[Pediatric drug development: ICH harmonized tripartite guideline E11 within the United States of America, the European Union, and Japan].

PubMed

Pflieger, M; Bertram, D

2014-10-01

To address the lack of appropriate pediatric drugs available on the global market, in 2000 the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) issued the ICH E11 guideline regarding the Clinical Investigation of Medicinal Products in the Pediatric Population. This guideline considerably changes the environment of drug development for children. It has been written specifically to harmonize, promote, and facilitate high-quality and ethical clinical research for children within the ICH regions, i.e., the United States of America (USA), the European Union (EU), and Japan. This article details the various regulations applicable in each ICH region following the publication of the guideline. The framework of rewards, incentives, and obligations for pharmaceutical companies established for the development of pediatric drugs are compared. It appears that the USA and the EU have both developed specific regulations for pediatric drug development while Japan has not. However, in Japan, pharmaceutical companies (PCs) are encouraged to develop pediatric drugs voluntarily, and they may be granted additional months of market exclusivity or the postponement of the drug re-examination deadline. In both the USA and the EU, regulations aimed to increase the number of clinical studies conducted in children, in order to ensure that the necessary data are generated, determining the conditions in which a drug may be authorized to treat the pediatric population. PCs are encouraged to develop pediatric assessment, including pediatric clinical trials, which is described in a pediatric plan submitted to the relevant authorities. A system of rewards for PCs submitting an application for marketing authorization containing pediatric use information has been put in place to cover the additional investment for testing drugs in children. Subject to conditions, these rewards consist in a 6-month extension of the patent or

Intracerebral hemorrhage (ICH) evaluation with a novel magnetic induction sensor: a preliminary study using the Chinese head model.

PubMed

Zhang, Ziyi; Liu, Peiguo; Zhou, Dongming; Zhang, Liang; Lei, Hengdong

2014-01-01

Biomedical magnetic induction measurement is a promising method for the detection of intracerebral hemorrhage (ICH), especially in China. Aiming at overcoming the problem of low sensitivity, a magnetic induction sensor is chosen to replace the conventional sensors. It uses a two-arm Archimedean spiral coil as the exciter and a circular coil as the receiver. In order to carry out high-fidelity simulations, the Chinese head model with real anatomical structure is introduced into this novel sensor for the first time. Simulations have been carried out upon early stage ICH measurements. By calculating the state sensitivity and time sensitivity of the perturbation phase of two types of sensors using the electromagnetic software, we conclude that the primary signal received can be largely reduced using the novel sensor, which could effectively increase the time and state sensitivity simultaneously.

A multi-site comparison of in vivo safety pharmacology studies conducted to support ICH S7A & B regulatory submissions.

PubMed

Ewart, Lorna; Milne, Aileen; Adkins, Debbie; Benjamin, Amanda; Bialecki, Russell; Chen, Yafei; Ericsson, Ann-Christin; Gardner, Stacey; Grant, Claire; Lengel, David; Lindgren, Silvana; Lowing, Sarah; Marks, Louise; Moors, Jackie; Oldman, Karen; Pietras, Mark; Prior, Helen; Punton, James; Redfern, Will S; Salmond, Ross; Skinner, Matt; Some, Margareta; Stanton, Andrea; Swedberg, Michael; Finch, John; Valentin, Jean-Pierre

2013-01-01

Parts A and B of the ICH S7 guidelines on safety pharmacology describe the in vivo studies that must be conducted prior to first time in man administration of any new pharmaceutical. ICH S7A requires a consideration of the sensitivity and reproducibility of the test systems used. This could encompass maintaining a dataset of historical pre-dose values, power analyses, as well as a demonstration of acceptable model sensitivity and robust pharmacological validation. During the process of outsourcing safety pharmacology studies to Charles River Laboratories, AstraZeneca set out to ensure that models were performed identically in each facility and saw this as an opportunity to review the inter-laboratory variability of these essential models. The five in vivo studies outsourced were the conscious dog telemetry model for cardiovascular assessment, the rat whole body plethysmography model for respiratory assessment, the rat modified Irwin screen for central nervous system assessment, the rat charcoal meal study for gastrointestinal assessment and the rat metabolic cage study for assessment of renal function. Each study was validated with known reference compounds and data were compared across facilities. Statistical power was also calculated for each model. The results obtained indicated that each of the studies could be performed with comparable statistical power and could achieve a similar outcome, independent of facility. The consistency of results obtained from these models across multiple facilities was high thus providing confidence that the models can be run in different facilities and maintain compliance with ICH S7A and B. Copyright © 2013 Elsevier Inc. All rights reserved.

Workshop on High Power ICH Antenna Designs for High Density Tokamaks

NASA Astrophysics Data System (ADS)

Aamodt, R. E.

1990-02-01

A workshop in high power ICH antenna designs for high density tokamaks was held to: (1) review the data base relevant to the high power heating of high density tokamaks; (2) identify the important issues which need to be addressed in order to ensure the success of the ICRF programs on CIT and Alcator C-MOD; and (3) recommend approaches for resolving the issues in a timely realistic manner. Some specific performance goals for the antenna system define a successful design effort. Simply stated these goals are: couple the specified power per antenna into the desired ion species; produce no more than an acceptable level of RF auxiliary power induced impurities; and have a mechanical structure which safely survives the thermal, mechanical and radiation stresses in the relevant environment. These goals are intimately coupled and difficult tradeoffs between scientific and engineering constraints have to be made.

A consortium-driven framework to guide the implementation of ICH M7 Option 4 control strategies.

PubMed

Barber, Chris; Antonucci, Vincent; Baumann, Jens-Christoph; Brown, Roland; Covey-Crump, Elizabeth; Elder, David; Elliott, Eric; Fennell, Jared W; Gallou, Fabrice; Ide, Nathan D; Jordine, Guido; Kallemeyn, Jeffrey M; Lauwers, Dirk; Looker, Adam R; Lovelle, Lucie E; McLaughlin, Mark; Molzahn, Robert; Ott, Martin; Schils, Didier; Oestrich, Rolf Schulte; Stevenson, Neil; Talavera, Pere; Teasdale, Andrew; Urquhart, Michael W; Varie, David L; Welch, Dennie

2017-11-01

The ICH M7 Option 4 control of (potentially) mutagenic impurities is based on the use of scientific principles in lieu of routine analytical testing. This approach can reduce the burden of analytical testing without compromising patient safety, provided a scientifically rigorous approach is taken which is backed up by sufficient theoretical and/or analytical data. This paper introduces a consortium-led initiative and offers a proposal on the supporting evidence that could be presented in regulatory submissions. Copyright © 2017 Elsevier Inc. All rights reserved.

Establishing best practise in the application of expert review of mutagenicity under ICH M7.

PubMed

Barber, Chris; Amberg, Alexander; Custer, Laura; Dobo, Krista L; Glowienke, Susanne; Van Gompel, Jacky; Gutsell, Steve; Harvey, Jim; Honma, Masamitsu; Kenyon, Michelle O; Kruhlak, Naomi; Muster, Wolfgang; Stavitskaya, Lidiya; Teasdale, Andrew; Vessey, Jonathan; Wichard, Joerg

2015-10-01

The ICH M7 guidelines for the assessment and control of DNA reactive (mutagenic) impurities in pharmaceuticals allows for the consideration of in silico predictions in place of in vitro studies. This represents a significant advance in the acceptance of (Q)SAR models and has resulted from positive interactions between modellers, regulatory agencies and industry with a shared purpose of developing effective processes to minimise risk. This paper discusses key scientific principles that should be applied when evaluating in silico predictions with a focus on accuracy and scientific rigour that will support a consistent and practical route to regulatory submission. Copyright © 2015 Elsevier Inc. All rights reserved.

Safety assessment of biotechnology-derived pharmaceuticals: ICH and beyond.

PubMed

Serabian, M A; Pilaro, A M

1999-01-01

Many scientific discussions, especially in the past 8 yr, have focused on definition of criteria for the optimal assessment of the preclinical toxicity of pharmaceuticals. With the current overlap of responsibility among centers within the Food and Drug Administration (FDA), uniformity of testing standards, when appropriate, would be desirable. These discussions have extended beyond the boundaries of the FDA and have culminated in the acceptance of formalized, internationally recognized guidances. The work of the International Committee on Harmonisation (ICH) and the initiatives developed by the FDA are important because they (a) represent a consensus scientific opinion, (b) promote consistency, (c) improve the quality of the studies performed, (d) assist the public sector in determining what may be generally acceptable to prepare product development plans, and (e) provide guidance for the sponsors in the design of preclinical toxicity studies. Disadvantages associated with such initiatives include (a) the establishment of a historical database that is difficult to relinquish, (b) the promotion of a check-the-box approach, i.e., a tendancy to perform only the minimum evaluation required by the guidelines, (c) the creation of a disincentive for industry to develop and validate new models, and (d) the creation of state-of-the-art guidances that may not allow for appropriate evaluation of novel therapies. The introduction of biotechnology-derived pharmaceuticals for clinical use has often required the application of unique approaches to assessing their safety in preclinical studies. There is much diversity among these products, which include the gene and cellular therapies, monoclonal antibodies, human-derived recombinant regulatory proteins, blood products, and vaccines. For many of the biological therapies, there will be unique product issues that may require specific modifications to protocol design and may raise additional safety concerns (e.g., immunogenicity

ICH E14 Q & A (R1) document: perspectives on the updated recommendations on thorough QT studies.

PubMed

Shah, Rashmi R; Morganroth, Joel

2013-04-01

The International Conference on Harmonization (ICH) guidance ICH E14 provides recommendations, focusing on a clinical 'thorough QT/QTc (TQT) study', to evaluate the QT liability of a drug during its development. An Implementation Working Group (IWG) was also established to assist the sponsors with any uncertainties and clarify any ambiguities. In April 2012, the IWG updated its June 2008 version of the Questions and Answers document to address additional issues. These include the gender of the study population, a reasonable approach to evaluating QTc changes in late stage clinical development and the recommended approach to correcting the measured QT interval. This commentary provides our observations and, when appropriate, recommendations, on these issues. We review briefly evidence that suggests that (i) the greater QT effect observed in females is not entirely related to differences in drug exposure and (ii) the Fridericia correction of measured QT interval is adequate for a majority of TQT studies. Until further evidence suggests otherwise, we recommend balanced gender representation in TQT studies, unless warranted otherwise, and for positive studies, subgroup analysis of key data by common demographic variables including the gender and ethnicity. We provide a general scheme for ECG monitoring in late phase clinical trials and consider that while intensive monitoring and centralized reading of ECGs in late phase clinical trials is the norm when a TQT study is positive, there are other circumstances that also call for high quality ECG reading. Therefore, locally read ECGs should only be acceptable as long as accurate high quality ECG data can be guaranteed. © 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.

Regulatory incentives to ensure better medicines for older people: From ICH E7 to the EMA reflection paper on quality aspects.

PubMed

van Riet-Nales, Diana A; Hussain, Nasir; Sundberg, Katarina A E; Eggenschwyler, Doris; Ferris, Cristina; Robert, Jean-Louis; Cerreta, Francesca

2016-10-30

Ageing comes with an increased propensity in the alteration of human organ and body functions, which can e.g. result in multi-morbidity, frailty, polypharmacy, altered medication safety and/or efficacy, and problems with the practical use of medicines in a real world setting. Such problems may e.g. involve difficulties opening containers, swallowing large tablets, breaking tablets by hand, or correctly understanding the user instruction. This review aims to summarize the European regulatory activities towards better medicines for older people, with a main focus on formulation development and the overall drug product design. It addresses the ICH E7 guideline "Studies in support of special populations, geriatrics", the ICH Q8 guideline "Pharmaceutical development", the EMA good practice guide on "Risk minimisation and prevention of medication errors" and the forthcoming EMA CHMP QWP reflection paper on the "Quality aspects (pharmaceutical development) of medicines for older people". In addition, three key aspects to the practical use of medicines by older people are discussed in a wider context: multi-particulates including small tablets (also referred to as mini-tablets), ease of opening and storage conditions. Furthermore, attention is paid to work in progress e.g. incentives by the European national drug regulatory authorities, and patient centric drug product development. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Prediction and prognostication of neurological deterioration in patients with acute ICH: a hospital-based cohort study

PubMed Central

Ovesen, Christian; Christensen, Anders Fogh; Havsteen, Inger; Krarup Hansen, Christine; Rosenbaum, Sverre; Kurt, Engin; Christensen, Hanne

2015-01-01

Objective Patients with intracerebral haemorrhage (ICH) are at high risk of neurological deterioration (ND). We aimed at establishing predictors of early ND (END) as well as late ND (LND) and at exploring the impact of neurological stability during the first week on long-term prognosis. Design We conducted this study as a retrospective cohort study. ND was evaluated based on the consciousness and severity of neurological symptoms. ND during the first 24 h after admission was defined as early ND and from 24 h to 7 days as LND. Patients were followed up until February 2015. Participants We included 300 patients with acute ICH (≤4.5 h from symptom onset) who were admitted to our institution from March 2009 to January 2015. Setting Section of Acute Neurology, Department of Neurology, Bispebjerg Hospital is a specialised referral centre receiving patients with acute stroke from the entire capital region of Denmark. Results We found that a spot sign on CT angiography (OR 10.7 CI 4.79 to 24.3) and extensive degree of interventricular haemorrhage (IVH) (OR 8.73 CI 2.87 to 26.5) were independent predictors of END, whereas a degree of comorbidity (Charlton Index), admission stroke severity and degree of IVH predicted LND. On follow-up imaging, haematoma expansion was independently associated with END (OR 6.1 CI 2.2 to 17.3), and expansion of IVH was independently associated with both END (OR 1.7 CI 1.2 to 2.3 per point increase) and LND (OR 2.3 CI 1.3 to 4.2 per point increase). ND during the first week was associated with a 1-year mortality of 60.5%, compared with 9.2% among the patients who remained stable. Conclusions These results suggest that stability during the first week entails an optimistic prognosis. A relatively easy and effective risk stratification of END and LND is possible on admission based on the spot sign, IVH and clinical parameters. PMID:26220872

Accelerated Stability Testing of a Clobetasol Propionate-Loaded Nanoemulsion as per ICH Guidelines.

PubMed

Ali, Mohammad Sajid; Alam, Mohammad Sarfaraz; Alam, Nawazish; Anwer, Tarique; Safhi, Mohammed Mohsen A

2013-01-01

The physical and chemical degradation of drugs may result in altered therapeutic efficacy and even toxic effects. Therefore, the objective of this work was to study the stability of clobetasol propionate (CP) in a nanoemulsion. The nanoemulsion formulation containing CP was prepared by the spontaneous emulsification method. For the formulation of the nanoemulsion, Safsol, Tween 20, ethanol, and distilled water were used. The drug was incorporated into an oil phase in 0.05% w/v. The lipophilic nature of the drug led to the O/W nanoemulsion formulation. This was characterized by droplet size, pH, viscosity, conductivity, and refractive index. Stability studies were performed as per ICH guidelines for a period of three months. The shelf life of the nanoemulsion formulation was also determined after performing accelerated stability testing (40°C ± 2°C and 75% ± 5% RH). We also performed an intermediate stability study (30°C ± 2°C/65% RH ± 5% RH). It was found that the droplet size, conductivity, and refractive index were slightly increased, while the viscosity and pH slightly decreased at all storage conditions during the 3-month period. However, the changes in these parameters were not statistically significant (p≥0.05). The degradation (%) of the optimized nanoemulsion of CP was determined and the shelf life was found to be 2.18 years at room temperature. These studies confirmed that the physical and chemical stability of CP were enhanced in the nanoemulsion formulation.

Patient Experience Assessment is a Requisite for Quality Evaluation: A Discussion of the In-Center Hemodialysis Consumer Assessment of Health Care Providers and Systems (ICH CAHPS) Survey.

PubMed

Cavanaugh, Kerri L

2016-01-01

Patient experience surveys provide a critical and unique perspective on the quality of patient-centered healthcare delivery. These surveys provide a mechanism to systematically express patients' voice on topics valued by patients to make decisions about choices in care. They also provide an assessment to healthcare organizations about their service that cannot be obtained from any other source. Regulatory agencies have mandated the assessment of patients' experience as part of healthcare value based purchasing programs and weighted the results to account for up to 30% of the total scoring. This is a testimony to the accepted importance of this metric as a fundamental assessment of quality. After more than a decade of rigorous research, there is a significant body of growing evidence supporting specifically the validity and use of the Consumer Assessment of Healthcare Providers and Systems (CAHPS) surveys, including a version specific to in-center hemodialysis (ICH CAHPS). This review will focus on the ICH CAHPS survey including a review of its development, content, administration, and also a discussion of common criticisms. Although it is suggested that the survey assesses activities and experiences that are not modifiable by the healthcare organization (or the dialysis facility in our case) emerging evidence suggests otherwise. Dialysis providers have an exclusive opportunity to lead the advancement of understanding the implications and serviceability of the evaluation of the patient experience in health care. © 2016 Wiley Periodicals, Inc.

New protocol for αAstree electronic tongue enabling full performance qualification according to ICH Q2.

PubMed

Pein, Miriam; Eckert, Carolin; Preis, Maren; Breitkreutz, Jörg

2013-09-01

Performance qualification (PQ) of taste sensing systems is mandatory for their use in pharmaceutical industry. According to ICH Q2 (R1) and a recent adaptation for taste sensing systems, non-specificity, log-linear relationships between the concentration of analytes and the sensor signal as well as a repeatability with relative standard deviation (RSD) values <4% were defined as basic requirements to pass a PQ. In the present work, the αAstree taste sensing system led to a successful PQ procedure by the use of recent sensor batches for pharmaceutical applications (sensor set #2) and a modified measurement protocol. Log-linear relationships between concentration and responses of each sensor were investigated for different bitter tasting active pharmaceutical ingredients (APIs). Using the new protocol, RSD values <2.1% were obtained in the repeatability study. Applying the visual evaluation approach, detection and quantitation limit could be determined for caffeine citrate with every sensor (LOD 0.05-0.5 mM, LOQ: 0.1-0.5 mM). In addition, the sensor set marketed for food applications (sensor set #5) was proven to show beneficial effects regarding the log-linear relationship between the concentration of quinine hydrochloride and the sensor signal. By the use of our proposed protocol, it is possible to implement the αAstree taste sensing system as a tool to assure quality control in the pharmaceutical industry. Copyright © 2013 Elsevier B.V. All rights reserved.

Dynamics of electron solvation in I(-)(CH3OH)n clusters (4 ≤ n ≤ 11).

PubMed

Young, Ryan M; Yandell, Margaret A; Neumark, Daniel M

2011-03-28

The dynamics of electron solvation following excitation of the charge-transfer-to-solvent precursor state in iodide-doped methanol clusters, I(-)(CH(3)OH)(n = 4-11), are studied with time-resolved photoelectron imaging. This excitation produces a I···(CH(3)OH)(n)(-) cluster that is unstable with respect to electron autodetachment and whose autodetachment lifetime increases monotonically from ~800 fs to 85 ps as n increases from 4 to 11. The vertical detachment energy (VDE) and width of the excited state feature in the photoelectron spectrum show complex time dependence during the lifetime of this state. The VDE decreases over the first 100-400 fs, then rises exponentially to a maximum with a ~1 ps time constant, and finally decreases by as much as 180 meV with timescales of 3-20 ps. The early dynamics are associated with electron transfer from the iodide to the methanol cluster, while the longer-time changes in VDE are attributed to solvent reordering, possibly in conjunction with ejection of neutral iodine from the cluster. Changes in the observed width of the spectrum largely follow those of the VDEs; the dynamics of both are attributed to the major rearrangement of the solvent cluster during relaxation. The relaxation dynamics are interpreted as a reorientation of at least one methanol molecule and the disruption and formation of the solvent network in order to accommodate the excess charge.

ICH guidance in practice: validated reversed-phase HPLC method for the determination of active mangiferin from extracts of Mangifera indica Linn.

PubMed

Gowda, Nagaraj; Kumar, Pradeep; Panghal, Surender; Rajshree, Mashru

2010-02-01

This study presents the development and validation of a reversed-phase liquid chromatographic method for the determination of mangiferin (MGN) in alcoholic extracts of mangifera indica. A Lichrospher 100 C(18)-ODS (250 x 4.6 mm, 5 microm size) (Merck, Whitehouse Station, NJ) prepacked column and a mobile phase of potassium dihydrogen orthophosphate (0.01M) pH 2.7 +/- 0.2-acetonitrile (15:85, v/v) with the flow rate of 1 mL/min was used. MGN detection was achieved at a wavelength monitored at 254 nm with SPD-M 10A vp PDA detector or SPD 10AD vp UV detector in combination with class LC 10A software. The proposed method was validated as prescribed by International Conference on Harmonization (ICH) with respect to linearity, specificity, accuracy, precision, stability, and quantification. The method validation was realized using alcoholic extracts and raw materials of leaves and barks. All the validation parameters were within the acceptable limits, and the developed analytical method can successfully be applied for MGN determination.

Impact of globalization under the ICH guidelines on the conduct of reproductive toxicity studies--report on current status in Japan, Europe and the U.S. by questionnaire survey.

PubMed

Mineshima, Hiroshi; Endo, Yoshihiko; Ogasawara, Hiroyuki; Nishigaki, Keiji; Numa, Toshiaki; Hirano, Fumiya; Matsuzawa, Toshiaki

2004-08-01

We surveyed interpretation of the ICH guidelines concerning reproductive toxicology. Valid responses were obtained from Japan (JPN), Europe (EUR) and the U.S. The results obtained were compared to those at the time of a previous survey targeted at JPN facilities in 1995-1996 as well as compared among all three regions. Compared to the previous survey in Japan, the number of facilities performing toxicokinetics (TK) in rats has slightly increased. This result was considered to represent changes of attitude toward TK in reproductive toxicity studies. Differences in interpretation of the guidelines between JPN, EUR and the US were widely seen. Clear differences were noted in sperm examinations, postnatal tests, fetal examinations, some examinations for F1 animals after culling and TK. Researchers in the West seemed to be interpreting the ICH guidelines more flexibly from the scientific point of view. JPN researchers appeared to interpret the guidelines, including notes, as rigid requirements. Most of the parts which produced different interpretations were the notes in the guidelines. The force of mention in the notes should be defined in the future. In addition, there were doubts about some parts, including notes, which had been found to have become unsuitable for the implementation of studies because of scientific progress or from long experience in using the guidelines. Therefore, updates of the guidelines may be needed in the future as well as the remedy of interpretation by JPN researchers. In JPN, the number of reproductive toxicity studies has decreased. The scanty experience in JPN therefore raises apprehension of appropriate selection and stagnating development of methodology, and might hinder the maintenance of the guidelines. In the future, the cooperation of CROs as well as global collaboration will be essential not only to scientific developments of reproductive toxicology but also updates of the guidelines.

International Conference on Harmonisation; Electronic Transmission of Postmarket Individual Case Safety Reports for Drugs and Biologics, Excluding Vaccines; Availability of Food and Drug Administration Regional Implementation Specifications for ICH E2B(R3) Reporting to the Food and Drug Administration Adverse Event Reporting System. Notice of Availability.

PubMed

2016-06-23

The Food and Drug Administration (FDA) is announcing the availability of its FDA Adverse Event Reporting System (FAERS) Regional Implementation Specifications for the International Conference on Harmonisation (ICH) E2B(R3) Specification. FDA is making this technical specifications document available to assist interested parties in electronically submitting individual case safety reports (ICSRs) (and ICSR attachments) to the Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER). This document, entitled "FDA Regional Implementation Specifications for ICH E2B(R3) Implementation: Postmarket Submission of Individual Case Safety Reports (ICSRs) for Drugs and Biologics, Excluding Vaccines" supplements the "E2B(R3) Electronic Transmission of Individual Case Safety Reports (ICSRs) Implementation Guide--Data Elements and Message Specification" final guidance for industry and describes FDA's technical approach for receiving ICSRs, for incorporating regionally controlled terminology, and for adding region-specific data elements when reporting to FAERS.

ICH S7B draft guideline on the non-clinical strategy for testing delayed cardiac repolarisation risk of drugs: a critical analysis.

PubMed

Cavero, Icilio; Crumb, William

2005-05-01

The International Conference on Harmonization (ICH) stems from the initiative of three major world partners (Japan, USA, European Community) who composed a mutually accepted body of regulations concerning the safety, quality and efficacy requirements that new medicines have to meet in order to receive market approval. Documents on non-clinical safety pharmacology already composed by this organisation include two guidelines: the S7A adopted in 2000 and, its companion, the S7B guideline, in a draft form since 2001. The S7A guideline deals with general principles and recommendations on safety pharmacology studies designed to protect healthy volunteers and patients from potential drug-induced adverse reactions. The S7B recommends a general non-clinical testing strategy for determining the propensity of non-cardiovascular pharmaceuticals to delay ventricular repolarisation, an effect that at times progresses into life-threatening ventricular arrhythmia. In the most recent version of this document (June 2004), the strategy proposes experimental assays and a critical examination of other pertinent information for applying an 'evidence of risk' label to a compound. Regrettably, the guideline fails to deal satisfactorily with a number of crucial issues such as scoring the evidence of risk and the clinical consequences of such scoring. However, in the latter case, the S7B relies on the new ICH guideline E14 which is currently in preparation. E14 is the clinical counterpart of the S7B guideline which states that non-clinical data are a poor predictor of drug-induced repolarisation delay in humans. The present contribution summarises and assesses salient aspects of the S7A guideline as its founding principles are also applicable to the S7B guideline. The differences in strategies proposed by the various existing drafts of the latter document are critically examined together with some unresolved, crucial problems. The need for extending the objective of the S7B document to

Primary Intracerebral Hemorrhage: A Closer Look at Hypertension and Cerebral Amyloid Angiopathy.

PubMed

Roh, David; Sun, Chung-Huan; Schmidt, J Michael; Gurol, Edip; Murthy, Santosh; Park, Soojin; Agarwal, Sachin; Connolly, E Sander; Claassen, Jan

2018-03-19

Primary intracerebral hemorrhage (ICH) studies often use hematoma location rather than ICH etiologies when assessing outcome. Characterizing ICH using hematoma location is effective/reproducible, but may miss heterogeneity among these ICH locations, particularly lobar ICH where competing primary ICH etiologies are possible. We subsequently investigated baseline characteristics/outcome differences of spontaneous, primary ICH by their etiologies: cerebral amyloid angiopathy (CAA) and hypertension. Primary ICH clinical/outcomes data were prospectively collected between 2009 and 2015. Modified Boston criteria were used to identify "probable/definite" and "possible" CAA-ICH, which were evaluated separately. SMASH-U criteria were used to identify hypertension ICH. Medication and systemic disease coagulopathy ICH were excluded. Baseline characteristics/outcomes among "probable/definite" CAA-ICH, "possible" CAA-ICH, and hypertension ICH were compared using logistic regression. Mortality models using ICH etiologies compared to hematoma location as predictor variables were assessed. Two hundred and four hypertension ICHs, 55 "probable/definite" CAA-ICHs, and 46 "possible" CAA-ICHs were identified. Despite older age and larger ICH volumes, lower hospital mortality was seen in "probable/definite" CAA-ICH versus hypertension ICH (OR 0.2; 95% CI 0.05-0.8; p = 0.02) after adjusting for female gender, components of ICH score, and EVD placement. There were no mortality differences between "possible" CAA-ICH and hypertension ICH. However, lower hospital mortality was seen in "probable/definite" versus "possible" CAA-ICH (OR 0.2; 95% CI 0.04-0.7; p = 0.02). When using ICH etiology rather than hematoma location, hospital mortality models significantly improved (χ 2 : [df = 2, N = 305] = 6.2; p = 0.01). Further investigation is required to confirm the mortality heterogeneity seen within our primary ICH cohort. Hematoma location may play a role for these findings, but the

Outcome of intracerebral hemorrhage associated with different oral anticoagulants

PubMed Central

Wilson, Duncan; Seiffge, David J.; Traenka, Christopher; Basir, Ghazala; Purrucker, Jan C.; Rizos, Timolaos; Sobowale, Oluwaseun A.; Sallinen, Hanne; Yeh, Shin-Joe; Wu, Teddy Y.; Ferrigno, Marc; Houben, Rik; Schreuder, Floris H.B.M.; Perry, Luke A.; Tanaka, Jun; Boulanger, Marion; Al-Shahi Salman, Rustam; Jäger, Hans R.; Ambler, Gareth; Shakeshaft, Clare; Yakushiji, Yusuke; Choi, Philip M.C.; Staals, Julie; Cordonnier, Charlotte; Jeng, Jiann-Shing; Veltkamp, Roland; Dowlatshahi, Dar; Engelter, Stefan T.; Parry-Jones, Adrian R.; Meretoja, Atte

2017-01-01

Objective: In an international collaborative multicenter pooled analysis, we compared mortality, functional outcome, intracerebral hemorrhage (ICH) volume, and hematoma expansion (HE) between non–vitamin K antagonist oral anticoagulation–related ICH (NOAC-ICH) and vitamin K antagonist–associated ICH (VKA-ICH). Methods: We compared all-cause mortality within 90 days for NOAC-ICH and VKA-ICH using a Cox proportional hazards model adjusted for age; sex; baseline Glasgow Coma Scale score, ICH location, and log volume; intraventricular hemorrhage volume; and intracranial surgery. We addressed heterogeneity using a shared frailty term. Good functional outcome was defined as discharge modified Rankin Scale score ≤2 and investigated in multivariable logistic regression. ICH volume was measured by ABC/2 or a semiautomated planimetric method. HE was defined as an ICH volume increase >33% or >6 mL from baseline within 72 hours. Results: We included 500 patients (97 NOAC-ICH and 403 VKA-ICH). Median baseline ICH volume was 14.4 mL (interquartile range [IQR] 3.6–38.4) for NOAC-ICH vs 10.6 mL (IQR 4.0–27.9) for VKA-ICH (p = 0.78). We did not find any difference between NOAC-ICH and VKA-ICH for all-cause mortality within 90 days (33% for NOAC-ICH vs 31% for VKA-ICH [p = 0.64]; adjusted Cox hazard ratio (for NOAC-ICH vs VKA-ICH) 0.93 [95% confidence interval (CI) 0.52–1.64] [p = 0.79]), the rate of HE (NOAC-ICH n = 29/48 [40%] vs VKA-ICH n = 93/140 [34%] [p = 0.45]), or functional outcome at hospital discharge (NOAC-ICH vs VKA-ICH odds ratio 0.47; 95% CI 0.18–1.19 [p = 0.11]). Conclusions: In our international collaborative multicenter pooled analysis, baseline ICH volume, hematoma expansion, 90-day mortality, and functional outcome were similar following NOAC-ICH and VKA-ICH. PMID:28381513

Outcome of intracerebral hemorrhage associated with different oral anticoagulants.

PubMed

Wilson, Duncan; Seiffge, David J; Traenka, Christopher; Basir, Ghazala; Purrucker, Jan C; Rizos, Timolaos; Sobowale, Oluwaseun A; Sallinen, Hanne; Yeh, Shin-Joe; Wu, Teddy Y; Ferrigno, Marc; Houben, Rik; Schreuder, Floris H B M; Perry, Luke A; Tanaka, Jun; Boulanger, Marion; Al-Shahi Salman, Rustam; Jäger, Hans R; Ambler, Gareth; Shakeshaft, Clare; Yakushiji, Yusuke; Choi, Philip M C; Staals, Julie; Cordonnier, Charlotte; Jeng, Jiann-Shing; Veltkamp, Roland; Dowlatshahi, Dar; Engelter, Stefan T; Parry-Jones, Adrian R; Meretoja, Atte; Werring, David J

2017-05-02

In an international collaborative multicenter pooled analysis, we compared mortality, functional outcome, intracerebral hemorrhage (ICH) volume, and hematoma expansion (HE) between non-vitamin K antagonist oral anticoagulation-related ICH (NOAC-ICH) and vitamin K antagonist-associated ICH (VKA-ICH). We compared all-cause mortality within 90 days for NOAC-ICH and VKA-ICH using a Cox proportional hazards model adjusted for age; sex; baseline Glasgow Coma Scale score, ICH location, and log volume; intraventricular hemorrhage volume; and intracranial surgery. We addressed heterogeneity using a shared frailty term. Good functional outcome was defined as discharge modified Rankin Scale score ≤2 and investigated in multivariable logistic regression. ICH volume was measured by ABC/2 or a semiautomated planimetric method. HE was defined as an ICH volume increase >33% or >6 mL from baseline within 72 hours. We included 500 patients (97 NOAC-ICH and 403 VKA-ICH). Median baseline ICH volume was 14.4 mL (interquartile range [IQR] 3.6-38.4) for NOAC-ICH vs 10.6 mL (IQR 4.0-27.9) for VKA-ICH ( p = 0.78). We did not find any difference between NOAC-ICH and VKA-ICH for all-cause mortality within 90 days (33% for NOAC-ICH vs 31% for VKA-ICH [ p = 0.64]; adjusted Cox hazard ratio (for NOAC-ICH vs VKA-ICH) 0.93 [95% confidence interval (CI) 0.52-1.64] [ p = 0.79]), the rate of HE (NOAC-ICH n = 29/48 [40%] vs VKA-ICH n = 93/140 [34%] [ p = 0.45]), or functional outcome at hospital discharge (NOAC-ICH vs VKA-ICH odds ratio 0.47; 95% CI 0.18-1.19 [ p = 0.11]). In our international collaborative multicenter pooled analysis, baseline ICH volume, hematoma expansion, 90-day mortality, and functional outcome were similar following NOAC-ICH and VKA-ICH. Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

Volume and functional outcome of intracerebral hemorrhage according to oral anticoagulant type

PubMed Central

Wilson, Duncan; Charidimou, Andreas; Shakeshaft, Clare; Ambler, Gareth; White, Mark; Cohen, Hannah; Yousry, Tarek; Al-Shahi Salman, Rustam; Lip, Gregory Y.H.; Brown, Martin M.; Jäger, Hans Rolf

2016-01-01

Objective: To compare intracerebral hemorrhage (ICH) volume and clinical outcome of non–vitamin K oral anticoagulants (NOAC)–associated ICH to warfarin-associated ICH. Methods: In this multicenter cross-sectional observational study of patients with anticoagulant-associated ICH, consecutive patients with NOAC-ICH were compared to those with warfarin-ICH selected from a population of 344 patients with anticoagulant-associated ICH. ICH volume was measured by an observer blinded to clinical details. Outcome measures were ICH volume and clinical outcome adjusted for confounding factors. Results: We compared 11 patients with NOAC-ICH to 52 patients with warfarin-ICH. The median ICH volume was 2.4 mL (interquartile range [IQR] 0.3–5.4 mL) for NOAC-ICH vs 8.9 mL (IQR 4.0–21.3 mL) for warfarin-ICH (p = 0.0028). In univariate linear regression, use of warfarin (difference in cube root volume 1.61; 95% confidence interval [CI] 0.69 to 2.53) and lobar ICH location (compared with nonlobar ICH; difference in cube root volume 1.52; 95% CI 2.20 to 0.85) were associated with larger ICH volumes. In multivariable linear regression adjusting for confounding factors (sex, hypertension, previous ischemic stroke, white matter disease burden, and premorbid modified Rankin Scale score [mRS]), warfarin use remained independently associated with larger ICH (cube root) volumes (coefficient 0.64; 95% CI 0.24 to 1.25; p = 0.042). Ordered logistic regression showed an increased odds of a worse clinical outcome (as measured by discharge mRS) in warfarin-ICH compared with NOAC-ICH: odds ratio 4.46 (95% CI 1.10 to 18.14; p = 0.037). Conclusions: In this small prospective observational study, patients with NOAC-associated ICH had smaller ICH volumes and better clinical outcomes compared with warfarin-associated ICH. PMID:26718576

Volume and functional outcome of intracerebral hemorrhage according to oral anticoagulant type.

PubMed

Wilson, Duncan; Charidimou, Andreas; Shakeshaft, Clare; Ambler, Gareth; White, Mark; Cohen, Hannah; Yousry, Tarek; Al-Shahi Salman, Rustam; Lip, Gregory Y H; Brown, Martin M; Jäger, Hans Rolf; Werring, David J

2016-01-26

To compare intracerebral hemorrhage (ICH) volume and clinical outcome of non-vitamin K oral anticoagulants (NOAC)-associated ICH to warfarin-associated ICH. In this multicenter cross-sectional observational study of patients with anticoagulant-associated ICH, consecutive patients with NOAC-ICH were compared to those with warfarin-ICH selected from a population of 344 patients with anticoagulant-associated ICH. ICH volume was measured by an observer blinded to clinical details. Outcome measures were ICH volume and clinical outcome adjusted for confounding factors. We compared 11 patients with NOAC-ICH to 52 patients with warfarin-ICH. The median ICH volume was 2.4 mL (interquartile range [IQR] 0.3-5.4 mL) for NOAC-ICH vs 8.9 mL (IQR 4.0-21.3 mL) for warfarin-ICH (p = 0.0028). In univariate linear regression, use of warfarin (difference in cube root volume 1.61; 95% confidence interval [CI] 0.69 to 2.53) and lobar ICH location (compared with nonlobar ICH; difference in cube root volume 1.52; 95% CI 2.20 to 0.85) were associated with larger ICH volumes. In multivariable linear regression adjusting for confounding factors (sex, hypertension, previous ischemic stroke, white matter disease burden, and premorbid modified Rankin Scale score [mRS]), warfarin use remained independently associated with larger ICH (cube root) volumes (coefficient 0.64; 95% CI 0.24 to 1.25; p = 0.042). Ordered logistic regression showed an increased odds of a worse clinical outcome (as measured by discharge mRS) in warfarin-ICH compared with NOAC-ICH: odds ratio 4.46 (95% CI 1.10 to 18.14; p = 0.037). In this small prospective observational study, patients with NOAC-associated ICH had smaller ICH volumes and better clinical outcomes compared with warfarin-associated ICH. © 2015 American Academy of Neurology.

Mixed-location cerebral hemorrhage/microbleeds: Underlying microangiopathy and recurrence risk.

PubMed

Pasi, Marco; Charidimou, Andreas; Boulouis, Gregoire; Auriel, Eitan; Ayres, Alison; Schwab, Kristin M; Goldstein, Joshua N; Rosand, Jonathan; Viswanathan, Anand; Pantoni, Leonardo; Greenberg, Steven M; Gurol, M Edip

2018-01-09

To assess the predominant type of cerebral small vessel disease (SVD) and recurrence risk in patients who present with a combination of lobar and deep intracerebral hemorrhage (ICH)/microbleed locations (mixed ICH). Of 391 consecutive patients with primary ICH enrolled in a prospective registry, 75 (19%) had mixed ICH. Their demographics, clinical/laboratory features, and SVD neuroimaging markers were compared to those of 191 patients with probable cerebral amyloid angiopathy (CAA-ICH) and 125 with hypertensive strictly deep microbleeds and ICH (HTN-ICH). ICH recurrence and case fatality were also analyzed. Patients with mixed ICH showed a higher burden of vascular risk factors reflected by a higher rate of left ventricular hypertrophy, higher creatinine values, and more lacunes and severe basal ganglia (BG) enlarged perivascular spaces (EPVS) than patients with CAA-ICH (all p < 0.05). In multivariable models mixed ICH diagnosis was associated with higher creatinine levels (odds ratio [OR] 2.5, 95% confidence interval [CI] 1.2-5.0, p = 0.010), more lacunes (OR 3.4, 95% CI 1.7-6.8), and more severe BG EPVS (OR 5.8, 95% CI 1.7-19.7) than patients with CAA-ICH. Conversely, when patients with mixed ICH were compared to patients with HTN-ICH, they were independently associated with older age (OR 1.03, 95% CI 1.02-1.1), more lacunes (OR 2.4, 95% CI 1.1-5.3), and higher microbleed count (OR 1.6, 95% CI 1.3-2.0). Among 90-day survivors, adjusted case fatality rates were similar for all 3 categories. Annual risk of ICH recurrence was 5.1% for mixed ICH, higher than for HTN-ICH but lower than for CAA-ICH (1.6% and 10.4%, respectively). Mixed ICH, commonly seen on MRI obtained during etiologic workup, appears to be driven mostly by vascular risk factors similar to HTN-ICH but demonstrates more severe parenchymal damage and higher ICH recurrence risk. Copyright © 2017 American Academy of Neurology.

Intracerebral hemorrhage and sleep-disordered breathing.

PubMed

Lisabeth, Lynda D; Scheer, Richard V; Li, Chengwei; Case, Erin; Chervin, Ronald D; Zahuranec, Darin B; Morgenstern, Lewis B; Garcia, Nelda M; Tower, Susan; Brown, Devin L

2018-06-01

Limited data are available on sleep-disordered breathing (SDB) following intracerebral hemorrhage (ICH). Our aim was to characterize the objective measures of post-ICH SDB and questionnaire-reported pre-ICH sleep characteristics, overall and by ethnicity. Participants with ICH who were enrolled in the population-based Brain Attack Surveillance in Corpus Christi project (2010-2016) reported their pre-ICH sleep duration and completed the Berlin Questionnaire to characterize pre-ICH risk of SDB. A subsample was screened for SDB (respiratory event index ≥10) using ApneaLink Plus portable monitoring. Ethnic differences in post-ICH SDB or questionnaire-reported pre-ICH sleep characteristics were assessed using a log binomial model or a linear regression model or a Fisher's exact test. ICH cases (n = 298) were enrolled (median age = 68 years, 67% Mexican American). Among 62 cases with complete ApneaLink data, median time to post-ICH SDB screening was 11 days (IQR: 6, 19). Post-ICH SDB prevalence was 46.8% (95% CI: 34.4-59.2), and this rate did not differ by ethnicity (p = 1.0). Berlin Questionnaires for 109 of the 298 ICH cases (36.6% (95% CI: 31.1-42.0)) suggested a high risk for pre-ICH SDB, and the median pre-ICH sleep duration was eight hours (IQR: 6, 8). After adjusting for confounders, there was no difference in ethnicity in high risk for pre-ICH SDB or pre-ICH sleep duration. Nearly half of the patients had objective confirmation of SDB after ICH, and more than one-third had questionnaire evidence of high risk for pre-ICH SDB. Opportunities to address SDB may be common both before and after ICH. Copyright © 2018 Elsevier B.V. All rights reserved.

Functional Long-Term Outcome after Left- versus Right-Sided Intracerebral Hemorrhage.

PubMed

Beuscher, Vanessa D; Kuramatsu, Joji B; Gerner, Stefan T; Köhn, Julia; Lücking, Hannes; Kloska, Stephan P; Huttner, Hagen B

2017-01-01

Hemispheric location might influence outcome after intracerebral hemorrhage (ICH). INTERACT suggested higher short-term mortality in right hemispheric ICH, yet statistical imbalances were not addressed. This study aimed at determining the differences in long-term functional outcome in patients with right- vs. left-sided ICH with a priori-defined sub-analysis of lobar vs. deep bleedings. Data from a prospective hospital registry were analyzed including patients with ICH admitted between January 2006 and August 2014. Data were retrieved from institutional databases. Outcome was assessed using the modified Rankin Scale (mRS) score. Outcome measures (long-term mortality and functional outcome at 12 months) were correlated with ICH location and hemisphere, and the imbalances of baseline characteristics were addressed by propensity score matching. A total of 831 patients with supratentorial ICH (429 left and 402 right) were analyzed. Regarding clinical baseline characteristics in the unadjusted overall cohort, there were differences in disfavor of right-sided ICH (antiplatelets: 25.2% in left ICH vs. 34.3% in right ICH; p < 0.01; previous ischemic stroke: 14.7% in left ICH vs. 19.7% in right ICH; p = 0.057; and presence/extent of intraventricular hemorrhage: 45.0% in left ICH vs. 53.0% in right ICH; p = 0.021; Graeb-score: 0 [0-4] in left ICH vs. 1 [0-5] in right ICH; p = 0.017). While there were no differences in mortality and in the proportion of patients with favorable vs. unfavorable outcome (mRS 0-3: 142/375 [37.9%] in left ICH vs. 117/362 [32.3%] in right ICH; p = 0.115), patients with left-sided ICH showed excellent outcome more frequently (mRS 0-1: 64/375 [17.1%] in left ICH vs. 43/362 [11.9%] in right ICH; p = 0.046) in the unadjusted analysis. After adjusting for confounding variables, a well-balanced group of patients (n = 360/hemisphere) was compared showing no differences in long-term functional outcome (mRS 0-3: 36.4% in left ICH vs. 33.9% in right ICH; p

A comparative study of ICH validated novel spectrophotometric techniques for resolving completely overlapping spectra of quaternary mixtures

NASA Astrophysics Data System (ADS)

Ali, Nouruddin W.; Abdelwahab, Nada S.; Abdelkawy, M.; Emam, Aml A.

2016-02-01

A pharmaceutically marketed mixture of Yohimbine, Alpha-tocopheryl acetate, Niacin, and Caffeine co-formulated as a promising therapy for erectile dysfunction. Simultaneous determination of the aforementioned pharmaceutical formulation without prior separation steps was applied using mean centering of ratio spectra and triple divisor spectrophotometric methods. Mean centering of ratio spectra method depended on using the mean centered ratio spectra in three successive steps which eliminated the derivative steps and so the signal to noise ratio was improved. The absorption spectra of the prepared solutions were measured in the wavelength range of 215-300 nm in the concentration ranges of 1-15, 3-15, 1-20, and 3-15 μg mL- 1 for Yohimbine, Alpha-tocopheryl acetate, Niacin, and Caffeine, respectively. The amplitudes of the mean centered third ratio spectra were measured at 250 nm and 268 nm for Yohimbine and Alpha-tocopheryl acetate, respectively and at peak to peak 272-273 and 262-263 nm for Niacin and Caffeine, respectively. In triple divisor method each drug in the quaternary mixture was determined by dividing the spectrum of the quaternary mixture by a standard spectrum of a mixture containing equal concentrations of the other three drugs. First derivative of these ratio spectra was obtained where determination could be achieved without any interference from the other three drugs. Amplitudes of 1-15, 3-15, 1-15, and 3-15 μg mL- 1 were used for selective determination of Yohimbine, Alpha-tocopheryl acetate, Niacin, and Caffeine, respectively. Laboratory prepared mixtures were analyzed by the developed novel methods to investigate their selectivity also, Super Act® capsules were successfully analyzed to ensure absence of interference from additives. The developed methods were validated according to the ICH guidelines. The proposed methods were statistically compared with each other and with the reported methods; using student t-test, F-test, and one way ANOVA

A comparative study of ICH validated novel spectrophotometric techniques for resolving completely overlapping spectra of quaternary mixtures.

PubMed

Ali, Nouruddin W; Abdelwahab, Nada S; Abdelkawy, M; Emam, Aml A

2016-02-05

A pharmaceutically marketed mixture of Yohimbine, Alpha-tocopheryl acetate, Niacin, and Caffeine co-formulated as a promising therapy for erectile dysfunction. Simultaneous determination of the aforementioned pharmaceutical formulation without prior separation steps was applied using mean centering of ratio spectra and triple divisor spectrophotometric methods. Mean centering of ratio spectra method depended on using the mean centered ratio spectra in three successive steps which eliminated the derivative steps and so the signal to noise ratio was improved. The absorption spectra of the prepared solutions were measured in the wavelength range of 215-300 nm in the concentration ranges of 1-15, 3-15, 1-20, and 3-15 μg mL(-1) for Yohimbine, Alpha-tocopheryl acetate, Niacin, and Caffeine, respectively. The amplitudes of the mean centered third ratio spectra were measured at 250 nm and 268 nm for Yohimbine and Alpha-tocopheryl acetate, respectively and at peak to peak 272-273 and 262-263 nm for Niacin and Caffeine, respectively. In triple divisor method each drug in the quaternary mixture was determined by dividing the spectrum of the quaternary mixture by a standard spectrum of a mixture containing equal concentrations of the other three drugs. First derivative of these ratio spectra was obtained where determination could be achieved without any interference from the other three drugs. Amplitudes of 1-15, 3-15, 1-15, and 3-15 μg mL(-1) were used for selective determination of Yohimbine, Alpha-tocopheryl acetate, Niacin, and Caffeine, respectively. Laboratory prepared mixtures were analyzed by the developed novel methods to investigate their selectivity also, Super Act® capsules were successfully analyzed to ensure absence of interference from additives. The developed methods were validated according to the ICH guidelines. The proposed methods were statistically compared with each other and with the reported methods; using student t-test, F-test, and one way ANOVA

Brain hemorrhage recurrence, small vessel disease type, and cerebral microbleeds

PubMed Central

Charidimou, Andreas; Imaizumi, Toshio; Moulin, Solene; Biffi, Alexandro; Samarasekera, Neshika; Yakushiji, Yusuke; Peeters, Andre; Vandermeeren, Yves; Laloux, Patrice; Baron, Jean-Claude; Hernandez-Guillamon, Mar; Montaner, Joan; Casolla, Barbara; Gregoire, Simone M.; Kang, Dong-Wha; Kim, Jong S.; Naka, H.; Smith, Eric E.; Viswanathan, Anand; Jäger, Hans R.; Al-Shahi Salman, Rustam; Greenberg, Steven M.; Cordonnier, Charlotte

2017-01-01

Objective: We evaluated recurrent intracerebral hemorrhage (ICH) risk in ICH survivors, stratified by the presence, distribution, and number of cerebral microbleeds (CMBs) on MRI (i.e., the presumed causal underlying small vessel disease and its severity). Methods: This was a meta-analysis of prospective cohorts following ICH, with blood-sensitive brain MRI soon after ICH. We estimated annualized recurrent symptomatic ICH rates for each study and compared pooled odds ratios (ORs) of recurrent ICH by CMB presence/absence and presumed etiology based on CMB distribution (strictly lobar CMBs related to probable or possible cerebral amyloid angiopathy [CAA] vs non-CAA) and burden (1, 2–4, 5–10, and >10 CMBs), using random effects models. Results: We pooled data from 10 studies including 1,306 patients: 325 with CAA-related and 981 CAA-unrelated ICH. The annual recurrent ICH risk was higher in CAA-related ICH vs CAA-unrelated ICH (7.4%, 95% confidence interval [CI] 3.2–12.6 vs 1.1%, 95% CI 0.5–1.7 per year, respectively; p = 0.01). In CAA-related ICH, multiple baseline CMBs (versus none) were associated with ICH recurrence during follow-up (range 1–3 years): OR 3.1 (95% CI 1.4–6.8; p = 0.006), 4.3 (95% CI 1.8–10.3; p = 0.001), and 3.4 (95% CI 1.4–8.3; p = 0.007) for 2–4, 5–10, and >10 CMBs, respectively. In CAA-unrelated ICH, only >10 CMBs (versus none) were associated with recurrent ICH (OR 5.6, 95% CI 2.1–15; p = 0.001). The presence of 1 CMB (versus none) was not associated with recurrent ICH in CAA-related or CAA-unrelated cohorts. Conclusions: CMB burden and distribution on MRI identify subgroups of ICH survivors with higher ICH recurrence risk, which may help to predict ICH prognosis with relevance for clinical practice and treatment trials. PMID:28747441

Ice cream headache in students and family history of headache: a cross-sectional epidemiological study.

PubMed

Zierz, Antonia Maria; Mehl, Theresa; Kraya, Torsten; Wienke, Andreas; Zierz, Stephan

2016-06-01

Headache attributed to ingestion of a cold stimulus (ICHD-3 beta 4.5.1) is also known as ice cream headache (ICH). This cross-sectional epidemiological study included 283 students (10-14-year-olds) attending a grammar school in Germany, their parents (n = 401), and 41 teachers. A self-administered questionnaire was used to analyze the prevalence and characteristics of ICH based on the ICHD classification. Additionally, the association between ICH and other headaches was investigated in students and parents. Prevalence of ICH in students was 62 % without gender difference. In adults, only 36 % of females and 22 % of males reported ICH. There was an increased risk for ICH in students when mother (OR 10.7) or father (OR 8.4) had ICH. Other headaches in parents had no influence on the prevalence of ICH in students. However, in the groups of students and parents itself there was a highly significant association between ICH and other headaches (students: OR 2.4, mothers: OR 2.9, fathers: OR 6.8). There was a decreased risk for ICH when parents and students had no headache at all (OR < 0.4). ICH in students clearly shows a familial disposition by both father and mother. There was also an association between ICH and other headaches within the student and adult groups. The absence of headache history seems to be a protective factor for ICH.

Location characteristics of early perihaematomal oedema

PubMed Central

McCarron, M O; McCarron, P; Alberts, M J

2006-01-01

Background The natural history and triggers of perihaematomal oedema (PHO) remain poorly understood. Cerebral amyloid angiopathy (a common cause of lobar haemorrhage) has localised anticoagulant and thrombolytic properties, which may influence PHO. We hypothesised that early (within 24 hours) oedema to haematoma volume ratios are smaller in patients with lobar intracerebral haemorrhage (ICH) than in patients with deep ICH. Methods Haematoma and PHO volumes were measured in consecutive patients admitted to an acute stroke unit with a diagnosis of spontaneous supratentorial ICH proven by computed tomography. The oedema to haematoma volume ratios were calculated and compared in patients with lobar ICH and deep ICH. Results In total, 44 patients with ICH were studied: 19 patients had deep ICH, median haematoma volume 8.4 ml (interquartile range (IQR) 4.8 to 20.8), median PHO 8.2 ml (2.8 to 16), and 25 had lobar ICHs, median haematoma volume 17.6 ml (6.6 to 33.1) and median oedema volume 10.2 ml (3.4 to 24.2). Patients with lobar ICH were older than those with deep ICH (65.7 v 57.4 years, p = 0.009) but ICH location did not differ by sex or race. There was no evidence that haematoma or oedema volumes were related to type of ICH (p = 0.23, p = 0.39 respectively). The median oedema to haematoma volume ratios were similar in patients with lobar and deep ICH (0.67 v 0.58, p = 0.71). Controlling for age, sex, and race made little difference to these comparisons. Conclusions There are no major location specific differences in PHO volumes within 24 hours of ICH onset. Deep and lobar ICH may have common therapeutic targets to reduce early PHO. PMID:16484648

Effect of statins on intracerebral hemorrhage outcome and recurrence.

PubMed

FitzMaurice, Emilie; Wendell, Lauren; Snider, Ryan; Schwab, Kristin; Chanderraj, Rishi; Kinnecom, Cathrine; Nandigam, Kaveer; Rost, Natalia S; Viswanathan, Anand; Rosand, Jonathan; Greenberg, Steven M; Smith, Eric E

2008-07-01

3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, or statins, have been associated with improved outcome after ischemic stroke and subarachnoid hemorrhage but an increased risk of incident intracerebral hemorrhage (ICH). We investigated (1) whether statin use before ICH was associated with functional independence at 90 days, and (2) whether survivors exposed to statins after ICH had an increased risk of recurrence. We analyzed 629 consecutive ICH patients with 90-day outcome data enrolled in a prospective cohort study between 1998 to 2005. Statin use was determined by patient interview at the time of ICH and supplemented by medical record review. Independent status was defined as Glasgow Outcome Scale 4 or 5. ICH survivors were followed by telephone interview every 6 months. Statins were used by 149/629 (24%) before ICH. There was no effect of pre-ICH statin use on the rates of functional independence (28% versus 29%, P=0.84) or mortality (46% versus 45%, P=0.93). Medical comorbidities and warfarin use were more common in statin users. Hematoma volumes were similar (median 28 cm(3) in pre-ICH statin users compared to 22 cm(3) in nonusers, P=0.18). The multivariable-adjusted odds ratio for independent status in pre-ICH statin users was 1.16 (95% CI 0.65 to 2.10, P=0.62). ICH survivors treated with statins after discharge did not have a higher risk of recurrence (adjusted HR 0.82, 95% CI 0.34 to 1.99, P=0.66). Pre-ICH statin use is not associated with improved ICH functional outcome or mortality. Post-ICH statin use is not associated with an increased risk of ICH recurrence.

Combining Spot Sign and Intracerebral Hemorrhage Score to Estimate Functional Outcome: Analysis From the PREDICT Cohort.

PubMed

Schneider, Hauke; Huynh, Thien J; Demchuk, Andrew M; Dowlatshahi, Dar; Rodriguez-Luna, David; Silva, Yolanda; Aviv, Richard; Dzialowski, Imanuel

2018-06-01

The intracerebral hemorrhage (ICH) score is the most commonly used grading scale for stratifying functional outcome in patients with acute ICH. We sought to determine whether a combination of the ICH score and the computed tomographic angiography spot sign may improve outcome prediction in the cohort of a prospective multicenter hemorrhage trial. Prospectively collected data from 241 patients from the observational PREDICT study (Prediction of Hematoma Growth and Outcome in Patients With Intracerebral Hemorrhage Using the CT-Angiography Spot Sign) were analyzed. Functional outcome at 3 months was dichotomized using the modified Rankin Scale (0-3 versus 4-6). Performance of (1) the ICH score and (2) the spot sign ICH score-a scoring scale combining ICH score and spot sign number-was tested. Multivariable analysis demonstrated that ICH score (odds ratio, 3.2; 95% confidence interval, 2.2-4.8) and spot sign number (n=1: odds ratio, 2.7; 95% confidence interval, 1.1-7.4; n>1: odds ratio, 3.8; 95% confidence interval, 1.2-17.1) were independently predictive of functional outcome at 3 months with similar odds ratios. Prediction of functional outcome was not significantly different using the spot sign ICH score compared with the ICH score alone (spot sign ICH score area under curve versus ICH score area under curve: P =0.14). In the PREDICT cohort, a prognostic score adding the computed tomographic angiography-based spot sign to the established ICH score did not improve functional outcome prediction compared with the ICH score. © 2018 American Heart Association, Inc.

Hyperbaric oxygen therapy ameliorates acute brain injury after porcine intracerebral hemorrhage at high altitude.

PubMed

Zhu, Hai-tao; Bian, Chen; Yuan, Ji-chao; Liao, Xiao-jun; Liu, Wei; Zhu, Gang; Feng, Hua; Lin, Jiang-kai

2015-06-15

Intracerebral hemorrhage (ICH) at high altitude is not well understood to date. This study investigates the effects of high altitude on ICH, and examines the acute neuroprotection of hyperbaric oxygen (HBO) therapy against high-altitude ICH. Minipigs were placed in a hypobaric chamber for 72 h before the operation. ICH was induced by an infusion of autologous arterial blood (3 ml) into the right basal ganglia. Animals in the high-altitude ICH group received HBO therapy (2.5 ATA for 60 min) 30 min after ICH. Blood gas, blood glucose and brain tissue oxygen partial pressure (PbtO2) were monitored continuously for animals from all groups, as were microdialysis products including glucose, lactate, pyruvate and glutamate in perihematomal tissue from 3 to 12 h post-ICH. High-altitude ICH animals showed significantly lower PbtO2, higher lactate/pyruvate ratio (LPR) and glutamate levels than low-altitude ICH animals. More severe neurological deficits, brain edema and neuronal damage were also observed in high-altitude ICH. After HBO therapy, PbtO2 was significantly increased and LPR and glutamate levels were significantly decreased. Brain edema, neurological deficits and neuronal damage were also ameliorated. The data suggested a more serious disturbance of tissue oxygenation and cerebral metabolism in the acute stage after ICH at high altitude. Early HBO treatment reduced acute brain injury, perhaps through a mechanism involving the amelioration of the derangement of cerebral oxygenation and metabolism following high-altitude ICH.

Risk score to predict hospital-acquired pneumonia after spontaneous intracerebral hemorrhage.

PubMed

Ji, Ruijun; Shen, Haipeng; Pan, Yuesong; Du, Wanliang; Wang, Penglian; Liu, Gaifen; Wang, Yilong; Li, Hao; Zhao, Xingquan; Wang, Yongjun

2014-09-01

We aimed to develop a risk score (intracerebral hemorrhage-associated pneumonia score, ICH-APS) for predicting hospital-acquired stroke-associated pneumonia (SAP) after ICH. The ICH-APS was developed based on the China National Stroke Registry (CNSR), in which eligible patients were randomly divided into derivation (60%) and validation (40%) cohorts. Variables routinely collected at presentation were used for predicting SAP after ICH. For testing the added value of hematoma volume measure, we separately developed 2 models with (ICH-APS-B) and without (ICH-APS-A) hematoma volume included. Multivariable logistic regression was performed to identify independent predictors. The area under the receiver operating characteristic curve (AUROC), Hosmer-Lemeshow goodness-of-fit test, and integrated discrimination index were used to assess model discrimination, calibration, and reclassification, respectively. The SAP was 16.4% and 17.7% in the overall derivation (n=2998) and validation (n=2000) cohorts, respectively. A 23-point ICH-APS-A was developed based on a set of predictors and showed good discrimination in the overall derivation (AUROC, 0.75; 95% confidence interval, 0.72-0.77) and validation (AUROC, 0.76; 95% confidence interval, 0.71-0.79) cohorts. The ICH-APS-A was more sensitive for patients with length of stay >48 hours (AUROC, 0.78; 95% confidence interval, 0.75-0.81) than those with length of stay <48 hours (AUROC, 0.64; 95% confidence interval, 0.55-0.73). The ICH-APS-A was well calibrated (Hosmer-Lemeshow test) in the derivation (P=0.20) and validation (P=0.66) cohorts. Similarly, a 26-point ICH-APS-B was established. The ICH-APS-A and ICH-APS-B were not significantly different in discrimination and reclassification for SAP after ICH. The ICH-APSs are valid risk scores for predicting SAP after ICH, especially for patients with length of stay >48 hours. © 2014 American Heart Association, Inc.

Risk factors for computed tomography angiography spot sign in deep and lobar intracerebral hemorrhage are shared.

