MeSH
• antikoagulancia aplikace a dávkování   škodlivé účinky   MeSH
• aplikace orální MeSH
• cerebrální krvácení chemicky indukované   mortalita   patologie   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• neurozobrazování MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• vitamin K antagonisté a inhibitory   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• Názvy látek
• antikoagulancia MeSH
• vitamin K MeSH