PubMed

Radmanesh, Farid; Falcone, Guido J; Anderson, Christopher D; Battey, Thomas W K; Ayres, Alison M; Vashkevich, Anastasia; McNamara, Kristen A; Schwab, Kristin; Romero, Javier M; Viswanathan, Anand; Greenberg, Steven M; Goldstein, Joshua N; Rosand, Jonathan; Brouwers, H Bart

2014-06-01

Patients with intracerebral hemorrhage (ICH) who present with a spot sign on computed tomography angiography are at increased risk of hematoma expansion and poor outcome. Because primary ICH is the acute manifestation of chronic cerebral small vessel disease, we investigated whether different clinical or imaging characteristics predict spot sign presence, using ICH location as a surrogate for arteriolosclerosis- and cerebral amyloid angiopathy-related ICH. Patients with primary ICH and available computed tomography angiography at presentation were included. Predictors of spot sign were assessed using uni- and multivariable regression, stratified by ICH location. Seven hundred forty-one patients were eligible, 335 (45%) deep and 406 (55%) lobar ICH. At least one spot sign was present in 76 (23%) deep and 102 (25%) lobar ICH patients. In multivariable regression, warfarin (odds ratio [OR], 2.42; 95% confidence interval [CI], 1.01-5.71; P=0.04), baseline ICH volume (OR, 1.20; 95% CI, 1.09-1.33, per 10 mL increase; P<0.001), and time from symptom onset to computed tomography angiography (OR, 0.89; 95% CI, 0.80-0.96, per hour; P=0.009) were associated with the spot sign in deep ICH. Predictors of spot sign in lobar ICH were warfarin (OR, 3.95; 95% CI, 1.87-8.51; P<0.001) and baseline ICH volume (OR, 1.20; 95% CI, 1.10-1.31, per 10 mL increase; P<0.001). The most potent associations with spot sign are shared between deep and lobar ICH, suggesting that the acute bleeding process that arises in the setting of different chronic small vessel diseases shares commonalities. © 2014 American Heart Association, Inc.

Association of Key Magnetic Resonance Imaging Markers of Cerebral Small Vessel Disease With Hematoma Volume and Expansion in Patients With Lobar and Deep Intracerebral Hemorrhage

PubMed Central

Boulouis, Gregoire; van Etten, Ellis S.; Charidimou, Andreas; Auriel, Eitan; Morotti, Andrea; Pasi, Marco; Haley, Kellen E.; Brouwers, H. Bart; Ayres, Alison M.; Vashkevich, Anastasia; Jessel, Michael J.; Schwab, Kristin M.; Viswanathan, Anand; Greenberg, Steven M.; Rosand, Jonathan; Goldstein, Joshua N.; Gurol, M. Edip

2017-01-01

IMPORTANCE Hematoma expansion is an important determinant of outcome in spontaneous intracerebral hemorrhage (ICH) due to small vessel disease (SVD), but the association between the severity of the underlying SVD and the extent of bleeding at the acute phase is unknown to date. OBJECTIVE To investigate the association between key magnetic resonance imaging (MRI) markers of SVD (as per the Standards for Reporting Vascular Changes on Neuroimaging [STRIVE] guidelines) and hematoma volume and expansion in patients with lobar or deep ICH. DESIGN, SETTING, AND PARTICIPANTS Analysis of data collected from 418 consecutive patients admitted with primary lobar or deep ICH to a single tertiary care medical center between January 1, 2000, and October 1, 2012. Data were analyzed on March 4, 2016. Participants were consecutive patients with computed tomographic images allowing ICH volume calculation and MRI allowing imaging markers of SVD assessment. MAIN OUTCOMES AND MEASURES The ICH volumes at baseline and within 48 hours after symptom onset were measured in 418 patients with spontaneous ICH without anticoagulant therapy, and hematoma expansion was calculated. Cerebral microbleeds, cortical superficial siderosis, and white matter hyperintensity volume were assessed on MRI. The associations between these SVD markers and ICH volume, as well as hematoma expansion, were investigated using multivariable models. RESULTS This study analyzed 254 patients with lobar ICH (mean [SD] age, 75 [11] years and 140 [55.1%] female) and 164 patients with deep ICH (mean [SD] age 67 [14] years and 71 [43.3%] female). The presence of cortical superficial siderosis was an independent variable associated with larger ICH volume in the lobar ICH group (odds ratio per quintile increase in final ICH volume, 1.49; 95% CI, 1.14–1.94; P = .004). In multivariable models, the absence of cerebral microbleeds was associated with larger ICH volume for both the lobar and deep ICH groups (odds ratios per

Association Between Blood Pressure Control and Risk of Recurrent Intracerebral Hemorrhage.

PubMed

Biffi, Alessandro; Anderson, Christopher D; Battey, Thomas W K; Ayres, Alison M; Greenberg, Steven M; Viswanathan, Anand; Rosand, Jonathan

2015-09-01

Intracerebral hemorrhage (ICH) is the most severe form of stroke. Survivors are at high risk of recurrence, death, and worsening functional disability. To investigate the association between blood pressure (BP) after index ICH and risk of recurrent ICH. Single-site, tertiary care referral center observational study of 1145 of 2197 consecutive patients with ICH presenting from July 1994 to December 2013. A total of 1145 patients with ICH survived at least 90 days and were followed up through December 2013 (median follow-up of 36.8 months [minimum, 9.8 months]). Blood pressure measurements at 3, 6, 9, and 12 months, and every 6 months thereafter, obtained from medical personnel (inpatient hospital or outpatient clinic medical or nursing staff) or via patient self-report. Exposure was characterized in 3 ways: (1) recorded systolic and diastolic measurements; (2) classification as adequate or inadequate BP control based on American Heart Association/American Stroke Association recommendations; and (3) stage of hypertension based on Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure 7 criteria. Recurrent ICH and its location within the brain (lobar vs nonlobar). There were 102 recurrent ICH events among 505 survivors of lobar ICH and 44 recurrent ICH events among 640 survivors of nonlobar ICH. During follow-up adequate BP control was achieved on at least 1 measurement by 625 patients (54.6% of total [range, 49.2%-58.7%]) and consistently (ie, at all available time points) by 495 patients (43.2% of total [range, 34.5%-51.0%]). The event rate for lobar ICH was 84 per 1000 person-years among patients with inadequate BP control compared with 49 per 1000 person-years among patients with adequate BP control. For nonlobar ICH the event rate was 52 per 1000 person-years with inadequate BP control compared with 27 per 1000 person-years for patients with adequate BP control. In analyses modeling BP control as a time

Early recombinant factor VIIa therapy in acute intracerebral hemorrhage: promising approach.

PubMed

Kumar, Sudhir; Badrinath, H R

2006-03-01

Intracerebral hemorrhage (ICH) is the most devastating form of stroke with a high morbidity and mortality. ICH constitutes about 20-30% of all strokes, with the prevalence being higher in Asian population. Treatment of ICH is predominantly conservative, which includes control of blood pressure, use of anti-cerebral edema measures such as mannitol and mechanical ventilation. The benefit of early surgery in ICH is debatable. Initial hematoma volume and subsequent growth in its size are important predictors of a poor outcome in ICH. This means that therapies aimed at preventing hematoma enlargement in the earliest possible window period could lead to a better outcome in ICH. Recombinant factor VIIa (rFVIIa) is one such agent, which has been shown to prevent hematoma expansion and improve outcome in acute ICH. The purpose of the current review is to focus on the evidence regarding the usefulness of rFVIIa in acute ICH.

Association of subdural hematoma with increased mortality in lobar intracerebral hemorrhage.

PubMed

Patel, Pratik V; FitzMaurice, Emilie; Nandigam, R N Kaveer; Auluck, Pavan; Viswanathan, Anand; Goldstein, Joshua N; Rosand, Jonathan; Greenberg, Steven M; Smith, Eric E

2009-01-01

To determine the prevalence of subdural hematoma (SDH) in patients presenting with primary nontraumatic lobar intracerebral hemorrhage (ICH) and characteristics associated with the presence of SDH. Retrospective analysis of data collected in a prospective cohort study. Hospital. Consecutive sample of 200 patients with primary lobar ICH and 75 patients with deep hemispheric ICH. Presence of SDH and mortality. Subdural hematoma was present in 40 of 200 patients (20%) with primary lobar ICH. By contrast, SDH was not present in any of 75 consecutive patients with deep hemispheric ICH (P < .001 for comparison with lobar ICH). Intracerebral hemorrhage volume higher than 60 cm3 was the only independent predictor of SDH (odds ratio [OR], 2.69; 95% confidence interval [CI], 1.14-6.34; P = .02). Subdural hematoma thickness more than 5 mm was an independent predictor of increased 30-day mortality (OR, 7.60; 95% CI, 1.86-30.99; P = .005) after controlling for other factors including ICH volume. Further analysis showed that the effect of SDH on mortality depended on ICH volume, with larger odds for mortality in those with low ICH volume (OR, 12.85; 95% CI, 2.42-68.23; P = .003 for those with ICH volume <30 cm3). Cerebral amyloid angiopathy was present in 8 of 9 patients with pathological specimens. Nontraumatic SDH frequently accompanies primary lobar ICH and is associated with higher 30-day mortality, particularly when the ICH volume is relatively low. Rupture of an amyloid-laden leptomeningeal vessel, with extravasation into the brain parenchyma and subdural space, may be the pathogenic mechanism.

Rapamycin protects against neuronal death and improves neurological function with modulation of microglia after experimental intracerebral hemorrhage in rats.

PubMed

Li, D; Liu, F; Yang, T; Jin, T; Zhang, H; Luo, X; Wang, M

2016-09-30

Intracerebral hemorrhage (ICH) results in a devastating brain disorder with high mortality and poor prognosis and effective therapeutic intervention for the disease remains a challenge at present. The present study investigated the neuroprotective effects of rapamycin on ICH-induced brain damage and the possible involvement of activated microglia. ICH was induced in rats by injection of type IV collagenase into striatum. Different dose of rapamycin was systemically administrated by intraperitoneal injection beginning at 1 h after ICH induction. Western blot analysis showed that ICH led to a long-lasting increase of phosphorylated mTOR and this hyperactivation of mTOR was reduced by systemic administration of rapamycin. Rapamycin treatment significantly improved the sensorimotor deficits induced by ICH, and attenuated ICH-induced brain edema formation as well as lesion volume. Nissl and Fluoro-Jade C staining demonstrated that administration with rapamycin remarkably decreased neuronal death surrounding the hematoma at 7 d after ICH insult. ELISA and real-time quantitative PCR demonstrated that rapamycin inhibited ICH-induced excessive expression of TNF-α and IL-1β in ipsilateral hemisphere. Furthermore, activation of microglia induced by ICH was significantly suppressed by rapamycin administration. These data indicated that treatment of rapamycin following ICH decreased the brain injuries and neuronal death at the peri-hematoma striatum, and increased neurological function, which associated with reduced the levels of proinflammatory cytokines and activated microglia. The results provide novel insight into the neuroprotective therapeutic strategy of rapamycin for ICH insult, which possibly involving the regulation of microglial activation.

Progress in translational research on intracerebral hemorrhage: Is there an end in sight?

PubMed Central

Xi, Guohua; Strahle, Jennifer; Hua, Ya; Keep, Richard F.

2013-01-01

Intracerebral hemorrhage (ICH) is a common and often fatal stroke subtype for which specific therapies and treatments remain elusive. To address this, many recent experimental and translational studies of ICH have been conducted, and these have led to several ongoing clinical trials. This review focuses on the progress of translational studies of ICH including those of the underlying causes and natural history of ICH, animal models of the condition, and effects of ICH on the immune and cardiac systems, among others. Current and potential clinical trials also are discussed for both ICH alone and with intraventricular extension. PMID:24139872

Application of the FOUR Score in Intracerebral Hemorrhage Risk Analysis.

PubMed

Braksick, Sherri A; Hemphill, J Claude; Mandrekar, Jay; Wijdicks, Eelco F M; Fugate, Jennifer E

2018-06-01

The Full Outline of Unresponsiveness (FOUR) Score is a validated scale describing the essentials of a coma examination, including motor response, eye opening and eye movements, brainstem reflexes, and respiratory pattern. We incorporated the FOUR Score into the existing ICH Score and evaluated its accuracy of risk assessment in spontaneous intracerebral hemorrhage (ICH). Consecutive patients admitted to our institution from 2009 to 2012 with spontaneous ICH were reviewed. The ICH Score was calculated using patient age, hemorrhage location, hemorrhage volume, evidence of intraventricular extension, and Glasgow Coma Scale (GCS). The FOUR Score was then incorporated into the ICH Score as a substitute for the GCS (ICH Score FS ). The ability of the 2 scores to predict mortality at 1 month was then compared. In total, 274 patients met the inclusion criteria. The median age was 73 years (interquartile range 60-82) and 138 (50.4%) were male. Overall mortality at 1 month was 28.8% (n = 79). The area under the receiver operating characteristic curve was .91 for the ICH Score and .89 for the ICH Score FS . For ICH Scores of 1, 2, 3, 4, and 5, 1-month mortality was 4.2%, 29.9%, 62.5%, 95.0%, and 100%. In the ICH Score FS model, mortality was 10.7%, 26.5%, 64.5%, 88.9%, and 100% for scores of 1, 2, 3, 4, and 5, respectively. The ICH Score and the ICH Score FS predict 1-month mortality with comparable accuracy. As the FOUR Score provides additional clinical information regarding patient status, it may be a reasonable substitute for the GCS into the ICH Score. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Retrospective Methods Analysis of Semiautomated Intracerebral Hemorrhage Volume Quantification From a Selection of the STICH II Cohort (Early Surgery Versus Initial Conservative Treatment in Patients With Spontaneous Supratentorial Lobar Intracerebral Haematomas).

PubMed

Haley, Mark D; Gregson, Barbara A; Mould, W Andrew; Hanley, Daniel F; Mendelow, Alexander David

2018-02-01

The ABC/2 method for calculating intracerebral hemorrhage (ICH) volume has been well validated. However, the formula, derived from the volume of an ellipse, assumes the shape of ICH is elliptical. We sought to compare the agreement of the ABC/2 formula with other methods through retrospective analysis of a selection of the STICH II cohort (Early Surgery Versus Initial Conservative Treatment in Patients With Spontaneous Supratentorial Lobar Intracerebral Haematomas). From 390 patients, 739 scans were selected from the STICH II image archive based on the availability of a CT scan compatible with OsiriX DICOM viewer. ICH volumes were calculated by the reference standard semiautomatic segmentation in OsiriX software and compared with calculated arithmetic methods (ABC/2, ABC/2.4, ABC/3, and 2/3SC) volumes. Volumes were compared by difference plots for specific groups: randomization ICH (n=374), 3- to 7-day postsurgical ICH (n=206), antithrombotic-associated ICH (n=79), irregular-shape ICH (n=703) and irregular-density ICH (n=650). Density and shape were measured by the Barras ordinal shape and density groups (1-5). The ABC/2.4 method had the closest agreement to the semiautomatic segmentation volume in all groups, except for the 3- to 7-day postsurgical ICH group where the ABC/3 method was superior. Although the ABC/2 formula for calculating elliptical ICH is well validated, it must be used with caution in ICH scans where the elliptical shape of ICH is a false assumption. We validated the adjustment of the ABC/2.4 method in randomization, antithrombotic-associated, heterogeneous-density, and irregular-shape ICH. URL: http://www.isrctn.com/ISRCTN22153967. Unique identifier: ISRCTN22153967. © 2018 American Heart Association, Inc.

Ideal cardiovascular health score at the ELSA-Brasil baseline and its association with sociodemographic characteristics.

PubMed

Machado, Lucas B M; Silva, Bianca L S; Garcia, Ana P; Oliveira, Renata A M; Barreto, Sandhi M; Fonseca, Maria de Jesus M; Lotufo, Paulo A; Bensenor, Isabela M; Santos, Itamar S

2018-03-01

The American Heart Association's ideal cardiovascular health (ICH) define criteria for seven metrics, four classified as lifestyle factors (diet, physical activity, smoking and body-mass index) and four classified as health factors (smoking, blood pressure, fasting plasma glucose and total cholesterol). We aimed to analyze ICH scores at the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) baseline assessment and the associations with sociodemographic characteristics (age, sex, race, educational level, and family income). We analyzed 13,356 ELSA-Brasil participants without cardiovascular disease using quasi-Poisson regression models to study the association between the ICH score and sociodemographic characteristics. Mean ICH scores were 2.5±1.3. Only 1047 (7.8%) participants had 5 or more ICH metrics. In adjusted models, age 65-74years was associated with lower ICH scores (-35.4%; 95% confidence interval [CI]: -37.6% to -33.1%) compared to age 35-44years. Women had higher ICH scores compared to men (+13.8%; 95%CI: +11.8% to +15.7%), mainly due to differences in the health factor ICH metrics. Participants of Black race had lower ICH scores compared to those of White race (-9.4%; 95%CI: -11.8% to -7.0%). Individuals with less than high school education had lower ICH scores than college-educated individuals (-17.2%; 95%CI: -20.0% to -14.2%). Low (<1245 USD) family income was also associated with lower ICH scores compared to those with high (≥3320 USD) family income (-4.4%, 95%CI: -7.2% to -1.6%). We found a low proportion of individuals with 5 or more ICH metrics. Age, sex, race, educational level and income were associated with ICH scores. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

[MRI semiotics features of experimental acute intracerebral hematomas].

PubMed

Burenchev, D V; Skvortsova, V I; Tvorogova, T V; Guseva, O I; Gubskiĭ, L V; Kupriianov, D A; Pirogov, Iu A

2009-01-01

The aim of this study was to assess the possibility of revealing intracerebral hematomas (ICH), using MRI, within the first hours after onset and to determine their MRI semiotics features. Thirty animals with experimental ICH were studied. A method of two-stage introduction of autologous blood was used to develop ICH as human spontaneous intracranial hematomas. Within 3-5h after blood introduction to the rat brain. The control MRI was performed in the 3rd and 7th days after blood injections. ICH were definitely identified in the first MRI scans. The MRI semiotics features of acute ICH and their transformations were assessed. The high sensitivity of MRI to ICH as well as the uniform manifestations in all animals were shown. In conclusion, the method has high specificity for acute ICH detection.

Changes in motor function, cognition, and emotion-related behavior after right hemispheric intracerebral hemorrhage in various brain regions of mouse.

PubMed

Zhu, Wei; Gao, Yufeng; Wan, Jieru; Lan, Xi; Han, Xiaoning; Zhu, Shanshan; Zang, Weidong; Chen, Xuemei; Ziai, Wendy; Hanley, Daniel F; Russo, Scott J; Jorge, Ricardo E; Wang, Jian

2018-03-01

Intracerebral hemorrhage (ICH) is a detrimental type of stroke. Mouse models of ICH, induced by collagenase or blood infusion, commonly target striatum, but not other brain sites such as ventricular system, cortex, and hippocampus. Few studies have systemically investigated brain damage and neurobehavioral deficits that develop in animal models of ICH in these areas of the right hemisphere. Therefore, we evaluated the brain damage and neurobehavioral dysfunction associated with right hemispheric ICH in ventricle, cortex, hippocampus, and striatum. The ICH model was induced by autologous whole blood or collagenase VII-S (0.075 units in 0.5 µl saline) injection. At different time points after ICH induction, mice were assessed for brain tissue damage and neurobehavioral deficits. Sham control mice were used for comparison. We found that ICH location influenced features of brain damage, microglia/macrophage activation, and behavioral deficits. Furthermore, the 24-point neurologic deficit scoring system was most sensitive for evaluating locomotor abnormalities in all four models, especially on days 1, 3, and 7 post-ICH. The wire-hanging test was useful for evaluating locomotor abnormalities in models of striatal, intraventricular, and cortical ICH. The cylinder test identified locomotor abnormalities only in the striatal ICH model. The novel object recognition test was effective for evaluating recognition memory dysfunction in all models except for striatal ICH. The tail suspension test, forced swim test, and sucrose preference test were effective for evaluating emotional abnormality in all four models but did not correlate with severity of brain damage. These results will help to inform future preclinical studies of ICH outcomes. Copyright © 2018 Elsevier Inc. All rights reserved.

Association of Subdural Hematoma With Increased Mortality in Lobar Intracerebral Hemorrhage

PubMed Central

Patel, Pratik V.; FitzMaurice, Emilie; Kaveer Nandigam, R. N.; Auluck, Pavan; Viswanathan, Anand; Goldstein, Joshua N.; Rosand, Jonathan; Greenberg, Steven M.; Smith, Eric E.

2011-01-01

Objective To determine the prevalence of subdural hematoma (SDH) in patients presenting with primary non-traumatic lobar intracerebral hemorrhage (ICH) and characteristics associated with the presence of SDH. Design Retrospective analysis of data collected in a prospective cohort study. Setting Hospital. Patients Consecutive sample of 200 patients with primary lobar ICH and 75 patients with deep hemispheric ICH. Main Outcome Measures Presence of SDH and mortality. Results Subdural hematoma was present in 40 of 200 patients (20%) with primary lobar ICH. By contrast, SDH was not present in any of 75 consecutive patients with deep hemispheric ICH (P<.001 for comparison with lobar ICH). Intracerebral hemorrhage volume higher than 60 cm3 was the only independent predictor of SDH (odds ratio [OR], 2.69; 95% confidence interval [CI], 1.14–6.34; P=.02). Subdural hematoma thickness more than 5 mm was an independent predictor of increased 30-day mortality (OR, 7.60; 95% CI, 1.86–30.99; P=.005) after controlling for other factors including ICH volume. Further analysis showed that the effect of SDH on mortality depended on ICH volume, with larger odds for mortality in those with low ICH volume (OR, 12.85; 95% CI, 2.42–68.23; P=.003 for those with ICH volume <30 cm3). Cerebral amyloid angiopathy was present in 8 of 9 patients with pathological specimens. Conclusions Nontraumatic SDH frequently accompanies primary lobar ICH and is associated with higher 30-day mortality, particularly when the ICH volume is relatively low. Rupture of an amyloid-laden leptomeningeal vessel, with extravasation into the brain parenchyma and subdural space, may be the pathogenic mechanism. PMID:19139303

Comparing intracerebral hemorrhages associated with direct oral anticoagulants or warfarin

PubMed Central

Kurogi, Ryota; Nishimura, Kunihiro; Nakai, Michikazu; Kada, Akiko; Kamitani, Satoru; Nakagawara, Jyoji; Toyoda, Kazunori; Ogasawara, Kuniaki; Ono, Junichi; Shiokawa, Yoshiaki; Aruga, Toru; Miyachi, Shigeru; Nagata, Izumi; Matsuda, Shinya; Yoshimura, Shinichi; Okuchi, Kazuo; Suzuki, Akifumi; Nakamura, Fumiaki; Onozuka, Daisuke; Ido, Keisuke; Kurogi, Ai; Mukae, Nobutaka; Nishimura, Ataru; Arimura, Koichi; Kitazono, Takanari; Hagihara, Akihito

2018-01-01

Objectives This cross-sectional survey explored the characteristics and outcomes of direct oral anticoagulant (DOAC)–associated nontraumatic intracerebral hemorrhages (ICHs) by analyzing a large nationwide Japanese discharge database. Methods We analyzed data from 2,245 patients who experienced ICHs while taking anticoagulants (DOAC: 227; warfarin: 2,018) and were urgently hospitalized at 621 institutions in Japan between April 2010 and March 2015. We compared the DOAC- and warfarin-treated patients based on their backgrounds, ICH severities, antiplatelet therapies at admission, hematoma removal surgeries, reversal agents, mortality rates, and modified Rankin Scale scores at discharge. Results DOAC-associated ICHs were less likely to cause moderately or severely impaired consciousness (DOAC-associated ICHs: 31.3%; warfarin-associated ICHs: 39.4%; p = 0.002) or require surgical removal (DOAC-associated ICHs: 5.3%; warfarin-associated ICHs: 9.9%; p = 0.024) in the univariate analysis. Propensity score analysis revealed that patients with DOAC-associated ICHs also exhibited lower mortality rates within 1 day (odds ratio [OR] 4.96, p = 0.005), within 7 days (OR 2.29, p = 0.037), and during hospitalization (OR 1.96, p = 0.039). Conclusions This nationwide study revealed that DOAC-treated patients had less severe ICHs and lower mortality rates than did warfarin-treated patients, probably due to milder hemorrhages at admission and lower hematoma expansion frequencies. PMID:29490916

Priorities for clinical research in intracerebral hemorrhage: report from a National Institute of Neurological Disorders and Stroke workshop.

PubMed

2005-03-01

Spontaneous intracerebral hemorrhage (ICH) is one of the most lethal stroke types. In December 2003, a National Institute of Neurological Disorders and Stroke (NINDS) workshop was convened to develop a consensus for ICH research priorities. The focus was clinical research aimed at acute ICH in patients. Workshop participants were divided into 6 groups: (1) current state of ICH research; (2) basic science; and (3) imaging, (4) medical, (5) surgical, and (6) clinical methodology. Each group formulated research priorities before the workshop. At the workshop, these were discussed and refined. Recent progress in management of hemorrhage growth, intraventricular hemorrhage, and limitations in the benefit of open craniotomy were noted. The workshop identified the importance of developing animal models to reflect human ICH, as well as the phenomena of rebleeding. More human ICH pathology is needed. Real-time, high-field magnets and 3-dimensional imaging, as well as high-resolution tissue probes, are ICH imaging priorities. Trials of acute blood pressure-lowering in ICH and coagulopathy reversal are medical priorities. The exact role of edema in human ICH pathology and its treatment requires intensive study. Trials of minimally invasive surgical techniques including mechanical and chemical surgical adjuncts are critically important. The methodologic challenges include establishing research networks and a multi-specialty approach. Waiver of consent issues and standardizing care in trials are important issues. Encouragement of young investigators from varied backgrounds to enter the ICH research field is critical. Increasing ICH research is crucial. A collaborative approach is likely to yield therapies for this devastating form of brain injury.

EPH Receptor B4 (EPHB4) Gene Polymorphisms and Risk of Intracranial Hemorrhage in Patients with Brain Arteriovenous Malformations

PubMed Central

Weinsheimer, Shantel; Kim, Helen; Pawlikowska, Ludmila; Chen, Yongmei; Lawton, Michael T.; Sidney, Stephen; Kwok, Pui-Yan; McCulloch, Charles E.; Young, William L.

2009-01-01

Background Brain arteriovenous malformations (BAVM) are a tangle of abnormal vessels directly shunting blood from the arterial to venous circulation and an important cause of intracranial hemorrhage (ICH). EphB4 is involved in arterial-venous determination during embryogenesis; altered signaling could lead to vascular instability resulting in ICH. We investigated the association of single-nucleotide polymorphisms (SNPs) and haplotypes in EPHB4 with risk of ICH at clinical presentation in BAVM patients. Methods and Results Eight haplotype-tagging SNPs spanning ∼29 kb were tested for association with ICH presentation in 146 Caucasian BAVM patients (phase I: 56 ICH, 90 non-ICH) using allelic, haplotypic, and principal components analysis. Associated SNPs were then genotyped in 102 additional cases (phase II: 37 ICH, 65 non-ICH) and data combined for multivariable logistic regression. Minor alleles of 2 SNPs were associated with reduced risk of ICH presentation (rs314313 C, P=0.005; rs314308 T, P=0.0004). Overall, haplotypes were also significantly associated with ICH presentation (χ2=17.24, 6 df, P=0.008); 2 haplotypes containing the rs314308 T allele (GCCTGGGT, P=0.003; GTCTGGGC, P=0.036) were associated with reduced risk. In principal components analysis, 2 components explained 91% of the variance, and complemented haplotype results by implicating 4 SNPs at the 5′ end, including rs314308 and rs314313. These 2 SNPs were replicated in the phase II cohort, and combined data resulted in greater significance (rs314313, P=0.0007; rs314308, P=0.00008). SNP association with ICH presentation persisted after adjusting for age, sex, BAVM size, and deep venous drainage. Conclusions EPHB4 polymorphisms are associated with risk of ICH presentation in BAVM patients, warranting further study. PMID:20031623

The incidence, risk and functional outcomes of intracranial haemorrhage in children with inherited bleeding disorders at one haemophilia center.

PubMed

Bladen, M; Main, E; Khair, K; Hubert, N; Koutoumanou, E; Liesner, R

2016-07-01

Intracranial haemorrhage (ICH) is the most serious bleeding event for patients with inherited bleeding disorders (IBD). The risks and long-term consequences remain unknown. This single-centre service evaluation aimed to identify the incidence, risks and long-term outcomes following ICH in patients with IBD. The IBD database and medical notes between 1987 and 2013 were reviewed. Children without apparent neurological deficit following ICH completed standardized assessments and supplementary information sheets. ICH was confirmed in 38/1111 children with IBD. The overall risk of ICH amongst children with IBD was 3.4% (95% CI: 2.5, 4.7%). However, 27/38 had an ICH in the first year of life, 18 of which were in the neonatal period. In children with IBD who had an ICH, the risks of ICH in the neonatal period or first year of life were 18/38 (47%) (95% CI: 32, 63%) and 27/38 (71%) (95% CI: 55, 83%) respectively. Mortality risk from ICH in children with an IBD was 5/38 (13%) (95% CI: 5.8, 27.3 %). Ten of 32 survivors had known neurological sequelae including motor disorder deficits (MDD) while 22 had no documented evidence of neurological impairment or MDD. Re-evaluation was possible in 17/22 children, 8 of whom demonstrated evidence of MDD. After re-evaluation, the risk of significant neurological MDD from ICH increased from 31% CI (95% CI: 18, 49%) to 56% CI (95% CI: 39, 72%). Risks and consequences of ICH in IBD were highest within the neonatal period and first year of life. MDD after ICH was not reliably identified in early life and ongoing monitoring in the first decade of life will facilitate educational support or physical rehabilitation. © 2016 John Wiley & Sons Ltd.

Risk factors for intracranial hemorrhage in acute ischemic stroke patients treated with recombinant tissue plasminogen activator: a systematic review and meta-analysis of 55 studies.

PubMed

Whiteley, William N; Slot, Karsten Bruins; Fernandes, Peter; Sandercock, Peter; Wardlaw, Joanna

2012-11-01

Recombinant tissue plasminogen activator (rtPA) is an effective treatment for acute ischemic stroke but is associated with an increased risk of intracranial hemorrhage (ICH). We sought to identify the risk factors for ICH with a systematic review of the published literature. We searched for studies of rtPA-treated stroke patients that reported an association between a variable measured before rtPA infusion and clinically important ICH (parenchymal ICH or ICH associated with clinical deterioration). We calculated associations between baseline variables and ICH with random-effect meta-analyses. We identified 55 studies that measured 43 baseline variables in 65 264 acute ischemic stroke patients. Post-rtPA ICH was associated with higher age (odds ratio, 1.03 per year; 95% confidence interval, 1.01-1.04), higher stroke severity (odds ratio, 1.08 per National Institutes of Health Stroke Scale point; 95% confidence interval, 1.06-1.11), and higher glucose (odds ratio, 1.10 per mmol/L; 95% confidence interval, 1.05-1.14). There was approximately a doubling of the odds of ICH with the presence of atrial fibrillation, congestive heart failure, renal impairment, previous antiplatelet agents, leukoaraiosis, and a visible acute cerebral ischemic lesion on pretreatment brain imaging. Little of the variation in the sizes of the associations among different studies was explained by the source of the cohort, definition of ICH, or degree of adjustment for confounding variables. Individual baseline variables were modestly associated with post-rtPA ICH. Prediction of post-rtPA ICH therefore is likely to be difficult if based on single clinical or imaging factors alone. These observational data do not provide a reliable method for the individualization of treatment according to predicted ICH risk.

Silymarin prevents NLRP3 inflammasome activation and protects against intracerebral hemorrhage.

PubMed

Yuan, Raorao; Fan, Hengyi; Cheng, Shiqi; Gao, WeiWei; Xu, Xin; Lv, Shigang; Ye, Minhua; Wu, Miaojing; Zhu, Xingen; Zhang, Yan

2017-09-01

Inflammatory response mediates secondary injury during intracerebral hemorrhage (ICH). In the present study, we determined oxidative stress and involvement of NLRP3 in ICH injury and analyzed whether silymarin might offer protective effect against ICH injury. Post 24h after ICH injury there was increased oxidative stress markers (reactive oxygen species (ROS) and lipid peroxides) compared to sham group. Silymarin (200mg/kg) treatment 30 mins post ICH injury prevented increase in oxidative stress markers and up-regulated antioxidant status. Further, there was significant increase in nuclear levels of NF-κB-p65 and pro-inflammatory cytokine expressions post ICH injury. NLRP3 inflammasome activation and downstream targets such as caspase-1 and IL-1β expressions were significantly up regulated in ICH injury. Silymarin treatment significantly down regulated the inflammatory responses by suppressing NF-κB-p65 levels and inflammasome-mediated caspase-1/IL-1β expressions. Further, treatment with silymarin post ICH injury increased Nrf-2/HO-1 and thereby improved overall cytoprotection. These findings together show that silymarin acts as neuroprotective compound by preventing inflammatory activation and up regulating Nrf-2/HO-1 signaling post ICH injury. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Computed tomography angiography spot sign predicts intraprocedural aneurysm rupture in subarachnoid hemorrhage.

PubMed

Burkhardt, Jan-Karl; Neidert, Marian Christoph; Stienen, Martin Nikolaus; Schöni, Daniel; Fung, Christian; Roethlisberger, Michel; Corniola, Marco Vincenzo; Bervini, David; Maduri, Rodolfo; Valsecchi, Daniele; Tok, Sina; Schatlo, Bawarjan; Bijlenga, Philippe; Schaller, Karl; Bozinov, Oliver; Regli, Luca

2017-07-01

To analyze whether the computed tomography angiography (CTA) spot sign predicts the intraprocedural rupture rate and outcome in patients with aneurysmal subarachnoid hemorrhage (aSAH). From a prospective nationwide multicenter registry database, 1023 patients with aneurysmal subarachnoid hemorrhage (aSAH) were analyzed retrospectively. Descriptive statistics and logistic regression analysis were used to compare spot sign-positive and -negative patients with aneurysmal intracerebral hemorrhage (aICH) for baseline characteristics, aneurysmal and ICH imaging characteristics, treatment and admission status as well as outcome at discharge and 1-year follow-up (1YFU) using the modified Rankin Scale (mRS). A total of 218 out of 1023 aSAH patients (21%) presented with aICH including 23/218 (11%) patients with spot sign. Baseline characteristics were comparable between spot sign-positive and -negative patients. There was a higher clip-to-coil ratio in patients with than without aICH (both spot sign positive and negative). Median aICH volume was significantly higher in the spot sign-positive group (50 ml, 13-223 ml) than in the spot sign-negative group (18 ml, 1-416; p < 0.0001). Patients with a spot sign-positive aICH thus were three times as likely as those with spot sign-negative aICH to show an intraoperative aneurysm rupture [odds ratio (OR) 3.04, 95% confidence interval (CI) 1.04-8.92, p = 0.046]. Spot sign-positive aICH patients showed a significantly worse mRS at discharge (p = 0.039) than patients with spot sign-negative aICH (median mRS 5 vs. 4). Logistic regression analysis showed that the spot sign was an aICH volume-dependent predictor for outcome. Both spot sign-positive and -negative aICH patients showed comparable rates of hospital death, death at 1YFU and mRS at 1YFU. In this multicenter data analysis, patients with spot sign-positive aICH showed higher aICH volumes and a higher rate of intraprocedural aneurysm rupture, but comparable long

Gastrointestinal bleeding after intracerebral hemorrhage: a retrospective review of 808 cases.

PubMed

Yang, Tie-Cheng; Li, Jian-Guo; Shi, Hong-Mei; Yu, Dong-Ming; Shan, Kai; Li, Li-Xia; Dong, Xiao-Yan; Ren, Tian-Hua

2013-10-01

This study examined the incidence and risk factors for gastrointestinal (GI) bleeding after spontaneous intracerebral hemorrhage (ICH). The available medical records of patients with ICH admitted from June 2008 to December 2009 for any episode of GI bleeding, possible precipitating factors and administration of ulcer prophylaxis were reviewed. The prevalence of GI bleeding was 26.7%, including 3 cases of severe GI bleeding (0.35%). Patients with GI bleeding had significantly longer hospital stay and higher in-hospital mortality compared with patients without GI bleeding. Multivariate logistic regression analyses showed that age, Glasgow Coma Scale scores, sepsis and ICH volume were independent predictors of GI bleeding. About 63.4% of patients with ICH received stress ulcer prophylaxis. GI bleeding occurred frequently after ICH, but severe events were rare. Age, Glasgow Coma Scale score, sepsis and ICH volume were independent predictors of GI bleeding occurring after ICH.

Motor Skills Training Enhances α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid Receptor Subunit mRNA Expression in the Ipsilateral Sensorimotor Cortex and Striatum of Rats Following Intracerebral Hemorrhage.

PubMed

Tamakoshi, Keigo; Ishida, Kazuto; Kawanaka, Kentaro; Takamatsu, Yasuyuki; Tamaki, Hiroyuki

2017-10-01

We investigated the effects of acrobatic training (AT) on expression of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) subunits in the sensorimotor cortex and striatum after intracerebral hemorrhage (ICH). Male Wistar rats were divided into 4 groups: ICH without AT (ICH), ICH with AT (ICH + AT), sham operation without AT (SHAM), and sham operation with AT (SHAM + AT). ICH was induced by collagenase injection into the left striatum. The ICH + AT group performed 5 acrobatic tasks daily on days 4-28 post ICH. Forelimb sensorimotor function was evaluated using the forelimb placing test. On days 14 and 29, mRNA expression levels of AMPAR subunits GluR1-4 were measured by real-time reverse transcription-polymerase chain reaction. Forelimb placing test scores were significantly higher in the ICH + AT group than in the ICH group. Expression levels of all AMPAR subunit mRNAs were significantly higher in the ipsilateral sensorimotor cortex of rats in the ICH + AT group than in that of rats in the ICH group on day 29. GluR3 and GluR4 expression levels were reduced in the ipsilateral striatum of rats in the ICH group compared with that of rats in the SHAM group on day 14. These changes may play a critical role in motor skills training-induced recovery after ICH. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

The Effect of Age on Characteristics and Mortality of Intracerebral Hemorrhage in the Oldest-Old.

PubMed

Forti, Paola; Maioli, Fabiola; Domenico Spampinato, Michele; Barbara, Carlotta; Nativio, Valeria; Coveri, Maura; Zoli, Marco; Simonetti, Luigi; Di Pasquale, Giuseppe; Procaccianti, Gaetano

2016-01-01

Incidence of acute intracerebral hemorrhage (ICH) increases with age, but there is a lack of information about ICH characteristics in the oldest-old (age ≥85 years). In particular, there is a need for information about hematoma volume, which is included in most clinical scales for prediction of mortality in ICH patients. Many of these scales also assume that, independent of ICH characteristics, the oldest-old have a higher mortality than younger elderly patients (age 65-74 years). However, supporting evidence from cohort studies is limited. We investigated ICH characteristics of oldest-old subjects compared to young (<65 years), young-old (65-74 years) and old-old (75-84 years) subjects. We also investigated whether age is an independent mortality predictor in elderly (age ≥65 years) subjects with acute ICH. We retrospectively collected clinical and neuroimaging data of 383 subjects (age 34-104 years) with acute supratentorial primary ICH who were admitted to an Italian Stroke Unit (SU) between October 2007 and December 2014. Measured ICH characteristics included hematoma location, volume and intraventricular extension of hemorrhage on admission CT scan; admission Glasgow Coma Scale ≤8 and hematoma expansion (HE) measured on follow-up CT-scans obtained after 24 h. General linear models and logistic models were used to investigate the association of age with ICH characteristics. These models were adjusted for pre-admission characteristics, hematoma location and time from symptom onset to admission CT scan. Limited to elderly subjects, Cox models were used to investigate the association of age with in-SU and 1-year mortality: the model for in-SU mortality adjusted for pre-admission and ICH admission characteristics and the model for 1-year mortality additionally adjusted for functional status and disposition at SU discharge. Independent of pre-admission characteristics, hematoma location and time from symptom onset to admission CT-scan, oldest-old subjects had

Alcohol intake and the risk of intracerebral hemorrhage in the elderly: The MUCH-Italy.

PubMed

Costa, Paolo; Grassi, Mario; Iacoviello, Licia; Zedde, Marialuisa; Marcheselli, Simona; Silvestrelli, Giorgio; DeLodovici, Maria Luisa; Sessa, Maria; Zini, Andrea; Paciaroni, Maurizio; Azzini, Cristiano; Gamba, Massimo; Del Sette, Massimo; Toriello, Antonella; Gandolfo, Carlo; Bonifati, Domenico Marco; Tassi, Rossana; Cavallini, Anna; Chiti, Alberto; Calabrò, Rocco Salvatore; Grillo, Francesco; Bovi, Paolo; Tomelleri, Giampaolo; Di Castelnuovo, Augusto; Ritelli, Marco; Agnelli, Giancarlo; De Vito, Alessandro; Pugliese, Nicola; Martini, Giuseppe; Lodigiani, Corrado; Morotti, Andrea; Poli, Loris; De Giuli, Valeria; Caria, Filomena; Cornali, Claudio; de Gaetano, Giovanni; Colombi, Marina; Padovani, Alessandro; Pezzini, Alessandro

2018-06-13

To investigate the role of alcohol as a causal factor for intracerebral hemorrhage (ICH) and whether its effects might vary according to the pathogenic mechanisms underlying cerebral bleeding. We performed a case-control analysis, comparing a cohort of consecutive white patients with ICH aged 55 years and older with a group of age- and sex-matched stroke-free controls, enrolled in the setting of the Multicenter Study on Cerebral Haemorrhage in Italy (MUCH-Italy) between 2002 and 2014. Participants were dichotomized into excessive drinkers (>45 g of alcohol) and light to moderate drinkers or nondrinkers. To isolate the unconfounded effect of alcohol on ICH, we used causal directed acyclic graphs and the back-door criterion to select a minimal sufficient adjustment set(s) of variables for multivariable analyses. Analyses were performed on the whole group as well as separately for lobar and deep ICH. We analyzed 3,173 patients (1,471 lobar ICH and 1,702 deep ICH) and 3,155 controls. After adjusting for the preselected variables in the minimal sufficient adjustments, heavy alcohol intake was associated with deep ICH risk (odds ratio [OR], 1.68; 95% confidence interval [CI], 1.36-2.09) as well as with the overall risk of ICH (OR, 1.38; 95% CI, 1.17-1.63), whereas no effect was found for lobar ICH (OR, 1.01; 95% CI, 0.77-1.32). In white people aged 55 years and older, high alcohol intake might exert a causal effect on ICH, with a prominent role in the vascular pathologies underlying deep ICH. © 2018 American Academy of Neurology.

New understandings of the genetic basis of isolated idiopathic central hypogonadism.

PubMed

Bonomi, Marco; Libri, Domenico Vladimiro; Guizzardi, Fabiana; Guarducci, Elena; Maiolo, Elisabetta; Pignatti, Elisa; Asci, Roberta; Persani, Luca

2012-01-01

Idiopathic hypogonadotropic hypogonadism is a rare disease that is characterized by delayed/absent puberty and/or infertility due to an insufficient stimulation of an otherwise normal pituitary-gonadal axis by gonadotrophin-releasing hormone (GnRH) action. Because reduced or normal luteinizing hormone (LH)/follicle-stimulating hormone (FSH) levels may be observed in the affected patients, the term idiopathic central hypogonadism (ICH) appears to be more appropriate. This disease should be distinguished from central hypogonadism that is combined with other pituitary deficiencies. Isolated ICH has a complex pathogenesis and is fivefold more prevalent in males. ICH frequently appears in a sporadic form, but several familial cases have also been reported. This finding, in conjunction with the description of numerous pathogenetic gene variants and the generation of several knockout models, supports the existence of a strong genetic component. ICH may be associated with several morphogenetic abnormalities, which include osmic defects that, with ICH, constitute the cardinal manifestations of Kallmann syndrome (KS). KS accounts for approximately 40% of the total ICH cases and has been generally considered to be a distinct subgroup. However, the description of several pedigrees, which include relatives who are affected either with isolated osmic defects, KS, or normo-osmic ICH (nICH), justifies the emerging idea that ICH is a complex genetic disease that is characterized by variable expressivity and penetrance. In this context, either multiple gene variants or environmental factors and epigenetic modifications may contribute to the variable disease manifestations. We review the genetic mechanisms that are presently known to be involved in ICH pathogenesis and provide a clinical overview of the 227 cases that have been collected by the collaborating centres of the Italian ICH Network.

Inflammation, edema and poor outcome are associated with hyperthermia in hypertensive intracerebral hemorrhages.

PubMed

Iglesias-Rey, Ramón; Rodríguez-Yáñez, Manuel; Arias, Susana; Santamaría, María; Rodríguez-Castro, Emilio; López-Dequidt, Iria; Hervella, Pablo; Sobrino, Tomás; Campos, Francisco; Castillo, José

2018-05-11

The deleterious effect of hyperthermia on intracerebral hemorrhage (ICH) has been studied, however the results are not completely conclusive and new studies are needed to elucidate clinical factors that condition the poor outcome. The aim of this study was to identify the clinical factors (including ICH etiology) that influence the poor outcome associated with hyperthermia on ICH. We additionally tried to identify potential mechanisms involved in hyperthermia during ICH. From a prospective registry, we conducted a retrospective study enrolling non-traumatic ICH patients. We used logistic regression models to analyze the influence of hyperthermia in relation to different inflammatory and endothelial dysfunction markers, hematoma growth and edema volume in hypertensive and non-hypertensive ICH patients. We included 887 ICH patients: 433 hypertensive, 50 amyloid, 117 by anticoagulants and 287 by other causes. Patients with hypertensive ICH showed the higher body temperature (37.5±0.8°C) as well as the maximum increase in temperature (0.9±0.1°C) within the first 24 hours. ICH patients with hypertensive etiologic origin, who presented hyperthermia, showed a 5.3 fold-higher risk to have poor outcome at 3 months. We found a positive relationship (r=0.717, P<0.0001) between edema volume and hyperthermia during the first 24 hours but only in ICH patients with hypertensive etiologic origin, and this relationship seems to be mediated by inflammatory markers. Our data suggest that hyperthermia, together with inflammation and edema is associated with poor outcome only in ICH from hypertensive etiology. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

New horizons for primary intracerebral hemorrhage treatment: experience from preclinical studies.

PubMed

Aronowski, Jaroslaw; Hall, Christiana E

2005-04-01

Intracerebral hemorrhage (ICH) remains a major medical problem, for which there is no effective treatment. However, extensive experimental and clinical research carried out in recent years has brought to light new exciting ideas for novel potential treatments. First, it was well documented that the management of hypertension helps to prevent new and recurrent ICH. Also, development of new guidelines for management of hypertension after the onset of the ICH may help in more effective ICH treatment. Existing contemporary data collected from preclinical studies indicates that ICH-induced inflammation represents a key factor leading to secondary brain damage, suggesting that some anti-inflammatory approaches can be used to treat hemorrhagic stroke. In this article, beyond discussing implications related to hypertension, we will summarize important (but not all) new discoveries connecting the role of inflammation to ICH pathology. Selected aspects of inflammatory response including the role of cytokines, transcription factor nuclear factor-kB, microglia activation, astrogliosis, and complement activation will be introduced. We will also discuss the role for reactive oxygen species and metalloproteinases in ICH pathogenesis and introduce basic knowledge on the nature of ICH-induced cell death including apoptosis. Potential targets for intervention and translation will be discussed.

Calcite raft geochemistry as a hydrological proxy for Holocene aquifer conditions in Hoyo Negro and Ich Balam (Sac Actun Cave System), Quintana Roo, Mexico

NASA Astrophysics Data System (ADS)

Kovacs, Shawn E.; Reinhardt, Eduard G.; Chatters, James C.; Rissolo, Dominique; Schwarcz, Henry P.; Collins, Shawn V.; Kim, Sang-Tae; Nava Blank, Alberto; Luna Erreguerena, Pilar

2017-11-01

Two cores from calcite rafts deposits located in Cenote Ich Balam and Hoyo Negro were dated and analyzed for 87Sr/86Sr, δ18O, δ13C, Sr/Ca and Cl/Ca. The geochemical records show changing aquifer salinity spanning the last ∼ 8.5 cal kyrs BP and interrelationships with Holocene climate trends (wet and dry periods). During the wet mid-Holocene, the salinity of the meteoric Water Mass (WM; at 7.8-8.3 cal kyrs BP) was relatively high at 1.5-2.7 ppt and then became less saline (1.0-1.5 ppt) during the last ∼ 7000 yrs as climate became progressively drier. High salinity of the meteoric WM during the wet mid-Holocene is attributed to increased turbulent mixing between the meteoric and underlying marine WM. Increased precipitation, in terms of amount, frequency, and intensity (e.g. hurricanes) causes higher flow of meteoric water towards the coast and mixing at the halocline, a phenomenon recorded with recent instrumental monitoring of the aquifer. Conversely, during dry periods reduced precipitation and flow in the meteoric WM would result in lower salinity. Karst properties and Holocene sea-level rise also seem to have an effect on the aquifer. When the regionally extensive network of shallow cave passages (∼ 10-12 m water depth) are flooded at ∼ 8000 cal yrs BP, there is a rapid shift in salinity. This study demonstrates that calcite raft deposits can be used as paleo-environmental recorders documenting the effects of sea level and climate change on aquifer condition.

Risk of intracerebral hemorrhage associated with phenprocoumon exposure: a nested case-control study in a large population-based German database.

PubMed

Behr, Sigrid; Andersohn, Frank; Garbe, Edeltraut

2010-07-01

Intracerebral hemorrhage (ICH) is the most serious complication of oral anticoagulation. This study investigated the risk of ICH for phenprocoumon which is the most widely used oral anticoagulant in Germany. We conducted a nested case-control study in a cohort of 13.4 million insurants of 4 German statutory health insurances (SHIs) who were continuously enrolled for 6 months prior to cohort entry. Cases were patients hospitalized for ICH. Ten controls were matched to each case by SHI, birth year, and sex using incidence density sampling. Rate ratios (RR) of ICH for current phenprocoumon use as compared to non-use were estimated from odds ratios calculated by conditional logistic regression analyses considering multiple risk factors. Analysis of the full cohort revealed a strong increase in incidence of ICH with increasing age. In the nested case-control study including 8138 cases of ICH and 81,373 matched controls, we observed an increased risk of ICH for current phenprocoumon exposure that varied with age. The phenprocoumon-associated risk of ICH was lower in older age groups with RRs from 4.20 (95% confidence interval (CI) 2.44-7.21) for phenprocoumon users less than 55 years of age to 2.43 (95%CI, 1.81-3.27) for those older than 85 years. Our study confirmed known risk factors of ICH. Phenprocoumon exposure was associated with an increased risk of ICH. The interaction of risk for phenprocoumon with age was unexpected and needs further study. (c) 2010 John Wiley & Sons, Ltd.

Not In-Service Railway Arched Bridges and Their Future/ Nieużytkowane Kolejowe Mosty Sklepione I Ich Przyszłość

NASA Astrophysics Data System (ADS)

Juszczyk, Artur; Dankowski, Marek; Wysokowski, Adam

2015-06-01

At the turn of the 19th and 20th century, on the areas of today northern and western Poland, the railway infrastructure was developing rapidly. In the late 80's of the previous century many of the railway lines, together with the whole infrastructure including bridges, were being closed down. The example of such practices can be the brick bridge located near Nojewo, Voivodeship wielkopolskie. This article presents the technical parameters of these bridges and their damages as well as ideas for the future development of the railway facilities. Na przełomie XIX i XX wieku na terenie dzisiejszej Polski zachodniej i północnej bardzo intensywnie rozwijana była infrastruktura kolejowa. W efekcie tych działań powstała sieć dróg żelaznych o dużym zagęszczeniu. Pod koniec lat 80-tych ubiegłego stulecia wiele z tych linii było stopniowo zamykanych. Na skutek tych przemian wiele linii oraz obiektów z nimi związanych, w tym obiekty mostowe, zostały pozostawione niekorzystnemu działaniu czasu. Przykładem takich wyłączonych z eksploatacji obiektów są mosty i wiadukty położone w okolicy miejscowości Nojewo. Wspomniane obiekty inżynierskie to ceglane konstrukcje sklepione znajdujące się w ciągu linii kolejowej nr 368 łączącej Szamotuły i Międzychód. W artykule zaprezentowano problem rewitalizacji nieużytkowanych mostów kolejowych na przykładzie obiektów w miejscowości Nojewo w województwie wielkopolskim. Opisano podstawowe parametry techniczne mostów oraz ich uszkodzenia. Przedstawiono propozycje zagospodarowania obiektów.

Audit of CT reporting standards in cases of intracerebral haemorrhage at a comprehensive stroke centre in Australia.

PubMed

Barras, Christen D; Asadi, Hamed; Phal, Pramit M; Tress, Brian M; Davis, Stephen M; Desmond, Patricia M

2016-12-01

Multiple CT-derived biomarkers that are predictive of intracerebral haemorrhage (ICH) growth and outcome have been described in the literature, but the extent to which these appear in imaging reports of ICH is unknown. The aim of this retrospective process audit was to determine which of the known predictors of ICH outcome was recorded in reports of the disease, with a view to providing reporting recommendations, as appropriate. We examined the initial CT report of patients diagnosed with ICH presenting to a metropolitan comprehensive stroke centre and meeting inclusion criteria during the audit period between 1 March 2013 and 28 February 2014. Each report was assessed for the inclusion of the following ICH characteristics: the number of measurement dimensions; volume; location; hydrocephalus; shape; density; 'CTA spot sign' (where CTA was performed). A total of 100 patients met audit inclusion criteria. At least one ICH dimension was recorded in 90% of reports; however, 39% did not include the measurements in three dimensions and volume was reported in just 6%. No ICH dimension was recorded in 10% of reports. With the exception of density and shape, reporting of other CT features exceeded 95%. Where CTA was performed (58%), 14 (24%) of 58 reported the 'CTA spot sign' status. In this audit, volume was the most under-reported of the established ICH characteristics predictive of ICH outcome. Readily calculated from multiplanar reformats using the ABC/2 technique, the routine reporting of ICH volume is recommended. More reporting attention to ICH density heterogeneity and shape irregularity is encouraged, given their emerging importance. Where acute CTA is performed, the presence of any dynamic haemorrhage (CTA spot sign) should be reported. © 2016 The Royal Australian and New Zealand College of Radiologists.

Cortical superficial siderosis and first-ever cerebral hemorrhage in cerebral amyloid angiopathy

PubMed Central

Boulouis, Gregoire; Xiong, Li; Jessel, Michel J.; Roongpiboonsopit, Duangnapa; Ayres, Alison; Schwab, Kristin M.; Rosand, Jonathan; Gurol, M. Edip; Greenberg, Steven M.; Viswanathan, Anand

2017-01-01

Objective: To investigate whether cortical superficial siderosis (cSS) is associated with increased risk of future first-ever symptomatic lobar intracerebral hemorrhage (ICH) in patients with cerebral amyloid angiopathy (CAA) presenting with neurologic symptoms and without ICH. Methods: Consecutive patients meeting modified Boston criteria for probable CAA in the absence of ICH from a single-center cohort were analyzed. cSS and other small vessel disease MRI markers were assessed according to recent consensus recommendations. Patients were followed prospectively for future incident symptomatic lobar ICH. Prespecified Cox proportional hazard models were used to investigate cSS and first-ever lobar ICH risk adjusting for potential confounders. Results: The cohort included 236 patients with probable CAA without lobar ICH at baseline. cSS prevalence was 34%. During a median follow-up of 3.26 years (interquartile range 1.42–5.50 years), 27 of 236 patients (11.4%) experienced a first-ever symptomatic lobar ICH. cSS was a predictor of time until first ICH (p = 0.0007, log-rank test). The risk of symptomatic ICH at 5 years of follow-up was 19% (95% confidence interval [CI] 11%–32%) for patients with cSS at baseline vs 6% (95% CI 3%–12%) for patients without cSS. In multivariable Cox regression models, cSS presence was the only independent predictor of increased symptomatic ICH risk during follow-up (HR 4.04; 95% CI 1.73–9.44, p = 0.001), after adjusting for age, lobar cerebral microbleeds burden, and white matter hyperintensities. Conclusions: cSS is consistently associated with an increased risk of future lobar ICH in CAA with potentially important clinical implications for patient care decisions such as antithrombotic use. PMID:28356458

New understandings of the genetic basis of isolated idiopathic central hypogonadism

PubMed Central

Bonomi, Marco; Vladimiro Libri, Domenico; Guizzardi, Fabiana; Guarducci, Elena; Maiolo, Elisabetta; Pignatti, Elisa; Asci, Roberta; Persani, Luca

2012-01-01

Idiopathic hypogonadotropic hypogonadism is a rare disease that is characterized by delayed/absent puberty and/or infertility due to an insufficient stimulation of an otherwise normal pituitary–gonadal axis by gonadotrophin-releasing hormone (GnRH) action. Because reduced or normal luteinizing hormone (LH)/follicle-stimulating hormone (FSH) levels may be observed in the affected patients, the term idiopathic central hypogonadism (ICH) appears to be more appropriate. This disease should be distinguished from central hypogonadism that is combined with other pituitary deficiencies. Isolated ICH has a complex pathogenesis and is fivefold more prevalent in males. ICH frequently appears in a sporadic form, but several familial cases have also been reported. This finding, in conjunction with the description of numerous pathogenetic gene variants and the generation of several knockout models, supports the existence of a strong genetic component. ICH may be associated with several morphogenetic abnormalities, which include osmic defects that, with ICH, constitute the cardinal manifestations of Kallmann syndrome (KS). KS accounts for approximately 40% of the total ICH cases and has been generally considered to be a distinct subgroup. However, the description of several pedigrees, which include relatives who are affected either with isolated osmic defects, KS, or normo-osmic ICH (nICH), justifies the emerging idea that ICH is a complex genetic disease that is characterized by variable expressivity and penetrance. In this context, either multiple gene variants or environmental factors and epigenetic modifications may contribute to the variable disease manifestations. We review the genetic mechanisms that are presently known to be involved in ICH pathogenesis and provide a clinical overview of the 227 cases that have been collected by the collaborating centres of the Italian ICH Network. PMID:22138902

Genetic Variations of the COL4A1 Gene and Intracerebral Hemorrhage Risk: A Case-Control Study in a Chinese Han Population.

PubMed

Lin, Sen; Xia, Chao; He, Sha; Yang, Jie; Li, Hao; Zheng, Jun; Liu, Ming; You, Chao

2018-04-01

To investigate the association between single nucleotide polymorphisms or haplotypes of the COL4A1 gene and the risk of intracerebral hemorrhage (ICH). We conducted a case-control study that included 181 patients from the Chinese Han population with hypertensive ICH and 197 hypertension patients without ICH. Genomic DNA was extracted by DNA extraction kit, and the 6 single nucleotide polymorphism genotypes of the COL4A1 gene were detected with a MassARRAY Analyzer. Unphased 3.1.4 and SPSS 19.0 were used to analyze the association between alleles, genotypes, and haplotypes of the COL4A1 gene and the risk of ICH. Compared with the control group, patients in the ICH group were significantly younger. There were no differences in gender, diabetes, hyperlipidemia, current smoking, and alcohol consumption between the 2 groups. Our association analysis showed that the rs3742207 A, rs11069830 A, and rs679505 A alleles were association factors of the risks of ICH; rs11069830 AA, rs544012 AC, and rs679505 AA genotypes were association factors of the risk of ICH; AA haplotype (rs3742207-rs11069830) was an association factor of the risk of ICH. After adjusting age and gender by multivariate logistic regression, the rs544012 AC and rs679505 AA genotypes were independently associated with the risk of ICH. Our study showed that the rs544012 AC and rs679505 AA genotypes were independently associated with the risk of ICH in the Chinese Han population and that the AA haplotype (rs3742207-rs11069830) in the COL4A1 gene may be related to the risk of ICH in the Chinese Han population; these conclusions need further confirmation in future studies with larger samples. Copyright © 2018. Published by Elsevier Inc.

Motor skills training promotes motor functional recovery and induces synaptogenesis in the motor cortex and striatum after intracerebral hemorrhage in rats.

PubMed

Tamakoshi, Keigo; Ishida, Akimasa; Takamatsu, Yasuyuki; Hamakawa, Michiru; Nakashima, Hiroki; Shimada, Haruka; Ishida, Kazuto

2014-03-01

We investigated the effects of motor skills training on several types of motor function and synaptic plasticity following intracerebral hemorrhage (ICH) in rats. Male Wistar rats were injected with collagenase into the left striatum to induce ICH, and they were randomly assigned to the ICH or sham groups. Each group was divided into the motor skills training (acrobatic training) and control (no exercise) groups. The acrobatic group performed acrobatic training from 4 to 28 days after surgery. Motor functions were assessed by motor deficit score, the horizontal ladder test and the wide or narrow beam walking test at several time points after ICH. The number of ΔFosB-positive cells was counted using immunohistochemistry to examine neuronal activation, and the PSD95 protein levels were analyzed by Western blotting to examine synaptic plasticity in the bilateral sensorimotor cortices and striata at 14 and 29 days after ICH. Motor skills training following ICH significantly improved gross motor function in the early phase after ICH and skilled motor coordinated function in the late phase. The number of ΔFosB-positive cells in the contralateral sensorimotor cortex in the acrobatic group significantly increased compared to the control group. PSD95 protein expression in the motor cortex significantly increased in the late phase, and in the striatum, the protein level significantly increased in the early phase by motor skills training after ICH compared to no training after ICH. We demonstrated that motor skills training improved motor function after ICH in rats and enhanced the neural activity and synaptic plasticity in the striatum and sensorimotor cortex. Copyright © 2013 Elsevier B.V. All rights reserved.

SIRT1/PGC-1α Signaling Promotes Mitochondrial Functional Recovery and Reduces Apoptosis after Intracerebral Hemorrhage in Rats

PubMed Central

Zhou, Yang; Wang, Shaohua; Li, Yixin; Yu, Shanshan; Zhao, Yong

2018-01-01

Silent information regulator 1 (SIRT1) exerts neuroprotection in many neurodegenerative diseases. However, it is not clear if SIRT1 has protective effects after intracerebral hemorrhage (ICH)-induced brain injury in rats. Thus, our goal was to examine the influence of SIRT1 on ICH injuries and any underlying mechanisms of this influence. Brain injury was induced by autologous arterial blood (60 μL) injection into rat brains, and data show that activation of SIRT1 with SRT1720 (5 mg/kg) restored nuclear SIRT1, deacetylation of PGC-1α, and mitochondrial biogenesis and decreased mortality, behavioral deficits, and brain water content without significant changes in phosphorylated AMP-activated protein kinase (pAMPK) induced by ICH. Activation of SIRT1 with SRT1720 also restored mitochondrial electron transport chain proteins and decreased apoptotic proteins in ICH; however, these changes were reversed after ICH. In contrast, treatment with PGC-1α siRNA yielded opposite effects. To explore the protective effects of SIRT1 after ICH, siRNAs were used to knockdown SIRT1. Treatment with SIRT1 siRNA increased mortality, behavioral deficits, brain water content, mitochondrial dysfunction, and neurocyte apoptosis after ICH. Thus, activation of SIRT1 promotes recovery of mitochondrial protein and function by increasing mitochondrial biogenesis and reduces apoptosis after ICH via the PGC-1α mitochondrial pathway. These data may suggest a new therapeutic approach for ICH injuries. PMID:29375306

Cerebral Amyloid Angiopathy: An Important Differential Diagnosis of Stroke in the Elderly

PubMed Central

AZMIN, Shahrul; OSMAN, Syazarina Sharis; MUKARI, Shahizon; SAHATHEVAN, Ramesh

2015-01-01

Cerebral amyloid angiopathy (CAA) accounts for approximately 10–20% of spontaneous intracerebral haemorrhage (ICH). This figure is thought to be higher in the elderly population. With the increasing life expectancy of our population, we anticipate that the prevalence of CAA- related ICH will increase in tandem. Although CAA-related ICH and hypertension-related ICH are distinct entities based on histopathology and imaging, the clinical presentation of the two conditions is similar. The use of brain computed tomography (CT) scans remain the ICH imaging modality of choice in Malaysia due to its availability, cost, and sensitivity in detecting acute bleeds. On the other hand, the use of brain magnetic resonance imaging (MRI) with susceptibility-weighted imaging (SWI) sequencing enables the clinician to determine the presence of chronic blood products in the brain, especially clinically silent microbleeds associated with CAA. However, the use of brain MRI scans in our country is limited and leads to a blurring of lines when differentiating between hypertension-related ICH and CAA-related ICH. How this misrepresentation affects the management of these conditions is unclear. In this study, we present two cases of ICH to illustrate this point and to serve as a springboard to question current practice and promote discussion. PMID:25892953

Hybrid Assistive Limb (HAL) Rehabilitation in Patients with Acute Hemorrhagic Stroke.

PubMed

Ogata, Toshiyasu; Abe, Hiroshi; Samura, Kazuhiro; Hamada, Omi; Nonaka, Masani; Iwaasa, Mitsutoshi; Higashi, Toshio; Fukuda, Hiroyuki; Shiota, Etsuji; Tsuboi, Yoshio; Inoue, Tooru

2015-01-01

The efficacy of hybrid assistive limb (HAL) rehabilitation in the acute phase of stroke remains unclear. The purpose of this study was to evaluate the outcomes of patients with acute intracranial hemorrhage (ICH) who were treated with or without HAL rehabilitation. Among 270 patients with acute ICH from 2009 to 2014, 91 patients with supratentorial ICH were included in this retrospective study. Of these, 14 patients (HAL group) received HAL rehabilitation at approximately 1 week after ICH occurrence, while the remaining 77 patients received usual rehabilitation without HAL (N-HAL group). We obtained various patient data from the hospitals where the patients were moved to for further rehabilitation. Statistical comparisons were performed for the characteristics of the ICH patients, and outcomes between the HAL and N-HAL groups. There were no differences in outcomes between the HAL and N-HAL groups. However, patients with right ICH in the HAL group exhibited a significant association with a functional independence measure (FIM) score of ≥ 110 compared with patients in the N-HAL group (HAL group: 81.8%, N-HAL group: 43.9%, P = 0.04). In patients with right ICH, HAL rehabilitation was associated with improved outcomes as evaluated by the FIM score. Thus, HAL rehabilitation may improve outcomes of acute ICH in appropriately selected patients.

Minocycline Effects on Intracerebral Hemorrhage-Induced Iron Overload in Aged Rats: Brain Iron Quantification With Magnetic Resonance Imaging.

PubMed

Cao, Shenglong; Hua, Ya; Keep, Richard F; Chaudhary, Neeraj; Xi, Guohua

2018-04-01

Brain iron overload is a key factor causing brain injury after intracerebral hemorrhage (ICH). This study quantified brain iron levels after ICH with magnetic resonance imaging R2* mapping. The effect of minocycline on iron overload and ICH-induced brain injury in aged rats was also determined. Aged (18 months old) male Fischer 344 rats had an intracerebral injection of autologous blood or saline, and brain iron levels were measured by magnetic resonance imaging R2* mapping. Some ICH rats were treated with minocycline or vehicle. The rats were euthanized at days 7 and 28 after ICH, and brains were used for immunohistochemistry and Western blot analyses. Magnetic resonance imaging (T2-weighted, T2* gradient-echo, and R2* mapping) sequences were performed at different time points. ICH-induced brain iron overload in the perihematomal area could be quantified by R2* mapping. Minocycline treatment reduced brain iron accumulation, T2* lesion volume, iron-handling protein upregulation, neuronal cell death, and neurological deficits ( P <0.05). Magnetic resonance imaging R2* mapping is a reliable and noninvasive method, which can quantitatively measure brain iron levels after ICH. Minocycline reduced ICH-related perihematomal iron accumulation and brain injury in aged rats. © 2018 American Heart Association, Inc.

Intracranial hemorrhage in congenital bleeding disorders.

PubMed

Tabibian, Shadi; Motlagh, Hoda; Naderi, Majid; Dorgalaleh, Akbar

2018-01-01

: Intracranial hemorrhage (ICH), as a life-threatening bleeding among all kinds of congenital bleeding disorders (CBDs), is a rare manifestation except in factor XIII (FXIII) deficiency, which is accompanied by ICH, early in life, in about one-third of patients. Most inherited platelet function disorders (IPFDs) are mild to moderate bleeding disorders that can never experience a severe bleeding as in ICH; however, Glanzmann's thrombasthenia, a common and severe inherited platelet function disorder, can lead to ICH and occasional death. This bleeding feature can also be observed in grey platelet syndrome, though less frequently than in Glanzmann's thrombasthenia. In hemophilia, intracerebral hemorrhage is affected by various risk factors one of which is the severity of the disease. The precise prevalence of ICH in these patients is not clear but an estimated incidence of 3.5-4% among newborns with hemophilia is largely ascertained. Although ICH is a rare phenomenon in CBDs, it can be experienced by every patient with severe hemophilia A and B, FXIII deficiency (FXIIID), FVIID, FXD, FVD, FIID, and afibrinogenemia. Upon observing the general signs and symptoms of ICH such as vomiting, seizure, unconsciousness, and headache, appropriate replacement therapies and cranial ultrasound scans must be done to decrease ICH-related morbidity and mortality.

European research priorities for intracerebral haemorrhage.

PubMed

Steiner, Thorsten; Petersson, Jesper; Al-Shahi Salman, Rustam; Christensen, Hanne; Cordonnier, Charlotte; Csiba, Laszlo; Harnof, Sagi; Krieger, Derk; Mendelow, David; Molina, Carlos; Montaner, Joan; Overgaard, Karsten; Roine, Risto O; Schmutzhard, Erich; Tatlisumak, Turgut; Toni, Danilo; Stapf, Christian

2011-01-01

Over 2 million people are affected by intracerebral haemorrhage (ICH) worldwide every year, one third of them dying within 1 month, and many survivors being left with permanent disability. Unlike most other stroke types, the incidence, morbidity and mortality of ICH have not declined over time. No standardised diagnostic workup for the detection of the various underlying causes of ICH currently exists, and the evidence for medical or surgical therapeutic interventions remains limited. A dedicated European research programme for ICH is needed to identify ways to reduce the burden of ICH-related death and disability. The European Research Network on Intracerebral Haemorrhage EURONICH is a multidisciplinary academic research collaboration that has been established to define current research priorities and to conduct large clinical studies on all aspects of ICH. Copyright © 2011 S. Karger AG, Basel.

Antithrombotic drug use, cerebral microbleeds, and intracerebral hemorrhage: a systematic review of published and unpublished studies.

PubMed

Lovelock, Caroline E; Cordonnier, Charlotte; Naka, Hiromitsu; Al-Shahi Salman, Rustam; Sudlow, Cathie L M; Sorimachi, Takatoshi; Werring, David J; Gregoire, Simone M; Imaizumi, Toshio; Lee, Seung-Hoon; Briley, Dennis; Rothwell, Peter M

2010-06-01

Cerebral microbleeds (MB) are potential risk factors for intracerebral hemorrhage (ICH), but it is unclear if they are a contraindication to using antithrombotic drugs. Insights could be gained by pooling data on MB frequency stratified by antithrombotic use in cohorts with ICH and ischemic stroke (IS)/transient ischemic attack (TIA). We performed a systematic review of published and unpublished data from cohorts with stroke or TIA to compare the presence of MB in: (1) antithrombotic users vs nonantithrombotic users with ICH; (2) antithrombotic users vs nonusers with IS/TIA; and (3) ICH vs ischemic events stratified by antithrombotic use. We also analyzed published and unpublished follow-up data to determine the risk of ICH in antithrombotic users with MB. In a pooled analysis of 1460 ICH and 3817 IS/TIA, MB were more frequent in ICH vs IS/TIA in all treatment groups, but the excess increased from 2.8 (odds ratio; range, 2.3-3.5) in nonantithrombotic users to 5.7 (range, 3.4-9.7) in antiplatelet users and 8.0 (range, 3.5-17.8) in warfarin users (P difference=0.01). There was also an excess of MB in warfarin users vs nonusers with ICH (OR, 2.7; 95% CI, 1.6-4.4; P<0.001) but none in warfarin users with IS/TIA (OR, 1.3; 95% CI, 0.9-1.7; P=0.33; P difference=0.01). There was a smaller excess of MB in antiplatelet users vs nonusers with ICH (OR, 1.7; 95% CI, 1.3-2.3; P<0.001), but findings were similar for antiplatelet users with IS/TIA (OR, 1.4; 95% CI, 1.2-1.7; P<0.001; P difference=0.25). In pooled follow-up data for 768 antithrombotic users, presence of MB at baseline was associated with a substantially increased risk of subsequent ICH (OR, 12.1; 95% CI, 3.4-42.5; P<0.001). The excess of MB in warfarin users with ICH compared to other groups suggests that MB increase the risk of warfarin-associated ICH. Limited prospective data corroborate these findings, but larger prospective studies are urgently required.

The radical scavenger edaravone improves neurologic function and perihematomal glucose metabolism after acute intracerebral hemorrhage.

PubMed

Shang, Hanbing; Cui, Derong; Yang, Dehua; Liang, Sheng; Zhang, Weifeng; Zhao, Weiguo

2015-01-01

Oxidative injury caused by reactive oxygen species plays an important role in the progression of intracerebral hemorrhage (ICH)-induced secondary brain injury. Previous studies have demonstrated that the free radical scavenger edaravone may prevent neuronal injury and brain edema after ICH. However, the influence of edaravone on cerebral metabolism in the early stages after ICH and the underlying mechanism have not been fully investigated. In the present study, we investigated the effect of edaravone on perihematomal glucose metabolism using (18)F-fluorordeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT). Additionally, the neurologic deficits, brain edemas, and cell death that followed ICH were quantitatively analyzed. After blood infusion, the rats treated with edaravone showed significant improvement in both forelimb placing and corner turn tests compared with those treated with vehicle. Moreover, the brain water content of the edaravone-treated group was significantly decreased compared with that of the vehicle group on day 3 after ICH. PET/CT images of ICH rats exhibited obvious decreases in FDG standardized uptake values in perihematomal region on day 3, and the lesion-to-normal ratio of the edaravone-treated ICH rats was significantly increased compared with that of the control rats. Calculation of the brain injury volumes from the PET/CT images revealed that the volumes of the blood-induced injuries were significantly smaller in the edaravone group compared with the vehicle group. Terminal Deoxynucleotidyl Transferase-mediated dUTP Nick End Labeling assays performed 3 days after ICH revealed that the numbers of apoptotic cells in perihematomal region of edaravone-treated ICH rats were decreased relative to the vehicle group. Thus, the present study demonstrates that edaravone has scavenging properties that attenuate neurologic behavioral deficits and brain edema in the early period of ICH. Additionally, edaravone may improve

Preexisting cognitive impairment in intracerebral hemorrhage.

PubMed

Laible, M; Horstmann, S; Möhlenbruch, M; Schueler, S; Rizos, T; Veltkamp, R

2017-06-01

Preexisting cognitive impairment is a predictor of cognitive decline after ischemic stroke, but evidence in intracerebral hemorrhage (ICH) is limited. We aimed to determine the prevalence of premorbid cognitive impairment in patients with ICH. We included patients with acute ICH. Pre-ICH cognitive impairment was determined based on the results of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) that uses information from close relatives. Patients were assessed as having been cognitively impaired with an IQCODE score of ≥3.44; an IQCODE ≥4.00 indicated pre-ICH dementia. CT and MRI images were reviewed to determine the extent of white matter lesions and to measure the radial width of the temporal horn as marker of brain atrophy. We investigated differences of cardiovascular risk factors and imaging data between patients with and without pre-ICH cognitive impairment using correlation analyses, uni- and multivariable regression models. Functional neurological state was assessed using the modified Rankin Scale (mRS). The mRS was dichotomized at the level of 3, and a premorbid mRS of 0-2 was considered as functional independency. Among the 89 participants, median age was 70 years (interquartile range 58-78) and 52 (58.4%) were male. IQCODE indicated pre-ICH cognitive impairment in 18.0% (16 of 89), and 83.1% were functionally independent before ICH. Cognitive impairment was associated with a premorbid mRS≥3 (chi squared test, P=0.009). In multivariable analysis, prior stroke/transient ischemic attack (OR 18.29, 95%-CI 1.945-172.033, P=.011) and hematoma volume (OR 0.90, 95%-CI 0.812-0.991, P=.033) were independently associated with pre-ICH cognitive impairment. In conclusion, cognitive impairment frequently precedes ICH. A higher frequency of cerebrovascular events suggests a role of vascular processes in the development of cognitive impairment before ICH. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Intracranial Hemorrhage: A Devastating Outcome of Congenital Bleeding Disorders-Prevalence, Diagnosis, and Management, with a Special Focus on Congenital Factor XIII Deficiency.

PubMed

Alavi, Seyed Ezatolla Rafiee; Jalalvand, Masumeh; Assadollahi, Vahideh; Tabibian, Shadi; Dorgalaleh, Akbar

2018-04-01

Intracranial hemorrhage (ICH) is a medical emergency. In congenital bleeding disorders, ICH is a devastating presentation accompanied with a high rate of morbidity and mortality. The prevalence of ICH is highly variable among congenital bleeding disorders, with the highest incidence observed in factor (F) XIII deficiency (FXIIID) (∼30%). This life-threatening presentation is less common in afibrinogenemia, FVIII, FIX, FVII, and FX deficiencies, and is rare in severe FV and FII deficiencies, type 3 von Willebrand disease and inherited platelet function disorders (IPFDs). In FXIIID, this diathesis most often occurs after trauma in children, whereas spontaneous ICH is more frequent in adults. About 15% of patients with FXIIID and ICH die; the bleeding causes 80% of deaths in this coagulopathy. Although in FXIIID, the bleed most commonly is intraparenchymal (> 90%), epidural, subdural, and subarachnoid hemorrhages also have been reported, albeit rarely. As this life-threatening bleeding causes neurological complications, early diagnosis can prevent further expansion of the hematoma and secondary damage. Neuroimaging plays a crucial role in the diagnosis of ICH, but signs and symptoms in patients with severe FXIIID should trigger replacement therapy even before establishment of the diagnosis. Although a high dose of FXIII concentrate can reduce the rate of morbidity and mortality of ICH in FXIIID, it may occasionally trigger inhibitor development, thus complicating ICH management and future prophylaxis. Nevertheless, replacement therapy is the mainstay of treatment for ICH in FXIIID. Neurosurgery is performed in patients with FXIIID and epidural hematoma and a hemorrhage diameter exceeding 2 cm or a volume of ICH is more than 30 cm 3 . Contact sports are not recommended in people with FXIIID as they can elicit ICH. However, a considerable number of safe sports and activities have been suggested to have more benefits than dangers for patients with congenital bleeding

Hemorrhage recurrence risk factors in cerebral amyloid angiopathy: Comparative analysis of the overall small vessel disease severity score versus individual neuroimaging markers.

PubMed

Boulouis, Gregoire; Charidimou, Andreas; Pasi, Marco; Roongpiboonsopit, Duangnapa; Xiong, Li; Auriel, Eitan; van Etten, Ellis S; Martinez-Ramirez, Sergi; Ayres, Alison; Vashkevich, Anastasia; Schwab, Kristin M; Rosand, Jonathan; Goldstein, Joshua N; Gurol, M Edip; Greenberg, Steven M; Viswanathan, Anand

2017-09-15

An MRI-based score of total small vessel disease burden (CAA-SVD-Score) in cerebral amyloid angiopathy (CAA) has been demonstrated to correlate with severity of pathologic changes. Evidence suggests that CAA-related intracerebral hemorrhage (ICH) recurrence risk is associated with specific disease imaging manifestations rather than overall severity. We compared the correlation between the CAA-SVD-Score with the risk of recurrent CAA-related lobar ICH versus the predictive role of each of its components. Consecutive patients with CAA-related ICH from a single-center prospective cohort were analyzed. Radiological markers of CAA related SVD damage were quantified and categorized according to the CAA-SVD-Score (0-6 points). Subjects were followed prospectively for recurrent symptomatic ICH. Adjusted Cox proportional hazards models were used to investigate associations between the CAA-SVD-Score as well as each of the individual MRI signatures of CAA and the risk of recurrent ICH. In 229 CAA patients with ICH, a total of 56 recurrent ICH events occurred during a median follow-up of 2.8years [IQR 0.9-5.4years, 781 person-years). Higher CAA-SVD-Score (HR=1.26 per additional point, 95%CI [1.04-1.52], p=0.015) and older age were independently associated with higher ICH recurrence risk. Analysis of individual markers of CAA showed that CAA-SVD-Score findings were due to the independent effect of disseminated superficial siderosis (HR for disseminated cSS vs none: 2.89, 95%CI [1.47-5.5], p=0.002) and high degree of perivascular spaces enlargement (RR=3.50-95%CI [1.04-21], p=0.042). In lobar CAA-ICH patients, higher CAA-SVD-Score does predict recurrent ICH. Amongst individual elements of the score, superficial siderosis and dilated perivascular spaces are the only markers independently associated with ICH recurrence, contributing to the evidence for distinct CAA phenotypes singled out by neuro-imaging manifestations. Copyright © 2017 Elsevier B.V. All rights reserved.

MRI scout images can detect the acute intracerebral hemorrhage on CT.

PubMed

Hayashi, Toshiyuki; Aoki, Junya; Suzuki, Kentaro; Sakamoto, Yuki; Suda, Satoshi; Okubo, Seiji; Mishina, Masahiro; Kimura, Kazumi

2018-04-15

Magnetic resonance imaging (MRI) has recently emerged as a first-line tool for investigating acute stroke. However, MRI requires long scan times, which could be detrimental for severe stroke patients with a large intracerebral hemorrhage (ICH). MRI scout images, which are taken prior to a study to determine the range of subsequent images, can be used to rapidly screen the whole brain. We examined whether MRI scout imaging can detect ICHs observed by computed tomography (CT). Between September 2014 and March 2016, consecutive acute ICH patients who underwent both MRI scout and CT imaging in the acute setting were studied. ICHs on MRI scout images were defined as space-occupying lesions. Two neurologists independently assessed the scout images. We investigated whether ICHs on CT scans can be detected on MRI scout images and the characteristics of ICHs not detected by MRI scout images. One hundred and forty-eight ICH patients (median age, 68 [interquartile range, 59-77] years; 99 [67%] males; median National Institutes of Health Stroke Scale score, 11 [4-17]) were enrolled. Among these, 138 (93%) patients were diagnosed as having ICH by MRI scout imaging (positive group), and 10 (7%) patients were not (negative group). The bleeding volume was 9.3 [4.5-22.4] ml in the positive group and 1.0 [0.4-2.0] ml in the negative group (p < .001). The cut-off value of bleeding volume calculated from the receiver operating characteristic curve was 2.0 ml. Regarding ICH lesions, 4 (44%) of the 9 pontine hemorrhages were detected on MRI scout images, whereas 134 (96%) of the 139 other hemorrhages were diagnosed (p < .001). We diagnosed >90% of ICHs using MRI scout images. Low levels of ICH and pontine hemorrhaging might be difficult to detect using MRI scout imaging. Copyright © 2018 Elsevier B.V. All rights reserved.

Statins and risk of poststroke hemorrhagic complications

PubMed Central

MacIsaac, Rachael L.; Abdul-Rahim, Azmil H.; Siegerink, Bob; Bath, Philip M.; Endres, Matthias; Lees, Kennedy R.; Nolte, Christian H.

2016-01-01

Objective: To assess whether statin treatment before or after acute ischemic stroke (AIS) affects the risk of acute intracerebral hemorrhage (ICH), postacute ICH, and mortality within 90 days. Methods: Data were sought from the Virtual International Stroke Trials Archive, an international repository of clinical trials data. Using propensity score matching, we retrospectively compared patients with prior statin treatment and newly initiated statin within 3 days after AIS to patients without statin exposure. Outcomes of interest were acute symptomatic ICH (sICH), any acute ICH, postacute ICH, and mortality during follow-up of 3 months. Results: A total of 8,535 patients (mean age 70 years, 54% male, median baseline NIH Stroke Scale score 13) were analyzed. After propensity score matching, prior statin use was not strongly associated with sICH (adjusted odds ratio [OR] 1.33, 95% confidence interval [CI] 0.83–2.14) or any ICH (adjusted OR 1.35, 95% CI 0.92–1.98). There was no evidence of an interaction between prior statin use and thrombolysis. New initiation of statins was not associated with postacute ICH (adjusted hazard ratio [HR] 1.60, 95% CI 0.70–3.65). There was a signal towards lower 90-day mortality in patients with prior statin use (adjusted HR 0.84, 95% CI 0.70–1.00) and especially early initiation of statins (adjusted HR 0.67, 95% CI 0.46–0.97). Conclusions: Statin use prior to AIS was not associated with early hemorrhagic complications, irrespective of treatment with thrombolysis. New initiation of statin treatment early after AIS did not affect risk of postacute ICH, but might be associated with reduced mortality. PMID:27016519

Antiparasitic efficacy of curcumin from Curcuma longa against Ichthyophthirius multifiliis in grass carp

USDA-ARS?s Scientific Manuscript database

Ichthyophthirius multifiliis (Ich) is a ciliated parasite that elicits great economic losses in aquaculture. In the present study, a polyphenol compound, curcumin, was obtained from the rhizome of Curcuma longa by bioassay-guided isolation based on the efficacy of anti-Ich theronts. Anti-Ich efficac...

Hybrid Assistive Limb (HAL) Rehabilitation in Patients with Acute Hemorrhagic Stroke

PubMed Central

OGATA, Toshiyasu; ABE, Hiroshi; SAMURA, Kazuhiro; HAMADA, Omi; NONAKA, Masani; IWAASA, Mitsutoshi; HIGASHI, Toshio; FUKUDA, Hiroyuki; SHIOTA, Etsuji; TSUBOI, Yoshio; INOUE, Tooru

2015-01-01

The efficacy of hybrid assistive limb (HAL) rehabilitation in the acute phase of stroke remains unclear. The purpose of this study was to evaluate the outcomes of patients with acute intracranial hemorrhage (ICH) who were treated with or without HAL rehabilitation. Among 270 patients with acute ICH from 2009 to 2014, 91 patients with supratentorial ICH were included in this retrospective study. Of these, 14 patients (HAL group) received HAL rehabilitation at approximately 1 week after ICH occurrence, while the remaining 77 patients received usual rehabilitation without HAL (N-HAL group). We obtained various patient data from the hospitals where the patients were moved to for further rehabilitation. Statistical comparisons were performed for the characteristics of the ICH patients, and outcomes between the HAL and N-HAL groups. There were no differences in outcomes between the HAL and N-HAL groups. However, patients with right ICH in the HAL group exhibited a significant association with a functional independence measure (FIM) score of ≥ 110 compared with patients in the N-HAL group (HAL group: 81.8%, N-HAL group: 43.9%, P = 0.04). In patients with right ICH, HAL rehabilitation was associated with improved outcomes as evaluated by the FIM score. Thus, HAL rehabilitation may improve outcomes of acute ICH in appropriately selected patients. PMID:26511112

Genetic variations of MMP9 gene and intracerebral hemorrhage susceptibility: a case-control study in Chinese Han population.

PubMed

Yang, Jie; Wu, Bo; Lin, Sen; Zhou, Junshan; Li, Yingbin; Dong, Wei; Arima, Hisatomi; Zhang, Chanfei; Liu, Yukai; Liu, Ming

2014-06-15

To investigate the association between genetic variations of matrix metalloproteinase 9 (MMP9) gene and intracerebral hemorrhage (ICH) susceptibility in Chinese Han population. The clinical data and peripheral blood samples from the patients with ICH and hypertension, and controlled subjects with hypertension only, were collected. MassARRAY Analyzer was used to genotype the tagger single nucleotide polymorphism (SNP) of MMP9 gene. Haploview4.2 and Unphased3.1.7 were employed to construct haplotypes and to analyze the association between genetic variations (alleles, genotypes and haplotypes) of MMP9 gene and ICH susceptibility. 181 patients with ICH and hypertension, and 197 patients with hypertension only, were recruited between Sep 2009 and Oct 2010. Patients in the ICH group were younger (61.80 ± 13.27 vs. 72.44 ± 12.71 years, p<0.05). Other conventional risk factors between the ICH and control groups were similar. There were 6 Tagger SNPs and 4 haplotypes of MMP9 gene in our sample population. Our logistical regression analysis showed that there were no significant associations between genetic variations of the MPP9 gene and ICH susceptibility (all p>0.05). The genetic variations of MMP9 gene were not significantly associated with ICH susceptibility in the Chinese Han population. Copyright © 2014 Elsevier B.V. All rights reserved.

Intraventricular Bleeding and Hematoma Size as Predictors of Infection Development in Intracerebral Hemorrhage: A Prospective Cohort Study.

PubMed

Vial, Felipe; Brunser, Alejandro; Lavados, Pablo; Illanes, Sergio

2016-11-01

Acute intracerebral hemorrhage (ICH) is associated with increased susceptibility to bacterial infection. The physiopathology of this phenomenon is not very clear. We conducted a prospective observational study investigating the correlation and independent predictors of infections in patients with ICH. Patients admitted between April 1997 and June 2013 with ICH diagnosis were evaluated for inclusion and exclusion criteria. Two hundred twenty-two patients were included in this study. Ninety four patients (42.6%) presented with an infection during hospitalization being more common than pneumonia (30%) and urinary tract infections (14%). Intraventricular hemorrhage (IVH) (95% confidence interval [CI], 62.7% versus 39.3%; P < .001) and higher ICH score (95% CI, 2.31% versus 1.67%; P = .0014) were more common in patients who had infections. We found the following risk factors for having an infection in patients with ICH: IVH (odds ratio [OR] 2.3; 95% IC, 1.3-4.1), each point of ICH score (OR 1.3; 95% CI, 1.1-1.6), and having a hematoma volume larger than 30 cc (OR 2.0; 95% CI, 1.1-3.5). The localization of the hematoma was not found to be relevant. ICH score, size of the hematoma, and presence of IVH are independent risk factors for having an infection after ICH. Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Heme oxygenase-1 exacerbates early brain injury after intracerebral haemorrhage

PubMed Central

Wang, Jian; Doré, Sylvain

2008-01-01

Because heme oxygenase (HO) is the rate limiting enzyme in the degradation of the pro-oxidant hemin/heme from blood, here we investigated the contribution of the inducible HO-1 to early brain injury produced by intracerebral haemorrhage (ICH). We found that after induction of ICH, HO-1 proteins were highly detectable in the peri-ICH region predominantly in microglia/macrophages and endothelial cells. Remarkably, the injury volume was significantly smaller in HO-1 knockout (HO-1−/−) mice than in wild-type controls 24 and 72 h after ICH. Although the brain water content did not appear to be significantly different, the protection in HO-1−/− mice was associated with a marked reduction in ICH-induced leucocyte infiltration, microglia/macrophage activation and free radical levels. These data reveal a previously unrecognized role of HO-1 in early brain injury after ICH. Thus, modulation of HO-1 signalling should be assessed further in clinical settings, especially for haemorrhagic states. PMID:17525142

A novel intracerebral hemorrhage-induced rat model of neurogenic voiding dysfunction: Analysis of lower urinary tract function

PubMed Central

CHO, YOUNG-SAM; KO, IL-GYU; KIM, CHANG-JU; KIM, KHAE-HAWN

2015-01-01

Neurogenic lower urinary tract dysfunction (NLUTD) is a major problem in patients with various neurological disorders, and may result in debilitating symptoms and serious complications, including chronic renal failure and recurrent urinary tract infections. Clinically, stroke is associated with voiding dysfunction. However, lower urinary tract function evaluation in an intracerebral hemorrhage (ICH) model has not, to the best of our knowledge, been reported. Therefore, in the present study, lower urinary tract function in ICH-induced rats was investigated and the results were compared with those obtained in normal rats. The effects of ICH on peripheral bladder function and central micturition centers [medial preoptic area, ventrolateral gray, pontaine micturition center and spinal cord (lumbar 4 (L4)-L5)] were also examined. Adult female Sprague-Dawley rats were divided into two groups: Control ICH-induced. Induction of ICH in the hippocampal CA1 region was performed using a stereotaxic frame and type IV collagenase. The effects of ICH on the central micturition centers were investigated by simultaneously determining the extent of neuronal activation (c-Fos) and nerve growth factor (NGF) expression, and assessing voiding function (urodynamically using cystometry). The results revealed that induction of ICH significantly enhanced bladder contraction pressure and time, while simultaneously reducing voiding pressure and time. Furthermore, the c-Fos and NGF expression levels in the neuronal voiding centers were significantly increased in the rats with induced ICH as compared with the control rats. Therefore, this ICH-induced NLUTD rat model may be a more appropriate method to analyze NLUTD in stroke patients than a cerebral infarction model, as the former more accurately reflects the nature of the hemorrhage in the two types of stroke. PMID:25954993

The incidence of traumatic intracranial hemorrhage in head-injured older adults transported by EMS with and without anticoagulant or antiplatelet use.

PubMed

Nishijima, Daniel Kiden; Gaona, Samuel D; Waechter, Trent; Maloney, Ric; Blitz, Adam; Elms, Andrew R; Farrales, Roel D; Montoya, James; Bair, Troy; Howard, Calvin; Gilbert, Megan; Trajano, Renee; Hatchel, Kaela; Faul, Mark; Bell, Jeneita M; Coronado, Victor; Vinson, David R; Ballard, Dustin W; Tancredi, Daniel J; Garzon, Hernando; Mackey, Kevin E; Shahlaie, Kiarash; Holmes, James F

2017-11-06

Field triage guidelines recommend transport of head-injured patients on anticoagulants or antiplatelets to a higher-level trauma center based on studies suggesting a high incidence of traumatic intracranial hemorrhage (tICH). We compared the incidence of tICH in older adults transported by EMS with and without anticoagulation or antiplatelet use and evaluated the accuracies of different sets of field triage criteria to identify tICH. This was a prospective, observational study at 5 EMS agencies and 11 hospitals. Older adults (≥55 years) with head trauma and transported by EMS from Aug 2015 to Sept 2016 were eligible. EMS providers completed standardized data forms and patients were followed through ED or hospital discharge. We enrolled 1,304 patients; 1147 (88%) received a cranial CT scan and were eligible for analysis. 434 (33%) patients had anticoagulant or antiplatelet use and 112 (10%) had tICH. The incidence of tICH in patients with (11%, 95%CI 8-14%) and without (9%, 95%CI 7-11%) anticoagulant or antiplatelet use was similar. Anticoagulant or antiplatelet use was not predictive of tICH on adjusted analysis. Steps 1-3 criteria alone were not sensitive in identifying tICH (27%) while the addition of anticoagulant or antiplatelet criterion improved sensitivity (63%). Other derived sets of triage criteria were highly sensitive (>98%) but poorly specific (<11%). The incidence of tICH was similar between patients with and without anticoagulant or antiplatelet use. Use of anticoagulant or antiplatelet medications was not a risk factor for tICH. We were unable to identify a set of triage criteria that was accurate for trauma center need.

Clinical course of untreated cerebral cavernous malformations: a meta-analysis of individual patient data.

PubMed

Horne, Margaret A; Flemming, Kelly D; Su, I-Chang; Stapf, Christian; Jeon, Jin Pyeong; Li, Da; Maxwell, Susanne S; White, Philip; Christianson, Teresa J; Agid, Ronit; Cho, Won-Sang; Oh, Chang Wan; Wu, Zhen; Zhang, Jun-Ting; Kim, Jeong Eun; Ter Brugge, Karel; Willinsky, Robert; Brown, Robert D; Murray, Gordon D; Al-Shahi Salman, Rustam

2016-02-01

Cerebral cavernous malformations (CCMs) can cause symptomatic intracranial haemorrhage (ICH), but the estimated risks are imprecise and predictors remain uncertain. We aimed to obtain precise estimates and predictors of the risk of ICH during untreated follow-up in an individual patient data meta-analysis. We invited investigators of published cohorts of people aged at least 16 years, identified by a systematic review of Ovid MEDLINE and Embase from inception to April 30, 2015, to provide individual patient data on clinical course from CCM diagnosis until first CCM treatment or last available follow-up. We used survival analysis to estimate the 5-year risk of symptomatic ICH due to CCMs (primary outcome), multivariable Cox regression to identify baseline predictors of outcome, and random-effects models to pool estimates in a meta-analysis. Among 1620 people in seven cohorts from six studies, 204 experienced ICH during 5197 person-years of follow-up (Kaplan-Meier estimated 5-year risk 15·8%, 95% CI 13·7-17·9). The primary outcome of ICH within 5 years of CCM diagnosis was associated with clinical presentation with ICH or new focal neurological deficit (FND) without brain imaging evidence of recent haemorrhage versus other modes of presentation (hazard ratio 5·6, 95% CI 3·2-9·7) and with brainstem CCM location versus other locations (4·4, 2·3-8·6), but age, sex, and CCM multiplicity did not add independent prognostic information. The 5-year estimated risk of ICH during untreated follow-up was 3·8% (95% CI 2·1-5·5) for 718 people with non-brainstem CCM presenting without ICH or FND, 8·0% (0·1-15·9) for 80 people with brainstem CCM presenting without ICH or FND, 18·4% (13·3-23·5) for 327 people with non-brainstem CCM presenting with ICH or FND, and 30·8% (26·3-35·2) for 495 people with brainstem CCM presenting with ICH or FND. Mode of clinical presentation and CCM location are independently associated with ICH within 5 years of CCM diagnosis. These

Learning with Intangible Heritage for a Sustainable Future: Guidelines for Educators in the Asia-Pacific Region

ERIC Educational Resources Information Center

Pillai, Janet; Achilles, Vanessa

2015-01-01

The guide provides teacher educators and teachers with an understanding of the concept of intangible cultural heritage (ICH) and explains why ICH should be integrated into the curriculum in tandem with the principles and perspectives of Education for Sustainable Development (ESD). This guide explains how the strategic incorporation of ICH elements…

Programmed death (PD)-1 attenuates macrophage activation and brain inflammation via regulation of fibrinogen-like protein 2 (Fgl-2) after intracerebral hemorrhage in mice.

PubMed

Yuan, Bangqing; Huang, Shaokuan; Gong, Shuangfeng; Wang, Feihong; Lin, Li; Su, Tonggang; Sheng, Hanchao; Shi, Hui; Ma, Kunlong; Yang, Zhao

2016-11-01

Neuroinflammation plays an important role in the recovery of brain injury in ICH. Macrophage is the major executor in the neuroinflammation and initiates neurological defects. Programmed death 1 (PD-1) delivers inhibitory signals that regulate the balance between T cell activation, tolerance, and immunopathology. PD-1 expression by macrophages plays a pathologic role in the innate inflammatory response. However, the exact role of PD-1 on inflammatory responses following ICH has not been well identified. In this experiment, PD-1 KO (PD-1 -/-) ICH mice and Wild-type (WT) ICH mice were caused by intracranial injection of type IV collagenase. The level of macrophage activation, inflammatory cytokines and fibrinogen-like protein 2 (Fgl-2) were detected using immunofluorescence staining and ELISA assays. In addition, brain edema and neurological scores of ICH mice were also measured. Our data demonstrated that ICH promoted PD-1 expression of macrophage and enhanced inflammatory cytokines and Fgl-2 concentrations. PD-1 -/- mice exhibited significantly higher expression of the inflammatory cytokines which initiate Fgl-2, than did their wild-type (WT) littermates. As a result, macrophage activation, cerebral edema and neurological deficit scores of PD-1 -/- mice were higher. In conclusion, our data demonstrate that PD-1 plays a vital role in brain inflammation via regulation of Fgl-2 after ICH, and that manipulation of PD-1 might be a promising therapeutical target in ICH. Copyright © 2016 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

Association Between Serum Calcium Level and Extent of Bleeding in Patients With Intracerebral Hemorrhage.

PubMed

Morotti, Andrea; Charidimou, Andreas; Phuah, Chia-Ling; Jessel, Michael J; Schwab, Kristin; Ayres, Alison M; Romero, Javier M; Viswanathan, Anand; Gurol, M Edip; Greenberg, Steven M; Anderson, Christopher D; Rosand, Jonathan; Goldstein, Joshua N

2016-11-01

Calcium is a key cofactor of the coagulation cascade and may play a role in the pathophysiology of intracerebral hemorrhage (ICH). To investigate whether a low serum calcium level is associated with an increase in the extent of bleeding in patients with ICH as measured by baseline hematoma volume and risk of hematoma expansion. Prospective cohort study of 2103 consecutive patients with primary ICH ascertained during the period between 1994 and 2015 at an academic medical center. The statistical analysis was performed in January 2016. Total calcium level was measured on admission, and hypocalcemia was defined as a serum calcium level of less than 8.4 mg/dL. Baseline and follow-up hematoma volumes, detected by noncontrast computed tomography, were measured using a computer-assisted semiautomatic analysis. Hematoma expansion was defined as an increase of more than 30% or 6 mL from baseline ICH volume. Associations between serum calcium level and baseline hematoma volume and between serum calcium level and ICH expansion were investigated in multivariable linear and logistic regression models, respectively. A total of 2123 patients with primary ICH were screened, and 2103 patients met the inclusion criteria (mean [SD] age, 72.7 [12.5] years; 54.3% male patients), of whom 229 (10.9%) had hypocalcemia on admission. Hypocalcemic patients had a higher median baseline hematoma volume than did normocalcemic patients (37 mL [IQR, 15-72 mL] vs 16 mL [IQR, 6-44 mL]; P < .001). Low calcium levels were independently associated with higher baseline ICH volume (β = -0.13, SE = .03, P < .001). A total of 1393 patients underwent follow-up noncontrast computed tomography and were included in the ICH expansion analysis. In this subgroup, a higher serum calcium level was associated with reduced risk of ICH expansion (odds ratio, 0.55 [95% CI, 0.35-0.86]; P = .01), after adjusting for other confounders. Hypocalcemia correlates with the extent of bleeding in patients

Stem Cell Therapy: A Promising Therapeutic Method for Intracerebral Hemorrhage.

PubMed

Gao, Liansheng; Xu, Weilin; Li, Tao; Chen, Jingyin; Shao, Anwen; Yan, Feng; Chen, Gao

2018-01-01

Spontaneous intracerebral hemorrhage (ICH) is one type of the most devastating cerebrovascular diseases worldwide, which causes high morbidity and mortality. However, efficient treatment is still lacking. Stem cell therapy has shown good neuroprotective and neurorestorative effect in ICH and is a promising treatment. In this study, our aim was to review the therapeutic effects, strategies, related mechanisms and safety issues of various types of stem cell for ICH treatment. Numerous studies had demonstrated the therapeutic effects of diverse stem cell types in ICH. The potential mechanisms include tissue repair and replacement, neurotrophy, promotion of neurogenesis and angiogenesis, anti-apoptosis, immunoregulation and anti-inflammation and so forth. The microenvironment of the central nervous system (CNS) can also influence the effects of stem cell therapy. The detailed therapeutic strategies for ICH treatment such as cell type, the number of cells, time window, and the routes of medication delivery, varied greatly among different studies and had not been determined. Moreover, the safety issues of stem cell therapy for ICH should not be ignored. Stem cell therapy showed good therapeutic effect in ICH, making it a promising treatment. However, safety should be carefully evaluated, and more clinical trials are required before stem cell therapy can be extensively applied to clinical use.

A critical appraisal of experimental intracerebral hemorrhage research

PubMed Central

MacLellan, Crystal L; Paquette, Rosalie; Colbourne, Frederick

2012-01-01

The likelihood of translating therapeutic interventions for stroke rests on the quality of preclinical science. Given the limited success of putative treatments for ischemic stroke and the reasons put forth to explain it, we sought to determine whether such problems hamper progress for intracerebral hemorrhage (ICH). Approximately 10% to 20% of strokes result from an ICH, which results in considerable disability and high mortality. Several animal models reproduce ICH and its underlying pathophysiology, and these models have been widely used to evaluate treatments. As yet, however, none has successfully translated. In this review, we focus on rodent models of ICH, highlighting differences among them (e.g., pathophysiology), issues with experimental design and analysis, and choice of end points. A Pub Med search for experimental ICH (years: 2007 to 31 July 2011) found 121 papers. Of these, 84% tested neuroprotectants, 11% tested stem cell therapies, and 5% tested rehabilitation therapies. We reviewed these to examine study quality (e.g., use of blinding procedures) and choice of end points (e.g., behavioral testing). Not surprisingly, the problems that have plagued the ischemia field are also prevalent in ICH literature. Based on these data, several recommendations are put forth to facilitate progress in identifying effective treatments for ICH. PMID:22293989

Does the Short-Term Effect of Air Pollution Influence the Incidence of Spontaneous Intracerebral Hemorrhage in Different Patient Groups? Big Data Analysis in Taiwan.

PubMed

Chien, Ting-Ying; Ting, Hsien-Wei; Chan, Chien-Lung; Yang, Nan-Ping; Pan, Ren-Hao; Lai, K Robert; Hung, Su-In

2017-12-10

Spontaneous intracerebral hemorrhage (sICH) has a high mortality rate. Research has demonstrated that the occurrence of sICH is related to air pollution. This study used big data analysis to explore the impact of air pollution on the risk of sICH in patients of differing age and geographic location. 39,053 cases were included in this study; 14,041 in the Taipei region (Taipei City and New Taipei City), 5537 in Taoyuan City, 7654 in Taichung City, 4739 in Tainan City, and 7082 in Kaohsiung City. The results of correlation analysis indicated that there were two pollutants groups, the CO and NO₂ group and the PM 2.5 and PM 10 group. Furthermore, variations in the correlations of sICH with air pollutants were identified in different age groups. The co-factors of the influence of air pollutants in the different age groups were explored using regression analysis. This study integrated Taiwan National Health Insurance data and air pollution data to explore the risk factors of sICH using big data analytics. We found that PM 2.5 and PM 10 are very important risk factors for sICH, and age is an important modulating factor that allows air pollutants to influence the incidence of sICH.

Does the Short-Term Effect of Air Pollution Influence the Incidence of Spontaneous Intracerebral Hemorrhage in Different Patient Groups? Big Data Analysis in Taiwan

PubMed Central

Chien, Ting-Ying; Ting, Hsien-Wei; Chan, Chien-Lung; Lai, K. Robert; Hung, Su-In

2017-01-01

Spontaneous intracerebral hemorrhage (sICH) has a high mortality rate. Research has demonstrated that the occurrence of sICH is related to air pollution. This study used big data analysis to explore the impact of air pollution on the risk of sICH in patients of differing age and geographic location. 39,053 cases were included in this study; 14,041 in the Taipei region (Taipei City and New Taipei City), 5537 in Taoyuan City, 7654 in Taichung City, 4739 in Tainan City, and 7082 in Kaohsiung City. The results of correlation analysis indicated that there were two pollutants groups, the CO and NO2 group and the PM2.5 and PM10 group. Furthermore, variations in the correlations of sICH with air pollutants were identified in different age groups. The co-factors of the influence of air pollutants in the different age groups were explored using regression analysis. This study integrated Taiwan National Health Insurance data and air pollution data to explore the risk factors of sICH using big data analytics. We found that PM2.5 and PM10 are very important risk factors for sICH, and age is an important modulating factor that allows air pollutants to influence the incidence of sICH. PMID:29232865

Spontaneous Intracerebral Hemorrhage Image Analysis Methods: A Survey

NASA Astrophysics Data System (ADS)

Pérez, Noel; Valdés, Jose; Guevara, Miguel; Silva, Augusto

Spontaneous intracerebral hemorrhages (ICH) account for 10-30% of all strokes and are a result of acute bleeding into the brain due to ruptures of small penetrating arteries. Despite major advancements in the management of ischemic strokes and other causes of hemorrhagic strokes, such as ruptured aneurysm, arteriovenous malformations (AVMs), or cavernous angioma, during the past several decades, limited progress has been made in the treatment of ICH, and the prognosis for patients who suffer them remains poor. The societal impact of these hemorrhagic strokes is magnified by the fact that affected patients typically are a decade younger than those afflicted with ischemic strokes. The ICH continues to kill or disable most of their victims. Some studies show that those who suffer ICH have a 30-day mortality rate of 35-44% and a 6-month mortality rate approaching 50%. Approximately 700,000 new strokes occur in the United States annually and approximately 15% are hem-orrhagic strokes related to ICH. The poor outcome associated with ICH is related to the extent of brain damage. ICH produces direct destruction and compression of surrounding brain tissue. Direct compression causes poor perfusion and venous drainage to surrounding penumbra at risk, resulting in ischemia to the tissues that most need perfusion [16].

Intracranial hypertension: classification and patterns of evolution

PubMed Central

Iencean, SM

2008-01-01

Intracranial hypertension (ICH) was systematized in four categories according to its aetiology and pathogenic mechanisms: parenchymatous ICH with an intrinsic cerebral cause; vascular ICH, which has its aetiology in disorders of cerebral blood circulation; ICH caused by disorders of cerebro–spinal fluid dynamics and idiopathic ICH. The increase of intracranial pressure is the first to happen and then intracranial hypertension develops from this initial effect becoming symptomatic; it then acquires its individuality, surpassing the initial disease. The intracranial hypertension syndrome corresponds to the stage at which the increased intracranial pressure can be compensated and the acute form of intracranial hypertension is equivalent to a decompensated ICH syndrome. The decompensation of intracranial hypertension is a condition of instability and appears when the normal intrinsic ratio of intracranial pressure – time fluctuation is changed. The essential conditions for decompensation of intracranial hypertension are: the speed of intracranial pressure increase over normal values, the highest value of abnormal intracranial pressure and the duration of high ICP values. Medical objectives are preventing ICP from exceeding 20 mm Hg and maintaining a normal cerebral blood flow. The emergency therapy is the same for the acute form but each of the four forms of ICH has a specific therapy, according to the pathogenic mechanism and if possible to aetiology. PMID:20108456

Risk of intracranial hemorrhage and cerebrovascular accidents in non-small cell lung cancer brain metastasis patients.

PubMed

Srivastava, Geetika; Rana, Vishal; Wallace, Suzy; Taylor, Sarah; Debnam, Matthew; Feng, Lei; Suki, Dima; Karp, Daniel; Stewart, David; Oh, Yun

2009-03-01

Brain metastases confer significant morbidity and a poorer survival in non-small cell lung cancer (NSCLC). Vascular endothelial growth factor-targeted antiangiogenic therapies (AAT) have demonstrated benefit for patients with metastatic NSCLC and are expected to directly inhibit the pathophysiology and morbidity of brain metastases, yet patients with brain metastases have been excluded from most clinical trials of AAT for fear of intracranial hemorrhage (ICH). The underlying risk of ICH from NSCLC brain metastases is low, but needs to be quantitated to plan clinical trials of AAT for NSCLC brain metastases. Data from MD Anderson Cancer Center Tumor Registry and electronic medical records from January 1998 to March 2006 was interrogated. Two thousand one hundred forty-three patients with metastatic NSCLC registering from January 1998 to September 2005 were followed till March 2006. Seven hundred seventy-six patients with and 1,367 patients without brain metastases were followed till death, date of ICH, or last date of study, whichever occurred first. The incidence of ICH seemed to be higher in those with brain metastasis compared with those without brain metastases, in whom they occurred as result of cerebrovascular accidents. However, the rates of symptomatic ICH were not significantly different. All ICH patients with brain metastasis had received radiation therapy for them and had been free of anticoagulation. Most of the brain metastasis-associated ICH's were asymptomatic, detected during increased radiologic surveillance. The rates of symptomatic ICH, or other cerebrovascular accidents in general were similar and not significantly different between the two groups. In metastatic NSCLC patients, the incidence of spontaneous ICH appeared to be higher in those with brain metastases compared with those without, but was very low in both groups without a statistically significant difference. These data suggest a minimal risk of clinically significant ICH for NSCLC

Increased expression of T cell immunoglobulin and mucin domain 3 aggravates brain inflammation via regulation of the function of microglia/macrophages after intracerebral hemorrhage in mice.

PubMed

Xu, ChangJun; Wang, Tao; Cheng, Si; Liu, YuGuang

2013-12-01

Microglia/macrophages are known to play important roles in initiating brain inflammation after spontaneous intracerebral hemorrhage (ICH). T cell immunoglobulin and mucin domain-3 (Tim-3) have been proven to play a critical part in several inflammatory diseases through regulation of both adaptive and innate immune responses. Tim-3 can be expressed by microglia/macrophages and regulates their function in the innate immune response. However, the effect of Tim-3 on inflammatory responses following ICH is unclear. In this study, we investigated Tim-3 expression, the inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), and brain water content in peri-hematomal brain tissue at 12 hours and at 1, 3, 5, and 7 days post-ICH in wild type (WT) ICH and Tim-3-/- ICH mice. The numbers of Tim-3 positive cells,astrocytes, neutrophils and microglia/macrophages were detected using immunofluorescence staining. Cytokines were measured by ELISA. Double immunofluorescence labeling was performed to identify the cellular source of Tim-3 expression. Mouse neurological deficit scores were assessed through animal behavior. Expression of Tim-3 increased early in mouse peri-hematomal brain tissue after autologous blood injection, peaked at day 1, and was positively correlated with the concentrations of TNF-α, IL-1β, and brain water content. Tim-3 was predominantly expressed in microglia/macrophages. Compared with WT mice, Tim-3-/- mice had reduced ICH-induced brain inflammation with decreased TNF-α and IL-1β, cerebral edema and neurological deficit scores. Moreover, Tim-/- inhibited activation of microglia/macrophages. The number of activated microglia/macrophages in Tim-3-/- ICH mice was much lower than that in WT ICH mice. Our findings demonstrate that Tim-3 plays an important role in brain inflammation after ICH, and may be a potential treatment target.

30-day mortality and readmission after hemorrhagic stroke among Medicare beneficiaries in Joint Commission primary stroke center-certified and noncertified hospitals.

PubMed

Lichtman, Judith H; Jones, Sara B; Leifheit-Limson, Erica C; Wang, Yun; Goldstein, Larry B

2011-12-01

Ischemic stroke patients treated at Joint Commission Primary Stroke Center (JC-PSC)-certified hospitals have better outcomes. Data reflecting the impact of JC-PSC status on outcomes after hemorrhagic stroke are limited. We determined whether 30-day mortality and readmission rates after hemorrhagic stroke differed for patients treated at JC-PSC-certified versus noncertified hospitals. The study included all fee-for-service Medicare beneficiaries aged 65 years or older with a primary discharge diagnosis of subarachnoid hemorrhage (SAH) or intracerebral hemorrhage (ICH) in 2006. Covariate-adjusted logistic and Cox proportional hazards regression assessed the effect of care at a JC-PSC-certified hospital on 30-day mortality and readmission. There were 2305 SAH and 8708 ICH discharges from JC-PSC-certified hospitals and 3892 SAH and 22 564 ICH discharges from noncertified hospitals. Unadjusted in-hospital mortality (SAH: 27.5% versus 33.2%, P<0.0001; ICH: 27.9% versus 29.6%, P=0.003) and 30-day mortality (SAH: 35.1% versus 44.0%, P<0.0001; ICH: 39.8% versus 42.4%, P<0.0001) were lower in JC-PSC hospitals, but 30-day readmission rates were similar (SAH: 17.0% versus 17.0%, P=0.97; ICH: 16.0% versus 15.5%, P=0.29). Risk-adjusted 30-day mortality was 34% lower (odds ratio, 0.66; 95% confidence interval, 0.58-0.76) after SAH and 14% lower (odds ratio, 0.86; 95% confidence interval, 0.80-0.92) after ICH for patients discharged from JC-PSC-certified hospitals. There was no difference in 30-day risk-adjusted readmission rates for SAH or ICH based on JC-PSC status. Patients treated at JC-PSC-certified hospitals had lower risk-adjusted mortality rates for both SAH and ICH but similar 30-day readmission rates as compared with noncertified hospitals.

The effect of monascin on hematoma clearance and edema after intracerebral hemorrhage in rats.

PubMed

Wang, Juan; Wang, Gaiqing; Yi, Jinying; Xu, Yi; Duan, Shuna; Li, Tong; Sun, Xin-Gang; Dong, Liang

2017-09-01

Intracerebral hemorrhage (ICH) is a particularly devastating form of stroke with high mortality and morbidity. Hematomas are the primary cause of neurologic deficits associated with ICH. The products of hematoma are recognized as neurotoxins and the main contributors to edema formation and tissue damage after ICH. Finding a means to efficiently promote absorption of hematoma is a novel clinical challenge for ICH. Peroxisome proliferator-activated receptor gamma (PPARγ) and nuclear factor erythroid 2-related factor 2 (Nrf2), had been shown that, can take potential roles in the endogenous hematoma clearance. However, monascin, a novel natural Nrf2 activator with PPARγ agonist, has not been reported to play a role in ICH. This study was designed to evaluate the effect of monascin on neurological deficits, hematoma clearance and edema extinction in a model of ICH in rats. 164 adult male Sprague-Dawley (SD) rats were randomly divided into sham; vehicle; monascin groups with low dosages (1mg/kg/day), middle dosages (5mg/kg/day) and high dosages (10mg/kg/day) respectively. Animals were euthanized at 1, 3 and 7days following neurological evaluation after surgery. We examined the effect of monascin on the brain water contents, blood brain barrier (BBB) permeability and hemoglobin levels, meanwhile reassessed the volume of hematoma and edema around the hematoma by Magnetic Resonance Imaging (MRI) in each group. The high dosage of monascin significantly improved neurological deficits, reduced the volume of hematoma in 1-7days after ICH, decreased BBB permeability and edema formation in 1-3days following ICH. Our study demonstrated that the high dosage of monascin played a neuroprotective role in ICH through reducing BBB permeability, edema and hematoma volume. Copyright © 2017 Elsevier Inc. All rights reserved.

Effect of hyperbaric oxygen preconditioning on peri-hemorrhagic focal edema and aquaporin-4 expression.

PubMed

Fang, Jinyong; Li, Hongling; Li, Guanglei; Wang, Lichun

2015-08-01

The aim of the present study was to investigate the effect of hyperbaric oxygen preconditioning (HBO-PC) on peri-hemorrhagic focal edema and aquaporin-4 (AQP-4) expression in an experimental intracerebral hemorrhage (ICH) rat model. Sixty-six Sprague Dawley® rats were divided into three groups: The sham-surgery group (SHG; n=6); the control group (A-ICH; n=30), in which the rats were injected with autologous blood; and the experimental HBO-PC group (P-HBO; n=30). The rats underwent brain edema and AQP-4 detection at 5 postoperative time-points (24, 48 and 72 h and 5 and 7 days). The water content in the brain tissues of the A-ICH animals was higher than that in the brain tissues of the SHG rats at each time-point (P<0.05), and the edema in the P-HBO was significantly more severe 24 and 48 h postoperatively than that at 7 days postoperatively (P<0.05). The difference between the P-HBO and A-ICH was significant at 48 and 72 h postoperatively (P<0.05). AQP-4 was expressed in the post-hemorrhagic rat brains of all groups; the SHG animals exhibited low expression, while the A-ICH animals exhibited an increased expression 24 h postoperatively. In the A-ICH, expression peaked at 48 h postoperatively and began to decrease gradually after 72 h. At the 7-day time-point, the expression level in the A-ICH was closer to but still higher than that of the SHG animals (P<0.05). The differences between the P-HBO and A-ICH animals at the postoperative 24-h, 48-h and 7-day time-points were statistically significant (P<0.05). In conclusion, HBO-PC may downregulate AQP-4 expression to reduce the intracerebral edema, thus strengthening tolerance to ICH and protecting the nerves.

Cardiovascular health in adolescents with type 1 diabetes: the SEARCH CVD study.

PubMed

Alman, Amy C; Talton, Jennifer W; Wadwa, R Paul; Urbina, Elaine M; Dolan, Lawrence M; Daniels, Stephen R; Hamman, Richard F; D'Agostino, Ralph B; Marcovina, Santica M; Mayer-Davis, Elizabeth J; Dabelea, Dana M

2014-11-01

In their Strategic Impact Goal Statement, the American Heart Association focused on primordial prevention of cardiovascular risk factors by defining metrics for ideal cardiovascular health (ICH). The prevalence of ICH among youth with type 1 diabetes is unknown. Youth with type 1 diabetes face an increased risk of cardiovascular disease (CVD) as they age. The purpose of this report was to examine the prevalence of ICH in a population of youth with type 1 diabetes and to examine the association of ICH with measures of cardiovascular structure and function. This report is based on SEARCH CVD an ancillary study to the SEARCH for Diabetes in Youth. A total of 190 adolescents with type 1 diabetes had complete data on all of the ICH metrics at baseline and had measures of arterial stiffness [pulse wave velocity (PWV), brachial distensibility (BrachD), and augmentation index (AIx)] and carotid intima-media thickness completed at a follow-up visit [on average 5 yr after baseline (interquartile range 4-5)]. No subjects met the ICH criteria for all 7 metrics. Meeting an increasing number of ICH metrics was significantly associated with lower arterial stiffness [lower PWV of the trunk (β = -0.02 ±0.01; p = 0.004) and AIx (β = -2.2 ±0.66; p = 0.001), and increased BrachD (β = 0.14 ±0.07; p = 0.04)]. Increasing number of ICH metrics was significantly associated with decreased arterial stiffness, but prevalence of ICH in this population was low. Youth with type 1 diabetes could benefit from improvements in their cardiovascular health. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Association between alanine aminotransferase and intracerebral hemorrhage in East Asian populations.

PubMed

Kim, Hyeon Chang; Oh, Sun Min; Pan, Wen-Harn; Ueshima, Hirotsugu; Gu, Dongfeng; Chuang, Shao-Yuan; Fujiyoshi, Akira; Li, Ying; Zhao, Liancheng; Suh, Il

2013-01-01

Intracerebral hemorrhage (ICH) and chronic liver disease are relatively common in East Asian countries. However, the relationship between the two diseases is unclear. Thus, we investigated the association between serum alanine aminotransferase (ALT) levels and ICH risk in East Asian populations. The East Asian Network for Stroke Prevention enrolled 279,982 participants with ALT measurements from four cohort studies in Korea, Taiwan, Japan and mainland China. Among them, 1,324 ICH events and 493 ICH deaths were observed. Cox's proportional hazard regression analysis was performed in each cohort to estimate the hazard ratio (HR) after adjusting for age, blood pressure, diabetes, total cholesterol, smoking and alcohol intake. Combined HRs were then estimated using pooled analyses with fixed-effects models. The multivariate-adjusted pooled HRs (with 95% confidence interval, CI) for ICH incidence per 10 IU/l increments of ALT were 1.04 (1.03-1.04) in men and 1.01 (0.98-1.04) in women. Corresponding HRs for ICH mortality were 1.04 (1.02-1.05) in men and 1.04 (1.00-1.08) in women. The pooled HRs for ICH incidence in participants with ALT levels greater than or equal to 50 IU/l compared to those with levels less than 20 IU/l were 1.74 (1.41-2.16) in men and 1.60 (1.06-2.40) in women. The corresponding HRs for ICH mortality were 1.72 (1.21-2.44) in men and 1.63 (0.79-3.36) in women. An elevated ALT level was independently and significantly associated with an increased risk of ICH in East Asian men, but the association was less prominent in women. © 2013 S. Karger AG, Basel.

Association between diabetes mellitus and the occurrence and outcome of intracerebral hemorrhage

PubMed Central

Boulanger, Marion; Poon, Michael T.C.; Wild, Sarah H.

2016-01-01

Objective: Whether diabetes mellitus (DM) is a risk factor for spontaneous intracerebral hemorrhage (ICH) and influences outcome after ICH remains unclear. Methods: One reviewer searched Ovid MEDLINE and Embase 1980–2014 inclusive for studies investigating the associations between DM and ICH occurrence or DM and ICH case fatality. Two reviewers independently confirmed each study's eligibility, assessed risk of bias, and extracted data. One reviewer combined studies using random effects meta-analysis. Results: Nineteen case-control studies involving 3,397 people with ICH and 5,747 people without ICH found an association between DM and ICH occurrence (unadjusted odds ratio [OR] 1.23, 95% confidence interval [CI] 1.04–1.45; I2 = 22%), which did not differ between 17 hospital-based and 2 population-based studies (pdiff = 0.70), and was similar in the 16 studies that controlled for age and sex (unadjusted OR 1.15, 95% CI 0.95–1.40; I2 = 14%). This association was not identified in 3 population-based cohort studies in which ICH occurred in 38 (0.66%) of 5,724 people with DM and 448 (0.57%) of 78,702 people without DM (unadjusted risk ratio [RR] 1.27, 95% CI 0.68–2.36; I2 = 69%). DM was associated with a higher case fatality by 30 days or hospital discharge in 18 cohort studies involving 813 people with DM and 3,714 people without DM (unadjusted RR 1.52, 95% CI 1.28–1.81; I2 = 49%). Conclusions: The findings suggest that there may be modest associations between DM and ICH occurrence and outcome, but further information from large, population-based studies that account for confounding is required before the association can be confirmed. PMID:27473136

Critical pathways for the management of stroke and intracerebral hemorrhage: a survey of US hospitals.

PubMed

Cooper, David; Jauch, Edward; Flaherty, Matthew L

2007-03-01

Thirty-day mortality rates in patients with spontaneous intracerebral hemorrhage (ICH) range from 35% to 50%, with only 10-20% of the survivors regaining functional independence. This high mortality and morbidity argues for the optimization of emergency medical services (EMS), emergency department (ED), and in-patient treatment paradigms. With the development of interventional strategies for ICH, both pharmacologic and surgical, time to treatment will be critical to improving outcomes. Similar to acute ischemic stroke care, proper preparation and role definition will be critical for efficient evaluation and treatment. We studied the existence and structure of ICH management protocols in US hospitals. A national survey of Emergency Medicine physicians was conducted to gather information regarding the existence of stroke and ICH treatment protocols at their institutions. A clearly established pathway for the management of ischemic stroke exists in most hospitals (78%). By contrast, only 30% of hospitals have a clearly defined pathway for ICH. Thus, while most hospitals are able to perform rapid computed tomography (CT) scans to diagnose ICH, the management of these patients post-CT is more fragmented and variable. Few hospitals have comprehensive protocols that include treatment policies for raised intracranial pressure or formal policies for the transfer of patients to centers with neurocritical care/neurosurgical resources. Integration of ICH critical pathways into stroke protocols could potentially improve the high mortality and disability associated with this condition and might facilitate ongoing studies of ICH-specific interventions. With stroke neurologists and neurocritical care specialists showing an increasing interest in ICH management, development of critical pathways may allow for a standardized approach to best treatment practices within institutions and networks as evidence grows for new treatments and management strategies. This may also allow a

Diagnosis of acute lymphoblastic leukemia from intracerebral hemorrhage and blast crisis. A case report and review of the literature.

PubMed

Naunheim, Matthew R; Nahed, Brian V; Walcott, Brian P; Kahle, Kristopher T; Soupir, Chad P; Cahill, Daniel P; Borges, Lawrence F

2010-09-01

Intracerebral hemorrhage (ICH) contributes significantly to the morbidity and mortality of patients suffering from acute leukemia. While ICH is often identified in autopsy studies of leukemic patients, it is rare for ICH to be the presenting sign that ultimately leads to the diagnosis of leukemia. We report a patient with previously undiagnosed acute precursor B-cell lymphoblastic leukemia (ALL) who presented with diffuse encephalopathy due to ICH in the setting of an acute blast crisis. The diagnosis of ALL was initially suspected, because of the hyperleukocytosis observed on presentation, then confirmed with a bone marrow biopsy and flow cytometry study of the peripheral blood. Furthermore, detection of the BCR/ABL Philadelphia translocation t(9:22)(q34:q11) in this leukemic patient by fluorescent in situ hybridization permitted targeted therapy of the blast crisis with imatinib (Gleevec). Understanding the underlying etiology of ICH is pivotal in its management. This case demonstrates that the presence of hyperleukocytosis in a patient with intracerebral hemorrhage should raise clinical suspicion for acute leukemia as the cause of the ICH.

Aging exacerbates intracerebral hemorrhage-induced brain injury.

PubMed

Lee, Jae-Chul; Cho, Geum-Sil; Choi, Byung-Ok; Kim, Hyoung Chun; Kim, Won-Ki

2009-09-01

Aging may be an important factor affecting brain injury by intracerebral hemorrhage (ICH). In the present study, we investigated the responses of glial cells and monocytes to intracerebral hemorrhage in normal and aged rats. ICH was induced by microinjecting autologous whole blood (15 microL) into the striatum of young (4 month old) and aged (24 month old) Sprague-Dawley rats. Age-dependent relations of brain tissue damage with glial and macrophageal responses were evaluated. Three days after ICH, activated microglia/macrophages with OX42-positive processes and swollen cytoplasm were more abundantly distributed around and inside the hemorrhagic lesions. These were more dramatic in aged versus the young rats. Western blot and immunohistochemistry analyses showed that the expression of interleukin-1beta protein after ICH was greater in aged rats, whereas the expression of GFAP and ciliary neurotrophic factor protein after ICH was significantly lower in aged rats. These results suggest that ICH causes more severe brain injury in aged rats most likely due to overactivation of microglia/macrophages and concomitant repression of reactive astrocytes.

Effect of Ichthyophthirius multifiliis parasitism on the survival, hematology and bacterial load in channel catfish previously exposed to Edwardsiella ictaluri.

PubMed

Shoemaker, Craig A; Martins, Maurício L; Xu, De-Hai; Klesius, Phillip H

2012-11-01

The effect of Ichthyophthirius multifiliis (Ich) parasitism on survival, hematology and bacterial load in channel catfish, Ictalurus punctatus, previously exposed to Edwardsiella ictaluri was studied. Fish were exposed to E. ictaluri 1 day prior to Ich in the following treatments: (1) infected by E. ictaluri and Ich at 2,500 theronts/fish; (2) infected by E. ictaluri only; (3) infected by Ich at 2,500 theronts/fish only; and (4) non infected control. Mortality was significantly higher in fish previously exposed to E. ictaluri and then infected by Ich (71.1 %). Mortalities were 26.7 %, 28.9 % and 0 % for fish infected by E. ictaluri only, by Ich only and non-infected control, respectively. Quantitative polymerase chain reaction demonstrated the presence of E. ictaluri in the brain, gill, kidney and liver of fish infected with E. ictaluri regardless of Ich parasitism. At day 8, E. ictaluri parasitized fish had significantly more bacteria present in the brain, gill and liver, with no bacteria detected in these organs in the E. ictaluri-only treatment, suggesting that the bacteria persisted longer in parasitized fish. Decreased red blood cells count and hematocrit in fish at days 8 and 19 after co-infection suggests chronic anemia. Lymphocyte numbers significantly decreased in all infected treatments versus the non-infected controls at days 2, 8 and 19. Lymphopenia suggests that lymphocytes were actively involved in the immune response. Bacterial clearance was probably influenced by the stress of parasitism and/or the mucosal response induced by ectoparasitic Ich that resulted in the higher mortality seen in the co-infected treatment.

Practice Patterns for Neurosurgical Utilization and Outcome in Acute Intracerebral Hemorrhage: Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trials 1 and 2 Studies.

PubMed

Guo, Rui; Blacker, David J; Wang, Xia; Arima, Hisatomi; Lavados, Pablo M; Lindley, Richard I; Chalmers, John; Anderson, Craig S; Robinson, Thompson

2017-12-01

The prognosis in acute spontaneous intracerebral hemorrhage (ICH) is related to hematoma volume, where >30 mL is commonly used to define large ICH as a threshold for neurosurgical decompression but without clear supporting evidence. To determine the factors associated with large ICH and neurosurgical intervention among participants of the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trials (INTERACT). We performed pooled analysis of the pilot INTERACT1 (n = 404) and main INTERACT2 (n = 2839) studies of ICH patients (<6 h of onset) with elevated systolic blood pressure (SBP, 150-220 mm Hg) who were randomized to intensive (target SBP < 140 mm Hg) or contemporaneous guideline-recommended (target SBP < 180 mm Hg) management. Neurosurgical intervention data were collected at 7 d postrandomization. Multivariable logistic regression was used to determine associations. There were 372 (13%) patients with large ICH volume (>30 mL), which was associated with nonresiding in China, nondiabetic status, severe neurological deficit (National Institutes of Health stroke scale [NIHSS] score ≥ 15), lobar location, intraventricular hemorrhage extension, raised leucocyte count, and hyponatremia. Significant predictors of those patients who underwent surgery (226 of 3233 patients overall; 83 of 372 patients with large ICH) were younger age, severe neurological deficit (lower Glasgow coma scale score, and NIHSS score ≥ 15), baseline ICH volume > 30 mL, and intraventricular hemorrhage. Early identification of severe ICH, based on age and clinical and imaging parameters, may facilitate neurosurgery and intensive monitoring of patients. Copyright © 2017 by the Congress of Neurological Surgeons

Prior Cannabis Use Is Associated with Outcome after Intracerebral Hemorrhage.

PubMed

Di Napoli, Mario; Zha, Alicia M; Godoy, Daniel A; Masotti, Luca; Schreuder, Floris H B M; Popa-Wagner, Aurel; Behrouz, Réza

2016-01-01

Recent evidence suggests that a potential harmful relationship exists between cannabis use and ischemic stroke. The purpose of this study was to determine the implications of cannabis use in intracerebral hemorrhage (ICH) patients. An analysis of an international, multicenter, observational database of consecutive patients with spontaneous ICH was conducted. We extracted the following characteristics on presentation: demographics, risk factors, antiplatelet or anticoagulant use, Glasgow Coma Scale, ICH score, neuroimaging parameters, and urine toxicology screen (UTS) results. Modified Rankin Scale (mRS) score was utilized for determination of outcome at discharge. Adjusted logistic ordinal regression was used as shift analysis to assess the impact of cannabis use on mRS score at discharge. The adjusted common OR measured the likelihood that cannabis use would lead to lower mRS scores. Within a cohort of 725 spontaneous ICH patients, UTS was positive for cannabinoids in 8.6%. Cannabinoids-positive (CB+) patients were more frequently Caucasian (p < 0.001), younger (p < 0.001), and had lower median ICH scores on admission (p = 0.017) than those who were cannabinoids-negative. CB+ patients also showed a shift toward better outcome in the distribution of mRS categories, with an adjusted common OR of 0.544 (95% CI 0.330-0.895, p = 0.017). In this multinational cohort, cannabis use was discovered in nearly 10% of patients with spontaneous ICH. Although there was no relationship between cannabis use and specific ICH characteristics, CB+ patients had milder ICH presentation and less disability at discharge. © 2016 S. Karger AG, Basel.

Enhanced electrical responsiveness in the cerebral cortex with oral melatonin administration after a small hemorrhage near the internal capsule in rats.

PubMed

Ueda, Yoshitomo; Masuda, Tadashi; Ishida, Akimasa; Misumi, Sachiyo; Shimizu, Yuko; Jung, Cha-Gyun; Hida, Hideki

2014-11-01

Intracerebral hemorrhage (ICH) can cause direct brain injury at the insult site and indirect damage in remote brain areas. Although a protective effect of melatonin (ML) has been reported for ICH, its detailed mechanisms and effects on remote brain injury remain unclear. To clarify the mechanism of indirect neuroprotection after ICH, we first investigated whether ML improved motor function after ICH and then examined the underlying mechanisms. The ICH model rat was made by collagenase injection into the left globus pallidus, adjacent to the internal capsule. ML oral administration (15 mg/kg) for 7 days after ICH resulted in significant recovery of motor function. Retrograde labeling of the corticospinal tract by Fluoro-Gold revealed a significant increase in numbers of positive neurons in the cerebral cortex. Immunohistological analysis showed that ML treatment induced no difference in OX41-positive activated microglia/macrophage at day 1 (D1) but a significant reduction in 8-hydroxydeoxyguanosin-positive cells at D7. Neutral red assay revealed that ML significantly prevented H2 O2 -induced cell death in cultured oligodendrocytes and astrocytes but not in neurons. Electrophysiological response in the cerebral cortex area where the number of Fluoro-Gold-positive cells was increased was significantly improved in ML-treated rats. These data suggest that ML improves motor abilities after ICH by protecting oligodendrocytes and astrocytes in the vicinity of the lesion in the corticospinal tract from oxidative stress and causes enhanced electrical responsiveness in the cerebral cortex remote to the ICH pathology. Copyright © 2014 Wiley Periodicals, Inc.

Outcomes Associated With Resuming Warfarin Treatment After Hemorrhagic Stroke or Traumatic Intracranial Hemorrhage in Patients With Atrial Fibrillation.

PubMed

Nielsen, Peter Brønnum; Larsen, Torben Bjerregaard; Skjøth, Flemming; Lip, Gregory Y H

2017-04-01

The increase in the risk for bleeding associated with antithrombotic therapy causes a dilemma in patients with atrial fibrillation (AF) who sustain an intracranial hemorrhage (ICH). A thrombotic risk is present; however, a risk for serious harm associated with resumption of anticoagulation therapy also exists. To investigate the prognosis associated with resuming warfarin treatment stratified by the type of ICH (hemorrhagic stroke or traumatic ICH). This nationwide observational cohort study included patients with AF who sustained an incident ICH event during warfarin treatment from January 1, 1998, through February 28, 2016. Follow-up was completed April 30, 2016. Resumption of warfarin treatment was evaluated after hospital discharge. No oral anticoagulant treatment or resumption of warfarin treatment, included as a time-dependent exposure. One-year observed event rates per 100 person-years were calculated, and treatment strategies were compared using time-dependent Cox proportional hazards regression models with adjustment for age, sex, length of hospital stay, comorbidities, and concomitant medication use. A total of 2415 patients with AF in this cohort (1481 men [61.3%] and 934 women [38.7%]; mean [SD] age, 77.1 years [9.1 years]) sustained an ICH event. Of these events, 1325 were attributable to hemorrhagic stroke and 1090 were secondary to trauma. During the first year, 305 patients with a hemorrhagic stroke (23.0%) died, whereas 210 in the traumatic ICH group (19.3%) died. Among patients with hemorrhagic stroke, resuming warfarin therapy was associated with a lower rate of ischemic stroke or systemic embolism (SE) (adjusted hazard ratio [AHR], 0.49; 95% CI, 0.24-1.02) and an increased rate of recurrent ICH (AHR, 1.31; 95% CI, 0.68-2.50) compared with not resuming warfarin therapy, but these differences did not reach statistical significance. For patients with traumatic ICH, resuming warfarin therapy also was associated with a lower rate of ischemic stroke

Outcomes Associated With Resuming Warfarin Treatment After Hemorrhagic Stroke or Traumatic Intracranial Hemorrhage in Patients With Atrial Fibrillation

PubMed Central

Larsen, Torben Bjerregaard; Skjøth, Flemming; Lip, Gregory Y. H.

2017-01-01

Importance The increase in the risk for bleeding associated with antithrombotic therapy causes a dilemma in patients with atrial fibrillation (AF) who sustain an intracranial hemorrhage (ICH). A thrombotic risk is present; however, a risk for serious harm associated with resumption of anticoagulation therapy also exists. Objective To investigate the prognosis associated with resuming warfarin treatment stratified by the type of ICH (hemorrhagic stroke or traumatic ICH). Design, Setting, and Participants This nationwide observational cohort study included patients with AF who sustained an incident ICH event during warfarin treatment from January 1, 1998, through February 28, 2016. Follow-up was completed April 30, 2016. Resumption of warfarin treatment was evaluated after hospital discharge. Exposures No oral anticoagulant treatment or resumption of warfarin treatment, included as a time-dependent exposure. Main Outcomes and Measures One-year observed event rates per 100 person-years were calculated, and treatment strategies were compared using time-dependent Cox proportional hazards regression models with adjustment for age, sex, length of hospital stay, comorbidities, and concomitant medication use. Results A total of 2415 patients with AF in this cohort (1481 men [61.3%] and 934 women [38.7%]; mean [SD] age, 77.1 years [9.1 years]) sustained an ICH event. Of these events, 1325 were attributable to hemorrhagic stroke and 1090 were secondary to trauma. During the first year, 305 patients with a hemorrhagic stroke (23.0%) died, whereas 210 in the traumatic ICH group (19.3%) died. Among patients with hemorrhagic stroke, resuming warfarin therapy was associated with a lower rate of ischemic stroke or systemic embolism (SE) (adjusted hazard ratio [AHR], 0.49; 95% CI, 0.24-1.02) and an increased rate of recurrent ICH (AHR, 1.31; 95% CI, 0.68-2.50) compared with not resuming warfarin therapy, but these differences did not reach statistical significance. For patients with

Wavelet entropy characterization of elevated intracranial pressure.

PubMed

Xu, Peng; Scalzo, Fabien; Bergsneider, Marvin; Vespa, Paul; Chad, Miller; Hu, Xiao

2008-01-01

Intracranial Hypertension (ICH) often occurs for those patients with traumatic brain injury (TBI), stroke, tumor, etc. Pathology of ICH is still controversial. In this work, we used wavelet entropy and relative wavelet entropy to study the difference existed between normal and hypertension states of ICP for the first time. The wavelet entropy revealed the similar findings as the approximation entropy that entropy during ICH state is smaller than that in normal state. Moreover, with wavelet entropy, we can see that ICH state has the more focused energy in the low wavelet frequency band (0-3.1 Hz) than the normal state. The relative wavelet entropy shows that the energy distribution in the wavelet bands between these two states is actually different. Based on these results, we suggest that ICH may be formed by the re-allocation of oscillation energy within brain.

Mesenchymal Stem Cell Therapy in Intracerebral Haemorrhagic Stroke.

PubMed

Bedini, Gloria; Bersano, Anna; Zanier, Elisa R; Pischiutta, Francesca; Parati, Eugenio A

2018-01-10

Spontaneous intracerebral haemorrhage (ICH) is a relatively common fatal disease, with an overall global incidence estimated at 24.6 per 100,000 person-years. Given the high degree of morbidity and mortality associated with ICH, therapies that may have neuroprotective effects are of increasing interest to clinicians. In this last context, cell therapies offer the promise of improving the disease course which cannot be addressed adequately by existing treatments. The aim of this review is to evaluate the protective effects and molecular mechanisms of mesenchymal stem cells (MSCs) on haemorrhagic brain following ICH. We also discuss possible emerging therapeutic approaches worth of further research. The available literature on the therapeutic potential of MSCs in ICH animal models clearly demonstrated that MSCs enhance the functional recovery and reduce the volume of the infarct size exerting anti-inflammatory and angiogenic properties. However, the quality of the original articles investigating the efficacy of stem cell therapies in ICH animal models is still poor and the lack of ICH clinical trial does not permit to reach any relevant conclusions. Further studies have to be implemented in order to achieve standardized methods of MSCs isolation, characterization and administration to improve ICH treatments with MSCs or MSC-derived products. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Intracranial hemorrhage alters scalp potential distribution in bioimpedance cerebral monitoring: Preliminary results from FEM simulation on a realistic head model and human subjects

PubMed Central

Atefi, Seyed Reza; Seoane, Fernando; Kamalian, Shervin; Rosenthal, Eric S.; Lev, Michael H.; Bonmassar, Giorgio

2016-01-01

Purpose: Current diagnostic neuroimaging for detection of intracranial hemorrhage (ICH) is limited to fixed scanners requiring patient transport and extensive infrastructure support. ICH diagnosis would therefore benefit from a portable diagnostic technology, such as electrical bioimpedance (EBI). Through simulations and patient observation, the authors assessed the influence of unilateral ICH hematomas on quasisymmetric scalp potential distributions in order to establish the feasibility of EBI technology as a potential tool for early diagnosis. Methods: Finite element method (FEM) simulations and experimental left–right hemispheric scalp potential differences of healthy and damaged brains were compared with respect to the asymmetry caused by ICH lesions on quasisymmetric scalp potential distributions. In numerical simulations, this asymmetry was measured at 25 kHz and visualized on the scalp as the normalized potential difference between the healthy and ICH damaged models. Proof-of-concept simulations were extended in a pilot study of experimental scalp potential measurements recorded between 0 and 50 kHz with the authors’ custom-made bioimpedance spectrometer. Mean left–right scalp potential differences recorded from the frontal, central, and parietal brain regions of ten healthy control and six patients suffering from acute/subacute ICH were compared. The observed differences were measured at the 5% level of significance using the two-sample Welch t-test. Results: The 3D-anatomically accurate FEM simulations showed that the normalized scalp potential difference between the damaged and healthy brain models is zero everywhere on the head surface, except in the vicinity of the lesion, where it can vary up to 5%. The authors’ preliminary experimental results also confirmed that the left–right scalp potential difference in patients with ICH (e.g., 64 mV) is significantly larger than in healthy subjects (e.g., 20.8 mV; P < 0.05). Conclusions: Realistic

Perihematomal Edema Expansion Rates and Patient Outcomes in Deep and Lobar Intracerebral Hemorrhage.

PubMed

Grunwald, Zachary; Beslow, Lauren A; Urday, Sebastian; Vashkevich, Anastasia; Ayres, Alison; Greenberg, Steven M; Goldstein, Joshua N; Leasure, Audrey; Shi, Fu-Dong; Kahle, Kristopher T; Battey, Thomas W K; Simard, J Marc; Rosand, Jonathan; Kimberly, W Taylor; Sheth, Kevin N

2017-04-01

Perihematomal edema (PHE) expansion rate may predict functional outcome following spontaneous intracerebral hemorrhage (ICH). We hypothesized that the effect of PHE expansion rate on outcome is greater for deep versus lobar ICH. Subjects (n = 115) were retrospectively identified from a prospective ICH cohort enrolled from 2000 to 2013. Inclusion criteria were age ≥ 18 years, spontaneous supratentorial ICH, and known onset time. Exclusion criteria were primary intraventricular hemorrhage (IVH), trauma, subsequent surgery, or warfarin-related ICH. ICH and PHE volumes were measured from CT scans and used to calculate expansion rates. Logistic regression assessed the association between PHE expansion rates and 90-day mortality or poor functional outcome (modified Rankin Scale > 2). Odds ratios are per 0.04 mL/h. PHE expansion rate from baseline to 24 h (PHE24) was associated with mortality for deep (p = 0.03, OR 1.13[1.02-1.26]) and lobar ICH (p = 0.02, OR 1.03[1.00-1.06]) in unadjusted regression and in models adjusted for age (deep p = 0.02, OR 1.15[1.02-1.28]; lobar p = 0.03, OR 1.03[1.00-1.06]), Glasgow Coma Scale (deep p = 0.03, OR 1.13[1.01-1.27]; lobar p = 0.02, OR 1.03[1.01-1.06]), or time to baseline CT (deep p = 0.046, OR 1.12[1.00-1.25]; lobar p = 0.047, OR 1.03[1.00-1.06]). PHE expansion rate from baseline to 72 h (PHE72) was associated with mRS > 2 for deep ICH in models that were unadjusted (p = 0.02, OR 4.04[1.25-13.04]) or adjusted for ICH volume (p = 0.02, OR 4.3[1.25-14.98]), age (p = 0.03, OR 5.4[1.21-24.11]), GCS (p = 0.02, OR 4.19[1.2-14.55]), or time to first CT (p = 0.03, OR 4.02[1.19-13.56]). PHE72 was associated with poor functional outcomes after deep ICH, whereas PHE24 was associated with mortality for deep and lobar ICH.

Intensive Blood Pressure Reduction and Spot Sign in Intracerebral Hemorrhage: A Secondary Analysis of a Randomized Clinical Trial.

PubMed

Morotti, Andrea; Brouwers, H Bart; Romero, Javier M; Jessel, Michael J; Vashkevich, Anastasia; Schwab, Kristin; Afzal, Mohammad Rauf; Cassarly, Christy; Greenberg, Steven M; Martin, Renee Hebert; Qureshi, Adnan I; Rosand, Jonathan; Goldstein, Joshua N

2017-08-01

The computed tomographic angiography (CTA) spot sign is associated with intracerebral hemorrhage (ICH) expansion and may mark those patients most likely to benefit from intensive blood pressure (BP) reduction. To investigate whether the spot sign is associated with ICH expansion across a wide range of centers and whether intensive BP reduction decreases hematoma expansion and improves outcome in patients with ICH and a spot sign. SCORE-IT (Spot Sign Score in Restricting ICH Growth) is a preplanned prospective observational study nested in the Antihypertensive Treatment of Acute Cerebral Hemorrhage II (ATACH-II) randomized clinical trial. Participants included consecutive patients with primary ICH who underwent a CTA within 8 hours from onset at 59 sites from May 15, 2011, through December 19, 2015. Data were analyzed for the present study from July 1 to August 31, 2016. Patients in ATACH-II were randomized to intensive (systolic BP target, <140 mm Hg) vs standard (systolic BP target, <180 mm Hg) BP reduction within 4.5 hours from onset. Expansion of ICH was defined as hematoma growth of greater than 33%, and an unfavorable outcome was defined as a 90-day modified Rankin Scale score of 4 or greater (range, 0-6). The association among BP reduction, ICH expansion, and outcome was investigated with multivariable logistic regression. A total of 133 patients (83 men [62.4%] and 50 women [37.6%]; mean [SD] age, 61.9 [13.1] years) were included. Of these, 53 (39.8%) had a spot sign, and 24 of 123 without missing data (19.5%) experienced ICH expansion. The spot sign was associated with expansion with sensitivity of 0.54 (95% CI, 0.34-0.74) and specificity of 0.63 (95% CI, 0.53-0.72). After adjustment for potential confounders, intensive BP treatment was not associated with a significant reduction of ICH expansion (relative risk, 0.83; 95% CI, 0.27-2.51; P = .74) or improved outcome (relative risk of 90-day modified Rankin Scale score ≥4, 1.24; 95% CI, 0.53-2.91; P�

Top 100 Most-Cited Articles on Spontaneous Intracerebral Hemorrhage: A Bibliometric Analysis.

PubMed

Nasir, Syed Ali Raza; Gilani, Jaleed Ahmed; Fatima, Kaneez; Faheem, Urooba; Kazmi, Omar; Siddiqi, Javed; Khosa, Faisal

2018-02-01

A bibliometric uses the citation count of an article to determine its impact on the clinical world. There is a paucity of literature concerning top article citations on spontaneous intracerebral hemorrhage (ICH). The main objective of this investigation was to bridge this gap and to provide understanding of the trends on the most influential articles written on this subject. The Scopus Library database was searched to determine the citations of all articles published on spontaneous ICH. Articles that focused on other forms of ICH, such as trauma-related hemorrhages, subarachnoid hemorrhages, or hemorrhages caused by anticoagulation, vascular malformations, or cavernomas, were excluded from our list. The articles were divided into 2 groups: "specific" articles, which focused specifically on spontaneous ICH, and "generalized" articles, which were about ICH in general, including spontaneous as well as other forms of ICH. We did not apply any time or study-type restriction in our search. The top 100 cited articles were selected and analyzed by 2 independent investigators. J. Broderick was the author with most publications in the list (n = 21). The largest subset of spontaneous ICH articles was published in the 5-year periods from 1996 to 2000 and 2001 to 2005 (n = 27 each). The United States had the highest number of articles (n = 49). The journal with the highest number of top 100 cited articles was Stroke, with 39, followed by Neurology with 16. Our study identifies the trends related to spontaneous ICH by analyzing the citation frequency of the most-cited articles in the field. Copyright © 2017 Elsevier Inc. All rights reserved.

Cerebellar Hematoma Location: Implications for the Underlying Microangiopathy.

PubMed

Pasi, Marco; Marini, Sandro; Morotti, Andrea; Boulouis, Gregoire; Xiong, Li; Charidimou, Andreas; Ayres, Alison M; Lee, Myung Joo; Biffi, Alessandro; Goldstein, Joshua N; Rosand, Jonathan; Gurol, M Edip; Greenberg, Steven M; Viswanathan, Anand

2018-01-01

Spontaneous cerebellar intracerebral hemorrhage (ICH) has been reported to be mainly associated with vascular changes secondary to hypertension. However, a subgroup of cerebellar ICH seems related to vascular amyloid deposition (cerebral amyloid angiopathy). We sought to determine whether location of hematoma in the cerebellum (deep and superficial regions) was suggestive of a particular hemorrhage-prone small-vessel disease pathology (cerebral amyloid angiopathy or hypertensive vasculopathy). Consecutive patients with cerebellar ICH from a single tertiary care medical center were recruited. Based on data from pathological reports, patients were divided according to the location of the primary cerebellar hematoma (deep versus superficial). Location of cerebral microbleeds (CMBs; strictly lobar, strictly deep, and mixed CMB) was evaluated on magnetic resonance imaging. One-hundred and eight patients (84%) had a deep cerebellar hematoma, and 20 (16%) a superficial cerebellar hematoma. Hypertension was more prevalent in deep than in patients with superficial cerebellar ICH (89% versus 65%, respectively; P <0.05). Among patients who underwent magnetic resonance imaging, those with superficial cerebellar ICH had higher prevalence of strictly lobar CMB (43%) and lower prevalence of strictly deep or mixed CMB (0%) compared with those with deep superficial cerebellar ICH (6%, 17%, and 38%, respectively). In a multivariable model, presence of strictly lobar CMB was associated with superficial cerebellar ICH (odds ratio, 3.8; 95% confidence interval, 1.5-8.5; P =0.004). Our study showed that superficial cerebellar ICH is related to the presence of strictly lobar CMB-a pathologically proven marker of cerebral amyloid angiopathy. Cerebellar hematoma location may thus help to identify those patients likely to have cerebral amyloid angiopathy pathology. © 2017 American Heart Association, Inc.

Regularization design for high-quality cone-beam CT of intracranial hemorrhage using statistical reconstruction

NASA Astrophysics Data System (ADS)

Dang, H.; Stayman, J. W.; Xu, J.; Sisniega, A.; Zbijewski, W.; Wang, X.; Foos, D. H.; Aygun, N.; Koliatsos, V. E.; Siewerdsen, J. H.

2016-03-01

Intracranial hemorrhage (ICH) is associated with pathologies such as hemorrhagic stroke and traumatic brain injury. Multi-detector CT is the current front-line imaging modality for detecting ICH (fresh blood contrast 40-80 HU, down to 1 mm). Flat-panel detector (FPD) cone-beam CT (CBCT) offers a potential alternative with a smaller scanner footprint, greater portability, and lower cost potentially well suited to deployment at the point of care outside standard diagnostic radiology and emergency room settings. Previous studies have suggested reliable detection of ICH down to 3 mm in CBCT using high-fidelity artifact correction and penalized weighted least-squared (PWLS) image reconstruction with a post-artifact-correction noise model. However, ICH reconstructed by traditional image regularization exhibits nonuniform spatial resolution and noise due to interaction between the statistical weights and regularization, which potentially degrades the detectability of ICH. In this work, we propose three regularization methods designed to overcome these challenges. The first two compute spatially varying certainty for uniform spatial resolution and noise, respectively. The third computes spatially varying regularization strength to achieve uniform "detectability," combining both spatial resolution and noise in a manner analogous to a delta-function detection task. Experiments were conducted on a CBCT test-bench, and image quality was evaluated for simulated ICH in different regions of an anthropomorphic head. The first two methods improved the uniformity in spatial resolution and noise compared to traditional regularization. The third exhibited the highest uniformity in detectability among all methods and best overall image quality. The proposed regularization provides a valuable means to achieve uniform image quality in CBCT of ICH and is being incorporated in a CBCT prototype for ICH imaging.

Higher mortality in patients with right hemispheric intracerebral haemorrhage: INTERACT1 and 2.

PubMed

Sato, Shoichiro; Heeley, Emma; Arima, Hisatomi; Delcourt, Candice; Hirakawa, Yoichiro; Pamidimukkala, Vijaya; Li, Zhendong; Tao, Qingling; Xu, Yuehong; Hennerici, Michael G; Robinson, Thompson; Tzourio, Christophe; Lindley, Richard I; Chalmers, John; Anderson, Craig S; Anderson, C S; Huang, Y; Wang, J G; Arima, H; Neal, B; Peng, B; Heeley, E; Skulina, C; Parsons, M W; Kim, J S; Tao, Q L; Li, Y C; Jiang, J D; Tai, L W; Zhang, L J; Xu, E; Cheng, Y; Heritier, S; Morgenstern, L B; Chalmers, J

2015-12-01

Controversy exists over the prognostic significance of the affected hemisphere in stroke. We aimed to determine the relationship between laterality of acute intracerebral haemorrhage (ICH) and poor clinical outcomes. A subsidiary analysis of the INTERACT Pilot and INTERACT2 studies--randomised controlled trials of patients with spontaneous acute ICH with elevated systolic blood pressure (BP), randomly assigned to intensive (target systolic BP <140 mm Hg) or guideline-based (<180 mm Hg) BP management. Outcomes were the combined and separate end points of death and major disability (modified Rankin scale (mRS) scores of 3-6, 6 and 3-5, respectively) at 90 days. A total of 2708 patients had supratentorial/hemispheric ICH and information on mRS at 90 days. Patients with right hemispheric ICH (1327, 49%) had a higher risk of death at 90 days compared to those with left hemispheric ICH after adjustment for potential confounding variables (OR, 1.77 (95% CI 1.33 to 2.37)). There were no differences between patients with right and left hemispheric ICH regarding the combined end point of death or major disability or major disability in the multivariable-adjusted models (1.07 (0.89 to 1.29) and 0.85 (0.72 to 1.01), respectively). Right hemispheric lesion was associated with increased risk of death in patients with acute ICH. The laterality of the ICH does not appear to affect the level of disability in survivors. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00226096 and NCT00716079. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Therapeutic targeting of oxygen-sensing prolyl hydroxylases abrogates ATF4-dependent neuronal death and improves outcomes after brain hemorrhage in several rodent models

DOE PAGES

Karuppagounder, Saravanan S.; Alim, Ishraq; Khim, Soah J.; ...

2016-03-02

Disability or death due to intracerebral hemorrhage (ICH) is attributed to blood lysis, liberation of iron and consequent oxidative stress. Iron chelators bind to free iron and prevent neuronal death induced by oxidative stress and disability due to ICH, but the mechanisms for this effect remain unclear. Here we show that the hypoxia-inducible factor prolyl-hydroxylase (HIF- PHD) family of iron-dependent oxygen sensing enzymes are effectors of iron chelation. Molecular reduction of the three HIF-PHD enzyme isoforms in mouse striatum improved functional recovery following ICH. A low molecular weight hydroxyquinoline inhibitor of the HIF-PHDs, adaptaquin, reduced neuronal death and behavioral deficitsmore » following ICH in several rodent models without affecting total iron or zinc distribution in the brain. Unexpectedly, protection from oxidative death in vitro or from ICH in vivo by adaptaquin was associated with suppression of expression of the prodeath factor ATF4 rather than activation of a HIF-dependent prosurvival pathway. In conclusion, together these findings demonstrate that brain-specific inactivation of the HIF-PHD metalloenzymes with the blood-brain barrier permeable inhibitor adaptaquin can improve functional outcomes following ICH in multiple rodent species.« less

Therapeutic targeting of oxygen-sensing prolyl hydroxylases abrogates ATF4-dependent neuronal death and improves outcomes after brain hemorrhage in several rodent models

PubMed Central

Karuppagounder, Saravanan S.; Alim, Ishraq; Khim, Soah J.; Bourassa, Megan W.; Sleiman, Sama F.; John, Roseleen; Thinnes, Cyrille C.; Yeh, Tzu-Lan; Demetriades, Marina; Neitemeier, Sandra; Cruz, Dana; Gazaryan, Irina; Killilea, David W.; Morgenstern, Lewis; Xi, Guohua; Keep, Richard F.; Schallert, Timothy; Tappero, Ryan V.; Zhong, Jian; Cho, Sunghee; Maxfield, Frederick R.; Holman, Theodore R.; Culmsee, Carsten; Fong, Guo-Hua; Su, Yijing; Ming, Guo-li; Song, Hongjun; Cave, John W.; Schofield, Christopher J.; Colbourne, Frederick; Coppola, Giovanni; Ratan, Rajiv R.

2017-01-01

Disability or death due to intracerebral hemorrhage (ICH) is attributed to blood lysis, liberation of iron, and consequent oxidative stress. Iron chelators bind to free iron and prevent neuronal death induced by oxidative stress and disability due to ICH, but the mechanisms for this effect remain unclear. We show that the hypoxia-inducible factor prolyl hydroxylase domain (HIF-PHD) family of iron-dependent, oxygen-sensing enzymes are effectors of iron chelation. Molecular reduction of the three HIF-PHD enzyme isoforms in the mouse striatum improved functional recovery after ICH. A low-molecular-weight hydroxyquinoline inhibitor of the HIF-PHD enzymes, adaptaquin, reduced neuronal death and behavioral deficits after ICH in several rodent models without affecting total iron or zinc distribution in the brain. Unexpectedly, protection from oxidative death in vitro or from ICH in vivo by adaptaquin was associated with suppression of activity of the prodeath factor ATF4 rather than activation of an HIF-dependent prosurvival pathway. Together, these findings demonstrate that brain-specific inactivation of the HIF-PHD metalloenzymes with the blood-brain barrier-permeable inhibitor adaptaquin can improve functional outcomes after ICH in several rodent models. PMID:26936506

Therapeutic targeting of oxygen-sensing prolyl hydroxylases abrogates ATF4-dependent neuronal death and improves outcomes after brain hemorrhage in several rodent models

DOE Office of Scientific and Technical Information (OSTI.GOV)

Karuppagounder, Saravanan S.; Alim, Ishraq; Khim, Soah J.

Disability or death due to intracerebral hemorrhage (ICH) is attributed to blood lysis, liberation of iron and consequent oxidative stress. Iron chelators bind to free iron and prevent neuronal death induced by oxidative stress and disability due to ICH, but the mechanisms for this effect remain unclear. Here we show that the hypoxia-inducible factor prolyl-hydroxylase (HIF- PHD) family of iron-dependent oxygen sensing enzymes are effectors of iron chelation. Molecular reduction of the three HIF-PHD enzyme isoforms in mouse striatum improved functional recovery following ICH. A low molecular weight hydroxyquinoline inhibitor of the HIF-PHDs, adaptaquin, reduced neuronal death and behavioral deficitsmore » following ICH in several rodent models without affecting total iron or zinc distribution in the brain. Unexpectedly, protection from oxidative death in vitro or from ICH in vivo by adaptaquin was associated with suppression of expression of the prodeath factor ATF4 rather than activation of a HIF-dependent prosurvival pathway. In conclusion, together these findings demonstrate that brain-specific inactivation of the HIF-PHD metalloenzymes with the blood-brain barrier permeable inhibitor adaptaquin can improve functional outcomes following ICH in multiple rodent species.« less

Changes in echogenicity of spinal subarachnoid space associated with intracranial hemorrhage: new observations.

PubMed

Rudas, G; Varga, E; Méder, U; Pataki, M; Taylor, G A

2000-11-01

The role of subarachnoid blood and secondary, sterile inflammation in the pathogenesis of posthemorrhagic hydrocephalus (PHH) is not well understood. The aims of this study were to study the frequency and rate of spread of blood into the spinal subarachnoid space (SSS) and to evaluate the relationship of this finding and PHH. Nine premature babies with major intracerebral hemorrhage (ICH, grade 3 or higher), and ten premature infants with minor ICH (grade 1) or no evidence of ICH (control group) were identified and underwent serial cranial and spinal sonography at the time of initial diagnosis, 12-24 h after the ICH and weekly thereafter for at least 9 weeks. Sagittal and axial scans of the thoracolumbar spine were obtained and evaluated for the presence of echogenic debris in the dorsal SSS. Six additional patients who had cranial and spinal sonography died within the 1st week of life and underwent post-mortem examinations. The SSS was echo-free (normal) in all cases at the time of initial sonographic diagnosis of ICH. Within 24 h, all babies with major ICH had developed increased echogenicity of the cervical and thoracic SSS. Echogenicity of the SSS decreased gradually over several weeks. Although transient ventricular dilatation was present in every patient, only one patient had rapidly progressive PHH requiring shunt placement. Transient cysts of the cervicothoracic subarachnoid space were identified in two patients 6-7 weeks after ICH. The subarachnoid space remained echo-free in all control infants At autopsy, all four infants with echogenic spinal debris had blood or blood products in the spinal subarachnoid space, whereas two infants with echo-free spinal images did not. Spread of blood from the ventricular system into the spinal subarachnoid space after ICH is common and can be seen within 24 h of initial ICH. Subarachnoid blood is associated with post-hemorrhagic ventricular dilatation and transient spinal subarachnoid cyst formation.

Increased Expression of T Cell Immunoglobulin and Mucin Domain 3 on CD14+ Monocytes Is Associated with Systemic Inflammatory Reaction and Brain Injury in Patients with Spontaneous Intracerebral Hemorrhage.

PubMed

Xu, ChangJun; Ge, HaiTao; Wang, Tao; Qin, JianBing; Liu, De; Liu, YuGuang

2018-05-01

To study the expression of T cell immunoglobulin and mucin domain 3 (Tim-3) on peripheral blood immunocytes, and the relationship between Tim-3 and the systemic inflammatory response or brain injury in patients with intracerebral hemorrhage (ICH). According to the volume of hematoma at 12 hours after onset of ICH, 60 newly diagnosed patients with ICH were divided into the small (volume of hematoma <30 mL, 30 cases) and large (volume of hematoma ≥30 mL, 30 cases) ICH groups. The expression of Tim-3 on peripheral blood immunocytes was analyzed by flow cytometry. Real-time reverse transcriptase polymerase chain reaction was used to detect Tim-3 mRNA on peripheral blood mononuclear cells (PBMCs). Meanwhile, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and S-100B protein were measured by enzyme-linked immunosorbent assay. Glasgow outcome scale (GOS) score at Day 30 was used to estimate prognosis of patients. The leukocyte count, neutrophil count, monocyte count, TNF-α, IL-1β, and S-100B protein increased remarkably after ICH. However, all of them in the large ICH group increased more obviously, and there were significant differences when compared with those in the small ICH group (P < .01). The expression of Tim-3 mRNA on PBMCs in the large ICH group increased remarkably, peaked at Day 3, and was positively associated with the concentrations of TNF-α, IL-1β, and S-100B protein (P < .01). Tim-3 was predominantly expressed itself on CD14 + monocytes. There was a negative correlation between GOS score and Tim-3 mRNA, TNF-α, IL-1β, or S-100B protein. The expression of Tim-3 on CD14 + monocytes involves in systemic inflammatory reaction after ICH and may be a novel treatment target. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

30-Day Mortality and Readmission after Hemorrhagic Stroke among Medicare Beneficiaries in Joint Commission Primary Stroke Center Certified and Non-Certified Hospitals

PubMed Central

Lichtman, Judith H.; Jones, Sara B.; Leifheit-Limson, Erica C.; Wang, Yun; Goldstein, Larry B.

2012-01-01

Background and Purpose Ischemic stroke patients treated at Joint Commission Primary Stroke Center (JC-PSC) certified hospitals have better outcomes. Data reflecting the impact of JC-PSC status on outcomes after hemorrhagic stroke are limited. We determined whether 30-day mortality and readmission rates after hemorrhagic stroke differed for patients treated at JC-PSC certified versus non-certified hospitals. Methods The study included all fee-for-service Medicare beneficiaries ≥65 years old with a primary discharge diagnosis of subarachnoid hemorrhage (SAH) or intracerebral hemorrhage (ICH) in 2006. Covariate-adjusted logistic and Cox proportional hazards regression assessed the effect of care at a JC-PSC certified hospital on 30-day mortality and readmission. Results There were 2,305 SAH and 8,708 ICH discharges from JC-PSC certified hospitals and 3,892 SAH and 22,564 ICH discharges from non-certified hospitals. Unadjusted in-hospital mortality (SAH: 27.5% vs. 33.2%, p<0.0001; ICH: 27.9% vs. 29.6%, p=0.003) and 30-day mortality (SAH: 35.1% vs. 44.0%, p<0.0001; ICH: 39.8% vs. 42.4%, p<0.0001) were lower in JC-PSC hospitals, but 30-day readmission rates were similar (SAH: 17.0% vs. 17.0%, p=0.97; ICH: 16.0% vs. 15.5%; p=0.29). Risk-adjusted 30-day mortality was 34% lower (OR 0.66, 95% CI 0.58–0.76) after SAH and 14% lower (OR 0.86, 95% CI 0.80–0.92) after ICH for patients discharged from JC-PSC certified hospitals. There was no difference in 30-day risk-adjusted readmission rates for SAH or ICH based on JC-PSC status. Conclusions Patients treated at JC-PSC certified hospitals had lower risk-adjusted mortality rates for both SAH and ICH but similar 30-day readmission rates as compared with non-certified hospitals. PMID:22033986

Effect of thrombin preconditioning on migration of subventricular zone-derived cells after intracerebral hemorrhage in rats.

PubMed

Guan, Jingxia; Zhang, Shaofeng; Zhou, Qin; Yuan, Zhenhua; Lu, Zuneng

2016-09-01

To investigate the effect of thrombin preconditioning (TPC) on the intracerebral hemorrhage (ICH)-induced proliferation, migration, and function of subventriclular zone (SVZ) cells and to find new strategies that enhance endogenous neurogenesis after ICH. Male Sprague-Dawley rats were randomly divided into 3 groups (ICH, TPC, and control group). Rats of each group were randomly divided into 5 subgroups (3-d, 7-d, 14-d, 21-d, and 28-d subgroup). ICH was caused by intrastrial stereotactic administration of collagenase type IV. Brdu was used to label newborn SVZ cells. Organotypic brain slices were cultured to dynamically observe the migration of SVZ cells at living brain tissue. Migration of Dil-labeled SVZ cells in living brain slices was traced by time-lapse microscopy. To assess whether SVZ cells migrating to injured striatum had the ability to form synapses with other cells, brain slices from each group were double immunolabeled with Brdu and synapsin I. The number of Brdu-positive cells markedly increased in the ipsilateral SVZ and striatum 3 days after TPC, peaked at 14 days (P < 0.01), continued to 21 days, and then gradually decreased at 28 days with significant difference compared to the ICH group at each time point (P < 0.01). Migration of Dil-labeled SVZ cells in brain slices in each group was observed and imaged during a 12-h period. Dil-labeled SVZ cells in the TPC group were observed to migrate laterally toward striatum with time with a faster velocity compared to the ICH group (P < 0.01). Our study also demonstrated that TPC induced strong colocalization of Brdu and synapsin I in the ipsilateral striatum between 3 and 28 days after injury.TPC made colocalization of Brdu and synapsin I appear earlier and continue for a longer time compared to the ICH group. Our results demonstrated that TPC could promote proliferation, migration, and function of SVZ cells after ICH, which may provide a new idea for enhancing endogenous neurogenesis and developing

Predicting symptomatic intracerebral hemorrhage versus lacunar disease in patients with longstanding hypertension.

PubMed

Marsh, Elisabeth B; Gottesman, Rebecca F; Hillis, Argye E; Maygers, Joyce; Lawrence, Erin; Llinas, Rafael H

2014-06-01

Hypertension results in a spectrum of subcortical cerebrovascular disease. It is unclear why some individuals develop ischemia and others develop hemorrhage. Risk factors may differ for each population. We identify factors that predispose an individual to subcortical symptomatic intracerebral hemorrhage (sICH) compared with ischemia. Demographic and laboratory data were prospectively collected for hypertensive patients presenting with ischemic stroke or sICH during an 8.5-year period. Neuroimaging was retrospectively reviewed for acute (subcortical lacunes [<2.0 cm] versus subcortical sICH) and chronic (periventricular white matter disease and cerebral microbleeds) findings. We evaluated the impact of age, race, sex, serum creatinine, erythrocyte sedimentation rate, low-density lipoprotein, presence of periventricular white matter disease or cerebral microbleeds, and other factors on the risk of sICH versus acute lacune using multivariate logistic regression. Five hundred seventy-one patients had subcortical pathology. The presence of cerebral microbleeds (adjusted odds ratio [OR], 3.39; confidence interval [CI], 2.09-5.50) was a strong predictor of sICH, whereas severe periventricular white matter disease predicted ischemia (OR, 0.56 risk of sICH; CI, 0.32-0.98). This association was strengthened when the number of microbleeds was evaluated; subjects with >5 microbleeds had an increased risk of sICH (OR, 4.11; CI, 1.96-8.59). It remained significant when individuals with only cortical microbleeds were removed (OR, 1.77, CI, 1.13-2.76). An elevated erythrocyte sedimentation rate (OR, 1.19 per 10 mm/h increase; CI, 1.06-1.34) was significantly associated with sICH, whereas low-density lipoprotein was associated with ischemic infarct (OR, 0.93 risk of sICH per 10 mg/dL increase; CI, 0.86-0.99). Subclinical pathology is the strongest predictor of the nature of subsequent symptomatic event. Low-density lipoprotein and erythrocyte sedimentation rate may also have a role

The Association between Specific Substances of Abuse and Subcortical Intracerebral Hemorrhage Versus Ischemic Lacunar Infarction.

PubMed

Kaplan, Emma H; Gottesman, Rebecca F; Llinas, Rafael H; Marsh, Elisabeth B

2014-01-01

Hypertension damages small vessels, resulting in both lacunar infarction and subcortical intracerebral hemorrhage (ICH). Substance abuse has also been linked to small vessel pathology. This study explores whether the use of specific substances (e.g., cocaine, tobacco) is associated with subcortical ICH over ischemia in hypertensive individuals. Patients with hypertension, admitted with lacunar infarcts (measuring <2.0 cm) or subcortical ICH, were included in analysis. Brain MRIs and head CTs were retrospectively reviewed along with medical records. Demographic information and history of substance use (illicit/controlled: cocaine, heroin, marijuana, benzodiazepines, and methadone; alcohol; and tobacco) was obtained. "Current use" and "history of use" were determined from patient history or a positive toxicology screen. "Heavy use" was defined as: smoking- ≥0.5 packs per day or 10 pack-years; alcohol- average of >1 drink per day (women), >2 drinks per day (men). Logistic regression was performed with ICH as the dependent variable comparing those presenting with ICH to those presenting with ischemia. Of the 580 patients included in analysis, 217 (37%) presented with ICH. The average age was similar between the two groups (64.7 versus 66.3 years). Illicit/controlled drug use was associated with a significantly increased risk of ICH over stroke in unadjusted models (25 versus 15%, p = 0.02), with the largest effect seen in users ≥65 years old (not statistically significant). Smoking was associated with ischemia over ICH in a dose-dependent manner: any history of smoking OR 1.84, CI 1.19-2.84; current use OR 2.23, CI 1.37-3.62; heavy use OR 2.48, CI 1.50-4.13. Alcohol use was not preferentially associated with either outcome (p = 0.29). In hypertensive patients, tobacco use is associated with an increased risk of subcortical ischemia compared to ICH, while use of illicit/controlled substances appears to be predictive of hemorrhage.

Effect of apolipoprotein C3 genetic polymorphisms on serum lipid levels and the risk of intracerebral hemorrhage.

PubMed

Jiang, Yan; Ma, Junpeng; Li, Hao; Liu, Yi; You, Chao

2015-05-22

Serum lipid levels are associated with the risk of intracerebral hemorrhage (ICH). Genetic variants in the apolipoprotein C3 (APOC3) gene were associated with plasma triglyceride (TG) and very-low-density lipoprotein (VLDL) levels. The aim of this study was to evaluate the effect of two genetic variants (1100 C/T and 3238 C/G) of APOC3 on serum lipid levels and risk of ICH. A prospective hospital-based case-control design and logistic regression analysis were utilized. We enrolled 150 ICH patients and 150 age- and gender-matched controls. The APOC3 gene polymorphisms were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). ICH patients had a significantly higher frequency of APOC3 3238 GG genotype [odds ratio (OR)=.97, 95% confidence interval (CI)=1.20, 7.38; P=0.02] and APOC3 3238 G allele (OR=.53, 95% CI=1.03, 2.27; P=0.04) than controls. The APOC3 3238 G allele was significantly associated with increasing plasma TG levels and VLDL levels both in ICH cases (P=0.01) and controls (P=0.02). No association was found between APOC3 1100 C/T polymorphisms and ICH. To the best of our knowledge, this is the first report in the literature that the APOC3 3238 GG genotype and G allele might contribute to an increased risk of ICH as a result of its effect on serum lipid levels.

Survival Outcomes After Intracranial Hemorrhage in Liver Disease.

PubMed

Lagman, Carlito; Nagasawa, Daniel T; Azzam, Daniel; Sheppard, John P; Chen, Cheng Hao Jacky; Ong, Vera; Nguyen, Thien; Prashant, Giyarpuram N; Niu, Tianyi; Tucker, Alexander M; Kim, Won; Kaldas, Fady M; Pouratian, Nader; Busuttil, Ronald W; Yang, Isaac

2018-05-15

Survival outcomes for patients with liver disease who suffer an intracranial hemorrhage (ICH) have not been thoroughly investigated. To understand survival outcomes for 3 groups: (1) patients with an admission diagnosis of liver disease (end-stage liver disease [ESLD] or non-ESLD) who developed an ICH in the hospital, (2) patients with ESLD who undergo either operative vs nonoperative management, and (3) patients with ESLD on the liver transplant waitlist who developed an ICH in the hospital. We retrospectively reviewed hospital charts from March 2006 through February 2017 of patients with liver disease and an ICH evaluated by the neurosurgery service at a single academic medical center. The primary outcome was survival. We included a total of 53 patients in this study. The overall survival for patients with an admission diagnosis of liver disease who developed an ICH (n = 29, 55%) in the hospital was 22%. Of those patients with an admission diagnosis of liver disease, 27 patients also had ESLD. Kaplan-Meier analysis found no significant difference in survival for ESLD patients (n = 33, 62%) according to operative status. There were 11 ESLD patients on the liver transplant waitlist. The overall survival for patients with ESLD on the liver transplant waitlist who suffered an in-hospital ICH (n = 7, 13%) was 14%. ICH in the setting of liver disease carries a grave prognosis. Also, a survival advantage for surgical hematoma evacuation in ESLD patients is not clear.

The critical care management of spontaneous intracranial hemorrhage: a contemporary review.

PubMed

de Oliveira Manoel, Airton Leonardo; Goffi, Alberto; Zampieri, Fernando Godinho; Turkel-Parrella, David; Duggal, Abhijit; Marotta, Thomas R; Macdonald, R Loch; Abrahamson, Simon

2016-09-18

Spontaneous intracerebral hemorrhage (ICH), defined as nontraumatic bleeding into the brain parenchyma, is the second most common subtype of stroke, with 5.3 million cases and over 3 million deaths reported worldwide in 2010. Case fatality is extremely high (reaching approximately 60 % at 1 year post event). Only 20 % of patients who survive are independent within 6 months. Factors such as chronic hypertension, cerebral amyloid angiopathy, and anticoagulation are commonly associated with ICH. Chronic arterial hypertension represents the major risk factor for bleeding. The incidence of hypertension-related ICH is decreasing in some regions due to improvements in the treatment of chronic hypertension. Anticoagulant-related ICH (vitamin K antagonists and the newer oral anticoagulant drugs) represents an increasing cause of ICH, currently accounting for more than 15 % of all cases. Although questions regarding the optimal medical and surgical management of ICH still remain, recent clinical trials examining hemostatic therapy, blood pressure control, and hematoma evacuation have advanced our understanding of ICH management. Timely and aggressive management in the acute phase may mitigate secondary brain injury. The initial management should include: initial medical stabilization; rapid, accurate neuroimaging to establish the diagnosis and elucidate an etiology; standardized neurologic assessment to determine baseline severity; prevention of hematoma expansion (blood pressure management and reversal of coagulopathy); consideration of early surgical intervention; and prevention of secondary brain injury. This review aims to provide a clinical approach for the practicing clinician.

Activation of the Notch-1 signaling pathway may be involved in intracerebral hemorrhage-induced reactive astrogliosis in rats.

PubMed

Zhong, Jian-Hua; Zhou, Hua-Jun; Tang, Tao; Cui, Han-Jin; Yang, A-Li; Zhang, Qi-Mei; Zhou, Jing-Hua; Zhang, Qiang; Gong, Xun; Zhang, Zhao-Hui; Mei, Zhi-Gang

2017-10-27

OBJECTIVE Reactive astrogliosis, a key feature that is characterized by glial proliferation, has been observed in rat brains after intracerebral hemorrhage (ICH). However, the mechanisms that control reactive astrogliosis formation remain unknown. Notch-1 signaling plays a critical role in modulating reactive astrogliosis. The purpose of this paper was to establish whether Notch-1 signaling is involved in reactive astrogliosis after ICH. METHODS ICH was induced in adult male Sprague-Dawley rats via stereotactic injection of autologous blood into the right globus pallidus. N-[ N-(3,5-difluorophenacetyl)-l-alanyl]- S-phenylglycine t-butyl ester (DAPT) was injected into the lateral ventricle to block Notch-1 signaling. The rats' brains were perfused to identify proliferating cell nuclear antigen (PCNA)-positive/GFAP-positive nuclei. The expression of GFAP, Notch-1, and the activated form of Notch-1 (Notch intracellular domain [NICD]) and its ligand Jagged-1 was assessed using immunohistochemical and Western blot analyses, respectively. RESULTS Notch-1 signaling was upregulated and activated after ICH as confirmed by an increase in the expression of Notch-1 and NICD and its ligand Jagged-1. Remarkably, blockade of Notch-1 signaling with the specific inhibitor DAPT suppressed astrocytic proliferation and GFAP levels caused by ICH. In addition, DAPT improved neurological outcome after ICH. CONCLUSIONS Notch-1 signaling is a critical regulator of ICH-induced reactive astrogliosis, and its blockage may be a potential therapeutic strategy for hemorrhagic injury.

Targeting Vascular Neural Network in Intracerebral Hemorrhage.

PubMed

Yin, Yi; Ge, Hongfei; Zhang, John H; Feng, Hua

2017-01-01

Intracerebral hemorrhage (ICH) is a common type of stroke associated with high mortality and morbidity. Recent randomized controlled trials could not prove that the current strategies are effective at improving the final outcome of the ICH patients. Here we want to explore potential intervention targets for ICH based on the framework of the vascular neural network (VNN). In this review, a brief history of the evolution of stroke pathophysiology from humoral theory to VNN is discussed. As current literature on pathophysiology of ICH is mainly focused on neuroprotection, here we want to evolve the central paradigm towards VNN. We stress mechanisms of vascular disruption and impaired blood flow harmony, which are clinically relevant but have received less attention in basic research. We propose that VNN could be a robust and practical paradigm in both ICH basic research and clinical practice. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Use of Risk Assessment Tool for Inpatient Traumatic Intracranial Hemorrhage after Falls in Acute Care Hospital Setting

PubMed Central

Toyabe, Shin-ichi

2012-01-01

Severe injuries such as intracranial hemorrhage (ICH) are the most serious problem after falls in hospital, but they have not been considered in risk assessment scores for falls. We tried to determine the risk factors for ICH after falls in 20,320 inpatients (696,364 patient-days) aged from 40 to 90 years who were admitted to a tertiary-care university hospital. Possible risk factors including STRATIFY risk score for falls and FRAX™ risk score for fractures were analyzed by univariate and multivariate analyses. Fallers accounted for 3.2% of the patients, and 5.0% of the fallers suffered major injuries, including peripheral bone fracture (59.6%) and ICH (23.4%). In addition to STRATIFY, FRAX™ was significantly associated not only with bone fractures but also ICH. Concomitant use of risk score for falls and risk score for fractures might be useful for the prediction of major injuries such as ICH after falls. PMID:22980233

Mortality after hemorrhagic stroke: data from general practice (The Health Improvement Network).

PubMed

González-Pérez, Antonio; Gaist, David; Wallander, Mari-Ann; McFeat, Gillian; García-Rodríguez, Luis A

2013-08-06

To investigate short-term case fatality and long-term mortality after intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH) using data from The Health Improvement Network database. Thirty-day case fatality was stratified by age, sex, and calendar year after ICH and SAH using logistic regression. Cox proportional hazards regression analyses were used to estimate the risk of death during the first year of follow-up and survivors at 1 year. Case fatality after ICH was 42.0%, compared with 28.7% after SAH. It increased with age (ICH: 29.7% for 20-49 years, 54.6% for 80-89 years; SAH: 20.3% for 20-49 years, 56.7% for 80-89 years; both p-trend < 0.001), and decreased over the period 2000-2001 to 2006-2008 (ICH: from 53.1% to 35.8%, p-trend < 0.001; SAH: from 33.3% to 24.7%, p-trend = 0.02). Risk of death was significantly higher among stroke patients during the first year of follow-up compared with controls (ICH: hazard ratio [HR] 2.60, 95% confidence interval [CI] 2.09-3.24, p < 0.01; SAH: HR 2.87, 95% CI 2.07-3.97, p < 0.01) and remained elevated among survivors at 1 year (ICH: HR 2.02, 95% CI 1.75-2.32, p < 0.01; SAH: HR 1.32, 95% CI 1.02-1.69, p = 0.03). More than one-third of individuals die in the first month after hemorrhagic stroke, and patients younger than 50 years are more likely to die after ICH than SAH. Short-term case fatality has decreased over time. Patients who survive hemorrhagic stroke have a continuing elevated risk of death compared with matched individuals from the general population.

Factors Associated with Fever in Intracerebral Hemorrhage.

PubMed

Gillow, Sabreena J; Ouyang, Bichun; Lee, Vivien H; John, Sayona

2017-06-01

Fever is common in patients with intracerebral hemorrhage (ICH). We sought to identify predictors of fever in patients hospitalized with ICH, and compare infectious fever with noninfectious fever. A retrospective review on consecutive spontaneous ICH patients from April 2009 to March 2010 was performed. Fever was defined as temperature 100.9°F or higher and attributed to infectious versus noninfectious etiology, based upon the National Healthcare Safety Network criteria. Univariate analysis and multivariable logistic regression model were used to determine factors associated with fever and with infection. Among the 351 ICH patients, 136 (39%) developed fever. Factors associated with fever included mean ICH volume, intraventricular hemorrhage (IVH), external ventricular drain (EVD) placement or surgical evacuation, positive microbial cultures, longer length of stay (LOS), and higher in-hospital mortality. Among patients with fever, 96 (71%) were noninfectious and 40 (29%) were infectious. Infectious fever was associated with higher LOS. Noninfectious fever was associated with higher in-hospital mortality. In multivariable analysis, ICH volume (OR = 1.01, P = .04), IVH (OR = 2.0, P = .03), EVD (OR = 3.7, P < .0001), and surgical evacuation (OR = 6.78, P < .0001) were significant predictors of fever. Infectious fever (OR = 5.26, P = .004), EVD (OR = 4.86, P = .01), and surgical evacuation (OR = 4.77, P = .04) correlated with prolonged LOS when dichotomized using a median of 15 days. Fever is common in ICH patients and is not associated with a clear infectious etiology in the majority of patients. Patients with noninfectious fever have higher in-hospital mortality, but survivors have shorter LOS. Further studies are warranted to better understand fevers in ICH. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

A cannabinoid receptor 2 agonist reduces blood-brain barrier damage via induction of MKP-1 after intracerebral hemorrhage in rats.

PubMed

Li, Lin; Yun, Debo; Zhang, Yuan; Tao, Yihao; Tan, Qiang; Qiao, Fei; Luo, Bo; Liu, Yi; Fan, Runjin; Xian, Jishu; Yu, Anyong

2018-06-07

The blood-brain barrier (BBB) disruption and the following development of brain edema, is the most life-threatening secondary injury after intracerebral hemorrhage (ICH). This study is to investigate a potential role and mechanism of JWH133, a selected cannabinoid receptor type2 (CB2R) agonist, on protecting blood-brain barrier integrity after ICH. 192 adult male Sprague-Dawley (SD) rats were randomly divided into Sham; ICH+Vehicle; ICH+JWH 1.0mg/kg, ICH+JWH 1.5mg/kg and ICH+JWH 2.0mg/kg; ICH+SR+JWH respectively. Animals were euthanized at 24 hours following western blots and immunofluorescence staining, we also examined the effect of JWH133 on the brain water contents, neurobehavioral deficits and blood brain barrier (BBB) permeability, meanwhile reassessed the inflammatory cytokines concentrations around the hematoma by enzyme-linked immunosorbent assay (ELISA) in each group. JWH133 (1.5mg/kg) administration ameliorated brain edema, neurological deficits and blood-brain barrier damage, as well as microglia activation. The expression of pro-inflammatory mediators interleukin 1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and matrix metallopeptidase-2/9(MMP2/9) were attenuated, but not monocyte chemoattractant protein-1 (MCP-1). Additionally, decreases in zonula occludens-1 (ZO-1) and claudin-5 expression were partially recovered by JWH133. Furthermore, JWH133 upregulated the expression level of MKP-1, which leads to the inhibition of MAPKs signaling pathway activation, especially for ERK and P38. However, these effects were reversed by pretreatment with a selective CB2R antagonist, SR144528. CB2R agonist alleviated neuroinflammation and protected blood-brain barrier permeability in a rat ICH model. Further molecular mechanisms revealed which is probably mediated by enhancing the expression of MKP-1, then inhibited MAPKs signal transduction. Copyright © 2018. Published by Elsevier B.V.

The spot sign and tranexamic acid on preventing ICH growth--AUStralasia Trial (STOP-AUST): protocol of a phase II randomized, placebo-controlled, double-blind, multicenter trial.

PubMed

Meretoja, Atte; Churilov, Leonid; Campbell, Bruce C V; Aviv, Richard I; Yassi, Nawaf; Barras, Christen; Mitchell, Peter; Yan, Bernard; Nandurkar, Harshal; Bladin, Christopher; Wijeratne, Tissa; Spratt, Neil J; Jannes, Jim; Sturm, Jonathan; Rupasinghe, Jayantha; Zavala, Jorge; Lee, Andrew; Kleinig, Timothy; Markus, Romesh; Delcourt, Candice; Mahant, Neil; Parsons, Mark W; Levi, Christopher; Anderson, Craig S; Donnan, Geoffrey A; Davis, Stephen M

2014-06-01

No evidence-based acute therapies exist for intracerebral hemorrhage. Intracerebral hemorrhage growth is an important determinant of patient outcome. Tranexamic acid is known to reduce hemorrhage in other conditions. The study aims to test the hypothesis that intracerebral hemorrhage patients selected with computed tomography angiography contrast extravasation 'spot sign' will have lower rates of hematoma growth when treated with intravenous tranexamic acid within 4.5-hours of stroke onset compared with placebo. The Spot sign and Tranexamic acid On Preventing ICH growth--AUStralasia Trial is a multicenter, prospective, 1:1 randomized, double-blind, placebo-controlled, investigator-initiated, academic Phase II trial. Intracerebral hemorrhage patients fulfilling clinical criteria (e.g. Glasgow Coma Scale >7, intracerebral hemorrhage volume <70 ml, no identified secondary cause of intracerebral hemorrhage, no thrombotic events within the previous 12 months, no planned surgery) and demonstrating contrast extravasation on computed tomography angiography will receive either intravenous tranexamic acid 1 g 10-min bolus followed by 1 g eight-hour infusion or placebo. A second computed tomography will be performed at 24 ± 3 hours to evaluate intracerebral hemorrhage growth and patients followed up for three-months. The primary outcome measure is presence of intracerebral hemorrhage growth by 24 ± 3 hours, defined as either >33% or >6 ml increase from baseline, and will be adjusted for baseline intracerebral hemorrhage volume. Secondary outcome measures include growth as a continuous measure, thromboembolic events, and the three-month modified Rankin Scale score. This is the first trial to evaluate the efficacy of tranexamic acid in intracerebral hemorrhage patients selected based on an imaging biomarker of high likelihood of hematoma growth. The trial is registered as NCT01702636. © 2013 The Authors. International Journal of Stroke © 2013 World Stroke Organization.

Intracerebral hemorrhage: a life-threatening complication of hypertension during pregnancy.

PubMed

Dai, Xuming; Diamond, Joseph A

2007-11-01

Intracerebral hemorrhage (ICH) is an infrequent but severe complication in pregnant women with hypertension. The authors describe a patient with chronic hypertension who developed superimposed preeclampsia and spontaneous ICH during the thirty-fifth week of pregnancy. ICH was diagnosed by computed tomographic scan. She underwent successful emergent cesarean section and neurosurgical decompression of the ICH. Both intraoperative surveillance and postoperative magnetic resonance angiographic examination of the cerebral vessels failed to identify an aneurysm or arteriovenous malformation. The authors discuss the diagnosis and management in this case and review the literature regarding this challenging complication of pregnancy and preeclampsia. Controversies regarding treatment of hypertension during pregnancy are discussed in light of the impact on the management of this patient.

The value and benefits of the International Conference on Harmonisation to drug regulatory authorities: advancing harmonization for better public health.

PubMed

Molzon, J A; Giaquinto, A; Lindstrom, L; Tominaga, T; Ward, M; Doerr, P; Hunt, L; Rago, L

2011-04-01

The International Conference on Harmonisation (ICH) is an unparalleled undertaking, which has brought together drug regulatory authorities and pharmaceutical trade associations from Europe, Japan, and the United States, to discuss the scientific and technical aspects of medical product registration. Launched in 1990, the value and benefits of ICH to regulators are being realized. ICH has harmonized submission requirements and created a harmonized submission format that is relieving both companies and regulatory authorities of the burdens of assembling and reviewing separate submissions for each region. As more countries embrace ICH guidelines, we anticipate additional benefits, including the promotion of good review practices and, ultimately, a common regulatory language that will facilitate further interactions among global drug regulatory authorities.

Treatment and Outcome of Hemorrhagic Transformation After Intravenous Alteplase in Acute Ischemic Stroke: A Scientific Statement for Healthcare Professionals From the American Heart Association/American Stroke Association.

PubMed

Yaghi, Shadi; Willey, Joshua Z; Cucchiara, Brett; Goldstein, Joshua N; Gonzales, Nicole R; Khatri, Pooja; Kim, Louis J; Mayer, Stephan A; Sheth, Kevin N; Schwamm, Lee H

2017-12-01

Symptomatic intracranial hemorrhage (sICH) is the most feared complication of intravenous thrombolytic therapy in acute ischemic stroke. Treatment of sICH is based on expert opinion and small case series, with the efficacy of such treatments not well established. This document aims to provide an overview of sICH with a focus on pathophysiology and treatment. A literature review was performed for randomized trials, prospective and retrospective studies, opinion papers, case series, and case reports on the definitions, epidemiology, risk factors, pathophysiology, treatment, and outcome of sICH. The document sections were divided among writing group members who performed the literature review, summarized the literature, and provided suggestions on the diagnosis and treatment of patients with sICH caused by systemic thrombolysis with alteplase. Several drafts were circulated among writing group members until a consensus was achieved. sICH is an uncommon but severe complication of systemic thrombolysis in acute ischemic stroke. Prompt diagnosis and early correction of the coagulopathy after alteplase have remained the mainstay of treatment. Further research is required to establish treatments aimed at maintaining integrity of the blood-brain barrier in acute ischemic stroke based on inhibition of the underlying biochemical processes. © 2017 American Heart Association, Inc.

A clinical characteristic analysis of pregnancy-associated intracranial haemorrhage in China.

PubMed

Liang, Zhu-Wei; Lin, Li; Gao, Wan-Li; Feng, Li-Min

2015-03-30

Intracerebral haemorrhage (ICH) occurring during pregnancy and the puerperium is an infrequent but severe complication with a high mortality and poor prognosis. Until recently, previous studies have mainly focused on the effect of different treatments on prognosis. However, few studies have provided solid evidence to clarify the key predisposing factors affecting the prognosis of ICH. In the present study, based on a unique sample with a high ICH incidence and mortality rate, we described the main clinical characteristics of ICH patients and found that the prognosis of patients who underwent surgical intervention was not better than that of patients who received other treatment modalities. However, pre-eclampsia patients had higher maternal and neonatal mortality rates than other aetiology groups. Furthermore, univariate regression analysis identified onset to diagnosis time (O-D time) and pre-eclampsia as the only factors showing independent correlation with poor maternal outcomes (modified Rankin Scale, mRS ≥ 3), and only O-D time was identified as a predictor of maternal mortality. These results revealed that the aetiology of ICH and O-D time might be crucial predisposing factors to prognosis, especially for patients with pre-eclampsia. The study highlighted a novel direction to effectively improve the prognosis of pregnancy-associated ICH.

Long noncoding ribonucleic acid NKILA induces the endoplasmic reticulum stress/autophagy pathway and inhibits the nuclear factor-k-gene binding pathway in rats after intracerebral hemorrhage.

PubMed

Jia, Jiaoying; Zhang, Mingming; Li, Qi; Zhou, Qian; Jiang, Yugang

2018-06-12

Long noncoding RNAs (lncRNAs) have emerged as an important class of molecules that have been associated with brain function and neurological disease, but the expression profiles of lncRNAs after intracerebral hemorrhage (ICH) remain to be elucidated. In this study, we determined the expression pattern of nuclear factor-k-gene binding (NF-kB) interacting lncRNA (NKILA) after ICH and examined its respective effects on the endoplasmic reticulum stress (ERS)/autophagy pathway, hippocampal neuron loss, and the NF-kB pathway after type VII collagenase-induced ICH in rats. The regulatory mechanisms of NKILA were investigated by an intraperitoneal injection of small interfering (siRNA) against NKILA into rats after ICH. NKILA inhibition mediated by siRNA against NKILA was shown to significantly reduce ERS and autophagy, activate the NF-kB pathway, decrease neurological deficits, brain edema, and injury, and induce blood-brain barrier breakdown, further leading to hippocampal neuron loss and the production of inflammation cytokines. Taken together, the demonstration that NKILA induces the ERS/autophagy pathway and inhibits the NF-kB pathway after ICH supports the concept that NKILA functions as a novel target that is required for the attenuation of brain injuries after ICH. © 2018 Wiley Periodicals, Inc.

Role for RIP1 in mediating necroptosis in experimental intracerebral hemorrhage model both in vivo and in vitro.

PubMed

Shen, Haitao; Liu, Chenglin; Zhang, Dongping; Yao, Xiyang; Zhang, Kai; Li, Haiying; Chen, Gang

2017-03-02

Cell death is a hallmark of second brain injury after intracerebral hemorrhage (ICH); however, the mechanism still has not been fully illustrated. In this study, we explored whether necroptosis, a type of regulated necrosis, has an essential role in brain injury after ICH. We found that inhibiting receptor-interacting protein 1 (RIP1) - a core element of the necroptotic pathway - by a specific chemical inhibitor or genetic knockdown attenuated brain injury in a rat model of ICH. Furthermore, necroptosis of cultured neurons could be induced by conditioned medium from microglia stimulated with oxygen hemoglobin, and this effect could be inhibited by TNF-α inhibitor, indicating that TNF-α secreted from activated microglia is an important factor in inducing necroptosis of neurons. Undoubtedly, overexpression of RIP1 increased conditioned medium-induced necroptosis in vitro, but this effect was partially diminished in mutation of serine kinase phosphorylation site of RIP1, showing that phosphorylation of RIP1 is the essential molecular mechanism of necroptosis, which was activated in the in vitro model of ICH. Collectively, our investigation identified that necroptosis is an important mechanism of cell death in brain injury after ICH, and inhibition of necroptosis may be a potential therapeutic intervention of ICH.

Role for RIP1 in mediating necroptosis in experimental intracerebral hemorrhage model both in vivo and in vitro

PubMed Central

Shen, Haitao; Liu, Chenglin; Zhang, Dongping; Yao, Xiyang; Zhang, Kai; Li, Haiying; Chen, Gang

2017-01-01

Cell death is a hallmark of second brain injury after intracerebral hemorrhage (ICH); however, the mechanism still has not been fully illustrated. In this study, we explored whether necroptosis, a type of regulated necrosis, has an essential role in brain injury after ICH. We found that inhibiting receptor-interacting protein 1 (RIP1) – a core element of the necroptotic pathway – by a specific chemical inhibitor or genetic knockdown attenuated brain injury in a rat model of ICH. Furthermore, necroptosis of cultured neurons could be induced by conditioned medium from microglia stimulated with oxygen hemoglobin, and this effect could be inhibited by TNF-α inhibitor, indicating that TNF-α secreted from activated microglia is an important factor in inducing necroptosis of neurons. Undoubtedly, overexpression of RIP1 increased conditioned medium-induced necroptosis in vitro, but this effect was partially diminished in mutation of serine kinase phosphorylation site of RIP1, showing that phosphorylation of RIP1 is the essential molecular mechanism of necroptosis, which was activated in the in vitro model of ICH. Collectively, our investigation identified that necroptosis is an important mechanism of cell death in brain injury after ICH, and inhibition of necroptosis may be a potential therapeutic intervention of ICH. PMID:28252651

Association Between Blood Glucose and Functional Outcome in Intracerebral Hemorrhage: A Systematic Review and Meta-Analysis.

PubMed

Zheng, Jun; Yu, Zhiyuan; Ma, Lu; Guo, Rui; Lin, Sen; You, Chao; Li, Hao

2018-03-16

Intracerebral hemorrhage (ICH) is a devastating subtype of stroke. Patients with ICH have poor functional outcomes. The association between blood glucose level and functional outcome in ICH remains unclear. This systematic review and meta-analysis aimed to investigate the association between blood glucose level and functional outcomes in patients with ICH. Literature was searched systemically in PubMed, EMBASE, Web of Science, and Cochrane Library. Published cohort studies evaluating the association between blood glucose and functional outcome in patients with ICH were included. This meta-analysis was performed using odds ratios (ORs) and 95% confidence intervals (CIs). A total of 16 studies were included in our meta-analysis. Our data show that hyperglycemia defined by cutoff values was significantly associated with unfavorable functional outcome (OR, 1.80; 95% CI, 1.36-2.39; P < 0.001). Our analysis also suggested a significant association between increased blood glucose levels and functional outcomes (OR, 1.05; 95% CI, 1.03-1.07; P < 0.001). High blood glucose level is significantly associated with poor functional outcome in ICH. Further studies with larger sample sizes, more time points, and longer follow-up times are necessary to confirm this association. Copyright © 2018 Elsevier Inc. All rights reserved.

Potential role of blood biomarkers in the management of nontraumatic intracerebral hemorrhage.

PubMed

Senn, Rebecca; Elkind, Mitchell S V; Montaner, Joan; Christ-Crain, Mirjam; Katan, Mira

2014-01-01

Intracerebral hemorrhage (ICH), a subtype of stroke associated with high mortality and disability, accounts for 13% of all strokes. Basic and clinical research has contributed to our understanding of the complex pathophysiology of neuronal injury in ICH. Outcome rates, however, remain stable, and questions regarding acute management of ICH remain unanswered. Newer research is aiming at matching measured levels of serum proteins, enzymes, or cells to different stages of brain damage, suggesting that blood biomarkers may assist in acute diagnosis, therapeutic decisions, and prognostication. This paper provides an overview on the most promising blood biomarkers and their potential role in the diagnosis and management of spontaneous ICH. Information was collected from studies, reviews, and guidelines listed in PubMed up to November 2013 on blood biomarkers of nontraumatic ICH in humans. We describe the potential role and limitations of GFAP, S100B/RAGE, and ApoC-III as diagnostic biomarkers, β-​Amyloid as a biomarker for etiological classification, and 27 biomarkers for prognosis of mortality and functional outcome. Within the group of prognostic markers we discuss markers involved in coagulation processes (e.g., D-Dimers), neuroendocrine markers (e.g., copeptin), systemic metabolic markers (e.g., blood glucose levels), markers of inflammation (e.g., IL-6), as well as growth factors (e.g., VEGF), and others (e.g., glutamate). Some of those blood biomarkers are agents of pathologic processes associated with hemorrhagic stroke but also other diseases, whereas others play more distinct pathophysiological roles and help in understanding the basic mechanisms of brain damage and/or recovery in ICH. Numerous blood biomarkers are associated with different pathophysiological pathways in ICH, and some of them promise to be useful in the management of ICH, eventually contributing additional information to current tools for diagnosis, therapy monitoring, risk stratification, or

Comparative genomics of the pathogenic ciliate Ichthyophthirius multifiliis, its free-living relatives and a host species provide insights into adoption of a parasitic lifestyle and prospects for disease control

PubMed Central

2011-01-01

Background Ichthyophthirius multifiliis, commonly known as Ich, is a highly pathogenic ciliate responsible for 'white spot', a disease causing significant economic losses to the global aquaculture industry. Options for disease control are extremely limited, and Ich's obligate parasitic lifestyle makes experimental studies challenging. Unlike most well-studied protozoan parasites, Ich belongs to a phylum composed primarily of free-living members. Indeed, it is closely related to the model organism Tetrahymena thermophila. Genomic studies represent a promising strategy to reduce the impact of this disease and to understand the evolutionary transition to parasitism. Results We report the sequencing, assembly and annotation of the Ich macronuclear genome. Compared with its free-living relative T. thermophila, the Ich genome is reduced approximately two-fold in length and gene density and three-fold in gene content. We analyzed in detail several gene classes with diverse functions in behavior, cellular function and host immunogenicity, including protein kinases, membrane transporters, proteases, surface antigens and cytoskeletal components and regulators. We also mapped by orthology Ich's metabolic pathways in comparison with other ciliates and a potential host organism, the zebrafish Danio rerio. Conclusions Knowledge of the complete protein-coding and metabolic potential of Ich opens avenues for rational testing of therapeutic drugs that target functions essential to this parasite but not to its fish hosts. Also, a catalog of surface protein-encoding genes will facilitate development of more effective vaccines. The potential to use T. thermophila as a surrogate model offers promise toward controlling 'white spot' disease and understanding the adaptation to a parasitic lifestyle. PMID:22004680

Oral anticoagulant re-initiation following intracerebral hemorrhage in non-valvular atrial fibrillation: Global survey of the practices of neurologists, neurosurgeons and thrombosis experts.

PubMed

Xu, Yan; Shoamanesh, Ashkan; Schulman, Sam; Dowlatshahi, Dar; Al-Shahi Salman, Rustam; Moldovan, Ioana Doina; Wells, Philip Stephen; AlKherayf, Fahad

2018-01-01

While oral anticoagulants (OACs) are highly effective for ischemic stroke prevention in atrial fibrillation, intracerebral hemorrhage (ICH) remains the most feared complication of OAC. Clinical controversy remains regarding OAC resumption and its timing for ICH survivors with atrial fibrillation because the balance between risks and benefits has not been investigated in randomized trials. To survey the practice of stroke neurologists, thrombosis experts and neurosurgeons on OAC re-initiation following OAC-associated ICH. An online survey was distributed to members of the International Society for Thrombosis and Haemostasis, Canadian Stroke Consortium, NAVIGATE-ESUS trial investigators (Clinicatrials.gov identifier NCT02313909) and American Association of Neurological Surgeons. Demographic factors and 11 clinical scenarios were included. Two hundred twenty-eight participants from 38 countries completed the survey. Majority of participants were affiliated with academic centers, and >20% managed more than 15 OAC-associated ICH patients/year. Proportion of respondents suggesting OAC anticoagulant resumption varied from 30% (for cerebral amyloid angiopathy) to 98% (for traumatic ICH). Within this group, there was wide distribution in response for timing of resumption: 21.4% preferred to re-start OACs after 1-3 weeks of incident ICH, while 25.3% opted to start after 1-3 months. Neurosurgery respondents preferred earlier OAC resumption compared to stroke neurologists or thrombosis experts in 5 scenarios (p<0.05 by Kendall's tau). Wide variations in current practice exist among management of OAC-associated ICH, with decisions influenced by patient- and provider-related factors. As these variations likely reflect the lack of high quality evidence, randomized trials are direly needed in this population.

Epidemiology of Mild Traumatic Brain Injury with Intracranial Hemorrhage: Focusing Predictive Models for Neurosurgical Intervention.

PubMed

Orlando, Alessandro; Levy, A Stewart; Carrick, Matthew M; Tanner, Allen; Mains, Charles W; Bar-Or, David

2017-11-01

To outline differences in neurosurgical intervention (NI) rates between intracranial hemorrhage (ICH) types in mild traumatic brain injuries and help identify which ICH types are most likely to benefit from creation of predictive models for NI. A multicenter retrospective study of adult patients spanning 3 years at 4 U.S. trauma centers was performed. Patients were included if they presented with mild traumatic brain injury (Glasgow Coma Scale score 13-15) with head CT scan positive for ICH. Patients were excluded for skull fractures, "unspecified hemorrhage," or coagulopathy. Primary outcome was NI. Stepwise multivariable logistic regression models were built to analyze the independent association between ICH variables and outcome measures. The study comprised 1876 patients. NI rate was 6.7%. There was a significant difference in rate of NI by ICH type. Subdural hematomas had the highest rate of NI (15.5%) and accounted for 78% of all NIs. Isolated subarachnoid hemorrhages had the lowest, nonzero, NI rate (0.19%). Logistic regression models identified ICH type as the most influential independent variable when examining NI. A model predicting NI for isolated subarachnoid hemorrhages would require 26,928 patients, but a model predicting NI for isolated subdural hematomas would require only 328 patients. This study highlighted disparate NI rates among ICH types in patients with mild traumatic brain injury and identified mild, isolated subdural hematomas as most appropriate for construction of predictive NI models. Increased health care efficiency will be driven by accurate understanding of risk, which can come only from accurate predictive models. Copyright © 2017 Elsevier Inc. All rights reserved.

A1 adenosine receptor attenuates intracerebral hemorrhage-induced secondary brain injury in rats by activating the P38-MAPKAP2-Hsp27 pathway.

PubMed

Zhai, Weiwei; Chen, Dongdong; Shen, Haitao; Chen, Zhouqing; Li, Haiying; Yu, Zhengquan; Chen, Gang

2016-06-14

This study was designed to determine the role of the A1 adenosine receptors in intracerebral hemorrhage (ICH)-induced secondary brain injury and the underlying mechanisms. A collagenase-induced ICH model was established in Sprague-Dawley rats, and cultured primary rat cortical neurons were exposed to oxyhemoglobin at a concentration of 10 μM to mimic ICH in vitro. The A1 adenosine receptor agonist N(6)-cyclohexyladenosine and antagonist 8-phenyl-1,3-dipropylxanthine were used to study the role of A1 adenosine receptor in ICH-induced secondary brain injury, and antagonists of P38 and Hsp27 were used to study the underlying mechanisms of A1 adenosine receptor actions. The protein level of A1 adenosine receptor was significantly increased by ICH, while there was no significant change in protein levels of the other 3 adenosine receptors. In addition, the A1 adenosine receptor expression could be increased by N(6)-cyclohexyladenosine and decreased by 8-phenyl-1,3-dipropylxanthine under ICH conditions. Activation of the A1 adenosine receptor attenuated neuronal apoptosis in the subcortex, which was associated with increased phosphorylation of P38, MAPK, MAPKAP2, and Hsp27. Inhibition of the A1 adenosine receptor resulted in opposite effects. Finally, the neuroprotective effect of the A1 adenosine receptor agonist N(6)-cyclohexyladenosine was inhibited by antagonists of P38 and Hsp27. This study demonstrates that activation of the A1 adenosine receptor by N(6)-cyclohexyladenosine could prevent ICH-induced secondary brain injury via the P38-MAPKAP2-Hsp27 pathway.

Phantom-based standardization of CT angiography images for spot sign detection.

PubMed

Morotti, Andrea; Romero, Javier M; Jessel, Michael J; Hernandez, Andrew M; Vashkevich, Anastasia; Schwab, Kristin; Burns, Joseph D; Shah, Qaisar A; Bergman, Thomas A; Suri, M Fareed K; Ezzeddine, Mustapha; Kirmani, Jawad F; Agarwal, Sachin; Shapshak, Angela Hays; Messe, Steven R; Venkatasubramanian, Chitra; Palmieri, Katherine; Lewandowski, Christopher; Chang, Tiffany R; Chang, Ira; Rose, David Z; Smith, Wade; Hsu, Chung Y; Liu, Chun-Lin; Lien, Li-Ming; Hsiao, Chen-Yu; Iwama, Toru; Afzal, Mohammad Rauf; Cassarly, Christy; Greenberg, Steven M; Martin, Renee' Hebert; Qureshi, Adnan I; Rosand, Jonathan; Boone, John M; Goldstein, Joshua N

2017-09-01

The CT angiography (CTA) spot sign is a strong predictor of hematoma expansion in intracerebral hemorrhage (ICH). However, CTA parameters vary widely across centers and may negatively impact spot sign accuracy in predicting ICH expansion. We developed a CT iodine calibration phantom that was scanned at different institutions in a large multicenter ICH clinical trial to determine the effect of image standardization on spot sign detection and performance. A custom phantom containing known concentrations of iodine was designed and scanned using the stroke CT protocol at each institution. Custom software was developed to read the CT volume datasets and calculate the Hounsfield unit as a function of iodine concentration for each phantom scan. CTA images obtained within 8 h from symptom onset were analyzed by two trained readers comparing the calibrated vs. uncalibrated density cutoffs for spot sign identification. ICH expansion was defined as hematoma volume growth >33%. A total of 90 subjects qualified for the study, of whom 17/83 (20.5%) experienced ICH expansion. The number of spot sign positive scans was higher in the calibrated analysis (67.8 vs 38.9% p < 0.001). All spot signs identified in the non-calibrated analysis remained positive after calibration. Calibrated CTA images had higher sensitivity for ICH expansion (76 vs 52%) but inferior specificity (35 vs 63%) compared with uncalibrated images. Normalization of CTA images using phantom data is a feasible strategy to obtain consistent image quantification for spot sign analysis across different sites and may improve sensitivity for identification of ICH expansion.

Run-up to participation in ATACH II in Japan

PubMed Central

Toyoda, K; Sato, S; Koga, M; Yamamoto, H; Nakagawara, J; Furui, E; Shiokawa, Y; Hasegawa, Y; Okuda, S; Sakai, N; Kimura, K; Okada, Y; Yoshimura, S; Hoshino, H; Uesaka, Y; Nakashima, T; Itoh, Y; Ueda, T; Nishi, T; Gotoh, J; Nagatsuka, K; Arihiro, S; Yamaguchi, T; Minematsu, K

2012-01-01

Intracerebral hemorrhage (ICH) is a major cause of morbidity and mortality in Japan. Seventeen Japanese institutions are participating in the Antihypertensive Treatment for Acute Cerebral Hemorrhage (ATACH) II Trial (ClinicalTrials.gov no. NCT01176565; UMIN 000006526). This phase III trial is designed to determine the therapeutic benefit of early intensive systolic blood pressure (BP) lowering for acute hypertension in ICH patients. This report explains the long run-up to reach the start of patient registration in ATACH II in Japan, including our preliminary study, a nationwide survey on antihypertensive treatment for acute ICH patients, a multicenter study for hyperacute BP lowering (the SAMURAI-ICH study), revision of the official Japanese label for intravenous nicardipine, and construction of the infrastructure for the trial. PMID:23230457

MRI-visible perivascular spaces in cerebral amyloid angiopathy and hypertensive arteriopathy

PubMed Central

Boulouis, Gregoire; Pasi, Marco; Auriel, Eitan; van Etten, Ellis S.; Haley, Kellen; Ayres, Alison; Schwab, Kristin M.; Martinez-Ramirez, Sergi; Goldstein, Joshua N.; Rosand, Jonathan; Viswanathan, Anand; Greenberg, Steven M.; Gurol, M. Edip

2017-01-01

Objective: To assess MRI-visible enlarged perivascular spaces (EPVS) burden and different topographical patterns (in the centrum semiovale [CSO] and basal ganglia [BG]) in 2 common microangiopathies: cerebral amyloid angiopathy (CAA) and hypertensive arteriopathy (HA). Methods: Consecutive patients with spontaneous intracerebral hemorrhage (ICH) from a prospective MRI cohort were included. Small vessel disease MRI markers, including cerebral microbleeds (CMBs), cortical superficial siderosis (cSS), and white matter hyperintensities (WMH), were rated. CSO-EPVS/BG-EPVS were assessed on a validated 4-point visual rating scale (0 = no EPVS, 1 = <10, 2 = 11–20, 3 = 21–40, and 4 = >40 EPVS). We tested associations of predefined high-degree (score >2) CSO-EPVS and BG-EPVS with other MRI markers in multivariable logistic regression. We subsequently evaluated associations with CSO-EPVS predominance (i.e., CSO-EPVS > BG-EPVS) and BG-EPVS predominance pattern (i.e., BG-EPVS > CSO-EPVS) in adjusted multinomial logistic regression (reference group, BG-EPVS = CSO-EPVS). Results: We included 315 patients with CAA-ICH and 137 with HA-ICH. High-degree CSO-EPVS prevalence was greater in CAA-related ICH vs HA-related ICH (43.8% vs 17.5%, p < 0.001). In multivariable logistic regression, high-degree CSO-EPVS was associated with lobar CMB (odds ratio [OR] 1.33, 95% confidence interval [CI] 1.10–1.61, p = 0.003) and cSS (OR 2.08, 95% CI 1.30–3.32, p = 0.002). Deep CMBs (OR 2.85, 95% CI 1.75–4.64, p < 0.0001) and higher WMH volume (OR 1.02, 95% CI 1.01–1.04, p = 0.010) were predictors of high-degree BG-EPVS. A CSO-EPVS–predominant pattern was more common in CAA-ICH than in HA-ICH (75.9% vs 39.4%, respectively, p < 0.0001). CSO-PVS predominance was associated with lobar CMB burden and cSS, while BG-EPVS predominance was associated with HA-ICH and WMH volumes. Conclusions: Different patterns of MRI-visible EPVS provide insights into the dominant underlying microangiopathy

Antiplatelet Treatment After Transient Ischemic Attack and Ischemic Stroke in Patients With Cerebral Microbleeds in 2 Large Cohorts and an Updated Systematic Review.

PubMed

Lau, Kui Kai; Lovelock, Caroline E; Li, Linxin; Simoni, Michela; Gutnikov, Sergei; Küker, Wilhelm; Mak, Henry Ka Fung; Rothwell, Peter M

2018-06-01

In patients with transient ischemic attack/ischemic stroke, microbleed burden predicts intracerebral hemorrhage (ICH), and ischemic stroke, but implications for antiplatelet treatment are uncertain. Previous cohort studies have had insufficient follow-up to assess the time course of risks, have not stratified risks by antithrombotic use, and have not reported extracranial bleeds or functional outcome of ICH versus ischemic stroke. In 2 independent prospective cohorts with transient ischemic attack/ischemic stroke (Oxford Vascular Study/mainly white; University of Hong Kong/mainly Chinese), antiplatelet treatment was started routinely irrespective of microbleed burden. Risks, time course and outcome of ICH, extracranial bleeds, and recurrent ischemic events were determined and stratified by microbleed burden (0 versus 1, 2-4, and ≥5), adjusting for age, sex, and vascular risk factors. Microbleeds were more frequent in the Chinese cohort (450 of 1003 versus 165 of 1080; P <0.0001), but risk associations were similar during 7433 patient-years of follow-up. Among 1811 patients on antiplatelet drugs, risk of major extracranial bleeds was unrelated to microbleed burden ( P trend =0.87), but the 5-year risk of ICH was steeply related ( P trend <0.0001), with 11 of 15 (73%) of ICH in 140 of 1811 (7.7%) patients with ≥5 microbleeds. However, risk of ischemic stroke also increased with microbleed burden ( P trend =0.013), such that risk of ischemic stroke and coronary events exceeded ICH and major extracranial bleeds during the first year, even among patients with ≥5 microbleeds (11.6% versus 3.9%). However, this ratio changed over time, with risk of hemorrhage (11.2%) matching that of ischemic events (12.0%) after 1 year. Moreover, whereas the association between microbleed burden and risk of ischemic stroke was due mainly to nondisabling events ( P trend =0.007), the association with ICH was accounted for ( P trend <0.0001) by disabling/fatal events (≥5 microbleeds

Identification of nine genes as novel susceptibility loci for early-onset ischemic stroke, intracerebral hemorrhage, or subarachnoid hemorrhage.

PubMed

Yamada, Yoshiji; Kato, Kimihiko; Oguri, Mitsutoshi; Horibe, Hideki; Fujimaki, Tetsuo; Yasukochi, Yoshiki; Takeuchi, Ichiro; Sakuma, Jun

2018-07-01

Given that substantial genetic components have been shown in ischemic stroke, intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH), heritability may be higher in early-onset than late-onset individuals with these conditions. Although genome-wide association studies (GWASs) have identified various genes and loci significantly associated with ischemic stroke, ICH, or intracranial aneurysm mainly in European ancestry populations, genetic variants that contribute to susceptibility to these disorders remain to be identified definitively. We performed exome-wide association studies (EWASs) to identify genetic variants that confer susceptibility to ischemic stroke, ICH, or SAH in early-onset subjects with these conditions. A total of 6,649 individuals aged ≤65 years were examined. For the EWAS of ischemic or hemorrhagic stroke, 6,224 individuals (450 subjects with ischemic stroke, 5,774 controls) or 6,179 individuals (261 subjects with ICH, 176 subjects with SAH, 5,742 controls), respectively, were examined. EWASs were performed with the use of Illumina Human Exome-12 v1.2 DNA Analysis BeadChip or Infinium Exome-24 v1.0 BeadChip. To compensate for multiple comparisons of allele frequencies with ischemic stroke, ICH, or SAH, we applied a false discovery rate (FDR) of <0.05 for statistical significance of association. The association of allele frequencies of 31,245 single nucleotide polymorphisms (SNPs) that passed quality control to ischemic stroke was examined with Fisher's exact test, and 31 SNPs were significantly (FDR <0.05) associated with ischemic stroke. The association of allele frequencies of 31,253 or 30,970 SNPs to ICH or SAH, respectively, was examined with Fisher's exact test, and six or two SNPs were significantly associated with ICH or SAH, respectively. Multivariable logistic regression analysis with adjustment for age, sex, and the prevalence of hypertension and diabetes mellitus revealed that 12 SNPs were significantly [P<0.0004 (0

Vascular disruption and blood–brain barrier dysfunction in intracerebral hemorrhage

PubMed Central

2014-01-01

This article reviews current knowledge of the mechanisms underlying the initial hemorrhage and secondary blood–brain barrier (BBB) dysfunction in primary spontaneous intracerebral hemorrhage (ICH) in adults. Multiple etiologies are associated with ICH, for example, hypertension, Alzheimer’s disease, vascular malformations and coagulopathies (genetic or drug-induced). After the initial bleed, there can be continued bleeding over the first 24 hours, so-called hematoma expansion, which is associated with adverse outcomes. A number of clinical trials are focused on trying to limit such expansion. Significant progress has been made on the causes of BBB dysfunction after ICH at the molecular and cell signaling level. Blood components (e.g. thrombin, hemoglobin, iron) and the inflammatory response to those components play a large role in ICH-induced BBB dysfunction. There are current clinical trials of minimally invasive hematoma removal and iron chelation which may limit such dysfunction. Understanding the mechanisms underlying the initial hemorrhage and secondary BBB dysfunction in ICH is vital for developing methods to prevent and treat this devastating form of stroke. PMID:25120903

White Matter Injury and Recovery after Hypertensive Intracerebral Hemorrhage

PubMed Central

Zuo, Shilun; Pan, Pengyu; Li, Qiang

2017-01-01

Hypertensive intracerebral hemorrhage (ICH) could very probably trigger white matter injury in patients. Through the continuous study of white matter injury after hypertensive ICH, we achieve a more profound understanding of the pathophysiological mechanism of its occurrence and development. At the same time, we found a series of drugs and treatment methods for the white matter repair. In the current reality, the research paradigm of white matter injury after hypertensive ICH is relatively obsolete or incomplete, and there are still lots of deficiencies in the research. In the face of the profound changes of stroke research perspective, we believe that the combination of the lenticulostriate artery, nerve nuclei of the hypothalamus-thalamus-basal ganglia, and the white matter fibers located within the capsula interna will be beneficial to the research of white matter injury and repair. This paper has classified and analyzed the study of white matter injury and repair after hypertensive ICH and also rethought the shortcomings of the current research. We hope that it could help researchers further explore and study white matter injury and repair after hypertensive ICH. PMID:28680884

Minimally invasive surgery for intracerebral haemorrhage.

PubMed

Barnes, Benjamin; Hanley, Daniel F; Carhuapoma, Juan R

2014-04-01

Spontaneous intracerebral haemorrhage (ICH) imposes a significant health and economic burden on society. Despite this, ICH remains the only stroke subtype without a definitive treatment. Without a clearly identified and effective treatment for spontaneous ICH, clinical practice varies greatly from aggressive surgery to supportive care alone. This review will discuss the current modalities of treatments for ICH including preliminary experience and investigative efforts to advance the care of these patients. Open surgery (craniotomy), prothrombotic agents and other therapeutic interventions have failed to significantly improve the outcome of these stroke victims. Recently, the Surgical Trial in Intracerebral Haemorrhage (STICH) II assessed the surgical management of patients with superficial intraparenchymal haematomas with negative results. MISTIE II and other trials of minimally invasive surgery (MIS) have shown promise for improving patient outcomes and a phase III trial started in late 2013. ICH lacks a definitive primary treatment as well as a therapy targeting surrounding perihematomal oedema and associated secondary damage. An ongoing phase III trial using MIS techniques shows promise for providing treatment for these patients.

Deadly intracranial bleed in patients with dengue fever: A series of nine patients and review of literature

PubMed Central

Sam, Jo Ee; Gee, Teak Sheng; Nasser, Abdul Wahab

2016-01-01

Introduction: Dengue fever is a global pandemic threat with increasing incidence. To date, there are no cures and the effectiveness of dengue vaccines is still uncertain. World Heath Organization introduced expanded dengue syndrome to include unusual presentations of dengue fever including severe neurologic complications. One of the deadly complications is intracranial hemorrhage (ICH). Methodology: We collected data of patients with ICH diagnosed via a plain computed tomography of the brain (CT brain) with thrombocytopenia and positive Dengue virus type 1 nonstructural protein (NS1) antigen test or positive dengue serology IgM from January 2014 till June 2015 at our center. Nine patients were included and all 20 other remaining patients reported in literature so far are discussed. Discussion: We found that all patients in our center requiring neurosurgical intervention died. Another interesting observation is that detection of Dengue IgG usually meant more severe ICH and poorer outcomes. From our series, platelet levels did not seem to influence the outcome. Conclusion: We recommend that for early detection of ICH, Dengue IgG should be routinely screened and a high index of suspicion be maintained. Future research should be focused on determining predictors of ICH in patients with dengue fever so that preventive steps can be taken as mortality is high and no treatment seems beneficial at the moment once severe ICH occurs. PMID:27365962

The growing clinical spectrum of cerebral amyloid angiopathy.

PubMed

Wermer, Marieke J H; Greenberg, Steven M

2018-02-01

Cerebral amyloid angiopathy (CAA) is diagnosed primarily as a cause of lobar intracerebral hemorrhages (ICH) in elderly patients. With improving MRI techniques, however, the role of CAA in causing other symptoms has become clear. Recognizing the full clinical spectrum of CAA is important for diagnosis and treatment. In this review we summarize recent insights in clinical CAA features, MRI biomarkers, and management. The rate of ICH recurrence in CAA is among the highest of all stroke subtypes. Cortical superficial siderosis (cSS) and cortical subarachnoid hemorrhage (cSAH) are important imaging predictors for recurrent ICH. CAA also causes cognitive problems in multiple domains. In patients with nondemented CAA, the risk of developing dementia is high especially after ICH. CAA pathology probably starts years before the first clinical manifestations. The first signs in hereditary CAA are white matter lesions, cortical microinfarcts, and impaired occipital cerebral vasoreactivity. Visible centrum semiovale perivascular spaces, lobar located lacunes, and cortical atrophy are new nonhemorrhagic MRI markers. CAA should be in the differential diagnosis of elderly patients with lobar ICH but also in those with cognitive decline and episodic transient neurological symptoms. Physicians should be aware of the cognitive effects of CAA. In patients with a previous ICH, cSS, or cSAH, anticoagulation should be considered risky. The increasing number of MRI markers may help to discriminate CAA from other small vessel diseases and dementia subtypes.

Fisetin Protects against Intracerebral Hemorrhage-Induced Neuroinflammation in Aged Mice.

PubMed

Chen, Cheng; Yao, Li; Cui, Jing; Liu, Bao

2018-01-01

Fisetin is commonly used as an anti-inflammatory and neuroprotective drug. In this study, we aimed to investigate the efficacy of fisetin in alleviating intracerebral hemorrhage (ICH)-induced brain injury. Mouse ICH models were constructed using the collagenase-induction method. ICH mice received fisetin treatment at the dose of 10-90 mg/kg, followed by the evaluation of neurological deficit through neurologic severity scores (mNSS), brain water content and terminal deoxynucleotidyl transferase dUTP nick end labeling analysis of cell apoptosis. Cytokine levels were also assessed with enzyme-linked immunosorbent assay. The activation of astrocytes and microglia was evaluated through S100 staining and Western blot analysis of ionized calcium-binding adaptor molecule 1 respectively. Nuclear factor kappa-B (NF-κB) signaling was also evaluated by Western blot. ICH mice demonstrated dramatic increase in mNSS, brain edema and cell apoptosis, indicating severe brain deficit. Fisetin treatment lowered these parameters, suggesting the alleviation of brain injury. Levels of proinflammatory cytokines were reduced, accompanied by a prominent decrease in activated astrocytes and microglia. NF-κB signaling was also attenuated by fisetin treatment. Fisetin effectively alleviates ICH by downregulating proinflammatory cytokines and attenuating NF-κB signaling. These data suggest fisetin as a valuable natural flavonol for clinical management of ICH-induced brain injury. © 2018 S. Karger AG, Basel.

Initial multicenter technical experience with the Apollo device for minimally invasive intracerebral hematoma evacuation.

PubMed

Spiotta, Alejandro M; Fiorella, David; Vargas, Jan; Khalessi, Alexander; Hoit, Dan; Arthur, Adam; Lena, Jonathan; Turk, Aquilla S; Chaudry, M Imran; Gutman, Frederick; Davis, Raphael; Chesler, David A; Turner, Raymond D

2015-06-01

No conventional surgical intervention has been shown to improve outcomes for patients with spontaneous intracerebral hemorrhage (ICH) compared with medical management. We report the initial multicenter experience with a novel technique for the minimally invasive evacuation of ICH using the Penumbra Apollo system (Penumbra Inc, Alameda, California). Institutional databases were queried to perform a retrospective analysis of all patients who underwent ICH evacuation with the Apollo system from May 2014 to September 2014 at 4 centers (Medical University of South Carolina, Stony Brook University, University of California at San Diego, and Semmes-Murphy Clinic). Cases were performed either in the neurointerventional suite, operating room, or in a hybrid operating room/angiography suite. Twenty-nine patients (15 female; mean age, 62 ± 12.6 years) underwent the minimally invasive evacuation of ICH. Six of these parenchymal hemorrhages had an additional intraventricular hemorrhage component. The mean volume of ICH was 45.4 ± 30.8 mL, which decreased to 21.8 ± 23.6 mL after evacuation (mean, 54.1 ± 39.1% reduction; P < .001). Two complications directly attributed to the evacuation attempt were encountered (6.9%). The mortality rate was 13.8% (n = 4). Minimally invasive evacuation of ICH and intraventricular hemorrhage can be achieved with the Apollo system. Future work will be required to determine which subset of patients are most likely to benefit from this promising technology.

Therapeutic temperature modulation for fever after intracerebral hemorrhage.

PubMed

Lord, Aaron S; Karinja, Sarah; Lantigua, Hector; Carpenter, Amanda; Schmidt, J Michael; Claassen, Jan; Agarwal, Sachin; Connolly, E Sander; Mayer, Stephan A; Badjatia, Neeraj

2014-10-01

We sought to determine whether therapeutic temperature modulation (TTM) to treat fever after intracerebral hemorrhage (ICH) is associated with improved hospital complications and discharge outcomes. We performed a retrospective case-control study of patients admitted with spontaneous ICH having two consecutive fevers ≥38.3 °C despite acetaminophen administration. Cases were enrolled from a prospective database of patients receiving TTM from 2006 to 2010. All cases received TTM for fever control with goal temperature of 37 °C with a shiver-control protocol. Controls were matched in severity by ICH score and retrospectively obtained from 2001 to 2004, before routine use of TTM for ICH. Primary outcome was discharge-modified Rankin score. Forty patients were enrolled in each group. Median admission ICH Score, ICH volume, and GCS were similar. TTM was initiated with a median of 3 days after ICH onset and for a median duration of 7 days. Mean daily T max was significantly higher in the control group over the first 12 days (38.1 vs. 38.7 °C, p ≤ 0.001). The TTM group had more days of IV sedation (median 8 vs. 1, p < 0.001) and mechanical ventilation (18 vs. 9, p = 0.003), and more frequently underwent tracheostomy (55 vs. 23 %, p = 0.005). Mean NICU length of stay was longer for TTM patients (15 vs. 11 days, p = 0.007). There was no difference in discharge outcomes between the two groups (overall mortality 33 %, moderate or severe disability 67 %). Therapeutic normothermia is associated with increased duration of sedation, mechanical ventilation, and NICU stay, but is not clearly associated with improved discharge outcome.

The Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) Study Protocol

PubMed Central

Woo, Daniel; Rosand, Jonathan; Kidwell, Chelsea; McCauley, Jacob L.; Osborne, Jennifer; Brown, Mark W.; West, Sandra E.; Rademacher, Eric W.; Waddy, Salina; Roberts, Jamie N.; Koch, Sebastian; Gonzales, Nicole R.; Sung, Gene; Kittner, Steven J.; Birnbaum, Lee; Frankel, Michael; Daniel Testai, Fernando; Hall, Christiana E.; Elkind, Mitchell S. V.; Flaherty, Matthew; Coull, Bruce; Chong, Ji Y.; Warwick, Tanya; Malkoff, Marc; James, Michael L.; Ali, Latisha K.; Worrall, Bradford B.; Jones, Floyd; Watson, Tiffany; Leonard, Anne; Martinez, Rebecca; Sacco, Ralph I; Langefeld, Carl D.

2013-01-01

Background and Purpose Epidemiologic studies of intracerebral hemorrhage (ICH) have consistently demonstrated variation in incidence, location, age at presentation, and outcomes among non-Hispanic white, black, and Hispanic populations. We report here the design and methods for this large, prospective, multi-center case-control study of ICH. Methods The ERICH study is a multi-center, prospective case-control study of ICH. Cases are identified by hot-pursuit and enrolled using standard phenotype and risk factor information and include neuroimaging and blood sample collection. Controls are centrally identified by random digit dialing to match cases by age (+/−5 years), race, ethnicity, gender and metropolitan region. Results As of March 22, 2013, 1,655 cases of ICH had been recruited into the study which is 101.5% of the target for that date and 851 controls had been recruited which is 67.2% of the target for that date (1,267 controls) for a total of 2,506 subjects which is 86.5% of the target for that date (2,897 subjects). Of the 1,655 cases enrolled, 1,640 cases had the case interview entered into the database of which 628 (38%) were non-Hispanic black, 458 (28%) were non-Hispanic white and 554 (34%) were Hispanic. Of the 1,197 cases with imaging submitted, 876 (73.2%) had a 24 hour follow-up CT available In addition to CT imaging, 607 cases have had MRI evaluation. Conclusion The ERICH study is a large, case-control study of ICH with particular emphasis on recruitment of minority populations for the identification of genetic and epidemiologic risk factors for ICH and outcomes after ICH. PMID:24021679

Risk of Intracranial Hemorrhage From Statin Use in Asians: A Nationwide Cohort Study.

PubMed

Chang, Chia-Hsuin; Lin, Chin-Hsien; Caffrey, James L; Lee, Yen-Chieh; Liu, Ying-Chun; Lin, Jou-Wei; Lai, Mei-Shu

2015-06-09

Reports of statin usage and increased risk of intracranial hemorrhage (ICH) have been inconsistent. This study examined potential associations between statin usage and the risk of ICH in subjects without a previous history of stroke. Patients initiating statin therapy between 2005 and 2009 without a previous history of ischemic or hemorrhagic stroke were identified from Taiwan's National Health Insurance database. Participants were stratified by advanced age (≥70 years), sex, and diagnosed hypertension. The outcome of interest was hospital admission for ICH (International Classification of Diseases, Ninth Revision, Clinical Modification codes 430, 431, 432). Cox regression models were applied to estimate the hazard ratio of ICH. The cumulative statin dosage stratified by quartile and adjusted for baseline disease risk score served as the primary variable using the lowest quartile of cumulative dosage as a reference. There were 1 096 547 statin initiators with an average follow-up of 3.3 years. The adjusted hazard ratio for ICH between the highest and the lowest quartile was nonsignificant at 1.06 with a 95% confidence interval spanning 1.00 (0.94-1.19). Similar nonsignificant results were found in sensitivity analyses using different outcome definitions or model adjustments, reinforcing the robustness of the study findings. Subgroup analysis identified an excess of ICH frequency in patients without diagnosed hypertension (adjusted hazard ratio 1.36 [1.11-1.67]). In general, no association was observed between cumulative statin use and the risk of ICH among subjects without a previous history of stroke. An increased risk was identified among the nonhypertensive cohort, but this finding should be interpreted with caution. © 2015 American Heart Association, Inc.

Safety of Endovascular Intervention for Stroke on Therapeutic Anticoagulation: Multicenter Cohort Study and Meta-Analysis.

PubMed

Kurowski, Donna; Jonczak, Karin; Shah, Qaisar; Yaghi, Shadi; Marshall, Randolph S; Ahmad, Haroon; McKinney, James; Torres, Jose; Ishida, Koto; Cucchiara, Brett

2017-05-01

Intravenous (IV) tissue plasminogen activator (tPA) is contraindicated in therapeutically anti-coagulated patients. Such patients may be considered for endovascular intervention. However, there are limited data on its safety. We performed a multicenter retrospective study of patients undergoing endovascular intervention for acute ischemic stroke while on therapeutic anticoagulation. We compared the observed rate of National Institute of Neurological Disorders and Stroke defined symptomatic intracerebral hemorrhage (sICH) with risk-adjusted historical control rates of sICH after IV tPA using weighted averages of the hemorrhage after thrombolysis (HAT) and Multicenter Stroke Survey (MSS) prediction scores. We also performed a metaanalysis of studies assessing risk of sICH with endovascular intervention in patients on anticoagulation. Of 94 cases, mean age was 73 years and median National Institutes of Health Stroke Scale was 19. Anticoagulation consisted of warfarin (n = 51), dabigatran (n = 6), rivaroxaban (n = 13), apixaban (n = 1), IV heparin (n = 19), low molecular weight heparin (n = 3), and combined warfarin and IV heparin (n = 3). sICH was seen in 7 patients (7%, 95% confidence interval 4-15), all on warfarin. Predicted sICH rates for the cohort based on HAT and MSS scoring were 12% and 7%, respectively. Meta-analysis of 6 studies showed no significant difference in sICH between patients undergoing endovascular intervention on anticoagulation and comparator groups. Endovascular intervention in subjects on therapeutic anticoagulation appears reasonably safe, with a sICH rate similar to patients not on anticoagulation receiving IV tPA. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Hemodialysis with end-stage renal disease did not raise the risk of intracranial hemorrhage after a head injury.

PubMed

Chen, Hsin-Hung; Hsu, Chien-Chin; Weng, Shih-Feng; Lin, Hung-Jung; Wang, Jhi-Joung; Guo, How-Ran; Su, Shih-Bin; Huang, Chien-Cheng; Chen, Jiann-Hwa

2015-10-28

Hemodialysis (HD) treatment for end-stage renal disease (ESRD) (HD(+ESRD)) may increase the risk of intracranial hemorrhage (ICH) after a head injury (HI) for which heparin is used. However, the results of noncontrast head computed tomography (CT) in such patients are not always clear. We aimed to evaluate the effect of HD on the risk of ICH in ESRD patients and in controls without ESRD with HD (HD(-ESRD)), and to determine whether to lower the threshold of head CT in HD(+ESRD) patients after HI. In this nationwide population-based study using Taiwan's National Health Insurance Research Database, we enrolled 6938 HD(+ESRD) HI patients for the case group and 13,876 randomly selected HD(-ESRD) HI patients for the control group. Measures of the post-HI association between HD(+ESRD) and ICH determined using conditional logistic regression. Five hundred sixty-eight (2.74 %) patients had post-HI ICH: 185 in the HD(+ESRD) group (2.67 % of cases) and 383 were from the HD(-ESRD) group (2.76 % of controls). Conditional logistic regression analysis revealed that after adjusting for age, gender, diabetes, hypertension, congestive heart failure, stroke, cancer, and liver disease, HD(+ESRD) patients had no higher odds of ICH (adjusted odds ratio [AOR]: 0.91; 95 % confidence interval [CI]: 0.75-1.11) than did HD(-ESRD) patients. In the subgroup analysis of immediate ICH, HD(+ESRD) patients had lower odds than did HD(-ESRD) patients (AOR: 0.73; 95 % CI: 0.56-0.94). HD(+ESRD) did not increase the post-HI risk of ICH. Therefore, it may not be necessary to lower the threshold of head CT in HD(+ESRD) patients.

[Brazilian guidelines for the manegement of intracerebral hemorrhage].

PubMed

Pontes-Neto, Octávio M; Oliveira-Filho, Jamary; Valiente, Raul; Friedrich, Maurício; Pedreira, Bruno; Rodrigues, Bruno Castelo Branco; Liberato, Bernardo; Freitas, Gabriel Rodriguez de

2009-09-01

Among the stroke subtypes, intracerebral hemorrhage (ICH) has the worst prognosis and still lacks a specific treatment. The present manuscript contains the Brazilian guidelines for the management of ICH. It was elaborated by the executive committee of the Brazilian Cerebrovascular Diseases Society and was based on a broad review of articles about the theme. The text aims to provide a rational for the management of patients with an acute ICH, with the diagnostic and therapeutic resources that are available in Brazil.

Comparison of Gender Differences in Intracerebral Hemorrhage in a Multi-Ethnic Asian Population.

PubMed

Hsieh, Justin T; Ang, Beng Ti; Ng, Yew Poh; Allen, John C; King, Nicolas K K

2016-01-01

Intracerebral hemorrhage (ICH) accounts for 10-15% of all first time strokes and with incidence twice as high in the Asian compared to Western population. This study aims to investigate gender differences in ICH patient outcomes in a multi-ethnic Asian population. Data for 1,192 patients admitted for ICH were collected over a four-year period. Multivariate logistic regression was used to identify independent predictors and odds ratios were computed for 30-day mortality and Glasgow Outcome Scale (GOS) comparing males and females. Males suffered ICH at a younger age than females (62.2 ± 13.2 years vs. 66.3 ± 15.3 years; P<0.001). The occurrence of ICH was higher among males than females at all ages until 80 years old, beyond which the trend was reversed. Females exhibited increased severity on admission as measured by Glasgow Coma Scale compared to males (10.9 ± 4.03 vs. 11.4 ± 4.04; P = 0.030). No difference was found in 30-day mortality between females and males (F: 30.5% [155/508] vs. M: 27.0% [186/688]), with unadjusted and adjusted odds ratio (F/M) of 1.19 (P = 0.188) and 1.21 (P = 0.300). At discharge, there was a non-statistically significant but potentially clinically relevant morbidity difference between the genders as measured by GOS (dichotomized GOS of 4-5: F: 23.7% [119/503] vs. M: 28.7% [194/677]), with unadjusted and adjusted odds ratio (F/M) of 0.77 (P = 0.055) and 0.87 (P = 0.434). In our multi-ethnic Asian population, males developed ICH at a younger age and were more susceptible to ICH than women at all ages other than the beyond 80-year old age group. In contrast to the Western population, neurological status of female ICH patients at admission was poorer and their 30-day mortality was not reduced. Although the study was not powered to detect significance, female showed a trend toward worse 30-day morbidity at discharge.

Intracranial hemorrhage among patients with atrial fibrillation anticoagulated with warfarin or rivaroxaban: the rivaroxaban once daily, oral, direct factor Xa inhibition compared with vitamin K antagonism for prevention of stroke and embolism trial in atrial fibrillation.

PubMed

Hankey, Graeme J; Stevens, Susanna R; Piccini, Jonathan P; Lokhnygina, Yuliya; Mahaffey, Kenneth W; Halperin, Jonathan L; Patel, Manesh R; Breithardt, Günter; Singer, Daniel E; Becker, Richard C; Berkowitz, Scott D; Paolini, John F; Nessel, Christopher C; Hacke, Werner; Fox, Keith A A; Califf, Robert M

2014-05-01

Intracranial hemorrhage (ICH) is a life-threatening complication of anticoagulation. We investigated the rate, outcomes, and predictors of ICH in 14 264 patients with atrial fibrillation from Rivaroxaban Once Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF). Cox proportional hazards modeling was used. During 1.94 years (median) of follow-up, 172 patients (1.2%) experienced 175 ICH events at a rate of 0.67% per year. The significant, independent predictors of ICH were race (Asian: hazard ratio, 2.02; 95% CI, 1.39-2.94; black: hazard ratio, 3.25; 95% CI, 1.43-7.41), age (1.35; 1.13-1.63 per 10-year increase), reduced serum albumin (1.39; 1.12-1.73 per 0.5 g/dL decrease), reduced platelet count below 210×10(9)/L (1.08; 1.02-1.13 per 10×10(9)/L decrease), previous stroke or transient ischemic attack (1.42; 1.02-1.96), and increased diastolic blood pressure (1.17; 1.01-1.36 per 10 mm Hg increase). Predictors of a reduced risk of ICH were randomization to rivaroxaban (0.60; 0.44-0.82) and history of congestive heart failure (0.65; 0.47-0.89). The ability of the model to discriminate individuals with and without ICH was good (C-index, 0.69; 95% CI, 0.64-0.73). Among patients with atrial fibrillation treated with anticoagulation, the risk of ICH was higher among Asians, blacks, the elderly, and in those with previous stroke or transient ischemic attack, increased diastolic blood pressure, and reduced platelet count or serum albumin at baseline. The risk of ICH was significantly lower in patients with heart failure and in those who were randomized to rivaroxaban instead of warfarin. The external validity of these findings requires testing in other atrial fibrillation populations.

WE-EF-207-03: Design and Optimization of a CBCT Head Scanner for Detection of Acute Intracranial Hemorrhage

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xu, J; Sisniega, A; Zbijewski, W

Purpose: To design a dedicated x-ray cone-beam CT (CBCT) system suitable to deployment at the point-of-care and offering reliable detection of acute intracranial hemorrhage (ICH), traumatic brain injury (TBI), stroke, and other head and neck injuries. Methods: A comprehensive task-based image quality model was developed to guide system design and optimization of a prototype head scanner suitable to imaging of acute TBI and ICH. Previously reported models were expanded to include the effects of x-ray scatter correction necessary for detection of low contrast ICH and the contribution of bit depth (digitization noise) to imaging performance. Task-based detectablity index provided themore » objective function for optimization of system geometry, x-ray source, detector type, anti-scatter grid, and technique at 10–25 mGy dose. Optimal characteristics were experimentally validated using a custom head phantom with 50 HU contrast ICH inserts imaged on a CBCT imaging bench allowing variation of system geometry, focal spot size, detector, grid selection, and x-ray technique. Results: The model guided selection of system geometry with a nominal source-detector distance 1100 mm and optimal magnification of 1.50. Focal spot size ∼0.6 mm was sufficient for spatial resolution requirements in ICH detection. Imaging at 90 kVp yielded the best tradeoff between noise and contrast. The model provided quantitation of tradeoffs between flat-panel and CMOS detectors with respect to electronic noise, field of view, and readout speed required for imaging of ICH. An anti-scatter grid was shown to provide modest benefit in conjunction with post-acquisition scatter correction. Images of the head phantom demonstrate visualization of millimeter-scale simulated ICH. Conclusions: Performance consistent with acute TBI and ICH detection is feasible with model-based system design and robust artifact correction in a dedicated head CBCT system. Further improvements can be achieved with

The acute management of intracerebral hemorrhage: a clinical review.

PubMed

Elliott, Justine; Smith, Martin

2010-05-01

Intracerebral hemorrhage (ICH) is a devastating disease with high rates of mortality and morbidity. The major risk factors for ICH include chronic arterial hypertension and oral anticoagulation. After the initial hemorrhage, hematoma expansion and perihematoma edema result in secondary brain damage and worsened outcome. A rapid onset of focal neurological deficit with clinical signs of increased intracranial pressure is strongly suggestive of a diagnosis of ICH, although cranial imaging is required to differentiate it from ischemic stroke. ICH is a medical emergency and initial management should focus on urgent stabilization of cardiorespiratory variables and treatment of intracranial complications. More than 90% of patients present with acute hypertension, and there is some evidence that acute arterial blood pressure reduction is safe and associated with slowed hematoma growth and reduced risk of early neurological deterioration. However, early optimism that outcome might be improved by the early administration of recombinant factor VIIa (rFVIIa) has not been substantiated by a large phase III study. ICH is the most feared complication of warfarin anticoagulation, and the need to arrest intracranial bleeding outweighs all other considerations. Treatment options for warfarin reversal include vitamin K, fresh frozen plasma, prothrombin complex concentrates, and rFVIIa. There is no evidence to guide the specific management of antiplatelet therapy-related ICH. With the exceptions of placement of a ventricular drain in patients with hydrocephalus and evacuation of a large posterior fossa hematoma, the timing and nature of other neurosurgical interventions is also controversial. There is substantial evidence that management of patients with ICH in a specialist neurointensive care unit, where treatment is directed toward monitoring and managing cardiorespiratory variables and intracranial pressure, is associated with improved outcomes. Attention must be given to fluid

Serum creatinine may indicate risk of symptomatic intracranial hemorrhage after intravenous tissue plasminogen activator (IV tPA).

PubMed

Marsh, Elisabeth B; Gottesman, Rebecca F; Hillis, Argye E; Urrutia, Victor C; Llinas, Rafael H

2013-11-01

Symptomatic intracranial hemorrhage (sICH) is a known complication following administration of intravenous tissue plasminogen activator (IV tPA) for acute ischemic stroke. sICH results in high rates of death or long-term disability. Our ability to predict its occurrence is important in clinical decision making and when counseling families. The initial National Institute of Neurological Disorders and Stroke (NINDS) investigators developed a list of relative contraindications to IV tPA meant to decrease the risk of subsequent sICH. To date, the impact of renal impairment has not been well studied. In the current study we evaluate the potential association between renal impairment and post-tPA intracranial hemorrhage (ICH). Admission serum creatinine and estimated glomerular filtration rate (eGFR) were recorded in 224 patients presenting within 4.5 hours from symptom onset and treated with IV tPA based on NINDS criteria. Neuroimaging was obtained 1 day post-tPA and for any change in neurologic status to evaluate for ICH. Images were retrospectively evaluated for hemorrhage by a board-certified neuroradiologist and 2 reviewers blinded to the patient's neurologic status. Medical records were reviewed retrospectively for evidence of neurologic decline indicating a "symptomatic" hemorrhage. sICH was defined as subjective clinical deterioration (documented by the primary neurology team) and hemorrhage on neuroimaging that was felt to be the most likely cause. Renal impairment was evaluated using both serum creatinine and eGFR in a number of ways: 1) continuous creatinine; 2) any renal impairment by creatinine (serum creatinine >1.0 mg/dL); 3) continuous eGFR; and 4) any renal impairment by eGFR (eGFR <60 mL/min per 1.73 m²). Student paired t tests, Fisher exact tests, and multivariable logistic regression (adjusted for demographics and vascular risk factors) were used to evaluate the relationship between renal impairment and ICH. Fifty-seven (25%) of the 224 patients had

Serum Creatinine May Indicate Risk of Symptomatic Intracranial Hemorrhage After Intravenous Tissue Plasminogen Activator (IV tPA)

PubMed Central

Marsh, Elisabeth B.; Gottesman, Rebecca F.; Hillis, Argye E.; Urrutia, Victor C.

2013-01-01

Abstract Symptomatic intracranial hemorrhage (sICH) is a known complication following administration of intravenous tissue plasminogen activator (IV tPA) for acute ischemic stroke. sICH results in high rates of death or long-term disability. Our ability to predict its occurrence is important in clinical decision making and when counseling families. The initial National Institute of Neurological Disorders and Stroke (NINDS) investigators developed a list of relative contraindications to IV tPA meant to decrease the risk of subsequent sICH. To date, the impact of renal impairment has not been well studied. In the current study we evaluate the potential association between renal impairment and post-tPA intracranial hemorrhage (ICH). Admission serum creatinine and estimated glomerular filtration rate (eGFR) were recorded in 224 patients presenting within 4.5 hours from symptom onset and treated with IV tPA based on NINDS criteria. Neuroimaging was obtained 1 day post-tPA and for any change in neurologic status to evaluate for ICH. Images were retrospectively evaluated for hemorrhage by a board-certified neuroradiologist and 2 reviewers blinded to the patient’s neurologic status. Medical records were reviewed retrospectively for evidence of neurologic decline indicating a “symptomatic” hemorrhage. sICH was defined as subjective clinical deterioration (documented by the primary neurology team) and hemorrhage on neuroimaging that was felt to be the most likely cause. Renal impairment was evaluated using both serum creatinine and eGFR in a number of ways: 1) continuous creatinine; 2) any renal impairment by creatinine (serum creatinine >1.0 mg/dL); 3) continuous eGFR; and 4) any renal impairment by eGFR (eGFR <60 mL/min per 1.73 m2). Student paired t tests, Fisher exact tests, and multivariable logistic regression (adjusted for demographics and vascular risk factors) were used to evaluate the relationship between renal impairment and ICH. Fifty-seven (25%) of the 224

Designated Stroke Center Status and Hospital Characteristics as Predictors of In-Hospital Mortality among Hemorrhagic Stroke Patients in New York, 2008-2012.

PubMed

Gatollari, Hajere J; Colello, Anna; Eisenberg, Bonnie; Brissette, Ian; Luna, Jorge; Elkind, Mitchell S V; Willey, Joshua Z

2017-01-01

Although designated stroke centers (DSCs) improve the quality of care and clinical outcomes for ischemic stroke patients, less is known about the benefits of DSCs for patients with intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH). Compared to non-DSCs, hospitals with the DSC status have lower in-hospital mortality rates for hemorrhagic stroke patients. We believed these effects would sustain over a period of time after adjusting for hospital-level characteristics, including hospital size, urban location, and teaching status. We evaluated ICH (International Classification of Diseases, Ninth Revision; ICD-9: 431) and SAH (ICD-9: 430) hospitalizations documented in the 2008-2012 New York State Department of Health Statewide Planning and Research Cooperative System inpatient sample database. Generalized estimating equation logistic regression was used to evaluate the association between DSC status and in-hospital mortality. We calculated ORs and 95% CIs adjusted for clustering of patients within facilities, other hospital characteristics, and individual level characteristics. Planned secondary analyses explored other hospital characteristics associated with in-hospital mortality. In 6,352 ICH and 3,369 SAH patients in the study sample, in-hospital mortality was higher among those with ICH compared to SAH (23.7 vs. 18.5%). Unadjusted analyses revealed that DSC status was related with reduced mortality for both ICH (OR 0.7, 95% CI 0.5-0.8) and SAH patients (OR 0.4, 95% CI 0.3-0.7). DSC remained a significant predictor of lower in-hospital mortality for SAH patients (OR 0.6, 95% CI 0.3-0.9) but not for ICH patients (OR 0.8, 95% CI 0.6-1.0) after adjusting for patient demographic characteristics, comorbidities, hospital size, teaching status and location. Admission to a DSC was independently associated with reduced in-hospital mortality for SAH patients but not for those with ICH. Other patient and hospital characteristics may explain the benefits of DSC

Resource Utilization for Patients with Intracerebral Hemorrhage Transferred to a Comprehensive Stroke Center.

PubMed

Nguyen, Claude; Mir, Osman; Vahidy, Farhaan; Wu, Tzu-Ching; Albright, Karen; Boehme, Amelia; Delgado, Rigoberto; Savitz, Sean

2015-12-01

As a comprehensive stroke center (CSC), we accept transfer patients with intracerebral hemorrhage (ICH) in our region. CSC guidelines mandate receipt of patients with ICH for higher level of care. We determined resource utilization of patients accepted from outside hospitals compared with patients directly arriving to our center. From our stroke registry, we compared patients with primary ICH transferred to those directly arriving to our CSC from March 2011-March 2012. We compared the proportion of patients who utilized at least one of these resources: neurointensive care unit (NICU), neurosurgical intervention, or clinical trial enrollment. Among the 362 patients, 210 (58%) were transfers. Transferred patients were older, had higher median Glasgow Coma Scale scores, and lower National Institutes of Health Stroke Scale scores than directly admitted patients. Transfers had smaller median ICH volumes (20.5 cc versus 15.2 cc; P = .04) and lower ICH scores (2.1 ± 1.4 versus 1.6 ± 1.3; P < .01). A smaller proportion of transfers utilized CSC-specific resources compared with direct admits (P = .02). Fewer transferred patients required neurosurgical intervention or were enrolled in trials. No significant difference was found in the proportion of patients who used NICU resources, although transferred patients had a significantly lower length of stay in the NICU. Average hospital stay costs were less for transferred patients than for direct admits. Patients with ICH transferred to our CSC underwent fewer neurosurgical procedures and had a shorter stay in the NICU. These results were reflected in the lower per-patient costs in the transferred group. Our results raise the need to analyze cost-benefits and resource utilization of transferring patients with milder ICH. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Brain microbleeds, anticoagulation, and hemorrhage risk: Meta-analysis in stroke patients with AF.

PubMed

Charidimou, Andreas; Karayiannis, Christopher; Song, Tae-Jin; Orken, Dilek Necioglu; Thijs, Vincent; Lemmens, Robin; Kim, Jinkwon; Goh, Su Mei; Phan, Thanh G; Soufan, Cathy; Chandra, Ronil V; Slater, Lee-Anne; Haji, Shamir; Mok, Vincent; Horstmann, Solveig; Leung, Kam Tat; Kawamura, Yuichiro; Sato, Nobuyuki; Hasebe, Naoyuki; Saito, Tsukasa; Wong, Lawrence K S; Soo, Yannie; Veltkamp, Roland; Flemming, Kelly D; Imaizumi, Toshio; Srikanth, Velandai; Heo, Ji Hoe

2017-12-05

To assess the association between cerebral microbleeds (CMBs) and future spontaneous intracerebral hemorrhage (ICH) risk in ischemic stroke patients with nonvalvular atrial fibrillation (AF) taking oral anticoagulants. This was a meta-analysis of cohort studies with >50 patients with recent ischemic stroke and documented AF, brain MRI at baseline, long-term oral anticoagulation treatment, and ≥6 months of follow-up. Authors provided summary-level data on stroke outcomes stratified by CMB status. We estimated pooled annualized ICH and ischemic stroke rates from Poisson regression. We calculated odds ratios (ORs) of ICH by CMB presence/absence, ≥5 CMBs, and CMB topography (strictly lobar, mixed, and strictly deep) using random-effects models. We established an international collaboration and pooled data from 8 centers including 1,552 patients. The crude CMB prevalence was 30% and 7% for ≥5 CMBs. Baseline CMB presence (vs no CMB) was associated with ICH during follow-up (OR 2.68, 95% confidence interval [CI] 1.19-6.01, p = 0.017). Presence of ≥5 CMB was related to higher future ICH risk (OR 5.50, 95% CI 2.07-14.66, p = 0.001). The pooled annual ICH incidence increased from 0.30% (95% CI 0.04-0.55) among CMB-negative patients to 0.81% (95% CI 0.17-1.45) in CMB-positive patients ( p = 0.01) and 2.48% (95% CI 1.2-6.2) in patients with ≥5 CMBs ( p = 0.001). There was no association between CMBs and recurrent ischemic stroke. The presence of CMB on MRI and the dichotomized cutoff of ≥5 CMBs might identify subgroups of ischemic stroke patients with AF with high ICH risk and after further validation could help in risk stratification, in anticoagulation decisions, and in guiding randomized trials and ongoing large observational studies. © 2017 American Academy of Neurology.

Early increase of neutrophil-to-lymphocyte ratio predicts 30-day mortality in patients with spontaneous intracerebral hemorrhage.

PubMed

Wang, Fei; Xu, Feng; Quan, Ye; Wang, Li; Xia, Jian-Jun; Jiang, Ting-Ting; Shen, Li-Juan; Kang, Wen-Hui; Ding, Yong; Mei, Li-Xia; Ju, Xue-Feng; Hu, Shan-You; Wu, Xiao

2018-05-16

To examine whether early rise of neutrophil-to-lymphocyte ratio (NLR) after patient hospitalization correlates with 30-day mortality in patients with spontaneous intracerebral hemorrhage (ICH). This retrospective study included all patients receiving treatment for spontaneous ICH between January 2015 and September 2016 at the Jiading District Central Hospital Affiliated Shanghai University of Medicine & Health Sciences in Shanghai, China. NLR was determined at admission (T1), at 24-48 hours (T2) and 5-7 days (T3). NLR and clinicopathologic features were compared between those who survived for >30 days vs not. Multivariate regression was used to identify risk factors for 30-day mortality. A total of 275 subjects were included in the analysis: 235 survived for at least 30 days; the remaining 40 subjects died within 30 days. The patients who died within 30 days had higher ICH score, larger ICH volume, and lower GCS score (all P < 0.05). In comparison with the baseline (NLR T 1 ), NLR at 24-48 hours (NLR T 2 ) and 5-7 days (NLR T 3 ) was significantly higher in patients who died within 30 days (P < 0.05), but not in patients surviving for >30 days. In the multivariate analysis, the 30-day mortality was associated with both NLR T 2 (OR 1.112, 95%CI 1.032-1.199, P = 0.006) and NLR T 3 (OR 1.163, 95%CI 1.067-1.268, P = 0.001). Spearman correlation analysis showed that both NLR T 2 and NLR T 3 correlated inversely with GCS score and positively with ICH score and ICH volume at the baseline. Early rise of NLR predicts 30-day mortality in patients with spontaneous ICH. © 2018 The Authors. CNS Neuroscience & Therapeutics Published by John Wiley & Sons Ltd.

Different utilization of intensive care services (ICSs) for patients dying of hemorrhagic and ischemic stroke, a hospital-based survey.

PubMed

Wang, Vinchi; Hsieh, Chieh-Chao; Huang, Yen-Ling; Chen, Chia-Ping; Hsieh, Yi-Ting; Chao, Tzu-Hao

2018-02-01

The intensive care service (ICS) saves lives and rescues the neurological function of stroke patients. We wondered the different utilization of ICS for patients with ischemic and hemorrhagic stroke, especially those who died within 30 days after stroke.Sixty-seven patients died during 2011 to 2015 due to acute stroke (42 due to intracranial hemorrhage [ICH]; 25 due to cerebral infarct [CI]). The durations of hospital stay (hospital staying days [HSDs]) and ICS staying days (ISDs) and codes of the do-not-resuscitate (DNR) were surveyed among these medical records. Statistics included chi-square and descriptive analyses.In this study, CI patients had a longer HSD (mean 14.3 days), as compared with ICH patients (mean 8.3 days); however, the ICH patients had a higher percentage of early entry within the first 24 hours of admission into ICS than CI group (95.1% vs 60.0%, P = .003). A higher rate of CI patients died in holidays or weekends than those with ICH (44.0% vs 21.4%, P = .051). DNR, requested mainly from direct descendants (children or grandchildren), was coded in all 25 CI patients (100.0%) and 38 ICH patients (90.5%). More cases with early DNR coded within 24 hours after admission occurred in ICH group (47%, 12% in CI patients, P = .003). None of the stroke patient had living wills. Withhold of endotracheal intubation (ETI) occurred among CI patients, more than for ICH patients (76.0% vs 18.4%, P < .005).In conclusion, CI patients longer HSD, ISD, higher mortality within holidays or weekends, and higher ETI withhold; but less percentage of ICS utilization expressed by a lower ISD/HSD ratio. This ICS utilization is a key issue of medical quality for stroke care.

Intranasal delivery of hypoxia-preconditioned bone marrow-derived mesenchymal stem cells enhanced regenerative effects after intracerebral hemorrhagic stroke in mice.

PubMed

Sun, Jinmei; Wei, Zheng Zachory; Gu, Xiaohuan; Zhang, James Ya; Zhang, Yongbo; Li, Jimei; Wei, Ling

2015-10-01

Intracerebral hemorrhagic stroke (ICH) causes high mortality and morbidity with very limited treatment options. Cell-based therapy has emerged as a novel approach to replace damaged brain tissues and promote regenerative processes. In this study we tested the hypothesis that intranasally delivered hypoxia-preconditioned BMSCs could reach the brain, promote tissue repair and improve functional recovery after ICH. Hemorrhagic stroke was induced in adult C57/B6 mice by injection of collagenase IV into the striatum. Animals were randomly divided into three groups: sham group, intranasal BMSC treatment group, and vehicle treatment group. BMSCs were pre-treated with hypoxic preconditioning (HP) and pre-labeled with Hoechst before transplantation. Behavior tests, including the mNSS score, rotarod test, adhesive removal test, and locomotor function evaluation were performed at varying days, up to 21days, after ICH to evaluate the therapeutic effects of BMSC transplantation. Western blots and immunohistochemistry were performed to analyze the neurotrophic effects. Intranasally delivered HP-BMSCs were identified in peri-injury regions. NeuN+/BrdU+ co-labeled cells were markedly increased around the hematoma region, and growth factors, including BDNF, GDNF, and VEGF were significantly upregulated in the ICH brain after BMSC treatment. The BMSC treatment group showed significant improvement in behavioral performance compared with the vehicle group. Our data also showed that intranasally delivered HP-BMSCs migrated to peri-injury regions and provided growth factors to increase neurogenesis after ICH. We conclude that intranasal administration of BMSC is an effective treatment for ICH, and that it enhanced neuroregenerative effects and promoted neurological functional recovery after ICH. Overall, the investigation supports the potential therapeutic strategy for BMSC transplantation therapy against hemorrhagic stroke. Copyright © 2015 Elsevier Inc. All rights reserved.

Minocycline attenuates brain injury and iron overload after intracerebral hemorrhage in aged female rats.

PubMed

Dai, Shuhui; Hua, Ya; Keep, Richard F; Novakovic, Nemanja; Fei, Zhou; Xi, Guohua

2018-06-05

Brain iron overload is involved in brain injury after intracerebral hemorrhage (ICH). There is evidence that systemic administration of minocycline reduces brain iron level and improves neurological outcome in experimental models of hemorrhagic and ischemic stroke. However, there is evidence in cerebral ischemia that minocycline is not protective in aged female animals. Since most ICH research has used male models, this study was designed to provide an overall view of ICH-induced iron deposits at different time points (1 to 28 days) in aged (18-month old) female Fischer 344 rat ICH model and to investigate the neuroprotective effects of minocycline in those rats. According to our previous studies, we used the following dosing regimen (20 mg/kg, i.p. at 2 and 12 h after ICH onset followed by 10 mg/kg, i.p., twice a day up to 7 days). T2-, T2 ⁎ -weighted and T2 ⁎ array MRI was performed at 1, 3, 7 and 28 days to measure brain iron content, ventricle volume, lesion volume and brain swelling. Immunohistochemistry was used to examine changes in iron handling proteins, neuronal loss and microglial activation. Behavioral testing was used to assess neurological deficits. In aged female rats, ICH induced long-term perihematomal iron overload with upregulated iron handling proteins, neuroinflammation, brain atrophy, neuronal loss and neurological deficits. Minocycline significantly reduced ICH-induced perihematomal iron overload and iron handling proteins. It further reduced brain swelling, neuroinflammation, neuronal loss, delayed brain atrophy and neurological deficits. These effects may be linked to the role of minocycline as an iron chelator as well as an inhibitor of neuroinflammation. Copyright © 2018 Elsevier Inc. All rights reserved.

5-HT1a activation in PO/AH area induces therapeutic hypothermia in a rat model of intracerebral hemorrhage

PubMed Central

Liang, Tan; Chen, Qianwei; Li, Qiang; Li, Rongwei; Tang, Jun; Hu, Rong; Zhong, Jun; Ge, Hongfei; Liu, Xin; Hua, Feng

2017-01-01

Therapeutic hypothermia is widely applied as a neuroprotective measure on intracerebral hemorrhage (ICH). However, several clinical trials regarding physical hypothermia encountered successive failures because of its side-effects in recent years. Increasing evidences indicate that chemical hypothermia that targets hypothalamic 5-HT1a has potential to down-regulate temperature set point without major side-effects. Thus, this study examined the efficacy and safety of 5-HT1a stimulation in PO/AH area for treating ICH rats. First, the relationship between head temperature and clinical outcomes was investigated in ICH patients and rat models, respectively. Second, the expression and distribution of 5-HT1a receptor in PO/AH area was explored by using whole-cell patch and confocal microscopy. In the meantime, the whole-cell patch was subsequently applied to investigate the involvement of 5-HT1a receptors in temperature regulation. Third, we compared the efficacy between traditional PH and 5-HT1a activation-induced hypothermia for ICH rats. Our data showed that more severe perihematomal edema (PHE) and neurological deficits was associated with increased head temperature following ICH. 5-HT1a receptor was located on warm-sensitive neurons in PO/AH area and 8-OH-DPAT (5-HT1a receptor agonist) significantly enhanced the firing rate of warm-sensitive neurons. 8-OH-DPAT treatment provided a steadier reduction in brain temperature without a withdrawal rebound, which also exhibited a superior neuroprotective effect on ICH-induced neurological dysfunction, white matter injury and BBB damage compared with physical hypothermia. These findings suggest that chemical hypothermia targeting 5-HT1a receptor in PO/AH area could act as a novel therapeutic manner against ICH, which may provide a breakthrough for therapeutic hypothermia. PMID:29088731

Effectiveness and Safety of Non-Vitamin K Antagonist Oral Anticoagulants in Asian Patients With Atrial Fibrillation.

PubMed

Cha, Myung-Jin; Choi, Eue-Keun; Han, Kyung-Do; Lee, So-Ryoung; Lim, Woo-Hyun; Oh, Seil; Lip, Gregory Y H

2017-11-01

There are limited real-world data comparing the effectiveness and safety of non-vitamin K antagonist oral anticoagulants (NOACs) and warfarin in Asians with nonvalvular atrial fibrillation. We aimed to compare the effectiveness and safety between NOACs and warfarin users in the Korean atrial fibrillation population, with particular focus on high-risk patients. Using the Korean National Health Insurance Service database, we analyzed the risk of ischemic stroke, intracranial hemorrhage (ICH) events, and all-cause death in NOAC users (n=11 611 total, n=5681 taking rivaroxaban, n=3741 taking dabigatran, and n=2189 taking apixaban) compared with propensity score-matched warfarin users (n=23 222) among patients with high-risk atrial fibrillation (CHA 2 DS 2 -VASc score ≥2) between 2014 and 2015. NOAC treatment was associated with similar risk of ischemic stroke and lower risk of ICH and all-cause mortality compared with warfarin. All 3 NOACs were associated with a similar risk of ischemic stroke and a lower risk of ICH compared with warfarin. Dabigatran and apixaban were associated with a lower risk of total mortality and the composite net clinical outcome (ischemic stroke, ICH, and all-cause death) compared with warfarin, whereas this was nonsignificant for rivaroxaban. Among previously oral anticoagulant-naive patients (n=23 262), dabigatran and apixaban were superior to warfarin for ICH prevention, whereas rivaroxaban and warfarin were associated with similar risk of ICH. In real-world practice among a high-risk Asian atrial fibrillation population, all 3 NOACs demonstrated similar risk of ischemic stroke and lower risk of ICH compared with warfarin. All-cause mortality was significantly lower only with dabigatran and apixaban. © 2017 American Heart Association, Inc.

Quantitative parameters of CT texture analysis as potential markersfor early prediction of spontaneous intracranial hemorrhage enlargement.

PubMed

Shen, Qijun; Shan, Yanna; Hu, Zhengyu; Chen, Wenhui; Yang, Bing; Han, Jing; Huang, Yanfang; Xu, Wen; Feng, Zhan

2018-04-30

To objectively quantify intracranial hematoma (ICH) enlargement by analysing the image texture of head CT scans and to provide objective and quantitative imaging parameters for predicting early hematoma enlargement. We retrospectively studied 108 ICH patients with baseline non-contrast computed tomography (NCCT) and 24-h follow-up CT available. Image data were assessed by a chief radiologist and a resident radiologist. Consistency analysis between observers was tested. The patients were divided into training set (75%) and validation set (25%) by stratified sampling. Patients in the training set were dichotomized according to 24-h hematoma expansion ≥ 33%. Using the Laplacian of Gaussian bandpass filter, we chose different anatomical spatial domains ranging from fine texture to coarse texture to obtain a series of derived parameters (mean grayscale intensity, variance, uniformity) in order to quantify and evaluate all data. The parameters were externally validated on validation set. Significant differences were found between the two groups of patients within variance at V 1.0 and in uniformity at U 1.0 , U 1.8 and U 2.5 . The intraclass correlation coefficients for the texture parameters were between 0.67 and 0.99. The area under the ROC curve between the two groups of ICH cases was between 0.77 and 0.92. The accuracy of validation set by CTTA was 0.59-0.85. NCCT texture analysis can objectively quantify the heterogeneity of ICH and independently predict early hematoma enlargement. • Heterogeneity is helpful in predicting ICH enlargement. • CTTA could play an important role in predicting early ICH enlargement. • After filtering, fine texture had the best diagnostic performance. • The histogram-based uniformity parameters can independently predict ICH enlargement. • CTTA is more objective, more comprehensive, more independently operable, than previous methods.

Serum cholesterol levels, HMG-CoA reductase inhibitors and the risk of intracerebral haemorrhage. The Multicenter Study on Cerebral Haemorrhage in Italy (MUCH-Italy).

PubMed

Pezzini, Alessandro; Grassi, Mario; Iacoviello, Licia; Zedde, Marialuisa; Marcheselli, Simona; Silvestrelli, Giorgio; DeLodovici, Maria Luisa; Sessa, Maria; Zini, Andrea; Paciaroni, Maurizio; Azzini, Cristiano; Gamba, Massimo; Del Sette, Massimo; Toriello, Antonella; Gandolfo, Carlo; Bonifati, Domenico Marco; Tassi, Rossana; Cavallini, Anna; Chiti, Alberto; Calabrò, Rocco Salvatore; Musolino, Rossella; Bovi, Paolo; Tomelleri, Giampaolo; Di Castelnuovo, Augusto; Vandelli, Laura; Ritelli, Marco; Agnelli, Giancarlo; De Vito, Alessandro; Pugliese, Nicola; Martini, Giuseppe; Lanari, Alessia; Ciccone, Alfonso; Lodigiani, Corrado; Malferrari, Giovanni; Del Zotto, Elisabetta; Morotti, Andrea; Costa, Paolo; Poli, Loris; De Giuli, Valeria; Bonaiti, Silvia; La Spina, Paolo; Marcello, Norina; Micieli, Giuseppe; de Gaetano, Giovanni; Colombi, Marina; Padovani, Alessandro

2016-09-01

Although a concern exists that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) might increase the risk of intracerebral haemorrhage (ICH), the contribution of these agents to the relationship between serum cholesterol and disease occurrence has been poorly investigated. We compared consecutive patients having ICH with age and sex-matched stroke-free control subjects in a case-control analysis, as part of the Multicenter Study on Cerebral Haemorrhage in Italy (MUCH-Italy), and tested the presence of interaction effects between total serum cholesterol levels and statins on the risk of ICH. A total of 3492 cases (mean age, 73.0±12.7 years; males, 56.6%) and 3492 control subjects were enrolled. Increasing total serum cholesterol levels were confirmed to be inversely associated with ICH. We observed a statistical interaction between total serum cholesterol levels and statin use for the risk of haemorrhage (Interaction OR (IOR), 1.09; 95% CI 1.05 to 1.12). Increasing levels of total serum cholesterol were associated with a decreased risk of ICH within statin strata (average OR, 0.87; 95% CI 0.86 to 0.88 for every increase of 0.26 mmol/l of total serum cholesterol concentrations), while statin use was associated with an increased risk (OR, 1.54; 95% CI 1.31 to 1.81 of the average level of total serum cholesterol). The protective effect of serum cholesterol against ICH was reduced by statins in strictly lobar brain regions more than in non-lobar ones. Statin therapy and total serum cholesterol levels exhibit interaction effects towards the risk of ICH. The magnitude of such effects appears higher in lobar brain regions. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Poorer cardiovascular health is associated with psychiatric comorbidity: results from the ELSA-Brasil Study.

PubMed

Szlejf, Claudia; Suemoto, Claudia K; Santos, Itamar S; Brunoni, Andre R; Nunes, Maria Angélica; Viana, Maria Carmen; Barreto, Sandhi Maria; Lotufo, Paulo A; Benseñor, Isabela M

2018-06-12

Common psychiatric symptoms may hinder achieving ideal cardiovascular health (ICH). We aimed to investigate the association between the ICH score and psychiatric disorders in Brazilian adults. In this cross-sectional analysis, 13,743 participants free of cardiovascular disease from the ELSA-Brasil study were assessed using the American Heart Association ICH score. Cardiovascular health was classified as poor (0-2 ideal metrics), intermediate (3-4 ideal metrics), and optimal (5-7 ideal metrics). We used the Clinical Interview Scheduled Revised (CIS-R) to assess psychiatric disorders and investigate their association with the ICH score and each non-ICH metric. The frequency of poor, intermediate, and optimal cardiovascular health were 54.1%, 38.1%, and 7.8%, respectively. Depressive and anxiety disorders were associated with poor cardiovascular health (depressive disorder: OR = 2.49, 95% CI = 1.62-3.80, p < 0.001; anxiety disorder: OR = 1.47, 95% CI = 1.22-1.78, p < 0.001), and intermediate cardiovascular health (depressive disorder: OR = 1.94, 95% CI = 1.26-2.98, p = 0.002; anxiety disorder: OR = 1.22, 95% CI = 1.01-1.47, p = 0.043). In the analysis stratified by sex, these associations were significant only among women. The disorders were also associated with the following non-ICH metrics: body mass index, physical activity, healthy diet score, and smoking. Participants with depressive disorder and anxiety disorder had expected lower global and lifestyle ICH score than participants without these conditions, with significant results among women in the stratified analysis. Psychiatric comorbidity was associated with poorer cardiovascular health. These conditions may compromise the adoption of healthy cardiovascular risk reduction behaviors. Copyright © 2017. Published by Elsevier B.V.

Electroacupuncture Exerts Neuroprotection through Caveolin-1 Mediated Molecular Pathway in Intracerebral Hemorrhage of Rats.

PubMed

Li, Hui-Qin; Li, Yan; Chen, Zi-Xian; Zhang, Xiao-Guang; Zheng, Xia-Wei; Yang, Wen-Ting; Chen, Shuang; Zheng, Guo-Qing

2016-01-01

Spontaneous intracerebral hemorrhage (ICH) is one of the most devastating types of stroke. Here, we aim to demonstrate that electroacupuncture on Baihui (GV20) exerts neuroprotection for acute ICH possibly via the caveolin-1/matrix metalloproteinase/blood-brain barrier permeability pathway. The model of ICH was established by using collagenase VII. Rats were randomly divided into three groups: Sham-operation group, Sham electroacupuncture group, and electroacupuncture group. Each group was further divided into 4 subgroups according to the time points of 6 h, 1 d, 3 d, and 7 d after ICH. The methods were used including examination of neurological deficit scores according to Longa's scale, measurement of blood-brain barrier permeability through Evans Blue content, in situ immunofluorescent detection of caveolin-1 in brains, western blot analysis of caveolin-1 in brains, and in situ zymography for measuring matrix metalloproteinase-2/9 activity in brains. Compared with Sham electroacupuncture group, electroacupuncture group has resulted in a significant improvement in neurological deficit scores and in a reduction in Evans Blue content, expression of caveolin-1, and activity of matrix metalloproteinase-2/9 at 6 h, 1 d, 3 d, and 7 d after ICH ( P < 0.05). In conclusion, the present results suggested that electroacupuncture on GV20 can improve neurological deficit scores and reduce blood-brain barrier permeability after ICH, and the mechanism possibly targets caveolin-1/matrix metalloproteinase/blood-brain barrier permeability pathway.

Clinical experience with three-factor prothrombin complex concentrate to reverse warfarin anticoagulation in intracranial hemorrhage.

PubMed

Switzer, Jeffrey A; Rocker, Jody; Mohorn, Phillip; Waller, Jennifer L; Hughes, Douglas; Bruno, Askiel; Nichols, Fenwick T; Hess, David C; Natarajan, Kavita; Fagan, Susan C

2012-09-01

The effectiveness of prothrombin complex concentrate (PCC) products available in the United States that contain low levels of factor VII (3-factor PCC) has not been tested. The purpose of this study was to review our experience with 3-factor PCC (Profilnine) in the setting of warfarin-associated intracranial hemorrhage (wICH). In November 2007, we implemented a protocol for reversal of anticoagulation in wICH using Profilnine. Additional treatment with fresh-frozen plasma was at the discretion of the treating physician. Medical records of all patients receiving PCC for wICH between November 1, 2007, and December 7, 2011 were reviewed. Correction of the international normalized rate (INR) was defined as an INR <1.4. Seventy wICH patients were treated with Profilnine, including 46 (66%) with intraparenchymal hemorrhage, 22 (31%) with subdural hemorrhage, and 2 (3%) with subarachnoid hemorrhage. Mean INR was reduced from 3.36 to 1.96, and in 44 (62.9%) patients the INR corrected to <1.4. Baseline INR ≥3.0 decreased the likelihood of INR correction. Concomitant administration of fresh-frozen plasma (mean, 2.6 U) did not increase the likelihood of INR correction. Seven (10%) patients had serious adverse events during their hospital course, including 2 sudden deaths from suspected pulmonary embolism. Reversal of coagulopathy in wICH with Profilnine was incomplete and associated with serious adverse events. In the absence of available 4-factor PCC, options for urgent reversal of anticoagulation in wICH remain limited.

The pros and cons about the digital recording of Intangible Cultural Heritage and some strategies

NASA Astrophysics Data System (ADS)

Yang, H.

2015-08-01

Intangible Cultural Heritage (referred to as ICH), whose fundamental nature different from the tangible cultural heritage is "Intangible", and the related physical presence of the heritage is not the core content. Digital means have irreplaceable advantages in recording intangible and dynamic ICH resources, while it also needs flexible and rigorous recording means as a support, thus striving to maximize resources recording and protection. This article will focus on the pros and cons about the digital recording of ICH, and preliminarily discuss some strategies used in the process of recording.

"In Mathe war ich immer schlecht"

NASA Astrophysics Data System (ADS)

Beutelspacher, Albrecht

Genauso wie bei vielen anderen Er scheinungsformen des Lebens (Philosophie, Musik, Liebe) kann Mathematik nicht eindeutig definiert werden. Jede Definition wäre entweder nichtssagend oder zu einengend. Man kann aber versuchen, Mathematik von verschiedenen Seiten zu beleuchten. Dabei offenbaren sich überraschende und tiefe Einblicke in das Wesen der Mathematik.

Developing the Clarity and Openness in Reporting: E3-based (CORE) Reference user manual for creation of clinical study reports in the era of clinical trial transparency.

PubMed

Hamilton, Samina; Bernstein, Aaron B; Blakey, Graham; Fagan, Vivien; Farrow, Tracy; Jordan, Debbie; Seiler, Walther; Shannon, Anna; Gertel, Art

2016-01-01

Interventional clinical studies conducted in the regulated drug research environment are reported using International Council for Harmonisation (ICH) regulatory guidance documents: ICH E3 on the structure and content of clinical study reports (CSRs) published in 1995 and ICH E3 supplementary Questions & Answers (Q & A) published in 2012.Since the ICH guidance documents were published, there has been heightened awareness of the importance of disclosure of clinical study results. The use of the CSR as a key source document to fulfil emerging obligations has resulted in a re-examination of how ICH guidelines are applied in CSR preparation. The dynamic regulatory and modern drug development environments create emerging reporting challenges. Regulatory medical writing and statistical professionals developed Clarity and Openness in Reporting: E3-based (CORE) Reference over a 2-year period. Stakeholders contributing expertise included a global industry association, regulatory agency, patient advocate, academic and Principal Investigator representatives. CORE Reference should help authors navigate relevant guidelines as they create CSR content relevant for today's studies. It offers practical suggestions for developing CSRs that will require minimum redaction and modification prior to public disclosure.CORE Reference comprises a Preface, followed by the actual resource. The Preface clarifies intended use and underlying principles that inform resource utility. The Preface lists references contributing to development of the resource, which broadly fall into 'regulatory' and 'public disclosure' categories. The resource includes ICH E3 guidance text, ICH E3 Q & A 2012-derived guidance text and CORE Reference text, distinguished from one another through the use of shading. Rationale comments are used throughout for clarification purposes.A separate mapping tool comparing ICH E3 sectional structure and CORE Reference sectional structure is also provided.Together, CORE Reference

Association of prothrombin complex concentrate administration and hematoma enlargement in non-vitamin K antagonist oral anticoagulant-related intracerebral hemorrhage.

PubMed

Gerner, Stefan T; Kuramatsu, Joji B; Sembill, Jochen A; Sprügel, Maximilian I; Endres, Matthias; Haeusler, Karl Georg; Vajkoczy, Peter; Ringleb, Peter A; Purrucker, Jan; Rizos, Timolaos; Erbguth, Frank; Schellinger, Peter D; Fink, Gereon R; Stetefeld, Henning; Schneider, Hauke; Neugebauer, Hermann; Röther, Joachim; Claßen, Joseph; Michalski, Dominik; Dörfler, Arnd; Schwab, Stefan; Huttner, Hagen B

2018-01-01

To investigate parameters associated with hematoma enlargement in non-vitamin K antagonist oral anticoagulant (NOAC)-related intracerebral hemorrhage (ICH). This retrospective cohort study includes individual patient data for 190 patients with NOAC-associated ICH over a 5-year period (2011-2015) at 19 departments of neurology across Germany. Primary outcome was the association of prothrombin complex concentrate (PCC) administration with hematoma enlargement. Subanalyses were calculated for blood pressure management and its association with the primary outcome. Secondary outcomes include associations with in-hospital mortality and functional outcome at 3 months assessed using the modified Rankin Scale. The study population for analysis of primary and secondary outcomes consisted of 146 NOAC-ICH patients with available follow-up imaging. Hematoma enlargement occurred in 49/146 (33.6%) patients with NOAC-related ICH. Parameters associated with hematoma enlargement were blood pressure ≥ 160mmHg within 4 hours and-in the case of factor Xa inhibitor ICH-anti-Xa levels on admission. PCC administration prior to follow-up imaging was not significantly associated with a reduced rate of hematoma enlargement either in overall NOAC-related ICH or in patients with factor Xa inhibitor intake (NOAC: risk ratio [RR] = 1.150, 95% confidence interval [CI] = 0.632-2.090; factor Xa inhibitor: RR = 1.057, 95% CI = 0.565-1.977), regardless of PCC dosage given or time interval until imaging or treatment. Systolic blood pressure levels < 160mmHg within 4 hours after admission were significantly associated with a reduction in the proportion of patients with hematoma enlargement (RR = 0.598, 95% CI = 0.365-0.978). PCC administration had no effect on mortality and functional outcome either at discharge or at 3 months. In contrast to blood pressure control, PCC administration was not associated with a reduced rate of hematoma enlargement in NOAC-related ICH

Impact of spontaneous intracerebral hemorrhage on cognitive functioning: An update.

PubMed

Planton, M; Raposo, N; Danet, L; Albucher, J-F; Péran, P; Pariente, J

Intracerebral hemorrhage (ICH) accounts for 15% of all strokes and approximately 50% of stroke-related mortality and disability worldwide. Patients who have experienced ICH are at high risk of negative outcome, including stroke and cognitive disorders. Vascular cognitive impairment are frequently seen after brain hemorrhage, yet little is known about them, as most studies have focused on neuropsychological outcome in ischemic stroke survivors, using well-documented acute and chronic cognitive scores. However, recent evidence supports the notion that ICH and dementia are closely related and each increases the risk of the other. The location of the lesion also plays a significant role as regards the neuropsychological profile, while the pathophysiology of ICH can indicate a specific pattern of dysfunction. Several cognitive domains may be affected, such as language, memory, executive function, processing speed and gnosis. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Prophylactic Antiepileptic Drug Use and Outcome in the Ethnic/Racial Variations of Intracerebral Hemorrhage Study.

PubMed

Sheth, Kevin N; Martini, Sharyl R; Moomaw, Charles J; Koch, Sebastian; Elkind, Mitchell S V; Sung, Gene; Kittner, Steven J; Frankel, Michael; Rosand, Jonathan; Langefeld, Carl D; Comeau, Mary E; Waddy, Salina P; Osborne, Jennifer; Woo, Daniel

2015-12-01

The role of antiepileptic drug (AED) prophylaxis after intracerebral hemorrhage (ICH) remains unclear. This analysis describes prevalence of prophylactic AED use, as directed by treating clinicians, in a prospective ICH cohort and tests the hypothesis that it is associated with poor outcome. Analysis included 744 patients with ICH enrolled in the Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) study before November 2012. Baseline clinical characteristics and AED use were recorded in standardized fashion. ICH location and volume were recorded from baseline neuroimaging. We analyzed differences in patient characteristics by AED prophylaxis, and we used logistic regression to test whether AED prophylaxis was associated with poor outcome. The primary outcome was 3-month modified Rankin Scale score, with 4 to 6 considered poor outcome. AEDs were used for prophylaxis in 289 (39%) of the 744 subjects; of these, levetiracetam was used in 89%. Patients with lobar ICH, craniotomy, or larger hematomas were more likely to receive prophlyaxis. Although prophylactic AED use was associated with poor outcome in an unadjusted model (odds ratio, 1.40; 95% confidence interval, 1.04-1.88; P=0.03), this association was no longer significant after adjusting for clinical and demographic characteristics (odds ratio, 1.11; 95% confidence interval, 0.74-1.65; P=0.62). We found no evidence that AED use (predominantly levetiracetam) is independently associated with poor outcome. A prospective study is required to assess for a more modest effect of AED use on outcome after ICH. © 2015 American Heart Association, Inc.

Low free triiodothyronine levels predict symptomatic intracranial hemorrhage and worse short-term outcome of thrombolysis in patients with acute ischemia stroke.

PubMed

Qiu, Mingjing; Fang, Min; Liu, Xueyuan

2017-11-01

The aim of the study was to determine whether thyroid hormones level on admission in patients with ischemic stroke, treated with intravenous recombinant tissue type plasminogen activator (rtPA), was associated with symptomatic intracranial hemorrhage (sICH) and worse outcomes at 3 months.Patients with acute ischemic stroke (AIS) receiving intravenous rtPA thrombolytic treatment on our stroke unit between January 2015 and June 2016 were included in this study. Serum-free triiodothyronine (fT3), free thyroxine (fT4), total triiodothyronine (tT3), total thyroxine (tT4), and thyroid-stimulating hormone (TSH) were detected on admission. The endpoints were sICH, and poor functional outcomes at 3 and 6 months.In all, 159 patients (106 males; mean age 65.36 ± 10.02 years) were included. FT3 was independently associated with sICH (odds ratio [OR] 0.204, 95% confidence interval [CI] 0.065-0.642) and poor outcomes at 3 months (OR 0.396, 95% CI 0.180-1.764). The cut-off values of fT3 for sICH was 3.54 pg/mL (sensitivity 83%; specificity 83%; area under the curve 0.88). FT3 values ≤3.54 pg/mL increased risk for sICH by 3.16-fold (95% CI 0.75-1.0) compared with fT3 values >3.54 pg/mL.Low fT3 levels at admission were independently associated with sICH and worse outcomes at 3 months in AIS patients receiving rtPA thrombolytic therapy.

Low Ambient Temperature and Intracerebral Hemorrhage: The INTERACT2 Study.

PubMed

Zheng, Danni; Arima, Hisatomi; Sato, Shoichiro; Gasparrini, Antonio; Heeley, Emma; Delcourt, Candice; Lo, Serigne; Huang, Yining; Wang, Jiguang; Stapf, Christian; Robinson, Thompson; Lavados, Pablo; Chalmers, John; Anderson, Craig S

2016-01-01

Rates of acute intracerebral hemorrhage (ICH) increase in winter months but the magnitude of risk is unknown. We aimed to quantify the association of ambient temperature with the risk of ICH in the Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial (INTERACT2) participants on an hourly timescale. INTERACT2 was an international, open, blinded endpoint, randomized controlled trial of patients with spontaneous ICH (<6h of onset) and elevated systolic blood pressure (SBP, 150-220 mmHg) assigned to intensive (target SBP <140 mmHg) or guideline-recommended (SBP <180 mmHg) BP treatment. We linked individual level hourly temperature to baseline data of 1997 participants, and performed case-crossover analyses using a distributed lag non-linear model with 24h lag period to assess the association of ambient temperature and risk of ICH. Results were presented as overall cumulative odds ratios (ORs) and 95% CI. Low ambient temperature (≤10°C) was associated with increased risks of ICH: overall cumulative OR was 1.37 (0.99-1.91) for 10°C, 1.92 (1.31-2.81) for 0°C, 3.13 (1.89-5.19) for -10°C, and 5.76 (2.30-14.42) for -20°C, as compared with a reference temperature of 20°C.There was no clear relation of low temperature beyond three hours after exposure. Results were consistent in sensitivity analyses. Exposure to low ambient temperature within several hours increases the risk of ICH. ClinicalTrials.gov NCT00716079.

CT angiography spot sign in intracerebral hemorrhage predicts active bleeding during surgery.

PubMed

Brouwers, H Bart; Raffeld, Miriam R; van Nieuwenhuizen, Koen M; Falcone, Guido J; Ayres, Alison M; McNamara, Kristen A; Schwab, Kristin; Romero, Javier M; Velthuis, Birgitta K; Viswanathan, Anand; Greenberg, Steven M; Ogilvy, Christopher S; van der Zwan, Albert; Rinkel, Gabriel J E; Goldstein, Joshua N; Klijn, Catharina J M; Rosand, Jonathan

2014-09-02

To determine whether the CT angiography (CTA) spot sign marks bleeding complications during and after surgery for spontaneous intracerebral hemorrhage (ICH). In a 2-center study of consecutive spontaneous ICH patients who underwent CTA followed by surgical hematoma evacuation, 2 experienced readers (blinded to clinical and surgical data) reviewed CTAs for spot sign presence. Blinded raters assessed active intraoperative and postoperative bleeding. The association between spot sign and active intraoperative bleeding, postoperative rebleeding, and residual ICH volumes was evaluated using univariable and multivariable logistic regression. A total of 95 patients met inclusion criteria: 44 lobar, 17 deep, 33 cerebellar, and 1 brainstem ICH; ≥1 spot sign was identified in 32 patients (34%). The spot sign was the only independent marker of active bleeding during surgery (odds ratio [OR] 3.4; 95% confidence interval [CI] 1.3-9.0). Spot sign (OR 4.1; 95% CI 1.1-17), female sex (OR 6.9; 95% CI 1.7-37), and antiplatelet use (OR 4.6; 95% CI 1.2-21) were predictive of postoperative rebleeding. Larger residual hematomas and postoperative rebleeding were associated with higher discharge case fatality (OR 3.4; 95% CI 1.1-11) and a trend toward increased case fatality at 3 months (OR 2.9; 95% CI 0.9-8.8). The CTA spot sign is associated with more intraoperative bleeding, more postoperative rebleeding, and larger residual ICH volumes in patients undergoing hematoma evacuation for spontaneous ICH. The spot sign may therefore be useful to select patients for future surgical trials. © 2014 American Academy of Neurology.

Survey of Prophylactic Antiseizure Drug Use for Nontraumatic Intracerebral Hemorrhage

PubMed Central

Jensen, Matthew B.; Sattar, Ahsan; Sherbini, Khalid Al

2013-01-01

Objective Prophylactic antiseizure drugs (PAD) are commonly prescribed for nontraumatic intracerebral hemorrhage (ICH) despite limited evidence for this indication. We sought to determine the current prescribing patterns of the use of a PAD for ICH. Methods A 36-item survey was distributed to physicians that manage ICH patients soliciting details of PAD prescription in their practice. Results A total of 199 physicians responded to the survey, all of who manage between one and 50 or more ICH patients per year. The respondents were neurologists (32%), neurosurgeons (11%), and intensivists (57%) in academia (69%) and private practice (31%). PAD prescriptions were used: never (33%), 1–33% (35%), 34–66% (14%), 67–99% (9%) of the time, or always (9%). Most respondents performed electroencephalographic and serum level monitoring in at least some patients. Levetiracetam was used most often (60%), followed by fos/phenytoin (37%), for a usual duration of days (36%), weeks (47%), or months (17%). PAD prescription varied by patient characteristics and physician specialty. Perception of physician community consensus regarding PAD use for ICH among respondents ranged from strongly (7%) or weakly (23%) against the practice, to a fairly equal division of opinion (41%), to weakly (27%) or strongly (4%) in favor of the practice. Conclusions We found variability of multiple aspects of the current prescribing patterns and opinions regarding the use of a PAD for ICH. This variability is likely secondary to insufficient data. Clinical equipoise exists for this issue, and controlled trials would be both justified and useful. PMID:23582711

Minocycline and matrix metalloproteinase inhibition in acute intracerebral hemorrhage: a pilot study.

PubMed

Chang, J J; Kim-Tenser, M; Emanuel, B A; Jones, G M; Chapple, K; Alikhani, A; Sanossian, N; Mack, W J; Tsivgoulis, G; Alexandrov, A V; Pourmotabbed, T

2017-11-01

Intracerebral hemorrhage (ICH) is a devastating cerebrovascular disorder with high morbidity and mortality. Minocycline is a matrix metalloproteinase-9 (MMP-9) inhibitor that may attenuate secondary mechanisms of injury in ICH. The feasibility and safety of minocycline in ICH patients were evaluated in a pilot, double-blinded, placebo-controlled randomized clinical trial. Patients with acute onset (<12 h from symptom onset) ICH and small initial hematoma volume (<30 ml) were randomized to high-dose (10 mg/kg) intravenous minocycline or placebo. The outcome events included adverse events, change in serial National Institutes of Health Stroke Scale score assessments, hematoma volume and MMP-9 measurements, 3-month functional outcome (modified Rankin score) and mortality. A total of 20 patients were randomized to minocycline (n = 10) or placebo (n = 10). The two groups did not differ in terms of baseline characteristics. No serious adverse events or complications were noted with minocycline infusion. The two groups did not differ in any of the clinical and radiological outcomes. Day 5 serum MMP-9 levels tended to be lower in the minocycline group (372 ± 216 ng/ml vs. 472 ± 235 ng/ml; P = 0.052). Multiple linear regression analysis showed that minocycline was associated with a 217.65 (95% confidence interval -425.21 to -10.10, P = 0.041) decrease in MMP-9 levels between days 1 and 5. High-dose intravenous minocycline can be safely administered to patients with ICH. Larger randomized clinical trials evaluating the efficacy of minocycline and MMP-9 inhibition in ICH patients are required. © 2017 EAN.

Neuroprotection of brain-permeable iron chelator VK-28 against intracerebral hemorrhage in mice.

PubMed

Li, Qian; Wan, Jieru; Lan, Xi; Han, Xiaoning; Wang, Zhongyu; Wang, Jian

2017-09-01

Iron overload plays a key role in the secondary brain damage that develops after intracerebral hemorrhage (ICH). The significant increase in iron deposition is associated with the generation of reactive oxygen species (ROS), which leads to oxidative brain damage. In this study, we examined the protective effects of VK-28, a brain-permeable iron chelator, against hemoglobin toxicity in an ex vivo organotypic hippocampal slice culture (OHSC) model and in middle-aged mice subjected to an in vivo, collagenase-induced ICH model. We found that the effects of VK-28 were similar to those of deferoxamine (DFX), a well-studied iron chelator. Both decreased cell death and ROS production in OHSCs and in vivo, decreased iron-deposition and microglial activation around hematoma in vivo, and improved neurologic function. Moreover, compared with DFX, VK-28 polarized microglia to an M2-like phenotype, reduced brain water content, deceased white matter injury, improved neurobehavioral performance, and reduced overall death rate after ICH. The protection of VK-28 was confirmed in a blood-injection ICH model and in aged-male and young female mice. Our findings indicate that VK-28 is protective against iron toxicity after ICH and that, at the dosage tested, it has better efficacy and less toxicity than DFX does.

Rheological behavior of clay-nanoparticle hybrid-added bentonite suspensions: specific role of hybrid additives on the gelation of clay-based fluids.

PubMed

Jung, Youngsoo; Son, You-Hwan; Lee, Jung-Kun; Phuoc, Tran X; Soong, Yee; Chyu, Minking K

2011-09-01

Two different types of clay nanoparticle hybrid, iron oxide nanoparticle clay hybrid (ICH) and Al(2)O(3)-SiO(2) nanoparticle clay hybrid (ASCH), were synthesized and their effects on the rheological properties of aqueous bentonite fluids in steady state and dynamic state were explored. When ICH particles were added, bentonite particles in the fluid cross-link to form relatively well-oriented porous structure. This is attributed to the development of positively charged edge surfaces in ICH that leads to strengthening of the gel structure of the bentonite susensions. The role of ASCH particles on the interparticle association of the bentonite fluids is different from that of ICH and sensitive to pH. As pH of ASCH-added bentonite suspensions increased, the viscosity, yield stress, storage modulus, and flow stress decreased. In contrast, at low pH, the clay suspensions containing ASCH additives were coagulated and their rheological properties become close to those of ICH added bentonite fluids. A correlation between the net surface charge of the hybrid additives and the rheological properties of the fluids indicates that the embedded nanoparticles within the interlayer space control the variable charge of the edge surfaces of the platelets and determine the particles association behavior of the clay fluids.

Management of venous thromboembolism in patients with glioma.

PubMed

Al Megren, Mosaad; De Wit, Carine; Al Qahtani, Mohammad; Le Gal, Grégoire; Carrier, Marc

2017-08-01

Venous thromboembolism (VTE) is a common complication among patients with glioma. However, data on the safety of therapeutic doses of anticoagulation is scarce in this patient population. The purpose of this study is to evaluate the risk of intracranial hemorrhage (ICH) in glioma patients receiving therapeutic anticoagulation for VTE treatment. We conducted a case-control study including glioma patients with and without acute VTE from Jan 2010 to March 2015. Controls were matched based on age, gender and tumor grade. 569 patients with glioma were identified, 76 (13.3%) developed acute VTE. Of the 70 patients treated with full dose anticoagulant therapy, 14 (20%) patients had a major bleeding including 11 (15.7%) ICH. The odds ratio for ICH in patients with glioma and VTE who were treated with anticoagulation compared to the control group was 7.5 (95% CI, 1.6-34.9) p=0.01. Overall survival was similar for VTE and control group (36 vs. 42months, p=0.93). Therapeutic anticoagulation is associated with a 7-fold increase risk of ICH in glioma patients. Data emerging from this study support the need for high quality studies to evaluate the risk of ICH in patients with glioma and VTE. Copyright © 2017 Elsevier Ltd. All rights reserved.

Early Erythrolysis in the Hematoma After Experimental Intracerebral Hemorrhage

PubMed Central

Dang, Ge; Yang, Yuefan; Wu, Gang; Hua, Ya; Keep, Richard F.; Xi, Guohua

2016-01-01

Erythrolysis occurs in the clot after intracerebral hemorrhage (ICH) and the release of hemoglobin causes brain injury but it is unclear when such lysis occurs. The present study examined early erythrolysis in rats. ICH rats had an intra-caudate injection of 100 µl autologous blood and sham rats had a needle insertion. All rats had T2 and T2* MRI scanning and brains were used for histology and CD163 (a hemoglobin scavenger receptor) and DARPP-32 (a neuronal marker) immunohistochemistry. There was marked heterogeneity within the hematoma on T2* MRI, with a hyper- or isointense core and a hypointense periphery. Hematoxylin and eosin staining in the same animals showed significant erythrolysis in the core with the formation of erythrocyte ghosts. The degree of erythrolysis correlated with the severity of perihematomal neuronal loss. Perihematomal CD163 was increased by day 1 after ICH and may be involved in clearing hemoglobin caused by early hemolysis. Furthermore, ICH resulted in more severe erythrolysis, neuronal loss and perihematomal CD163 upregulation in spontaneously hypertensive rats compared to Wistar Kyoto rats. In conclusions, T2*MRI detectable early erythrolysis occurred in the clot after ICH, and activated CD163. Hypertension is associated with enhanced erythrolysis in the hematoma. PMID:27783383

Neural Injuries Induced by Hydrostatic Pressure Associated With Mass Effect after Intracerebral Hemorrhage.

PubMed

Guo, Tingwang; Ren, Peng; Li, Xiaofei; Luo, Tiantian; Gong, Yuhua; Hao, Shilei; Wang, Bochu

2018-06-15

Mass effect induced by growing hematoma is one of the mechanisms by which intracerebral hemorrhage (ICH) may result in brain injuries. Our goal was to investigate the damage mechanism of hydrostatic pressure associated with mass effect and the cooperative effect of hydrostatic pressure plus hemoglobin on neural injuries. Loading hydrostatic pressure on neurons and injecting agarose gel in the right striatum of rats was performed to establish the in vitro and vivo ICH models, respectively. The elevated hydrostatic pressure associated with ICH suppressed neurons and neural tissues viability, and disturbed the axons and dendrites in vitro and vivo. Moreover, hydrostatic pressure could upregulate the expression of cleaved-caspase-3 and BAX, and downregulate Bcl-2 and Bcl-xL. Meanwhile, the toxicity of hemoglobin would be enhanced when conducted with hydrostatic pressure together. Furthermore, the exclusive hydrostatic pressure could upregulate the Piezo-2 expression, which reached a plateau at 8 h after ICH. And hemoglobin increased Piezo-2 expression significantly in vivo, and that was also promoted significantly by the elevated volume of Gel in the cooperative groups. Results indicated that hydrostatic pressure induced by mass effect not only gave rise to brain injuries directly, but also increased the toxicity of hemoglobin in the progress of secondary brain injury after ICH.

Electric double-layer capacitor based on an ionic clathrate hydrate.

PubMed

Lee, Wonhee; Kwon, Minchul; Park, Seongmin; Lim, Dongwook; Cha, Jong-Ho; Lee, Huen

2013-07-01

Herein, we suggest a new approach to an electric double-layer capacitor (EDLC) that is based on a proton-conducting ionic clathrate hydrate (ICH). The ice-like structures of clathrate hydrates, which are comprised of host water molecules and guest ions, make them suitable for applications in EDLC electrolytes, owing to their high proton conductivities and thermal stabilities. The carbon materials in the ICH Me4NOH⋅5 H2O show a high specific capacitance, reversible charge-discharge behavior, and a long cycle life. The ionic-hydrate complex provides the following advantages in comparison with conventional aqueous and polymer electrolytes: 1) The ICH does not cause leakage problems under normal EDLC operating conditions. 2) The hydrate material can be utilized itself, without requiring any pre-treatments or activation for proton conduction, thus shortening the preparation procedure of the EDLC. 3) The crystallization of the ICH makes it possible to tailor practical EDLC dimensions because of its fluidity as a liquid hydrate. 4) The hydrate solid electrolyte exhibits more-favorable electrochemical stability than aqueous and polymer electrolytes. Therefore, ICH materials are expected to find practical applications in versatile energy devices that incorporate electrochemical systems. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Cofilin Knockdown Attenuates Hemorrhagic Brain Injury-induced Oxidative Stress and Microglial Activation in Mice.

PubMed

Alhadidi, Qasim; Nash, Kevin M; Alaqel, Saleh; Sayeed, Muhammad Shahdaat Bin; Shah, Zahoor A

2018-05-08

Intracerebral hemorrhage (ICH) resulting from the rupture of the blood vessels in the brain is associated with significantly higher mortality and morbidity. Clinical studies focused on alleviating the primary injury, hematoma formation and expansion, were largely ineffective, suggesting that secondary injury-induced inflammation and the formation of reactive species also contribute to the overall injury process. In this study, we explored the effects of cofilin knockdown in a mouse model of ICH. Animals given stereotaxic injections of cofilin siRNA, 72-h prior to induction of ICH by collagenase injection within the area of siRNA administration showed significantly decreased cofilin expression levels and lower hemorrhage volume and edema, and the animals performed significantly better in neurobehavioral tasks i.e., rotarod, grip strength and neurologic deficit scores. Cofilin siRNA knocked-down mice had reduced ICH-induced DNA fragmentation, blood-brain barrier disruption and microglial activation, with a concomitant increase in astrocyte activation. Increased expression of pro-survival proteins and decreased markers of oxidative stress were also observed in cofilin siRNA-treated mice possibly due to the reduced levels of cofilin. Our results suggest that cofilin plays a major role in ICH-induced secondary injury, and could become a potential therapeutic target. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

Risk Profile of Symptomatic Lacunar Stroke Versus Nonlobar Intracerebral Hemorrhage.

PubMed

Morotti, Andrea; Paciaroni, Maurizio; Zini, Andrea; Silvestrelli, Giorgio; Del Zotto, Elisabetta; Caso, Valeria; Dell'Acqua, Maria Luisa; Simone, Anna Maria; Lanari, Alessia; Costa, Paolo; Poli, Loris; De Giuli, Valeria; Gamba, Massimo; Ciccone, Alfonso; Ritelli, Marco; Di Castelnuovo, Augusto; Iacoviello, Licia; Colombi, Marina; Agnelli, Giancarlo; Grassi, Mario; de Gaetano, Giovanni; Padovani, Alessandro; Pezzini, Alessandro

2016-08-01

Although lacunar stroke (LS) and deep intracerebral hemorrhage (dICH) represent acute manifestations of the same pathological process involving cerebral small vessels (small vessel disease), it remains unclear what factors predispose to one phenotype rather than the other at individual level. Consecutive patients with either acute symptomatic LS or dICH were prospectively enrolled as part of a multicenter Italian study. We compared the risk factor profile of the 2 subgroups using multivariable logistic regression. During a time course of 9.5 years, 1931 subjects (1434 LS and 497 dICH; mean age, 71.3±13.3 years; males, 55.5%) qualified for the analysis. Current smoking was associated with LS (odds ratio [OR], 2.17; P<0.001). Conversely, dICH cases were more likely to be hypertensive (OR, 1.87; P<0.001), excessive alcohol consumers (OR, 1.70; P=0.001), and more frequently under treatment with warfarin (OR, 2.05; P=0.010) and statins (OR, 3.10; P<0.001). Hypercholesterolemia, diabetes mellitus, and antiplatelet treatment were not associated with a specific small vessel disease manifestation. The risk factor profile of dICH differs from that associated with LS. This might be used for disease risk stratification at individual level. © 2016 American Heart Association, Inc.

76 FR 57746 - Conference on the International Conference on Harmonisation Q10 Pharmaceutical Quality System: A...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-16

... ``Pharmaceutical Quality System (ICH Q10) Conference: A Practical Approach to Effective Life- Cycle Implementation... Pharmaceutical Quality System across the product life cycle according to the ICH Q10 model. These companies are...] Conference on the International Conference on Harmonisation Q10 Pharmaceutical Quality System: A Practical...

Parasiticidal effects of Morus alba root bark extracts against Ichthyophthirius multifiliis infecting grass carp

USDA-ARS?s Scientific Manuscript database

Ichthyophthirius multifiliis (Ich) is an important fish parasite that can result in significant losses in aquaculture. In order to find efficacious drugs to control Ich, the root bark of Morus alba, a traditional Chinese medicine, was evaluated for its antiprotozoal activity. The M. alba root bark w...

78 FR 34393 - Electronic Submission of Tobacco Product Applications and Other Information; Public Workshop...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-07

... manufacturers experienced with electronic Common Technical Document (eCTD); vendors of software used to support... electronic submission workshop will include discussion on eCTD, which is an International Conference on Harmonization (ICH) specification developed by ICH and its member parties. The eCTD provides an organizational...

[Comparative assessment of MR-semiotics of acutest intracerebral hematomas in low- and extra high-field frequency magnetic resonance tomography].

PubMed

Skvortsova, V I; Burenchev, D V; Tvorogova, T V; Guseva, O I; Prokhorov, A V; Smirnov, A M; Kupriianov, D A; Pirogov, Iu A

2009-01-01

An objective of the study was to compare sensitivity of low- and extra high-field frequency magnetic resonance (MR) tomography of acutest intracerebral hematomas (ICH) and to assess differences between symptoms in obtained images. A study was conducted using experimental ICH in rats (n=6). Hematomas were formed by two injections of autologic blood into the brain. MR-devices "Bio Spec 70/30" with magnetic field strength of 7 T and "Ellipse-150" with magnetic field strength of 0,15 T were used in the study. MR-tomography was carried out 3-5 h after the injections. Both MR-devices revealed the presence of pathological lesion in all animals. Extra highfield frequency MR-tomography showed the specific signs of ICH caused by the paramagnetic effect of deoxyhemoglobin in T2 and T2*-weighted images (WI) and low frequency MR-tomography - in T2*-WI only. The comparable sensitivity of low- and extra high-field frequency MR-devices in acutest ICH was established.

An Ichor-dependent apical extracellular matrix regulates seamless tube shape and integrity

PubMed Central

Rosa, Jeffrey B.; Metzstein, Mark M.

2018-01-01

During sprouting angiogenesis in the vertebrate vascular system, and primary branching in the Drosophila tracheal system, specialized tip cells direct branch outgrowth and network formation. When tip cells lumenize, they form subcellular (seamless) tubes. How these seamless tubes are made, shaped and maintained remains poorly understood. Here we characterize a Drosophila mutant called ichor (ich), and show that ich is essential for the integrity and shape of seamless tubes in tracheal terminal cells. We find that Ich regulates seamless tubulogenesis via its role in promoting the formation of a mature apical extracellular matrix (aECM) lining the lumen of the seamless tubes. We determined that ich encodes a zinc finger protein (CG11966) that acts, as a transcriptional activator required for the expression of multiple aECM factors, including a novel membrane-anchored trypsin protease (CG8213). Thus, the integrity and shape of seamless tubes are regulated by the aECM that lines their lumens. PMID:29309404

Electroacupuncture improves neurobehavioral function and brain injury in rat model of intracerebral hemorrhage.

PubMed

Zhu, Yan; Deng, Li; Tang, Huajun; Gao, Xiaoqing; Wang, Youhua; Guo, Kan; Kong, Jiming; Yang, Chaoxian

2017-05-01

Acupuncture has been widely used as a treatment for stroke in China for a long time. Recently, studies have demonstrated that electroacupuncture (EA) can accelerate intracerebral hemorrhage (ICH)-induced angiogenesis in rats. In the present study, we investigated the effect of EA on neurobehavioral function and brain injury in ICH rats. ICH was induced by stereotactic injection of collagenase type I and heparin into the right caudate putamen. Adult ICH rats were randomly divided into the following three groups: model control group (MC), EA at non-acupoint points group (non-acupoint EA) and EA at Baihui and Dazhui acupoints group (EA). The neurobehavioral deficits of ICH rats were assessed by modified neurological severity score (mNSS) and gait analysis. The hemorrhage volume and glucose metabolism of hemorrhagic foci were detected by PET/CT. The expression levels of MBP, NSE and S100-B proteins in serum were tested by ELISA. The histopathological features were examined by haematoxylin-eosin (H&E) staining. Apoptosis-associated proteins in the perihematomal region were observed by immunohistochemistry. EA treatment significantly promoted the recovery of neurobehavioral function in ICH rats. Hemorrhage volume reduced in EA group at day 14 when compared with MC and non-acupoint EA groups. ELISA showed that the levels of MBP, NSE and S100-B in serum were all down-regulated by EA treatment. The brain tissue of ICH rat in the EA group was more intact and compact than that in the MC and non-acupoint groups. In the perihematomal regions, the expression of Bcl-2 protein increased and expressions of Caspase-3 and Bax proteins decreased in the EA group vs MC and non-acupoint EA groups. Our data suggest that EA treatment can improve neurobehavioral function and brain injury, which were likely connected with the absorption of hematoma and regulation of apoptosis-related proteins. Copyright © 2017 Elsevier Inc. All rights reserved.

Natural History of Perihematomal Edema and Impact on Outcome After Intracerebral Hemorrhage.

PubMed

Wu, Teddy Y; Sharma, Gagan; Strbian, Daniel; Putaala, Jukka; Desmond, Patricia M; Tatlisumak, Turgut; Davis, Stephen M; Meretoja, Atte

2017-04-01

Edema may worsen outcome after intracerebral hemorrhage (ICH). We assessed its natural history, factors influencing growth, and association with outcome. We estimated edema volumes in ICH patients from the Helsinki ICH study using semiautomated planimetry. We assessed the correlation between edema extension distance (EED) and time from ICH onset, creating an edema growth trajectory model up to 3 weeks. We interpolated expected EED at 72 hours and identified clinical and imaging characteristics associated with faster edema growth. Association of EED and mortality was assessed using logistic regression adjusting for predictors of ICH outcome. From 1013 consecutive patients, 861 were included. There was a strong inverse correlation between EED growth rate (cm/d) and time from onset (days): EED growth=0.162*days exp(-0.927), R 2 =0.82. Baseline factors associated with larger than expected EED were older age (71 versus 68; P =0.002), higher National Institutes of Health Stroke Scale score (14 versus 8; P <0.001), and lower Glasgow Coma scale score (13 versus 15; P <0.001), larger ICH volume (19.7 versus 12.7 mL; P <0.001), larger initial EED (0.42 versus 0.30; P <0.001), irregularly shaped hematoma (55% versus 42%; P <0.001), and higher glucose (7.6 versus 6.9 mmol/L; P =0.001). Patients with faster edema growth had more midline shift (50% versus 31%; P <0.001), herniation (12% versus 4%; P <0.001), and higher 6-month (46% versus 26%; P <0.001) mortality. In the logistic regression model, higher-than-expected EED was associated with 6-month mortality (odds ratio, 1.60; 95% confidence interval, 1.04-2.46; P =0.032). Edema growth can be readily monitored and is an independent determinant of mortality after ICH, providing an important treatment target for strategies to improve patient outcome. © 2017 American Heart Association, Inc.

The influence of an intermediate care hospital on health care utilization among elderly patients--a retrospective comparative cohort study.

PubMed

Dahl, Unni; Johnsen, Roar; Sætre, Rune; Steinsbekk, Aslak

2015-02-01

An intermediate care hospital (ICH) was established in a municipality in Central Norway in 2007 to improve the coordination of services and follow-up among elderly and chronically ill patients after hospital discharge. The aim of this study was to compare health care utilization by elderly patients in a municipality with an ICH to that of elderly patients in a municipality without an ICH. This study was a retrospective comparative cohort study of all hospitalized patients aged 60 years or older in two municipalities. The data were collected from the national register of hospital use from 2005 to 2012, and from the local general hospital and two primary health care service providers from 2008 to 2012 (approx. 1,250 patients per follow-up year). The data were analyzed using descriptive statistics and analysis of covariance (ANCOVA). The length of hospital stay decreased from the time the ICH was introduced and remained between 10% and 22% lower than the length of hospital stay in the comparative municipality for the next five years. No differences in the number of readmissions or admissions during one year follow-up after the index stay at the local general hospital or changes in primary health care utilization were observed. In the year after hospital discharge, the municipality with an ICH offered more hour-based care to elderly patients living at home (estimated mean = 234 [95% CI 215-252] versus 175 [95% CI 154-196] hours per person and year), while the comparative municipality had a higher utilization of long-term stays in nursing homes (estimated mean = 33.3 [95% CI 29.0-37.7] versus 21.9 [95% CI 18.0-25.7] days per person and year). This study indicates that the introduction of an ICH rapidly reduces the length of hospital stay without exposing patients to an increased health risk. The ICH appears to operate as an extension of the general hospital, with only a minor impact on the pattern of primary health care utilization.

Prospective Study of Fasting Blood Glucose and Intracerebral Hemorrhagic Risk.

PubMed

Jin, Cheng; Li, Guohong; Rexrode, Kathryn M; Gurol, Mahmut E; Yuan, Xiaodong; Hui, Ying; Ruan, Chunyu; Vaidya, Anand; Wang, Yanxiu; Wu, Shouling; Gao, Xiang

2018-01-01

Although diabetes mellitus is an established independent risk factor for ischemic stroke, the association between fasting blood glucose and intracerebral hemorrhage (ICH) is limited and inconsistent. The objective of the current study was to examine the potential impact of long-term fasting blood glucose concentration on subsequent risk of ICH. This prospective study included 96 110 participants of the Kailuan study, living in Kailuan community, Tangshan city, China, who were free of cardiovascular diseases and cancer at baseline (2006). Fasting blood glucose concentration was measured in 2006, 2008, 2010, and 2012. Updated cumulative average fasting blood glucose concentration was used as primary exposure of the current study. Incident ICH from 2006 to 2015 was confirmed by review of medical records. During 817 531 person-years of follow-up, we identified 755 incident ICH cases. The nadir risk of ICH was observed at fasting blood glucose concentration of 5.3 mmol/L. The adjusted hazard ratios and their 95% confidence intervals (CIs) of ICH were 1.59 (95% CI, 1.26-2.02) for diabetes mellitus or fasting blood glucose ≥7.00 mmol/L, 1.31 (95% CI, 1.02-1.69) for impaired fasting blood glucose (fasting blood glucose, 6.10-6.99 mmol/L), 0.98 (95% CI, 0.78-1.22) for fasting blood glucose 5.60 to 6.09 mmol/L, and 2.04 (95% CI, 1.23-3.38) for hypoglycemia (fasting blood glucose, <4.00 mmol/L), comparing with normal fasting blood glucose 4.00 to 5.59 mmol/L. The results persisted after excluding individuals who used hypoglycemic, aspirin, antihypertensive agents, or anticoagulants, and those with intracerebral hemorrhagic cases occurred in the first 2 years of follow-up. In this large community-based cohort, low (<4.0 mmol/L) and high (≥6.1 mmol/L) fasting blood glucose concentrations were associated with higher risk of incident ICH, relative to fasting blood glucose concentrations of 4.00 to 6.09 mmol/L. © 2017 American Heart Association, Inc.

75 FR 53973 - International Conference on Harmonisation; Guidance on Q4B Evaluation and Recommendation of...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-02

...] International Conference on Harmonisation; Guidance on Q4B Evaluation and Recommendation of Pharmacopoeial Texts... and Recommendation of Pharmacopoeial Texts for Use in the ICH Regions; Annex 12: Analytical Sieving... provides the results of the ICH Q4B evaluation of the Analytical Sieving General Chapter harmonized text...

Amyloid Angiopathy in Brain Hemorrhage: A Postmortem Neuropathological-Magnetic Resonance Imaging Study.

PubMed

Guidoux, Celine; Hauw, Jean-Jacques; Klein, Isabelle F; Labreuche, Julien; Berr, Claudine; Duyckaerts, Charles; Amarenco, Pierre

2018-01-01

Risk factors for intracerebral hemorrhage (ICH) include hypertension and cerebral amyloid angiopathy (CAA). The objective of this study was to determine the autopsy prevalence of CAA and the potential overlap with other risk factors among patients who died from ICH and also the correlation of CAA with cerebral microbleeds. We analyzed 81 consecutive autopsy brains from patients with ICH. Staining for CAA detection was performed. We used an age- and sex-matched control group of routine brain autopsies of nonneurological patients to determine the frequencies of CAA and hypertension. Postmortem 3D T2-weighted gradient-echo magnetic resonance imaging (MRI) with a 1.5-T magnet was performed in 11 brains with ICH (5 with CAA and 6 without) and histological correlation was performed when microbleeds were detected. Hypertension and CAA were found in 69.1 and 24.7% of cases respectively. Among patients with CAA, 65.0% also had hypertension. The prevalence of CAA was similar among non-hypertensive cases and controls (33.3 and 23.1%; p = 0.54), whereas a significant difference was found between hypertensive cases vs. controls (28.9% vs. 0; p = 0.01). MRI documented 48 microbleeds and all 5 brains with CAA had ≥1 microbleed, compared to 3/6 brains without CAA. Among 48 microbleeds on MRI, 45 corresponded histologically to microbleeds surrounding microvessels (23 <200 µm in diameter, 19 between 200 µm and 2 mm, 3 were hemosiderin granules). Both hypertension and CAA frequently coexist in patients with ICH. MRI-detected microbleeds, proven by histological analysis, were twice as common in patients with CAA as in those with hypertensive ICH. © 2018 S. Karger AG, Basel.

Childhood Stature and Growth in Relation to First Ischemic Stroke or Intracerebral Hemorrhage.

PubMed

Gjærde, Line Klingen; Truelsen, Thomas Clement; Baker, Jennifer Lyn

2018-03-01

Attained height, an indicator of genetic potential and childhood growth environment, is inversely associated with stroke, but the mechanisms are poorly understood. We investigated whether childhood height and growth are associated with ischemic stroke (IS) and intracerebral hemorrhage (ICH). In a cohort of Danish schoolchildren born 1930 to 1989, with measured height from 7 to 13 years, we investigated associations of childhood stature and growth with risks of adult IS and ICH. Cox proportional hazards regressions were performed to estimate hazard ratios (HRs) with CIs separately for women and men. Among 311 009 individuals, 10 412 were diagnosed with IS and 2546 with ICH. Height at 7 years was inversely and significantly associated with IS in both sexes (per z score, equivalent to ≈5.2 cm in women and 5.1 cm in men; women: HR=0.89 [95% CI: 0.87-0.92]; men: HR=0.90 [95% CI: 0.88-0.92]) and with ICH in men (HR=0.89 [95% CI: 0.84-0.94]) but not in women (HR=0.97 [95% CI: 0.91-1.04]). Associations were similar at older childhood ages and were stable throughout the study period. No statistically significant associations for growth from 7 to 13 years were observed for IS or ICH. Short stature at 7 to 13 years is significantly associated with increased risks of IS in both sexes and with ICH in men. Growth during this period of childhood is not significantly associated with either of these stroke subtypes, suggesting that underlying mechanisms linking height with risks of stroke may exert their influence already by early childhood. © 2018 American Heart Association, Inc.

Systematic Review and Meta-Analysis: Is Pre-Injury Antiplatelet Therapy Associated with Traumatic Intracranial Hemorrhage?

PubMed

van den Brand, Crispijn L; Tolido, Tanya; Rambach, Anna H; Hunink, Myriam G M; Patka, Peter; Jellema, Korné

2017-01-01

The objective of this systematic review and meta-analysis is to evaluate whether the pre-injury use of antiplatelet therapy (APT) is associated with increased risk of traumatic intracranial hemorrhage (tICH) on CT scan. PubMed, Medline, Embase, Cochrane Central, reference lists, and national guidelines on traumatic brain injury were used as data sources. Eligible studies were cohort studies and case-control studies that assessed the relationship between APT and tICH. Studies without control group were not included. The primary outcome of interest was tICH on CT. Two reviewers independently selected studies, assessed methodological quality, and extracted outcome data. This search resulted in 10 eligible studies with 20,247 patients with head injury that were included in the meta-analysis. The use of APT in patients with head injury was associated with significant increased risk of tICH compared with control (odds ratio [OR] 1.87, 95% confidence interval [CI]1.27-2.74). There was significant heterogeneity in the studies (I 2 84%), although almost all showed an association between APT use and tICH. This association could not be established for patients receiving aspirin monotherapy. When considering only patients with mild traumatic brain injury (mTBI), the OR is 2.72 (95% CI 1.92-3.85). The results were robust to sensitivity analysis on study quality. In summary, APT in patients with head injury is associated with increased risk of tICH; this association is most relevant in patients with mTBI. Whether this association is the result of a causal relationship and whether this relationship also exists for patients receiving aspirin monotherapy cannot be established with the current review and meta-analysis.

Gastrointestinal bleeding and intracranial hemorrhage in concomitant users of warfarin and antihyperlipidemics.

PubMed

Leonard, Charles E; Brensinger, Colleen M; Bilker, Warren B; Kimmel, Stephen E; Han, Xu; Nam, Young Hee; Gagne, Joshua J; Mangaali, Margaret J; Hennessy, Sean

2017-02-01

Drug interactions, particularly those involving warfarin, are a major clinical and public health problem. Minimizing serious bleeding caused by anticoagulants is a recent major focus of the United States (US) Department of Health and Human Services. This study quantified the risk of gastrointestinal bleeding (GIB) and intracranial hemorrhage (ICH) among concomitant users of warfarin and individual antihyperlipidemics. The authors conducted a high-dimensional propensity score-adjusted cohort study of new concomitant users of warfarin and an antihyperlipidemic, among US Medicaid beneficiaries from five states during 1999-2011. Exposure was defined by concomitant use of warfarin plus one of eight antihyperlipidemics. The primary outcome measure was a composite of GIB/ICH within the first 30days of concomitant use. As a secondary outcome measure, GIB/ICH was examined within the first 180days of concomitant use. Among 236,691 persons newly-exposed to warfarin and an antihyperlipidemic, the crude incidence of GIB/ICH was 13.2 (95% confidence interval 12.7 to 13.8) per 100person-years. Users were predominantly older, female, and Caucasian. Adjusted hazard ratios (aHRs) for warfarin and individual statins were consistent with no association. Warfarin+gemfibrozil was associated with an 80% increased risk of GIB/ICH within the first month of concomitant use (aHR=1.8, 1.4 to 2.4). Warfarin+fenofibrate was associated with a similar increased risk (aHR=1.8, 1.2 to 2.7), yet with an onset during the second month of concomitant use. Among warfarin-treated persons, the use of fibrates-but not statins-increases the risk of hospital presentation for GIB/ICH. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Local hemostatic matrix for endoscope-assisted removal of intracerebral hemorrhage is safe and effective.

PubMed

Luh, Hui-Tzung; Huang, Abel Po-Hao; Yang, Shih-Hung; Chen, Chien-Ming; Cho, Der-Yang; Chen, Chun-Chung; Kuo, Lu-Ting; Li, Chieh-Hsun; Wang, Kuo-Chuan; Tseng, Wei-Lung; Hsing, Ming-Tai; Yang, Bing-Shiang; Lai, Dar-Ming; Tsai, Jui-Chang

2018-01-01

Minimally invasive endoscope-assisted (MIE) evacuation of spontaneous intracerebral hemorrhage (ICH) is simple and effective, but the limited working space may hinder meticulous hemostasis and might lead to rebleeding. Management of intraoperative hemorrhage is therefore a critical issue of this study. This study presents experience in the treatment of patients with various types of ICH by MIE evacuation followed by direct local injection of FloSeal Hemostatic Matrix (Baxter Healthcare Corp, Fremont, CA, USA) for hemostasis. The retrospective nonrandomized clinical and radiology-based analysis enrolled 42 patients treated with MIE evacuation of ICH followed by direct local injection of FloSeal Hemostatic Matrix. Rebleeding, morbidity, and mortality were the primary endpoints. The percentage of hematoma evacuated was calculated from the pre- and postoperative brain computed tomography (CT) scans. Extended Glasgow Outcome Scale (GOSE) was evaluated at 6 months postoperatively. Forty-two ICH patients were included in this study, among these, 23 patients were putaminal hemorrhage, 16 were thalamic ICH, and the other three were subcortical type. Surgery-related mortality was 2.4%. The average percentage of hematoma evacuated was 80.8%, and the rebleeding rate was 4.8%. The mean operative time was 102.7 minutes and the average blood loss was 84.9 mL. The mean postoperative GOSE score was 4.55 at 6-months' follow-up. This study shows that local application of FloSeal Hemostatic Matrix is safe and effective for hemostasis during MIE evacuation of ICH. In our experience, this shortens the operation time, especially in cases with intraoperative bleeding. A large, prospective, randomized trial is needed to confirm the findings. Copyright © 2017. Published by Elsevier B.V.

Low Ambient Temperature and Intracerebral Hemorrhage: The INTERACT2 Study

PubMed Central

Zheng, Danni; Arima, Hisatomi; Sato, Shoichiro; Gasparrini, Antonio; Heeley, Emma; Delcourt, Candice; Lo, Serigne; Huang, Yining; Wang, Jiguang; Stapf, Christian; Robinson, Thompson; Lavados, Pablo; Chalmers, John; Anderson, Craig S.

2016-01-01

Background Rates of acute intracerebral hemorrhage (ICH) increase in winter months but the magnitude of risk is unknown. We aimed to quantify the association of ambient temperature with the risk of ICH in the Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial (INTERACT2) participants on an hourly timescale. Methods INTERACT2 was an international, open, blinded endpoint, randomized controlled trial of patients with spontaneous ICH (<6h of onset) and elevated systolic blood pressure (SBP, 150–220 mmHg) assigned to intensive (target SBP <140 mmHg) or guideline-recommended (SBP <180 mmHg) BP treatment. We linked individual level hourly temperature to baseline data of 1997 participants, and performed case-crossover analyses using a distributed lag non-linear model with 24h lag period to assess the association of ambient temperature and risk of ICH. Results were presented as overall cumulative odds ratios (ORs) and 95% CI. Results Low ambient temperature (≤10°C) was associated with increased risks of ICH: overall cumulative OR was 1.37 (0.99–1.91) for 10°C, 1.92 (1.31–2.81) for 0°C, 3.13 (1.89–5.19) for -10°C, and 5.76 (2.30–14.42) for -20°C, as compared with a reference temperature of 20°C.There was no clear relation of low temperature beyond three hours after exposure. Results were consistent in sensitivity analyses. Conclusions Exposure to low ambient temperature within several hours increases the risk of ICH. Trial Registration ClinicalTrials.gov NCT00716079 PMID:26859491

Aspirin for acute stroke of unknown etiology in resource-limited settings: a decision analysis.

PubMed

Berkowitz, Aaron L; Westover, M Brandon; Bianchi, Matt T; Chou, Sherry H-Y

2014-08-26

To analyze the potential impact of aspirin on outcome at hospital discharge after acute stroke in resource-limited settings without access to neuroimaging to distinguish ischemic stroke from intracerebral hemorrhage (ICH). A decision analysis was conducted to evaluate aspirin use in all patients with acute stroke of unknown type for the duration of initial hospitalization. Data were obtained from the International Stroke Trial and Chinese Acute Stroke Trial. Predicted in-hospital mortality and stroke recurrence risk were determined across the worldwide reported range of the proportion of strokes caused by ICH. Sensitivity analyses were performed on aspirin-associated relative risks in patients with ICH. At the highest reported proportion of strokes due to ICH from a large epidemiologic study (34% in sub-Saharan Africa), aspirin initiation after acute stroke of undetermined etiology is predicted to reduce in-hospital mortality (from 85/1,000 without treatment to 81/1,000 with treatment), in-hospital stroke recurrence (58/1,000 to 50/1,000), and combined risk of in-hospital mortality or stroke recurrence (127/1,000 to 114/1,000). Benefits of aspirin therapy remained in sensitivity analyses across a range of plausible parameter estimates for relative risks associated with aspirin initiation after ICH. Aspirin treatment for the period of initial hospitalization after acute stroke of undetermined etiology is predicted to decrease acute stroke-related mortality and in-hospital stroke recurrence even at the highest reported proportion of acute strokes due to ICH. In the absence of clinical trials to test this approach empirically, clinical decisions require patient-specific evaluation of risks and benefits of aspirin in this context. © 2014 American Academy of Neurology.

Low free triiodothyronine levels predict symptomatic intracranial hemorrhage and worse short-term outcome of thrombolysis in patients with acute ischemia stroke

PubMed Central

Qiu, Mingjing; Fang, Min; Liu, Xueyuan

2017-01-01

Abstract The aim of the study was to determine whether thyroid hormones level on admission in patients with ischemic stroke, treated with intravenous recombinant tissue type plasminogen activator (rtPA), was associated with symptomatic intracranial hemorrhage (sICH) and worse outcomes at 3 months. Patients with acute ischemic stroke (AIS) receiving intravenous rtPA thrombolytic treatment on our stroke unit between January 2015 and June 2016 were included in this study. Serum-free triiodothyronine (fT3), free thyroxine (fT4), total triiodothyronine (tT3), total thyroxine (tT4), and thyroid-stimulating hormone (TSH) were detected on admission. The endpoints were sICH, and poor functional outcomes at 3 and 6 months. In all, 159 patients (106 males; mean age 65.36 ± 10.02 years) were included. FT3 was independently associated with sICH (odds ratio [OR] 0.204, 95% confidence interval [CI] 0.065–0.642) and poor outcomes at 3 months (OR 0.396, 95% CI 0.180–1.764). The cut-off values of fT3 for sICH was 3.54 pg/mL (sensitivity 83%; specificity 83%; area under the curve 0.88). FT3 values ≤3.54 pg/mL increased risk for sICH by 3.16-fold (95% CI 0.75–1.0) compared with fT3 values >3.54 pg/mL. Low fT3 levels at admission were independently associated with sICH and worse outcomes at 3 months in AIS patients receiving rtPA thrombolytic therapy. PMID:29137061

Determinants and Prognostic Significance of Hematoma Sedimentation Levels in Acute Intracerebral Hemorrhage.

PubMed

Sato, Shoichiro; Delcourt, Candice; Zhang, Shihong; Arima, Hisatomi; Heeley, Emma; Zheng, Danni; Al-Shahi Salman, Rustam; Stapf, Christian; Tzourio, Christophe; Robinson, Thompson; Lindley, Richard I; Chalmers, John; Anderson, Craig S

2016-01-01

This study aimed at identifying the determinants and prognostic significance of a sedimentation level (fluid-blood level) in the hematoma among patients with acute intracerebral hemorrhage (ICH) who participated in the main Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT2). Post-hoc analysis of the INTERACT2 dataset, a randomized controlled trial of patients with acute ICH with elevated systolic blood pressure (SBP), randomly assigned to intensive (target SBP <140 mm Hg) or guideline-based (<180 mm Hg) BP management. Patients with a sedimentation level at baseline assessment on CT, and modified Rankin Scale score at 90-day, were included in these analyses. Factors associated with a sedimentation level and its significance in relation to 90-day clinical outcomes were assessed in univariable and multivariable logistic regression models. Of 2,065 participants, 19 (1%) had sedimentation level on baseline CT, which was independently associated with warfarin use (p = 0.006) and lobar ICH (p = 0.025). Sedimentation level was also associated with death or major disability at 90-day in both crude (84 vs. 53%; p = 0.014) and multivariable analyses adjusted for age, gender, Chinese region, warfarin use, baseline National Institutes of Health Stroke Scale score, onset to CT time, volume and location of ICH, intraventricular extension, and randomized intensive BP lowering (OR 3.94, 95% CI 1.01-15.37; p = 0.049). The presence of hematoma sedimentation level on baseline CT is associated with warfarin use and lobar location of ICH, and predicts a worse outcome. Although uncommon, sedimentation level is an easily detectable prognostic factor in acute ICH. © 2015 S. Karger AG, Basel.

Negative spot sign in primary intracerebral hemorrhage: potential impact in reducing imaging.

PubMed

Romero, Javier M; Hito, Rania; Dejam, Andre; Ballesteros, Laia Sero; Cobos, Camilo Jaimes; Liévano, J Ortiz; Ciura, Viesha A; Barnaure, Isabelle; Ernst, Marielle; Liberato, Afonso P; Gonzalez, Gilberto R

2017-02-01

Intracerebral hemorrhage (ICH) is one of the most devastating and costly diagnoses in the USA. ICH is a common diagnosis, accounting for 10-15 % of all strokes and affecting 20 out of 100,000 people. The CT angiography (CTA) spot sign, or contrast extravasation into the hematoma, is a reliable predictor of hematoma expansion, clinical deterioration, and increased mortality. Multiple studies have demonstrated a high negative predictive value (NPV) for ICH expansion in patients without spot sign. Our aim is to determine the absolute NPV of the spot sign and clinical characteristics of patients who had ICH expansion despite the absence of a spot sign. This information may be helpful in the development of a cost effective imaging protocol of patients with ICH. During a 3-year period, 204 patients with a CTA with primary intracerebral hemorrhage were evaluated for subsequent hematoma expansion during their hospitalization. Patients with intraventricular hemorrhage were excluded. Clinical characteristics and antithrombotic treatment on admission were noted. The number of follow-up NCCT was recorded. Of the resulting 123 patients, 108 had a negative spot sign and 7 of those patients subsequently had significant hematoma expansion, 6 of which were on antithrombotic therapy. The NPV of the CTA spot sign was calculated at 0.93. In patients without antithrombotic therapy, the NPV was 0.98. In summary, the negative predictive value of the CTA spot sign for expansion of ICH, in the absence of antithrombotic therapy and intraventricular hemorrhage (IVH) on admission, is very high. These results have the potential to redirect follow-up imaging protocols and reduce cost.

MRI markers of small vessel disease in lobar and deep hemispheric intracerebral hemorrhage

PubMed Central

Smith, Eric E.; Nandigam, Kaveer R.N.; Chen, Yu-Wei; Jeng, Jed; Salat, David; Halpin, Amy; Frosch, Matthew; Wendell, Lauren; Fazen, Louis; Rosand, Jonathan; Viswanathan, Anand; Greenberg, Steven M.

2014-01-01

Background MRI evidence of small vessel disease is common in intracerebral hemorrhage (ICH). We hypothesized that ICH caused by cerebral amyloid angiopathy (CAA) or hypertensive vasculopathy would have different distributions of MRI T2 white matter hyperintensity (WMH) and microbleeds (MB). Methods Data were analyzed from 133 consecutive patients with primary supratentorial ICH and adequate MRI sequences. CAA was diagnosed using the Boston criteria. WMH segmentation was performed using a validated semi-automated method. WMH and MB were compared according to site of symptomatic hematoma origin (lobar vs. deep) or by pattern of hemorrhages, including both hematomas and MB, on MRI GRE sequence (grouped as lobar only--probable CAA, lobar only--possible CAA, deep hemispheric only, or mixed lobar and deep hemorrhages). Results Lobar and deep hemispheric hematoma patients had similar median nWMH volumes (19.5 cm vs. 19.9 cm3, p=0.74) and prevalence of ≥1 MB (54% vs. 52%, p=0.99). The supratentorial WMH distribution was similar according to hemorrhage location category, however the prevalence of brainstem T2 hyperintensity was lower in lobar hematoma vs. deep hematoma (54% vs. 70%, p=0.004). Mixed ICH was common (23%). Mixed ICH patients had large nWMH volumes and a posterior distribution of cortical hemorrhages similar to that seen in CAA. Conclusions WMH distribution is largely similar between CAA-related and non-CAA-related ICH. Mixed lobar and deep hemorrhages are seen on MRI GRE in up to one quarter of patients; in these patients both hypertension and CAA may be contributing to the burden of WMH. PMID:20689084

MRI markers of small vessel disease in lobar and deep hemispheric intracerebral hemorrhage.

PubMed

Smith, Eric E; Nandigam, Kaveer R N; Chen, Yu-Wei; Jeng, Jed; Salat, David; Halpin, Amy; Frosch, Matthew; Wendell, Lauren; Fazen, Louis; Rosand, Jonathan; Viswanathan, Anand; Greenberg, Steven M

2010-09-01

MRI evidence of small vessel disease is common in intracerebral hemorrhage (ICH). We hypothesized that ICH caused by cerebral amyloid angiopathy (CAA) or hypertensive vasculopathy would have different distributions of MRI T2 white matter hyperintensity (WMH) and microbleeds. Data were analyzed from 133 consecutive patients with primary supratentorial ICH and adequate MRI sequences. CAA was diagnosed using the Boston criteria. WMH segmentation was performed using a validated semiautomated method. WMH and microbleeds were compared according to site of symptomatic hematoma origin (lobar versus deep) or by pattern of hemorrhages, including both hematomas and microbleeds, on MRI gradient recalled echo sequence (grouped as lobar only-probable CAA, lobar only-possible CAA, deep hemispheric only, or mixed lobar and deep hemorrhages). Patients with lobar and deep hemispheric hematoma had similar median normalized WMH volumes (19.5 cm versus 19.9 cm(3), P=0.74) and prevalence of >or=1 microbleed (54% versus 52%, P=0.99). The supratentorial WMH distribution was similar according to hemorrhage location category; however, the prevalence of brain stem T2 hyperintensity was lower in lobar hematoma versus deep hematoma (54% versus 70%, P=0.004). Mixed ICH was common (23%). Patients with mixed ICH had large normalized WMH volumes and a posterior distribution of cortical hemorrhages similar to that seen in CAA. WMH distribution is largely similar between CAA-related and non-CAA-related ICH. Mixed lobar and deep hemorrhages are seen on MRI gradient recalled echo sequence in up to one fourth of patients; in these patients, both hypertension and CAA may be contributing to the burden of WMH.

Pretreatment Blood Brain Barrier Damage and Post Treatment Intracranial Hemorrhage in Patients Receiving IV tPA

PubMed Central

Leigh, Richard; Jen, Shyian S.; Hillis, Argye E.; Krakauer, John W.; Barker, Peter B.

2014-01-01

Background and Purpose Early blood brain barrier (BBB) damage after acute ischemic stroke (AIS) has previously been qualitatively linked to subsequent intracranial hemorrhage (ICH). In this quantitative study, it was investigated whether the amount of BBB damage evident on pre-tPA MRI scans was related to the degree of post-tPA ICH in patients with AIS. Methods Analysis was performed on a database of patients with AIS provided by the STIR and VISTA Imaging Investigators. Patients with perfusion-weighted imaging (PWI) lesions >10mL and negative gradient-recalled echo (GRE) imaging prior to IV tPA were included. Post processing of the PWI source images was performed to estimate changes in BBB permeability within the perfusion deficit relative to the unaffected hemisphere. Follow-up GRE images were reviewed for evidence of ICH and divided into three groups according to ECASS criteria: no hemorrhage (NH), hemorrhagic infarction (HI), and parenchymal hematoma (PH). Results 75 patients from the database met the inclusion criteria, 28 of whom experienced ICH, of which 19 were classified as HI, and nine were classified as PH. The mean permeability (±standard deviations), expressed as an index of contrast leakage, was 17.0%±8.8 in the NH group, 19.4%±4.0 in the HI group, and 24.6%±4.5 in the PH group. Permeability was significantly correlated with ICH grade in univariate (p=0.007) and multivariate (p=0.008) linear regression modeling. Conclusions A PWI-derived index of BBB damage measured prior to IV tPA is associated with the severity of ICH after treatment in patients with AIS. PMID:24876245

75 FR 17148 - International Conference on Harmonisation; Guidance on Q4B Evaluation and Recommendation of...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-05

...] International Conference on Harmonisation; Guidance on Q4B Evaluation and Recommendation of Pharmacopoeial Texts... Recommendation of Pharmacopoeial Texts for Use in the ICH Regions; Annex 7: Dissolution Test General Chapter... results of the ICH Q4B evaluation of the Dissolution Test General Chapter harmonized text from each of the...

75 FR 17147 - International Conference on Harmonisation; Guidance on Q4B Evaluation and Recommendation of...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-05

...] International Conference on Harmonisation; Guidance on Q4B Evaluation and Recommendation of Pharmacopoeial Texts... Recommendation of Pharmacopoeial Texts for Use in the ICH Regions; Annex 9: Tablet Friability General Chapter... results of the ICH Q4B evaluation of the Tablet Friability General Chapter harmonized text from each of...

Regulatory T cells ameliorate intracerebral hemorrhage-induced inflammatory injury by modulating microglia/macrophage polarization through the IL-10/GSK3β/PTEN axis.

PubMed

Zhou, Kai; Zhong, Qi; Wang, Yan-Chun; Xiong, Xiao-Yi; Meng, Zhao-You; Zhao, Ting; Zhu, Wen-Yao; Liao, Mao-Fan; Wu, Li-Rong; Yang, Yuan-Rui; Liu, Juan; Duan, Chun-Mei; Li, Jie; Gong, Qiu-Wen; Liu, Liang; Yang, Mei-Hua; Xiong, Ao; Wang, Jian; Yang, Qing-Wu

2017-03-01

Inflammation mediated by the peripheral infiltration of inflammatory cells plays an important role in intracerebral hemorrhage (ICH) induced secondary injury. Previous studies have indicated that regulatory T lymphocytes (Tregs) might reduce ICH-induced inflammation, but the precise mechanisms that contribute to ICH-induced inflammatory injury remain unclear. Our results show that the number of Tregs in the brain increases after ICH. Inducing Tregs deletion using a CD25 antibody or Foxp3 DTR -mice increased neurological deficient scores (NDS), the level of inflammatory factors, hematoma volumes, and neuronal degeneration. Meanwhile, boosting Tregs using a CD28 super-agonist antibody reduced the inflammatory injury. Furthermore, Tregs depletion shifted microglia/macrophage polarization toward the M1 phenotype while boosting Tregs shifted this transition toward the M2 phenotype. In vitro, a transwell co-culture model of microglia and Tregs indicated that Tregs changed the polarization of microglia, decreased the expression of MHC-II, IL-6, and TNF-α and increased CD206 expression. IL-10 originating from Tregs mediated the microglia polarization by increasing the expression of Glycogen Synthase Kinase 3 beta (GSK3β), which phosphorylates and inactivates Phosphatase and Tensin homologue (PTEN) in microglia, TGF-β did not participate in this conversion. Thus, Tregs ameliorated ICH-induced inflammatory injury by modulating microglia/macrophage polarization toward the M2 phenotype through the IL-10/GSK3β/PTEN axis.

Severe bleeding complications other than intracranial hemorrhage in neonatal alloimmune thrombocytopenia: a case series and review of the literature.

PubMed

Winkelhorst, Dian; Kamphuis, Marije M; de Kloet, Liselotte C; Zwaginga, Jaap Jan; Oepkes, Dick; Lopriore, Enrico

2016-05-01

The most feared bleeding complication in fetal and neonatal alloimmune thrombocytopenia (FNAIT) is an intracranial hemorrhage (ICH). However, FNAIT may also lead to other severe bleeding problems. The aim was to analyze this spectrum and evaluate the occurrence of severe hemorrhages other than ICH in fetuses or neonates with FNAIT. A retrospective chart analysis of cases of FNAIT presenting with severe bleeding complications other than ICH at our institution from 1990 to 2015 was conducted. Additionally, a review of the literature was performed to identify case reports and case series on FNAIT presenting with extracranial hemorrhage. Of 25 fetuses or neonates with severe bleeding due to FNAIT, three had isolated severe internal organ hemorrhage other than ICH, two pulmonary hemorrhages and one gastrointestinal hemorrhage. Two of these three neonates died due to this bleeding. Eighteen cases of extracranial bleeding complications as a first presentation of FNAIT were found in the literature, including ocular, gastrointestinal, spinal cord, pulmonary, renal, subgaleal, and genitourinary hemorrhages. Bleeding complications other than ICH may be more extensive, and the presentation of FNAIT may have a greater spectrum than previously described. A high index of suspicion on the possible diagnosis of FNAIT with any bleeding complication in a fetus or neonate may enable adequate diagnostics, adequate treatment, and appropriate follow-up in future pregnancies, as is especially relevant for FNAIT. © 2016 AABB.

Motor Skills Training Improves Sensorimotor Dysfunction and Increases Microtubule-Associated Protein 2 mRNA Expression in Rats with Intracerebral Hemorrhage.

PubMed

Tamakoshi, Keigo; Kawanaka, Kentaro; Onishi, Hideaki; Takamatsu, Yasuyuki; Ishida, Kazuto

2016-08-01

In this study, we examined the effects of motor skills training on the sensorimotor function and the expression of genes associated with synaptic plasticity after intracerebral hemorrhage (ICH) in rats. Male Wistar rats were subjected to ICH or sham operation. ICH was caused by the injection of collagenase into the left striatum. Rats were randomly assigned to no training, acrobatic training, and sham groups. The acrobatic group performed 5 types of acrobatic tasks from 4 to 28 days after surgery. The forelimb sensorimotor function was evaluated over time using forepaw grasping, forelimb placing, and postural instability tests. At 14 and 29 days after the lesion, we analyzed the mRNA expression levels of microtubule-associated protein 2 (MAP2), brain-derived neurotrophic factor, and growth-associated protein 43 in the bilateral sensorimotor cortex (forelimb area) by real-time reverse transcription-polymerase chain reaction. Motor skills training in ICH rats improved the sensorimotor dysfunction significantly from the early phase. The mRNA expression level of MAP2 was upregulated in the ipsilesional sensorimotor cortex by motor skills training at 29 days after the lesion. Our results suggest that sensorimotor functional recovery following motor skills training after ICH is promoted by dendritic growth in the ipsilesional sensorimotor cortex. Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Combinatorial interaction between CCM pathway genes precipitates hemorrhagic stroke.

PubMed

Gore, Aniket V; Lampugnani, Maria Grazia; Dye, Louis; Dejana, Elisabetta; Weinstein, Brant M

2008-01-01

Intracranial hemorrhage (ICH) is a particularly severe form of stroke whose etiology remains poorly understood, with a highly variable appearance and onset of the disease (Felbor et al., 2006; Frizzell, 2005; Lucas et al., 2003). In humans, mutations in any one of three CCM genes causes an autosomal dominant genetic ICH disorder characterized by cerebral cavernous malformations (CCM). Recent evidence highlighting multiple interactions between the three CCM gene products and other proteins regulating endothelial junctional integrity suggests that minor deficits in these other proteins could potentially predispose to, or help to initiate, CCM, and that combinations of otherwise silent genetic deficits in both the CCM and interacting proteins might explain some of the variability in penetrance and expressivity of human ICH disorders. Here, we test this idea by combined knockdown of CCM pathway genes in zebrafish. Reducing the function of rap1b, which encodes a Ras GTPase effector protein for CCM1/Krit1, disrupts endothelial junctions in vivo and in vitro, showing it is a crucial player in the CCM pathway. Importantly, a minor reduction of Rap1b in combination with similar reductions in the products of other CCM pathway genes results in a high incidence of ICH. These findings support the idea that minor polygenic deficits in the CCM pathway can strongly synergize to initiate ICH.

Risk of Symptomatic Intracerebral Hemorrhage After Intravenous Thrombolysis in Patients With Acute Ischemic Stroke and High Cerebral Microbleed Burden: A Meta-analysis.

PubMed

Tsivgoulis, Georgios; Zand, Ramin; Katsanos, Aristeidis H; Turc, Guillaume; Nolte, Christian H; Jung, Simon; Cordonnier, Charlotte; Fiebach, Jochen B; Scheitz, Jan F; Klinger-Gratz, Pascal P; Oppenheim, Catherine; Goyal, Nitin; Safouris, Apostolos; Mattle, Heinrich P; Alexandrov, Anne W; Schellinger, Peter D; Alexandrov, Andrei V

2016-06-01

Cerebral microbleeds (CMBs) have been established as an independent predictor of cerebral bleeding. There are contradictory data regarding the potential association of CMB burden with the risk of symptomatic intracerebral hemorrhage (sICH) in patients with acute ischemic stroke (AIS) treated with intravenous thrombolysis (IVT). To investigate the association of high CMB burden (>10 CMBs on a pre-IVT magnetic image resonance [MRI] scan) with the risk of sICH following IVT for AIS. Eligible studies were identified by searching Medline and Scopus databases. No language or other restrictions were imposed. The literature search was conducted on October 7, 2015. This meta-analysis has adopted the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and was written according to the Meta-analysis of Observational Studies in Epidemiology (MOOSE) proposal. Eligible prospective study protocols that reported sICH rates in patients with AIS who underwent MRI for CMB screening prior to IVT. The reported rates of sICH complicating IVT in patients with AIS with pretreatment MRI were extracted independently for groups of patients with 0 CMBs (CMB absence), 1 or more CMBs (CMB presence), 1 to 10 CMBs (low to moderate CMB burden), and more than 10 CMBs (high CMB burden). An individual-patient data meta-analysis was also performed in the included studies that provided complete patient data sets. Symptomatic intracerebral hemorrhage based on the European Cooperative Acute Stroke Study-II definition (any intracranial bleed with ≥4 points worsening on the National Institutes of Health Stroke Scale score). We included 9 studies comprising 2479 patients with AIS. The risk of sICH after IVT was found to be higher in patients with evidence of CMB presence, compared with patients without CMBs (risk ratio [RR], 2.36; 95% CI, 1.21-4.61; P = .01). A higher risk for sICH after IVT was detected in patients with high CMB burden (>10 CMBs) when compared with

Kawachin na ri kitzij-kipixab' Qanan Qatat--Florezcan las palabras de los hombres de maiz (The Blossoming of Our Ancestors' Words). [CD-ROM].

ERIC Educational Resources Information Center

Academy for Educational Development, Washington, DC.

This CD-ROM is part of an interactive and dynamic multimedia package of information and games for learning K'iche' and Ixil. This CD-ROM contains selected radio programs for preschool students, scripted from the four storybooks created by Project "Enlace Quiche." It includes stories in K'iche', Ixil, and Spanish. (VWL)

Glial glutamate transporters expression, glutamate uptake, and oxidative stress in an experimental rat model of intracerebral hemorrhage.

PubMed

Neves, J D; Vizuete, A F; Nicola, F; Da Ré, C; Rodrigues, A F; Schmitz, F; Mestriner, R G; Aristimunha, D; Wyse, A T S; Netto, C A

2018-06-01

Glial glutamate transporters (EAAT1 and EAAT2), glutamate uptake, and oxidative stress are important players in the pathogenesis of ischemic brain injury. However, the changes in EAAT1 and EAAT2 expression, glutamate uptake and the oxidative profile during intracerebral hemorrhage (ICH) development have not been described. The present study sought to investigate the changes of the above-mentioned variables, as well as the Na + /K + -ATP ase and glutamine synthetase activities (as important contributors of glutamate homeostasis) and the percentage of neuronal cells after 6 h, 24 h, 72 h and 7 days of ICH. An injection of 0.2U of bacterial collagenase in the ipsilateral striatum was used to induce ICH in male Wistar rats; naïve animals were used as controls. EAAT1 and EAAT2 expression and glutamate uptake in the ipsilateral striatum were assessed. Additionally, the percentage of MAP2+ cells, Na + /K + -ATP ase and GS activities, as well as the oxidative profile were analyzed. It is shown a decrease of EAAT1 expression and glutamate uptake 6 h post-ICH, whereas EAAT2 decreased 72 h after the event; conversely EAAT2 and glutamate uptake were increased after 7 days. The oxidative stress and endogenous defense system exhibited a remarkable response at 72 h of injury. ICH also increased Na + /K + -ATP ase activity and selectively decreased GS activity, variables known to be important contributors of glial glutamate transporters activities. Altogether, present findings indicate that ICH induces different temporal EAAT1 and EAAT2 responses, culminating with an imbalance of glutamate uptake capacity, increased oxidative stress and sustained neuronal loss. Copyright © 2018 Elsevier Ltd. All rights reserved.

Intraoperative imaging for patient safety and QA: detection of intracranial hemorrhage using C-arm cone-beam CT

NASA Astrophysics Data System (ADS)

Schafer, Sebastian; Wang, Adam; Otake, Yoshito; Stayman, J. W.; Zbijewski, Wojciech; Kleinszig, Gerhard; Xia, Xuewei; Gallia, Gary L.; Siewerdsen, Jeffrey H.

2013-03-01

Intraoperative imaging could improve patient safety and quality assurance (QA) via the detection of subtle complications that might otherwise only be found hours after surgery. Such capability could therefore reduce morbidity and the need for additional intervention. Among the severe adverse events that could be more quickly detected by high-quality intraoperative imaging is acute intracranial hemorrhage (ICH), conventionally assessed using post-operative CT. A mobile C-arm capable of high-quality cone-beam CT (CBCT) in combination with advanced image reconstruction techniques is reported as a means of detecting ICH in the operating room. The system employs an isocentric C-arm with a flat-panel detector in dual gain mode, correction of x-ray scatter and beam-hardening, and a penalized likelihood (PL) iterative reconstruction method. Performance in ICH detection was investigated using a quantitative phantom focusing on (non-contrast-enhanced) blood-brain contrast, an anthropomorphic head phantom, and a porcine model with injection of fresh blood bolus. The visibility of ICH was characterized in terms of contrast-to-noise ratio (CNR) and qualitative evaluation of images by a neurosurgeon. Across a range of size and contrast of the ICH as well as radiation dose from the CBCT scan, the CNR was found to increase from ~2.2-3.7 for conventional filtered backprojection (FBP) to ~3.9-5.4 for PL at equivalent spatial resolution. The porcine model demonstrated superior ICH detectability for PL. The results support the role of high-quality mobile C-arm CBCT employing advanced reconstruction algorithms for detecting subtle complications in the operating room at lower radiation dose and lower cost than intraoperative CT scanners and/or fixedroom C-arms. Such capability could present a potentially valuable aid to patient safety and QA.

Predictors of symptomatic intracranial haemorrhage in patients with an ischaemic stroke with neurological deterioration after intravenous thrombolysis.

PubMed

James, Brandon; Chang, Andrew D; McTaggart, Ryan A; Hemendinger, Morgan; Mac Grory, Brian; Cutting, Shawna M; Burton, Tina M; Reznik, Michael E; Thompson, Bradford; Wendell, Linda; Mahta, Ali; Siket, Matthew; Madsen, Tracy E; Sheth, Kevin N; Nouh, Amre; Furie, Karen L; Jayaraman, Mahesh V; Khatri, Pooja; Yaghi, Shadi

2018-02-27

Early neurological deterioration prompting urgent brain imaging occurs in nearly 15% of patients with ischaemic stroke receiving intravenous tissue plasminogen activator (tPA). We aim to determine risk factors associated with symptomatic intracranial haemorrhage (sICH) in patients with ischaemic stroke undergoing emergent brain imaging for early neurological deterioration after receiving tPA. We abstracted data from our prospective stroke database and included all patients receiving tPA for ischaemic stroke between 1 March 2015 and 1 March 2017. We then identified patients with neurological deterioration who underwent urgent brain imaging prior to their per-protocol surveillance imaging and divided patients into two groups: those with and without sICH. We compared baseline demographics, clinical variables, in-hospital treatments and functional outcomes at 90 days between the two groups. We identified 511 patients who received tPA, of whom 108 (21.1%) had an emergent brain CT. Of these patients, 17.5% (19/108) had sICH; 21.3% (23/108) of emergent scans occurred while tPA was infusing, though only 4.3% of these scans (1/23) revealed sICH. On multivariable analyses, the only predictor of sICH was a change in level of consciousness (OR 6.62, 95% CI 1.64 to 26.70, P=0.008). Change in level of consciousness is associated with sICH among patients undergoing emergent brain imaging after receiving tPA. In this group of patients, preparation of tPA reversal agents while awaiting brain imaging may reduce reversal times. Future studies are needed to study the cost-effectiveness of this approach. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Do Intracerebral Hemorrhage Nonexpanders Actually Expand Into the Ventricular Space?

PubMed

Dowlatshahi, Dar; Deshpande, Anirudda; Aviv, Richard I; Rodriguez-Luna, David; Molina, Carlos A; Blas, Yolanda Silva; Dzialowski, Imanuel; Kobayashi, Adam; Boulanger, Jean-Martin; Lum, Cheemun; Gubitz, Gordon J; Padma, Vasantha; Roy, Jayanta; Kase, Carlos S; Bhatia, Rohit; Hill, Michael D; Demchuk, Andrew M

2018-01-01

The computed tomographic angiography spot sign as a predictor of hematoma expansion is limited by its modest sensitivity and positive predictive value. It is possible that hematoma expansion in spot-positive patients is missed because of decompression of intracerebral hemorrhage (ICH) into the ventricular space. We hypothesized that revising hematoma expansion definitions to include intraventricular hemorrhage (IVH) expansion will improve the predictive performance of the spot sign. Our objectives were to determine the proportion of ICH nonexpanders who actually have IVH expansion, determine the proportion of false-positive spot signs that have IVH expansion, and compare the known predictive performance of the spot sign to a revised definition incorporating IVH expansion. We analyzed patients from the multicenter PREDICT ICH spot sign study. We defined hematoma expansion as ≥6 mL or ≥33% ICH expansion or >2 mL IVH expansion and compared spot sign performance using this revised definition with the conventional 6 mL/33% definition using receiver operating curve analysis. Of 311 patients, 213 did not meet the 6-mL/33% expansion definition (nonexpanders). Only 13 of 213 (6.1%) nonexpanders had ≥2 mL IVH expansion. Of the false-positive spot signs, 4 of 40 (10%) had >2 mL ventricular expansion. The area under the curve for spot sign to predict significant ICH expansion was 0.65 (95% confidence interval, 0.58-0.72), which was no different than when IVH expansion was added to the definition (area under the curve, 0.66; 95% confidence interval, 0.58-0.71). Although IVH expansion does indeed occur in a minority of ICH nonexpanders, its inclusion into a revised hematoma expansion definition does not alter the predictive performance of the spot sign. © 2017 American Heart Association, Inc.

Anemia on admission increases the risk of mortality at 6 months and 1 year in hemorrhagic stroke patients in China.

PubMed

Zeng, Yi-Jun; Liu, Gai-Fen; Liu, Li-Ping; Wang, Chun-Xue; Zhao, Xing-Quan; Wang, Yong-Jun

2014-07-01

The relationship between anemia and intracerebral hemorrhage is not clear. We investigated the associations between anemia at the onset and mortality or dependency in patients with intracerebral hemorrhage (ICH) registered at the China National Stroke Registry (CNSR). The CNSR recruited consecutive patients with diagnoses of ICH in 2007-2008. Their vascular risk factors, clinical presentations, and outcomes were recorded. The mortality and dependency at 1, 3, and 6 months and at 1 year were compared between ICH patients with and without anemia. A favorable outcome was defined as a modified Rankin Scale (mRS) score of 2 or less and a poor outcome as an mRS score of 3 or more. Multivariable logistic regression was performed to analyze the association between anemia and the 2 outcomes after adjusting for age, gender, body mass index, history of smoking and heavy drinking, National Institutes of Health Stroke Scale score on admission, random glucose value on admission, and hematoma volume. Anemia was identified in 484 (19%) ICH patients. Compared with ICH patients without anemia, patients with anemia had no difference in mortality rate at discharge and at 1 month. The rate of mortality at 3 months, 6 months, 1 year, and dependency at 1 year were significantly higher for those patients with anemia than those without (P<.05, P<.001, P<.001, and P<.05, respectively). After adjusting for potential confounders, anemia was an independent risk factor for death at 6 months and 1 year (adjusted odds ratio [OR]=1.338, 95% confidence interval 1.01-1.78, and adjusted OR=1.326, 95% confidence interval 1.00-1.75) in ICH patients. Anemia independently predicted mortality at 6 months and 1 year after the initial episode of intercerebral hemorrhage. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

The association of ideal cardiovascular health with incident type 2 diabetes mellitus: the Multi-Ethnic Study of Atherosclerosis.

PubMed

Joseph, Joshua J; Echouffo-Tcheugui, Justin B; Carnethon, Mercedes R; Bertoni, Alain G; Shay, Christina M; Ahmed, Haitham M; Blumenthal, Roger S; Cushman, Mary; Golden, Sherita H

2016-09-01

Levels of ideal cardiovascular health (ICH) and incident type 2 diabetes mellitus have not been examined in a multiethnic population. We assessed the total and race/ethnicity-specific incidence of diabetes based on American Heart Association (AHA) ICH components. Incident diabetes was assessed among 5341 participants in the Multi-Ethnic Study of Atherosclerosis without prevalent diabetes between 2002 and 2012. ICH components (total cholesterol, BP, dietary intake, tobacco use, physical activity and BMI) were assessed at baseline and participants were categorised as having ideal, intermediate or poor cardiovascular health, as defined by the AHA 2020 impact goals. We developed a scoring system based on the number of ICH components (0-1 'poor', 2-3 'intermediate', and ≥4 'ideal'). HRs were calculated using Cox models. During a median follow-up of 11.1 years, we identified 587 cases of incident diabetes. After multivariable adjustment, participants with 2-3 and ≥4 ICH components vs 0-1 components had a 34% lower (HR 0.66; 95% CI 0.54, 0.80) and a 75% lower (HR 0.25; 95% CI 0.18, 0.35) diabetes incidence, respectively. There were significant differences by race/ethnicity: African-American and Hispanic-American participants with ≥4 ICH components had diabetes incidence rates per 1000 person-years of 5.6 (95% CI 3.1, 10.1) and 10.5 (95% CI 6.7, 16.4), respectively, compared with 2.2 (95% CI 1.3, 3.7) among non-Hispanic white Americans. Meeting an increasing number of AHA 2020 impact goals for dietary intake, physical activity, smoking, BP, cholesterol and BMI was associated with a dose-dependent lower risk of diabetes with significant variation by race/ethnicity.

In-hospital mortality after pre-treatment with antiplatelet agents or oral anticoagulants and hematoma evacuation of intracerebral hematomas.

PubMed

Stein, Marco; Misselwitz, Björn; Hamann, Gerhard F; Kolodziej, Malgorzata; Reinges, Marcus H T; Uhl, Eberhard

2016-04-01

Pre-treatment with antiplatelet agents is described to be a risk factor for mortality after spontaneous intracerebral hemorrhage (ICH). However, the impact of antithrombotic agents on mortality in patients who undergo hematoma evacuation compared to conservatively treated patients with ICH remains controversial. This analysis is based on a prospective registry for quality assurance in stroke care in the State of Hesse, Germany. Patients' data were collected between January 2008 and December 2012. Only patients with the diagnosis of spontaneous ICH were included (International Classification of Diseases 10th Revision codes I61.0-I61.9). Predictors of in-hospital mortality were determined by univariate analysis. Predictors with P<0.1 were included in a binary logistic regression model. The binary logistic regression model was adjusted for age, initial Glasgow Coma Score (GCS), the presence of intraventricular hemorrhage (IVH), and pre-ICH disability prior to ictus. In 8,421 patients with spontaneous ICH, pre-treatment with oral anticoagulants or antiplatelet agents was documented in 16.3% and 25.1%, respectively. Overall in-hospital mortality was 23.2%. In-hospital mortality was decreased in operatively treated patients compared to conservatively treated patients (11.6% versus 24.0%; P<0.001). Patients with antiplatelet pre-treatment had a significantly higher risk of death during the hospital stay after hematoma evacuation (odds ratio [OR]: 2.5; 95% confidence interval [CI]: 1.24-4.97; P=0.010) compared to patients without antiplatelet pre-treatment treatment (OR: 0.9; 95% CI: 0.79-1.09; P=0.376). In conclusion a higher rate of in-hospital mortality after pre-treatment with antiplatelet agents in combination with hematoma evacuation after spontaneous ICH was observed in the presented cohort. Copyright © 2015 Elsevier Ltd. All rights reserved.

Low cholesterol level associated with severity and outcome of spontaneous intracerebral hemorrhage: Results from Taiwan Stroke Registry

PubMed Central

Chen, Yu-Wei; Li, Chen-Hua; Yang, Chih-Dong; Liu, Chung-Hsiang; Chen, Chih-Hung; Sheu, Jau-Jiuan; Lin, Shinn-Kuang; Chen, An-Chih; Chen, Ping-Kun; Chen, Po-Lin; Yeh, Chung-Hsin; Chen, Jiunn-Rong; Hsiao, Yu-Jen; Lin, Ching-Huang; Hsu, Shih-Pin; Chen, Tsang-Shan; Sung, Sheng-Feng; Yu, Shih-Chieh; Muo, Chih-Hsin; Wen, Chi Pang; Sung, Fung-Chang; Jeng, Jiann-Shing; Hsu, Chung Y.

2017-01-01

The relationship between cholesterol level and hemorrhagic stroke is inconclusive. We hypothesized that low cholesterol levels may have association with intracerebral hemorrhage (ICH) severity at admission and 3-month outcomes. This study used data obtained from a multi-center stroke registry program in Taiwan. We categorized acute spontaneous ICH patients, based on their baseline levels of total cholesterol (TC) measured at admission, into 3 groups with <160, 160–200 and >200 mg/dL of TC. We evaluated risk of having initial stroke severity, with National Institutes of Health Stroke Scale (NIHSS) >15 and unfavorable outcomes (modified Rankin Scale [mRS] score >2, 3-month mortality) after ICH by the TC group. A total of 2444 ICH patients (mean age 62.5±14.2 years; 64.2% men) were included in this study and 854 (34.9%) of them had baseline TC <160 mg/dL. Patients with TC <160 mg/dL presented more often severe neurological deficit (NIHSS >15), with an adjusted odds ratio [aOR] of 1.80; 95% confidence interval [CI], 1.41–2.30), and 3-month mRS >2 (aOR, 1.41; 95% CI, 1.11–1.78) using patients with TC >200 mg/dL as reference. Those with TC >160 mg/dL and body mass index (BMI) <22 kg/m2 had higher risk of 3-month mortality (aOR 3.94, 95% CI 1.76–8.80). Prior use of lipid-lowering drugs (2.8% of the ICH population) was not associated with initial severity and 3-month outcomes. A total cholesterol level lower than 160 mg/dL was common in patients with acute ICH and was associated with greater neurological severity on presentation and poor 3-month outcomes, especially with lower BMI. PMID:28422955

Educational Placement after Pediatric Intracerebral Hemorrhage

PubMed Central

Hawks, Charlotte; Jordan, Lori C.; Gindville, Melissa; Ichord, Rebecca N.; Licht, Daniel J.; Beslow, Lauren A.

2016-01-01

Objectives This study describes educational placement of school-aged children after spontaneous intracerebral hemorrhage (ICH) and examines whether educational placement is associated with severity of neurological deficits. Methods Children with spontaneous ICH presenting from 2007 to 2013 were prospectively enrolled at 3 tertiary children’s hospitals. The pediatric stroke outcome measure (PSOM) and a parental questionnaire gathered information about neurological outcome, school attendance, and educational placement. Results The cohort of 92 enrolled children included 42 school-aged children (6–17 years) with ICH. Four died; 1 was excluded due to preexisting cognitive deficits. Thirty-seven completed 3-month follow-up, and 30 completed 12-month follow-up. At 12 months, 14 (46.7%) received regular age-appropriate programming, 12 (40%) attended school with in-class services, 3 (10%) were in special education programs, and one child (3.3%) received home-based services due to ICH-related deficits. Of 30 children with 3-month and 12-month follow-up, 14 children (46.7%) improved their education status, 13 (43.3%) remained at the same education level, and 3 (10%) began to receive in-class services. Increasing PSOM score predicted the need for educational modifications at 3 months (OR 3.3, 95% CI 1.4–7.9, p=0.007) and at 12 months (OR 2.1, 95% CI 1.1–3.9, p=0.025). Conclusions Most children returned to school within a year after ICH and many had a reduction in the intensity of educational support. However, a great need for educational services persisted at 12 months after ICH with fewer than half enrolled in regular age-appropriate classes. Worse deficits on the PSOM were associated with remedial educational placement. PMID:27262667

Intracerebral hemorrhage location and outcome among INTERACT2 participants.

PubMed

Delcourt, Candice; Sato, Shoichiro; Zhang, Shihong; Sandset, Else Charlotte; Zheng, Danni; Chen, Xiaoying; Hackett, Maree L; Arima, Hisatomi; Hata, Jun; Heeley, Emma; Al-Shahi Salman, Rustam; Robinson, Thompson; Davies, Leo; Lavados, Pablo M; Lindley, Richard I; Stapf, Christian; Chalmers, John; Anderson, Craig S

2017-04-11

To clarify associations between intracerebral hemorrhage (ICH) location and clinical outcomes among participants of the main phase Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT2). Associations between ICH sites and poor outcomes (death [6] or major disability [3-5] of modified Rankin Scale) and European Quality of Life Scale (EQ-5D) utility scores at 90 days were assessed in logistic regression models. Of 2,066 patients included in the analyses, associations were identified between ICH sites and poor outcomes: involvement of posterior limb of internal capsule increased risks of death or major disability (odds ratio [OR] 2.10) and disability (OR 1.81); thalamic involvement increased risks of death or major disability (OR 2.24) and death (OR 1.97). Involvement of the posterior limb of the internal capsule, thalamus, and infratentorial sites were each associated with poor EQ-5D utility score (≤0.7 [median]; OR 1.87, 2.14, and 2.81, respectively). Posterior limb of internal capsule involvement was strongly associated with low scores across all health-related quality of life domains. ICH encompassing the thalamus and posterior limb of internal capsule were associated with death or major disability, major disability, and poor EQ-5D utility score (OR 1.72, 2.26, and 1.71, respectively). Poor clinical outcomes are related to ICH affecting the posterior limb of internal capsule, thalamus, and infratentorial sites. The highest association with death or major disability and poor EQ-5D utility score was seen in ICH encompassing the thalamus and posterior limb of internal capsule. NCT00716079. Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

SMASH-U: a proposal for etiologic classification of intracerebral hemorrhage.

PubMed

Meretoja, Atte; Strbian, Daniel; Putaala, Jukka; Curtze, Sami; Haapaniemi, Elena; Mustanoja, Satu; Sairanen, Tiina; Satopää, Jarno; Silvennoinen, Heli; Niemelä, Mika; Kaste, Markku; Tatlisumak, Turgut

2012-10-01

The purpose of this study was to provide a simple and practical clinical classification for the etiology of intracerebral hemorrhage (ICH). We performed a retrospective chart review of consecutive patients with ICH treated at the Helsinki University Central Hospital, January 2005 to March 2010 (n=1013). We classified ICH etiology by predefined criteria as structural vascular lesions (S), medication (M), amyloid angiopathy (A), systemic disease (S), hypertension (H), or undetermined (U). Clinical and radiological features and mortality by SMASH-U (Structural lesion, Medication, Amyloid angiopathy, Systemic/other disease, Hypertension, Undetermined) etiology were analyzed. Structural lesions, namely cavernomas and arteriovenous malformations, caused 5% of the ICH, anticoagulation 14%, and systemic disease 5% (23 liver cirrhosis, 8 thrombocytopenia, and 17 various rare conditions). Amyloid angiopathy (20%) and hypertensive angiopathy (35%) were common, but etiology remained undetermined in 21%. Interrater agreement in classifying cases was high (κ, 0.89; 95% CI, 0.82-0.96). Patients with structural lesions had the smallest hemorrhages (median volume, 2.8 mL) and best prognosis (3-month mortality 4%), whereas anticoagulation-related ICHs were largest (13.4 mL) and most often fatal (54%). Overall, median ICH survival was 5½ years, varying strongly by etiology (P<0.001). After adjustment for baseline characteristics, patients with structural lesions had the lowest 3-month mortality rates (OR, 0.06; 95% CI, 0.01-0.37) and those with anticoagulation (OR, 1.9; 1.0-3.6) or other systemic cause (OR, 4.0; 1.6-10.1) the highest. In our patients, performing the SMASH-U classification was feasible and interrater agreement excellent. A plausible etiology was determined in most patients but remained elusive in one in 5. In this series, SMASH-U based etiology was strongly associated with survival.

Stroke and Intracranial Hemorrhage in HeartMate II and HeartWare Left Ventricular Assist Devices: A Systematic Review.

PubMed

Cho, Sung M; Moazami, Nader; Frontera, Jennifer A

2017-08-01

Ischemic stroke and intracranial hemorrhage (ICH) following left ventricular assist device (LVAD) placement are major causes of morbidity. The incidence and mortality associated with these events stratified by device type have not been systematically explored. A systematic review of PubMed was conducted from January 2007 through June 2016 for all English-language articles involving HeartMate II (HMII) and HeartWare LVAD patients. Ischemic stroke and/or ICH incidence (events per patient-year) and associated mortality rates were abstracted for each device type. Of 735 articles reviewed, 48 (11,310 patients) met inclusion criteria (33 HMII, six HeartWare, eight both devices, and one unspecified). The median duration of device support was 112 days (total 13,723 patient-years). Overall, ischemic stroke or ICH occurred in 9.8% (1110 persons and 0.08 events per patient year [EPPY]). Ischemic stroke occurred in a median of 6.0% or 0.06 EPPY (range 0-16% or 0-0.21 EPPY) of HMII patients versus 7.5% or 0.09 EPPY (range 4-17.1% or 0.01-0.94 EPPY) of HeartWare patients. ICH occurred in a median of 3.0% or 0.04 EPPY (range 0-13.5% or 0-0.13 EPPY) of HMII and 8.0% or 0.08 EPPY (range 3-23% or 0.01-0.56 EPPY) of HeartWare patients. The median mortality rate for LVAD-associated ischemic stroke was 31% (HMII: 33%, [range 2.4-75%] and HeartWare: 11.5% [range 3.9-40%]), and the median mortality rate following ICH was 71% (HMII: 75%, [range 3.9-100%] and HeartWare: 44%, [range 3.1-88%]). Ischemic stroke and ICH are common after LVAD placement, but heterogeneous event rates are reported in the literature. Given the high associated mortality, further prospective study is warranted.

Black Hole Sign Predicts Poor Outcome in Patients with Intracerebral Hemorrhage.

PubMed

Li, Qi; Yang, Wen-Song; Chen, Sheng-Li; Lv, Fu-Rong; Lv, Fa-Jin; Hu, Xi; Zhu, Dan; Cao, Du; Wang, Xing-Chen; Li, Rui; Yuan, Liang; Qin, Xin-Yue; Xie, Peng

2018-01-01

In spontaneous intracerebral hemorrhage (ICH), black hole sign has been proposed as a promising imaging marker that predicts hematoma expansion in patients with ICH. The aim of our study was to investigate whether admission CT black hole sign predicts hematoma growth in patients with ICH. From July 2011 till February 2016, patients with spontaneous ICH who underwent baseline CT scan within 6 h of symptoms onset and follow-up CT scan were recruited into the study. The presence of black hole sign on admission non-enhanced CT was independently assessed by 2 readers. The functional outcome was assessed using the modified Rankin Scale (mRS) at 90 days. Univariate and multivariable logistic regression analyses were performed to assess the association between the presence of the black hole sign and functional outcome. A total of 225 patients (67.6% male, mean age 60.3 years) were included in our study. Black hole sign was identified in 32 of 225 (14.2%) patients on admission CT scan. The multivariate logistic regression analysis demonstrated that age, intraventricular hemorrhage, baseline ICH volume, admission Glasgow Coma Scale score, and presence of black hole sign on baseline CT independently predict poor functional outcome at 90 days. There are significantly more patients with a poor functional outcome (defined as mRS ≥4) among patients with black hole sign than those without (84.4 vs. 32.1%, p < 0.001; OR 8.19, p = 0.001). The CT black hole sign independently predicts poor outcome in patients with ICH. Early identification of black hole sign is useful in prognostic stratification and may serve as a potential therapeutic target for anti-expansion clinical trials. © 2018 S. Karger AG, Basel.

Relaxation pathways of photoexcited iodide-methanol clusters: a computational investigation.

PubMed

Mak, Chun C; Peslherbe, Gilles H

2014-06-26

Upon photoexcitation of iodide-methanol clusters, I(-)(CH3OH)n, to a charge-transfer-to-solvent (CTTS) excited state, extensive relaxation was found to occur, accompanied by a convoluted modulation of the stability of the excited electron, which ultimately decreases substantially. In order to develop a molecular-level understanding of the relaxation processes of CTTS excited I(-)(CH3OH)n, high-level quantum chemical calculations are first used to investigate the ground, excited, and ionized states of I(-)(CH3OH)n (n = 2). Because of the relatively small size of I(-)(CH3OH)2, it was possible to characterize the contributions of solvent-solvent interactions to the stability of the CTTS excited cluster relative to dissociation into methanol, iodine, and a free electron, which exhibits a substantial dependence on the cluster geometric configuration. Ab initio molecular dynamics simulations of CTTS excited I(-)(CH3OH)3 are then performed to shed some light onto the nature of the relaxation pathways involved in the modulation of the stability of the excited electron in larger clusters. Simulation results suggest that separation of I and (CH3OH)3(-) accompanied by solvent reorganization in the latter can initially stabilize the excited electron, while gradual cluster fragmentation to I, (CH3OH)2(-), and CH3OH ultimately destabilizes it. This work shows, for the first time, that the inability of small CTTS excited I(-)(CH3OH)n to retain a solvated electron may be attributed to the limited hydrogen-bonding capacity of CH3OH, which increases the propensity for fragmentation to smaller clusters with lower excess-electron binding energies, and highlights the critical role of intricate molecular interactions in the electron solvation process.

Cerebral microbleeds and recurrent stroke risk: systematic review and meta-analysis of prospective ischemic stroke and transient ischemic attack cohorts.

PubMed

Charidimou, Andreas; Kakar, Puneet; Fox, Zoe; Werring, David J

2013-04-01

To evaluate cerebral microbleeds (CMBs) and future stroke risk (including intracerebral hemorrhage [ICH]) in patients with ischemic stroke (IS) or transient ischemic attack. A systematic review and meta-analysis of prospective cohorts with recent IS/transient ischemic attack. We critically appraised studies and calculated pooled odds ratios (ORs), using the Mantel-Haenszel fixed-effects method, for ICH or recurrent IS, in patients with versus without CMBs. We pooled data from 10 cohorts, including 3067 patients. CMBs were associated with a significant increased risk of any recurrent stroke (OR, 2.25; 95% confidence interval [95% CI], 1.70-2.98; P<0.0001), ICH (OR, 8.52; 95%CI, 4.23-17.18; P=0.007), and IS (OR, 1.55; 95%CI, 1.12-2.13; P<0.0001). When stratified by study population ethnicity (Asian versus Western [mainly white European]), the association of CMBs with ICH was significant for Asian cohorts (5 studies; n=1915; OR, 10.43; 95%CI, 4.59-23.72; P<0.0001) but borderline and of lower magnitude for Western cohorts (4 studies; n=885; OR, 3.87; 95%CI, 0.91-16.4; P=0.066). By contrast, there was a significant association of CMBs with recurrent IS in Western (3 studies; n=899) but not Asian cohorts (4 studies; n=1357; OR, 2.23; 95%CI, 1.29-3.85; P=0.004 compared with OR, 1.30; 95%CI, 0.88-1.93; P=0.192, respectively). There is consistent evidence of an increased risk of recurrent stroke after IS or transient ischemic attack in patients with CMBs. The risk for spontaneous ICH appears to be greater than the risk for recurrent IS. Our findings also suggest that the balance of risk for ICH versus IS differs between Asian and Western cohorts.

The association of ideal cardiovascular health with incident type 2 diabetes mellitus: the Multi-Ethnic Study of Atherosclerosis

PubMed Central

Joseph, Joshua J.; Echouffo Tcheugui, Justin B.; Carnethon, Mercedes R.; Bertoni, Alain G.; Shay, Christina M.; Ahmed, Haitham M.; Blumenthal, Roger S.; Cushman, Mary; Golden, Sherita H.

2016-01-01

Aims/hypothesis Levels of ideal cardiovascular health (ICH) and incident type 2 diabetes mellitus have not been examined in a multiethnic population. We assessed the total and race/ethnicity-specific incidence of diabetes based on American Heart Association (AHA) ICH components. Methods Incident diabetes was assessed among 5,341 participants in the Multi-Ethnic Study of Atherosclerosis without prevalent diabetes between 2002 and 2012. ICH components (total cholesterol, BP, dietary intake, tobacco use, physical activity and BMI) were assessed at baseline and participants were categorised as having ideal, intermediate or poor cardiovascular health, as defined by the AHA 2020 impact goals. We developed a scoring system based on the number of ICH components (0–1 ‘poor’, 2–3 ‘intermediate’, and ≥4 ‘ideal’). HRs were calculated using Cox models. Results During a median follow-up of 11.1 years, we identified 587 cases of incident diabetes. After multivariable adjustment, participants with 2-3 and ≥4 ICH components vs 0-1 components had a 34% lower (HR 0.66; 95% CI 0.54, 0.80) and a 75% lower (HR 0.25; 95% CI 0.18, 0.35) diabetes incidence, respectively. There were significant differences by race/ethnicity: African-American and Hispanic-American participants with ≥4 ICH components had diabetes incidence rates per 1,000 person-years of 5.6 (95% CI 3.1, 10.1) and 10.5 (95% CI 6.7, 16.4), respectively, compared with 2.2 (95% CI 1.3, 3.7) among non-Hispanic white Americans. Conclusions/interpretation Meeting an increasing number of AHA 2020 impact goals for dietary intake, physical activity, smoking, BP, cholesterol and BMI was associated with a dose-dependent lower risk of diabetes with significant variation by race/ethnicity. PMID:27272340

Influence of stroke subtype on quality of care in the Get With The Guidelines-Stroke Program.

PubMed

Smith, E E; Liang, L; Hernandez, A; Reeves, M J; Cannon, C P; Fonarow, G C; Schwamm, L H

2009-09-01

Little is known about in-hospital care for hemorrhagic stroke. We examined quality of care in intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH) admissions in the national Get With The Guidelines-Stroke (GWTG-Stroke) database, and compared them to ischemic stroke (IS) or TIA admissions. Between April 1, 2003, and December 30, 2007, 905 hospitals contributed 479,284 consecutive stroke and TIA admissions. The proportions receiving each quality of care measure were calculated by dividing the total number of patients receiving the intervention by the total number of patients eligible for the intervention, excluding ineligible patients or those with contraindications to treatment. Logistic regression models were used to determine associations between measure compliance and stroke subtype, controlling for patient and hospital characteristics. Stroke subtypes were 61.7% IS, 23.8% TIA, 11.1% ICH, and 3.5% SAH. Performance on care measures was generally lower in ICH and SAH compared to IS/TIA, including guideline-recommended measures for deep venous thrombosis (DVT) prevention (for ICH) and smoking cessation (for SAH) (multivariable-adjusted p < 0.001 for all comparisons). Exceptions were that ICH patients were more likely than IS/TIA to have door-to-CT times <25 minutes (multivariable-adjusted p < 0.001) and to undergo dysphagia screening (multivariable-adjusted p < 0.001). Time spent in the GWTG-Stroke program was associated with improvements in many measures of care for ICH and SAH patients, including DVT prevention and smoking cessation therapy (multivariable-adjusted p < 0.001). Many hospital-based acute care and prevention measures are underutilized in intracerebral hemorrhage and subarachnoid hemorrhage compared to ischemic stroke /TIA. Duration of Get With The Guidelines-Stroke participation is associated with improving quality of care for hemorrhagic stroke.

Cognitive functioning over 2 years after intracerebral hemorrhage in school-aged children.

PubMed

Murphy, Lexa K; Compas, Bruce E; Gindville, Melissa C; Reeslund, Kristen L; Jordan, Lori C

2017-11-01

Previous research investigating outcomes after pediatric intracerebral hemorrhage (ICH) has generally been limited to global and sensorimotor outcomes. This study examined cognitive outcomes after spontaneous ICH in school-aged children with serial assessments over 2 years after stroke. Seven children (age range 6-16y, median 13; six males, one female; 57% white, 43% black) presenting with spontaneous ICH (six arteriovenous malformations) were assessed at 3 months, 12 months, and 24 months after stroke. The Pediatric Stroke Outcome Measure (PSOM) quantified neurological outcome and Wechsler Intelligence Scales measured cognitive outcomes: verbal comprehension, perceptual reasoning, working memory, and processing speed. PSOM scales showed improved neurological function over the first 12 months, with mild to no sensorimotor deficits and moderate overall deficits at 1- and 2-year follow-ups (median 2-year sensorimotor PSOM=0.5, total PSOM=1.5). Changes in cognitive function indicated a different trajectory; verbal comprehension and perceptual reasoning improved over 24 months; low performance was sustained in processing speed and working memory. Age-normed centile scores decreased between 1- and 2-year follow-ups for working memory, suggesting emerging deficits compared with peers. Early and serial cognitive testing in children with ICH is needed to assess cognitive functioning and support children in school as they age and cognitive deficits become more apparent and important for function. In children with intracerebral hemorrhage (ICH), motor function improved between 3 months and 24 months. Improvements in cognitive function were variable between 3 months and 24 months. Working memory centiles declined, suggesting emerging deficits compared with peers. Processing speed improved but remained significantly below the 50th centile. Cognitive impact of ICH may increase with age in children. © 2017 Mac Keith Press.

Reta'maxik Qatzij--Conociendo Nuestro Idioma (Knowing Our Language). [CD-ROM].

ERIC Educational Resources Information Center

Academy for Educational Development, Washington, DC.

This CD-ROM is part of an interactive and dynamic multimedia package of information and games for learning K'iche' and Ixil. This CD-ROM includes six books in electronic format with interactive exercises that support improved bilingual and intercultural education and teacher training, specifically in the languages of K'iche' and Ixil. Books…

Interleukin-4 Ameliorates the Functional Recovery of Intracerebral Hemorrhage Through the Alternative Activation of Microglia/Macrophage.

PubMed

Yang, Jianjing; Ding, Saidan; Huang, Weilong; Hu, Jiangnan; Huang, Shengwei; Zhang, Yu; Zhuge, Qichuan

2016-01-01

Neuro-inflammation plays an important role in the recovery of brain injury after stroke. Microglia/macrophage is the major executor in the neuro-inflammation, which can be polarized into two distinct phenotypes: injurious/toxic classical activation (M1 phenotype) and protective alternative activation (M2 phenotype). Here, we investigated whether intracerebral administration of interleukin-4 (IL-4) at an early stage could affect the activation of microglia/macrophage and the corresponding outcome after intracerebral hemorrhage (ICH). The neuro-behavior was recorded between different groups in the rat ICH model. The M1 and M2 markers were then determined by qRT-PCR, western blotting, ELISA, and immunofluorescence, respectively. We observed aberrant activation of microglia/macrophage after ICH. After intracerebral injection of IL-4, M1 activation was greatly inhibited while M2 activation was enhanced, along with improving neurobehavioral recovery from deficits after ICH. Our study showed that early intracerebral injection of IL-4 potentially promotes neuro-functional recovery, probably through enhancing the alternative activation of microglia/macrophage.

Der Organismus der Mathematik - mikro-, makro- und mesoskopisch betrachtet

NASA Astrophysics Data System (ADS)

Winkler, Reinhard

Meist enden ähnliche Gespräche über Mathematik etwa an diesem Punkt, ohne dass der Nichtmathematiker von der Sinnhaftigkeit mathematischer Forschung, ja mathematischer Tätigkeit generell überzeugt werden konnte. Ich glaube nicht, dass dem Laien Blindheit für die Großartigkeit unserer Wissenschaft vorzuwerfen ist, wenn hier keine befriedigendere Kommunikation zustande kommt. Ich sehe als Ursache eher ein stark verkürztes Bild von der Mathematik, welches auch Fachleute oft zeichnen, weil ihnen eine angemessenere Darstellung ihres Faches zu viel Mühe macht - und das obwohl Mathematik nur betreiben kann, wer geistige Mühen sonst keineswegs scheut. Ich will versuchen, den Ursachen dieses eigentümlichen Phänomens auf den Grund zu gehen.

Experimental hypertension increases spontaneous intracerebral hemorrhages in a mouse model of cerebral amyloidosis

PubMed Central

Passos, Giselle F; Kilday, Kelley; Gillen, Daniel L; Vasilevko, Vitaly

2015-01-01

Hypertension and cerebral amyloid angiopathy (CAA) are major risk factors for intracerebral hemorrhage (ICH); however the mechanisms of interplay between the two are not fully understood. We investigated the effect of hypertension in a transgenic mouse model with Alzheimer’s-like pathology (Tg2576) treating them with angiontensin II and L-NG-nitroarginine methyl ester. A similar increase in systolic blood pressure was observed in both Tg2576 and control mice; however Tg2576 mice developed signs of stroke with a markedly shorter latency. Cerebral deposition of amyloid beta promotes the hypertension-induced ICH, thus supporting the notion that hypertension is a risk factor for ICH among patients with CAA. PMID:26661173

Uwachib'alil Qach'ab'al--Asi se Ilustra mi Palabra (Illustrating My Words). [CD-ROM].

ERIC Educational Resources Information Center

Academy for Educational Development, Washington, DC.

This CD-ROM is part of an interactive and dynamic multimedia package of information and games for learning K'iche' and Ixil. This CD-ROM contains a database of 3,000 culturally-relevant vocabulary words in K'iche', Ixil, and Spanish, with appropriate illustrations that describe traditional Mayan rituals, foods, beliefs, clothing, and other topics.…

Attempting to Predict Success in the Qualifying Round of the International Chemistry Olympiad

ERIC Educational Resources Information Center

Urhahne, Detlef; Ho, Lok Hang; Parchmann, Ilka; Nick, Sabine

2012-01-01

The aim of this study was trying to predict success in the qualifying round for the International Chemistry Olympiad (IChO) on the basis of the expectancy-value model of achievement motivation by Eccles et al. The investigation with 52 participants, including 14 females, was conducted during the third of four qualifying rounds of the IChO in…

Role of ghrelin in small intestinal motility following pediatric intracerebral hemorrhage in mice.

PubMed

Zan, Jieyu; Song, Lei; Wang, Jiejie; Zou, Rong; Hong, Fei; Zhao, Jinhua; Cheng, Yijun; Xu, Ming

2017-11-01

Small intestinal motility (SIM) disorder is a common complication following pediatric intracerebral hemorrhage (ICH), leading to a poor prognosis in patients. Previous studies have shown that ghrelin is involved in SIM in various diseases; however, the role of ghrelin in pediatric ICH‑induced SIM disorder remains to be elucidated. The present study was designed to investigate the association between ghrelin and SIM post‑ICH, and to examine the effect of exogenous ghrelin administration on SIM in vivo. An ICH model was induced in mice by autologous blood infusion. Neurobehavioral deficits were evaluated using a Rotarod test, forelimb placing test, and corner turn test. Intestinal mucosal damage was examined using hematoxylin and eosin staining. SIM was measured using charcoal meal staining. An enzyme‑linked immunosorbent assay was used to evaluate serum levels of ghrelin and nitric oxide (NO). Reverse transcription‑quantitative polymerase chain reaction and western blot analyses were performed to determine the levels of inducible nitric oxide synthase (iNOS), neuronal nitric oxide synthase (nNOS) and endothelial nitric oxide synthase (eNOS) at the mRNA and protein levels. Nω‑nitro‑L‑arginine methyl ester hydrochloride (L‑NAME), L‑arginine, atropine, phentolamine and propranolol were used to manipulate the putative pathways induced by ghrelin. Neurological dysfunction was observed post‑ICH. ICH caused damage to the intestinal mucosa and delayed SIM. Serum levels of ghrelin increased between 3 h and 3 days, peaking at 12 h, and showed a significant negative correlation with SIM post‑ICH. Ghrelin administration dose‑dependently attenua-ted ICH‑induced SIM disorder. Ghrelin also decreased NO levels by downregulating the mRNA and protein expression levels of iNOS, but not those of nNOS or eNOS, post‑ICH. Consistently, the effect was enhanced by L‑NAME and weakened by L‑arginine, respectively. The protective effect of ghrelin was

Leukoaraiosis, cerebral hemorrhage and outcome after IV thrombolysis for acute ischemic stroke: A meta-analysis (v1)

PubMed Central

Charidimou, Andreas; Pasi, Marco; Fiorelli, Marco; Shams, Sara; von Kummer, Rüdiger; Pantoni, Leonardo; Rost, Natalia

2016-01-01

Background-and-Purpose We performed a meta-analysis to assess whether leukoaraiosis on brain CT scans of acute ischemic stroke patients treated with intravenous (IV) thrombolysis is associated with an increased risk of symptomatic intracerebral hemorrhage (sICH) and/or poor functional outcome at 3–6 months post-stroke. Methods We searched PubMed and pooled relevant data in meta-analyses using random effects models. Using odds ratios (OR), we quantified the strength of association between the presence and severity of leukoaraiosis and post-thrombolysis sICH or 3–6 month modified Rankin Score (mRS) >2. Results Eleven eligible studies (n=7194) were pooled in meta-analysis. The risk of sICH was higher in patients with leukoaraiosis (OR: 1.55; 95%CI: 1.17–2.06, p=0.002) and severe leukoaraiosis (OR: 2.53; 95%CI: 1.92–3.34, p<0.0001), compared to patients without leukoaraiosis. Leukoaraiosis was an independent predictor of sICH in six included studies (n=4976, adjusted-OR: 1.75, 95%CI: 1.35–2.27; p<0.0001). OR for leukoaraiosis and poor 3–6 month outcome was 2.02 (95%CI: 1.54–2.65, p<0.0001), with significant statistical heterogeneity (I2:75.7%, p=0.002). In adjusted analysed, leukoaraiosis was an independent predictor of poor outcome (n=3688, adjusted-OR: 1.61, 95%CI: 1.44–1.79; p<0.0001). In post-hoc analyses, including only leukoaraiosis patients in RCTs (IST-3, NINDS, ECASS-1-2; n=2234), tPA vs. control was associated with higher sICH risk (OR: 5.50; 95%CI: 2.49–12.13), but lower poor outcome risk (OR: 0.75; 95%CI: 0.60–0.95). Conclusions Leukoaraiosis might increase post-IV thrombolysis sICH risk and poor outcome post-stroke. Despite increased sICH risk, IV tPA treatment has net clinical benefit in patients with leukoaraiosis. Given the risk of bias/confounding, these results should be considered hypothesis-generating and do not justify withholding IV thrombolysis. PMID:27491738

Risks and benefits of CT angiography in spontaneous intracerebral hemorrhage.

PubMed

Hotta, Kazuko; Sorimachi, Takatoshi; Osada, Takahiro; Baba, Tanefumi; Inoue, Go; Atsumi, Hideki; Ishizaka, Hideo; Matsuda, Minako; Hayashi, Naokazu; Matsumae, Mitsunori

2014-05-01

Few studies have examined the risk of computed tomography angiography (CTA) during the acute phase of spontaneous intracerebral hemorrhage (ICH), while the benefits of CTA in ICH have been well-documented. The present study investigated both the benefits of identifying spot signs, which are supposed to indicate hematoma enlargement after admission, and risks of CTA performed during the acute phase of ICH. We retrospectively assessed 323 consecutive patients with spontaneous ICHs admitted to our hospital between April 2009 and March 2012 and who underwent CTA on admission. In 80 patients (24.7 %), spot signs were demonstrated on CTA source images. Multivariate analysis revealed two independent factors correlated with presence of the spot sign: age and hematoma volume (p < 0.05 each). The presence of spot sign was associated with unfavorable outcomes at discharge and hematoma growth after admission (p < 0.05 each). Adverse events related to CTA occurred in 17 patients (5.2 %), including transient renal dysfunction in 16 patients and allergy to contrast medium in one patient. All adverse events completely resolved within 1 week. Presence of the spot sign indicated the possibility of hematoma growth and unfavorable outcomes. A small number of adverse events occurred in association with CTA, but without any permanent deficits. Given the potential benefits and risks, we believe that CTA performed at admission in all patients with ICH is beneficial to improve the outcomes.

Molecular and Genetic Analyses of Collagen Type IV Mutant Mouse Models of Spontaneous Intracerebral Hemorrhage Identify Mechanisms for Stroke Prevention.

PubMed

Jeanne, Marion; Jorgensen, Jeff; Gould, Douglas B

2015-05-05

Collagen type IV alpha1 (COL4A1) and alpha2 (COL4A2) form heterotrimers critical for vascular basement membrane stability and function. Patients with COL4A1 or COL4A2 mutations suffer from diverse cerebrovascular diseases, including cerebral microbleeds, porencephaly, and fatal intracerebral hemorrhage (ICH). However, the pathogenic mechanisms remain unknown, and there is a lack of effective treatment. Using Col4a1 and Col4a2 mutant mouse models, we investigated the genetic complexity and cellular mechanisms underlying the disease. We found that Col4a1 mutations cause abnormal vascular development, which triggers small-vessel disease, recurrent hemorrhagic strokes, and age-related macroangiopathy. We showed that allelic heterogeneity, genetic context, and environmental factors such as intense exercise or anticoagulant medication modulated disease severity and contributed to phenotypic heterogeneity. We found that intracellular accumulation of mutant collagen in vascular endothelial cells and pericytes was a key triggering factor of ICH. Finally, we showed that treatment of mutant mice with a US Food and Drug Administration-approved chemical chaperone resulted in a decreased collagen intracellular accumulation and a significant reduction in ICH severity. Our data are the first to show therapeutic prevention in vivo of ICH resulting from Col4a1 mutation and imply that a mechanism-based therapy promoting protein folding might also prevent ICH in patients with COL4A1 and COL4A2 mutations. © 2015 American Heart Association, Inc.

Intracranial hemorrhage after blunt head trauma in children with bleeding disorders.

PubMed

Lee, Lois K; Dayan, Peter S; Gerardi, Michael J; Borgialli, Dominic A; Badawy, Mohamed K; Callahan, James M; Lillis, Kathleen A; Stanley, Rachel M; Gorelick, Marc H; Dong, Li; Zuspan, Sally Jo; Holmes, James F; Kuppermann, Nathan

2011-06-01

To determine computerized tomography (CT) use and prevalence of traumatic intracranial hemorrhage (ICH) in children with and without congenital and acquired bleeding disorders. We compared CT use and ICH prevalence in children with and without bleeding disorders in a multicenter cohort study of 43 904 children <18 years old with blunt head trauma evaluated in 25 emergency departments. A total of 230 children had bleeding disorders; all had Glasgow Coma Scale (GCS) scores of 14 to 15. These children had higher CT rates than children without bleeding disorders and GCS scores of 14 to 15 (risk ratio, 2.29; 95% CI, 2.15 to 2.44). Of the children who underwent imaging with CT, 2 of 186 children with bleeding disorders had ICH (1.1%; 95% CI, 0.1 to 3.8) , compared with 655 of 14 969 children without bleeding disorders (4.4%; 95% CI, 4.1-4.7; rate ratio, 0.25; 95% CI, 0.06 to 0.98). Both children with bleeding disorders and ICHs had symptoms; none of the children required neurosurgery. In children with head trauma, CTs are obtained twice as often in children with bleeding disorders, although ICHs occurred in only 1.1%, and these patients had symptoms. Routine CT imaging after head trauma may not be required in children without symptoms who have congenital and acquired bleeding disorders. Copyright © 2011 Mosby, Inc. All rights reserved.

Optical imaging of intracranial hemorrhages in newborns: modern strategies in diagnostics and direction for future research

NASA Astrophysics Data System (ADS)

Pavlov, A. N.; Semyachkina-Glushkovskaya, O. V.; Lychagov, V. V.; Bibikova, O. A.; Sindeev, S. S.; Pavlova, O. N.; Shuvalova, E. P.; Tuchin, V. V.

2014-05-01

Using Doppler optical coherence tomography (DOCT) we study stress-related intracranial hemorrhages (ICHs) in newborn rats. We investigate a masked stage of ICH development that corresponds to the first 4 h after the stress. We show that this period is characterized by significant changes in the diameter of the sagittal vein and the velocity of the cerebral venous blood flow (CVBF). We discuss diagnostic abilities of wavelet-based methods and consider an adaptive technique allowing us to reveal clearest distinctions in the dynamics of CVBF between normal and stressed newborn rats. Finally, we conclude that the venous insufficiency in newborns and a reduced response of the sagittal vein to adrenaline are related to important prognostic markers of the risk of ICH development.

Ischemic stroke and intracranial hemorrhage in patients with recurrent glioblastoma multiforme, treated with bevacizumab.

PubMed

Auer, Timo A; Renovanz, Mirjam; Marini, Federico; Brockmann, Marc A; Tanyildizi, Yasemin

2017-07-01

Bevacizumab (BVZ), a monoclonal antibody directed against vascular endothelial growth factor (VEGF), has been suspected to increase the incidence of ischemic stroke (IS) and intracranial hemorrhage (ICH) in GBM patients. Intracranial vascular events, such as IS and ICH, were retrospectively analyzed in 364 MRI scans of 82 patients with recurrent GBM (1st/2nd/3rd relapse). Out of these 82 patients, 40 were treated with BVZ (178 scans) in addition to basic treatment, whereas 42 patients matching for age and gender received basic treatment (186 scans). Distribution of typical vascular risk factors between both groups was analyzed retrospectively. In seven out of 82 patients (8%) vascular events were detected in MRI. Four vascular events were recorded in the BVZ-group (3 IS and 1 ICH), and 3 vascular events were found in the Control-group (1 IS and 2 ICH; p > 0.05 between both groups). Likewise, vascular risk factors (arterial hypertension, diabetes mellitus, obesity, former vascular event, hyperlipidemia, tobacco consumption and/or hypercholesterolemia) did not differ significantly between both groups. BVZ treatment does not seem to be associated with an increased risk for vascular events in patients with GBM in recurrence.

The Evaluation and Management of Adult Intracerebral Hemorrhage.

PubMed

Cai, Xuemei; Rosand, Jonathan

2015-12-01

Intracerebral hemorrhage (ICH) is the most disabling and deadly form of stroke. Although mortality remains high, new data suggest that outcomes can be improved with standardized medical care. In this review, the authors outline the most up-to-date knowledge, including the results of the latest phase III clinical trials on the specialized care needed to treat patients with ICH. They provide an overview on how to achieve rapid diagnosis and the initial steps of intervention to reduce hematoma volume or prevent expansion by modifying potentially treatable conditions, such as underlying vascular etiologies, blood pressure control, and coagulopathies. Grading scales can help identify patients at risk for hematoma expansion and functional disabilities and guide clinical decision making. Other medical management topics important to recovery and prevention of secondary brain injury include seizure prevention and treatment, glycemic control, temperature control, and deep venous thrombosis prophylaxis and treatment. Treatment options in surgery are also possible in select patients; there are emerging studies regarding minimally invasive surgery for the management of ICH. These aggressive therapies are essential to lower the morbidity and mortality of patients presenting with ICH. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Tranexamic Acid as Antifibrinolytic Agent in Non Traumatic Intracerebral Hemorrhages

PubMed Central

ARUMUGAM, Ananda; A RAHMAN, Noor Azman; THEOPHILUS, Sharon Casilda; SHARIFFUDIN, Ashraf; ABDULLAH, Jafri Malin

2015-01-01

Background: Mortality and morbidity associated with intracerebral hemorrhage is still high. Up to now, there are no evidence-based effective treatments for acute ICH. This study is to assess the effect of tranexamic acid (TXA) on hematoma growth of patients with spontaneous ICH compared to a placebo. Methods: We performed a single-blinded, randomised placebo-controlled trial of TXA (intravenous 1g bolus, followed by infusion TXA 1 g/hour for 8 hours) in acute (< 8 hours) primary ICH. Strict blood pressure control (target SBP 140-160 mmHg). A repeat Computed Tomography brain was done after 24 hours to reassess hematoma growth. The primary objective is to test the effect of TXA on hematoma growth. Other objective was to test the feasibility, tolerability, and adverse events of TXA in primary ICH. Results: Statistical analysis showed significant hematoma growth in control group after 24 hours compared to baseline (14.3300 vs 17.9940, P = 0.001) whereas the treatment group there is no significant hematoma size expansion between baseline and after 24 hours (P = 0.313). Conclusions: This study showed a significant hematoma volume expansion in the control group compared to the treatment group. PMID:27006639

Tranexamic Acid as Antifibrinolytic Agent in Non Traumatic Intracerebral Hemorrhages.

PubMed

Arumugam, Ananda; A Rahman, Noor Azman; Theophilus, Sharon Casilda; Shariffudin, Ashraf; Abdullah, Jafri Malin

2015-12-01

Mortality and morbidity associated with intracerebral hemorrhage is still high. Up to now, there are no evidence-based effective treatments for acute ICH. This study is to assess the effect of tranexamic acid (TXA) on hematoma growth of patients with spontaneous ICH compared to a placebo. We performed a single-blinded, randomised placebo-controlled trial of TXA (intravenous 1g bolus, followed by infusion TXA 1 g/hour for 8 hours) in acute (< 8 hours) primary ICH. Strict blood pressure control (target SBP 140-160 mmHg). A repeat Computed Tomography brain was done after 24 hours to reassess hematoma growth. The primary objective is to test the effect of TXA on hematoma growth. Other objective was to test the feasibility, tolerability, and adverse events of TXA in primary ICH. Statistical analysis showed significant hematoma growth in control group after 24 hours compared to baseline (14.3300 vs 17.9940, P = 0.001) whereas the treatment group there is no significant hematoma size expansion between baseline and after 24 hours (P = 0.313). This study showed a significant hematoma volume expansion in the control group compared to the treatment group.

Correlation mapping method of OCT for visualization blood vessels in brain

NASA Astrophysics Data System (ADS)

Izotova, O. A.; Kalyanov, A. L.; Lychagov, V. V.; Semyachkina-Glushkovskaya, O. V.

2013-11-01

The burning issue in modern medicine is the diagnosis and treatment of various life-threatening diseases, in particular the diseases of brain. One of them is intracranial hemorrhage (ICH). It occurs especially among newborn babies and is hard-diagnosed. In order to understand the nature of the ICH, the microcirculation of blood, which serves key functions within the body, is analyzed. On this basis a series of experiments was done, in the results of which it was showed, that latent stage of ICH is characterized by decrease of venous blood outflow and the loss of sensitivity of sagittal vein to vasoconstrictor effect of adrenaline. So, stress-related changes of the cerebral venous blood flow (CVBF) can be the source of this disease. In this paper registration CVBF was made with the help of commercially available Thorlabs Swept Source OCT System, using the correlation mapping method. In this method values of correlation coefficient of several images are analyzed. In the result of the algorithm the correlation map was obtained. By the resulting map the diameter of vessels was calculated, which is necessary for examination of effects of adrenalin to the vessels and identification symptoms of ICH.

External Validation of the Prestroke Independence, Sex, Age, National Institutes of Health Stroke Scale Score for Predicting Pneumonia After Stroke Using Data From the China National Stroke Registry.

PubMed

Zhang, Runhua; Ji, Ruijun; Pan, Yuesong; Jiang, Yong; Liu, Gaifen; Wang, Yilong; Wang, Yongjun

2017-05-01

Pneumonia is an important risk factor for mortality and morbidity after stroke. The Prestroke Independence, Sex, Age, National Institutes of Health Stroke Scale (ISAN) score was shown to be a useful tool for predicting stroke-associated pneumonia based on UK multicenter cohort study. We aimed to externally validate the score using data from the China National Stroke Registry (CNSR). Eligible patients with acute ischemic stroke (AIS) and intracerebral hemorrhage (ICH) in the CNSR from 2007 to 2008 were included. The area under the receiver operating characteristic (AUC) curve was used to evaluate discrimination. The Hosmer-Lemeshow goodness of fit test and Pearson correlation coefficient were performed to assess calibration of the model. A total of 19,333 patients (AIS = 14400; ICH = 4933) were included and the overall pneumonia rate was 12.7%. The AUC was .76 (95% confidence interval [CI]: .75-.78) for the subgroup of AIS and .70 (95% CI: .68-.72) for the subgroup of ICH. The Hosmer-Lemeshow test showed the ISAN score with the good calibration for AIS and ICH (P = .177 and .405, respectively). The plot of observed versus predicted pneumonia rates suggested higher correlation for patients with AIS than with ICH (Pearson correlation coefficient = .99 and .83, respectively). The ISAN score was a useful tool for predicting in-hospital pneumonia after acute stroke, especially for patients with AIS. Further validations need to be done in different populations. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Imaging of Hemorrhagic Stroke.

PubMed

Hakimi, Ryan; Garg, Ankur

2016-10-01

Hemorrhagic stroke comprises approximately 15% to 20% of all strokes. This article provides readers with an understanding of the indications and significance of various neuroimaging techniques available for patients presenting with hemorrhagic strokes of distinct causes. The most common initial neuroimaging study is a noncontrast head CT, which allows for the identification of hemorrhage. Once an intracranial hemorrhage has been identified, the pattern of blood and the patient's medical history, neurologic examination, and laboratory studies lead the practitioner to pursue further neuroimaging studies to guide the medical, surgical, and interventional management. Given that hemorrhagic stroke constitutes a heterogeneous collection of diagnoses, the subsequent neuroimaging pathway necessary to better evaluate and care for these patients is variable based on the etiology.With an increasing incidence and prevalence of atrial fibrillation associated with the aging population and the introduction of three new direct factor Xa inhibitors and one direct thrombin inhibitor to complement vitamin K antagonists, oral anticoagulant use continues to increase. Patients on oral anticoagulants have a sevenfold to tenfold increased risk for intracerebral hemorrhage (ICH). Furthermore, patients who have an ICH associated with oral anticoagulant use have a higher mortality rate than those with primary ICH. Despite the reduced incidence of hypertension-related ICH over the past decade, it is expected that the incidence of ICH will continue to increase. Neuroimaging studies are integral to the identification of hemorrhagic stroke, determination of the underlying etiology, prevention of hematoma expansion, treatment of acute complications, and treatment of the underlying etiology, if indicated. Neuroimaging is essential for prognostication and thus directly impacts patient care.

Glial responses, neuron death and lesion resolution after intracerebral hemorrhage in young vs. aged rats.

PubMed

Wasserman, Jason K; Yang, Helen; Schlichter, Lyanne C

2008-10-01

Intracerebral hemorrhage (ICH) usually affects older humans but almost no experimental studies have assessed aged animals. We address how aging alters inflammation, neuron death and lesion resolution after a hemorrhage in the rat striatum. In the normal aged brain, microglia displayed a 'dystrophic' phenotype, with shorter cellular processes and large gaps between adjacent cells, and there was more astrocyte reactivity. The ICH injury was monitored as hematoma volume and number of dying neurons at 1 and 3 days, and the volume of the residual lesion, ventricles and lost tissue at 28 days. Inflammation at 1 and 3 days was assessed from densities of microglia with resting vs. activated morphologies, or expressing the lysosomal marker ED1. Despite an initial delay in neuron death in aged animals, by 28 days, there was no difference in neuron density or volume of tissue lost. However, lesion resolution was impaired in aged animals and there was less compensatory ventricular expansion. At 1 day after ICH, there were fewer activated microglia/macrophages in the aged brain, but by 3 days there were more of these cells at the edge of the hematoma and in the surrounding parenchyma. In both age groups a glial limitans had developed by 3 days, but astrocyte reactivity and the spread of activated microglia/macrophages into the surrounding parenchyma was greater in the aged. These findings have important implications for efforts to reduce secondary injury after ICH and to develop anti-inflammatory therapies to treat ICH in aged humans.

Cortical hemorrhage-associated neurological deficits and tissue damage in mice are ameliorated by therapeutic treatment with nicotine.

PubMed

Anan, Junpei; Hijioka, Masanori; Kurauchi, Yuki; Hisatsune, Akinori; Seki, Takahiro; Katsuki, Hiroshi

2017-09-01

Intracerebral hemorrhage (ICH) is associated with diverse sets of neurological symptoms and prognosis, depending on the site of bleeding. Relative rate of hemorrhage occurring in the cerebral cortex (lobar hemorrhage) has been increasing, but there is no report on effective pharmacotherapeutic approaches for cortical hemorrhage either in preclinical or clinical studies. The present study aimed to establish an experimental model of cortical hemorrhage in mice for evaluation of effects of therapeutic drug candidates. Type VII collagenase at 0.015 U, injected into the parietal cortex, induced hemorrhage expanding into the whole layer of the posterior parts of the sensorimotor cortex in male C57BL/6 mice. Mice with ICH under these conditions exhibited significant motor deficits as revealed by beam-walking test. Daily administration of nicotine (1 and 2 mg/kg), with the first injection given at 3 hr after induction of ICH, improved motor performance of mice in a dose-dependent manner, although nicotine did not alter the volume of hematoma. Immunohistochemical examinations revealed that the number of neurons was drastically decreased within the hematoma region. Nicotine at 2 mg/kg partially but significantly increased the number of remaining neurons within the hematoma at 3 days after induction of ICH. ICH also resulted in inflammatory activation of microglia/macrophages in the perihematoma region, and nicotine (1 and 2 mg/kg) significantly attenuated the increase of microglia. These results suggest that nicotine can provide a therapeutic effect on cortical hemorrhage, possibly via its neuroprotective and anti-inflammatory actions. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Grave prognosis on spontaneous intracerebral haemorrhage: GP on STAGE score.

PubMed

Poungvarin, Niphon; Suwanwela, Nijasri C; Venketasubramanian, Narayanaswamy; Wong, Lawrence K S; Navarro, Jose C; Bitanga, Ester; Yoon, Byung Woo; Chang, Hui M; Alam, Sardar M

2006-11-01

Spontaneous intracerebral haemorrhage (ICH) is more common in Asia than in western countries, and has a high mortality rate. A simple prognostic score for predicting grave prognosis of ICH is lacking. Our objective was to develop a simple and reliable score for most physicians. ICH patients from seven Asian countries were enrolled between May 2000 and April 2002 for a prospective study. Clinical features such as headache and vomiting, vascular risk factors, Glasgow coma scale (GCS), body temperature (BT), blood pressure on arrival, location and size of haematoma, intraventricular haemorrhage (IVH), hydrocephalus, need for surgical treatment, medical treatment, length of hospital stay and other complications were analyzed to determine the outcome using a modified Rankin scale (MRS). Grave prognosis (defined as MRS of 5-6) was judged on the discharge date. 995 patients, mean age 59.5 +/- 14.3 years were analyzed, after exclusion of incomplete data in 87 patients. 402 patients (40.4%) were in the grave prognosis group (MRS 5-6). Univariable analysis and then multivariable analysis showed only four statistically significant predictors for grave outcome of ICH. They were fever (BT > or = 37.8 degrees c), low GCS, large haematoma and IVH. The grave prognosis on spontaneous intracerebral haemorrhage (GP on STAGE) score was derived from these four factors using a multiple logistic model. A simple and pragmatic prognostic score for ICH outcome has been developed with high sensitivity (82%) and specificity (82%). Furthermore, it can be administered by most general practitioners. Validation in other populations is now required.

Diagnostic utility of amyloid PET in cerebral amyloid angiopathy-related symptomatic intracerebral hemorrhage

PubMed Central

Baron, Jean-Claude; Farid, Karim; Dolan, Eamon; Turc, Guillaume; Marrapu, Siva T; O'Brien, Eoin; Aigbirhio, Franklin I; Fryer, Tim D; Menon, David K; Warburton, Elizabeth A; Hong, Young T

2014-01-01

By detecting β-amyloid (Aβ) in the wall of cortical arterioles, amyloid positron emission tomography (PET) imaging might help diagnose cerebral amyloid angiopathy (CAA) in patients with lobar intracerebral hemorrhage (l-ICH). No previous study has directly assessed the diagnostic value of 11C-Pittsburgh compound B (PiB) PET in probable CAA-related l-ICH against healthy controls (HCs). 11C-PiB-PET and magnetic resonance imaging (MRI) including T2* were obtained in 11 nondemented patients fulfilling the Boston criteria for probable CAA-related symptomatic l-ICH (sl-ICH) and 20 HCs without cognitive complaints or impairment. After optimal spatial normalization, cerebral spinal fluid (CSF)-corrected PiB distribution volume ratios (DVRs) were obtained. There was no significant difference in whole cortex or regional DVRs between CAA patients and age-matched HCs. The whole cortex DVR was above the 95% confidence limit in 4/9 HCs and 10/11 CAA patients (sensitivity=91%, specificity=55%). Region/frontal or occipital ratios did not have better discriminative value. Similar but less accurate results were found using visual analysis. In patients with sl-ICH, 11C-PiB-PET has low specificity for CAA due to the frequent occurrence of high 11C-PiB uptake in the healthy elderly reflecting incipient Alzheimer's disease (AD), which might also be present in suspected CAA. However, a negative PiB scan rules out CAA with excellent sensitivity, which has clinical implications for prognostication and selection of candidates for drug trials. PMID:24619277

Risk analysis of new oral anticoagulants for gastrointestinal bleeding and intracranial hemorrhage in atrial fibrillation patients: a systematic review and network meta-analysis.

PubMed

Xu, Wei-Wei; Hu, Shen-Jiang; Wu, Tao

2017-07-01

Antithrombotic therapy using new oral anticoagulants (NOACs) in patients with atrial fibrillation (AF) has been generally shown to have a favorable risk-benefit profile. Since there has been dispute about the risks of gastrointestinal bleeding (GIB) and intracranial hemorrhage (ICH), we sought to conduct a systematic review and network meta-analysis using Bayesian inference to analyze the risks of GIB and ICH in AF patients taking NOACs. We analyzed data from 20 randomized controlled trials of 91 671 AF patients receiving anticoagulants, antiplatelet drugs, or placebo. Bayesian network meta-analysis of two different evidence networks was performed using a binomial likelihood model, based on a network in which different agents (and doses) were treated as separate nodes. Odds ratios (ORs) and 95% confidence intervals (CIs) were modeled using Markov chain Monte Carlo methods. Indirect comparisons with the Bayesian model confirmed that aspirin+clopidogrel significantly increased the risk of GIB in AF patients compared to the placebo (OR 0.33, 95% CI 0.01-0.92). Warfarin was identified as greatly increasing the risk of ICH compared to edoxaban 30 mg (OR 3.42, 95% CI 1.22-7.24) and dabigatran 110 mg (OR 3.56, 95% CI 1.10-8.45). We further ranked the NOACs for the lowest risk of GIB (apixaban 5 mg) and ICH (apixaban 5 mg, dabigatran 110 mg, and edoxaban 30 mg). Bayesian network meta-analysis of treatment of non-valvular AF patients with anticoagulants suggested that NOACs do not increase risks of GIB and/or ICH, compared to each other.

Surgical Craniotomy for Intracerebral Haemorrhage.

PubMed

Mendelow, A David

2015-01-01

Craniotomy is probably indicated for patients with superficial spontaneous lobar supratentorial intracerebral haemorrhage (ICH) when the level of consciousness drops below 13 within the first 8 h of the onset of the haemorrhage. Once the level drops below 9, it is probably too late to consider craniotomy for these patients, so clinical vigilance is paramount. While this statement is only backed up by evidence that is moderately strong, meta-analysis of available data suggests that it is true in the rather limited number of patients with ICH. Meta-analyses like this can often predict the results of future prospective randomised controlled trials a decade or more before the trials are completed and published. Countless such examples exist in the literature, as is the case for thrombolysis in patients with myocardial infarction in the last millennium: meta-analysis determined the efficacy more than a decade BEFORE the last trial (ISIS-2) confirmed the benefit of thrombolysis for myocardial infarction. Careful examination of the meta-analysis' Forest plots in this chapter will demonstrate why this statement is made at the outset. Other meta-analyses of surgery for ICH have also indicated that minimal interventional techniques using topical thrombolysis or endoscopy via burrholes or even twist drill aspiration may be particularly successful for the treatment of supratentorial ICH, especially when the clot is deep seated. Ongoing clinical trials (CLEAR III and MISTIE III) should confirm this in the fullness of time. There are 2 exceptions to these generalisations. First, based on trial evidence, aneurysmal ICH is best treated with surgery. Second, cerebellar ICH represents a special case because of the development of hydrocephalus, which may require expeditious drainage as the intracranial pressure rises. The cerebellar clot will then require evacuation, usually via posterior fossa craniectomy, rather than craniotomy. Technical advances suggest that image-guided surgery

Evaluation of the Consumer Assessment of Healthcare Providers and Systems In-Center Hemodialysis Survey

PubMed Central

Paoli, Carly J.; Hays, Ron D.; Taylor-Stokes, Gavin; Piercy, James; Gitlin, Matthew

2014-01-01

Background and objectives The US Centers for Medicare and Medicaid Services (CMS) End Stage Renal Disease Prospective Payment System and Quality Incentive Program requires that dialysis centers meet predefined criteria for quality of patient care to ensure future funding. The CMS selected the Consumer Assessment of Healthcare Providers and Systems In-Center Hemodialysis (CAHPS-ICH) survey for the assessment of patient experience of care. This analysis evaluated the psychometric properties of the CAHPS-ICH survey in a sample of hemodialysis patients. Design, setting, participants, & measurements Data were drawn from the Adelphi CKD Disease Specific Program (a retrospective, cross-sectional survey of nephrologists and patients). Selected United States–based nephrologists treating patients receiving hemodialysis completed patient record forms and provided information on their dialysis center. Patients (n=404) completed the CAHPS-ICH survey (comprising 58 questions) providing six scores for the assessment of patient experience of care. CAHPS-ICH item-scale convergence, discrimination, and reliability were evaluated for multi-item scales. Floor and ceiling effects were estimated for all six scores. Patient (demographics, dialysis history, vascular access method) and facility characteristics (size, ratio of patients-to-physicians, nurses, and technicians) associated with the CAHPS-ICH scores were also evaluated. Results Item-scale correlations and internal consistency reliability estimates provided support for the nephrologists’ communication (range, 0.16–0.71; α=0.81) and quality of care (range, 0.16–0.76; α=0.90) composites. However, the patient information composite had low internal consistency reliability (α=0.55). Provider-to-patient ratios (range, 2.37 for facilities with >36 patients per physician to 2.8 for those with <8 patients per physician) and time spent in the waiting room (3.44 for >15 minutes of waiting time to 3.75 for 5 to <10 minutes) were

Hospitalized hemorrhagic stroke patients with renal insufficiency: clinical characteristics, care patterns, and outcomes.

PubMed

Ovbiagele, Bruce; Schwamm, Lee H; Smith, Eric E; Grau-Sepulveda, Maria V; Saver, Jeffrey L; Bhatt, Deepak L; Hernandez, Adrian F; Peterson, Eric D; Fonarow, Gregg C

2014-10-01

There is a paucity of information on clinical characteristics, care patterns, and clinical outcomes for hospitalized intracerebral hemorrhage (ICH) patients with chronic kidney disease (CKD). We assessed characteristics, care processes, and in-hospital outcome among ICH patients with CKD in the Get With the Guidelines-Stroke (GWTG-Stroke) program. We analyzed 113,059 ICH patients hospitalized at 1472 US centers participating in the GWTG-Stroke program between January 2009 and December 2012. In-hospital mortality and use of 2 predefined ICH performance measures were examined based on glomerular filtration rate. Renal dysfunction was categorized as a dichotomous (+CKD = estimated glomerular filtration rate <60) or rank ordered variable as CKD (<60), and by clinical stage: (normal [≥90], mild [≥60-<90], moderate [≥30-<60], severe [≥15-<30], and/or kidney failure [<15 or dialysis]). There were 33,219 (29%) ICH patients with CKD. Patients with CKD were more likely to be older, female, and with comorbid conditions such as diabetes. Compared with patients with normal kidney function, those with CKD were slightly less likely to receive deep venous thrombosis (DVT) prophylaxis but similarly received discharge smoking cessation intervention. Inpatient mortality was also higher for those with CKD (adjusted odds ratio [OR], 1.47; 95% confidence interval [CI], 1.42-1.52), mild dysfunction (adjusted OR, 1.12; 95% CI, 1.08-1.16), moderate dysfunction (adjusted OR, 1.46; 95% CI, 1.39-1.53), severe dysfunction (adjusted OR, 1.96; 95% CI, 1.81-2.12), and kidney failure (adjusted OR, 2.22; 95% CI, 2.04-2.43) relative to those with normal renal function. Chronic kidney disease is present in nearly a third of patients hospitalized with ICH and is associated with slightly worse care and substantially higher mortality than those with normal renal function. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Recurrent stroke risk and cerebral microbleed burden in ischemic stroke and TIA

PubMed Central

Wilson, Duncan; Charidimou, Andreas; Ambler, Gareth; Fox, Zoe V.; Gregoire, Simone; Rayson, Phillip; Imaizumi, Toshio; Fluri, Felix; Naka, Hiromitsu; Horstmann, Solveig; Veltkamp, Roland; Rothwell, Peter M.; Kwa, Vincent I.H.; Thijs, Vincent; Lee, Yong-Seok; Kim, Young Dae; Huang, Yining; Wong, Ka Sing; Jäger, Hans Rolf

2016-01-01

Objective: To determine associations between cerebral microbleed (CMB) burden with recurrent ischemic stroke (IS) and intracerebral hemorrhage (ICH) risk after IS or TIA. Methods: We identified prospective studies of patients with IS or TIA that investigated CMBs and stroke (ICH and IS) risk during ≥3 months follow-up. Authors provided aggregate summary-level data on stroke outcomes, with CMBs categorized according to burden (single, 2–4, and ≥5 CMBs) and distribution. We calculated absolute event rates and pooled risk ratios (RR) using random-effects meta-analysis. Results: We included 5,068 patients from 15 studies. There were 115/1,284 (9.6%) recurrent IS events in patients with CMBs vs 212/3,781 (5.6%) in patients without CMBs (pooled RR 1.8 for CMBs vs no CMBs; 95% confidence interval [CI] 1.4–2.5). There were 49/1,142 (4.3%) ICH events in those with CMBs vs 17/2,912 (0.58%) in those without CMBs (pooled RR 6.3 for CMBs vs no CMBs; 95% CI 3.5–11.4). Increasing CMB burden increased the risk of IS (pooled RR [95% CI] 1.8 [1.0–3.1], 2.4 [1.3–4.4], and 2.7 [1.5–4.9] for 1 CMB, 2–4 CMBs, and ≥5 CMBs, respectively) and ICH (pooled RR [95% CI] 4.6 [1.9–10.7], 5.6 [2.4–13.3], and 14.1 [6.9–29.0] for 1 CMB, 2–4 CMBs, and ≥5 CMBs, respectively). Conclusions: CMBs are associated with increased stroke risk after IS or TIA. With increasing CMB burden (compared to no CMBs), the risk of ICH increases more steeply than that of IS. However, IS absolute event rates remain higher than ICH absolute event rates in all CMB burden categories. PMID:27590288

Early Therapy Intensity Level (TIL) Predicts Mortality in Spontaneous Intracerebral Hemorrhage.

PubMed

Ziai, Wendy C; Siddiqui, Aazim A; Ullman, Natalie; Herrick, Daniel B; Yenokyan, Gayane; McBee, Nichol; Lane, Karen; Hanley, Daniel F

2015-10-01

Outcome from spontaneous intracerebral hemorrhage (sICH) may depend on patient-care variability. We developed as ICH-specific therapy intensity level (TIL) metric using evidence-based elements in a high severity sICH cohort. This is a cohort study of 170 patients with sICH and any intraventricular hemorrhage treated in 2 academic neuroICUs. Pre-defined quality indicators were identified based on current guidelines, scientific evidence, and likelihood of care documentation in first 72 h of hospital admission. We assessed performance on each indicator and association with discharge mortality. Significant indicators were aggregated to develop a TIL score. The predictive validity of the best fit TIL score was tested with threefold cross-validation of multivariate logistic regression models of in-hospital survival and good outcome (modified Rankin score 0-3). Median ICH score was 3; discharge mortality was 51.2%. Five/19 tested variables were significantly associated with lower discharge mortality: no DNR/withdrawal of treatment within 24 h of admission, target glucose within 4 h of high glucose, no recurrent hyperpyrexia, clinical reversal of herniation/intracranial pressure >20 mmHg within 60 min of detection, and reversal of INR (<1.4) within 2 h of first elevation. One point was given for each or if not applicable. Median TIL score was significantly higher in survivors versus non-survivors (5[1] vs. 3[1]; P < 0.001). A 4-point aggregated TIL score was most predictive of discharge survival (area under receiving operating characteristic curve 0.85, 95% CI 0.80-0.90) and good outcome (AUC 0.84) and was an independent predictor of both (survival: OR 7.10; 95% CI 3.57-14.11; P < 0.001; good outcome: OR 3.10; 95% CI 1.06-8.79; P < 0.001). A simplified TIL score using evidenced-based patient-care parameters within first 3 days of admission after sICH was significantly associated with early mortality and good outcome. The next step is prospective validation of the

Microbleeds, Cerebral Hemorrhage, and Functional Outcome After Stroke Thrombolysis: Individual Patient Data Meta-Analysis.

PubMed

Charidimou, Andreas; Turc, Guillaume; Oppenheim, Catherine; Yan, Shenqiang; Scheitz, Jan F; Erdur, Hebun; Klinger-Gratz, Pascal P; El-Koussy, Marwan; Takahashi, Wakoh; Moriya, Yusuke; Wilson, Duncan; Kidwell, Chelsea S; Saver, Jeffrey L; Sallem, Asma; Moulin, Solene; Edjlali-Goujon, Myriam; Thijs, Vincent; Fox, Zoe; Shoamanesh, Ashkan; Albers, Gregory W; Mattle, Heinrich P; Benavente, Oscar R; Jäger, H Rolf; Ambler, Gareth; Aoki, Junya; Baron, Jean-Claude; Kimura, Kazumi; Kakuda, Wataru; Takizawa, Shunya; Jung, Simon; Nolte, Christian H; Lou, Min; Cordonnier, Charlotte; Werring, David J

2017-07-18

We assessed whether the presence, number, and distribution of cerebral microbleeds (CMBs) on pre-intravenous thrombolysis MRI scans of acute ischemic stroke patients are associated with an increased risk of intracerebral hemorrhage (ICH) or poor functional outcome. We performed an individual patient data meta-analysis, including prospective and retrospective studies of acute ischemic stroke treated with intravenous tissue-type plasminogen activator. Using multilevel mixed-effects logistic regression, we investigated associations of pre-treatment CMB presence, burden (1, 2-4, ≥5, and >10), and presumed pathogenesis (cerebral amyloid angiopathy defined as strictly lobar CMBs and noncerebral amyloid angiopathy) with symptomatic ICH, parenchymal hematoma (within [parenchymal hemorrhage, PH] and remote from the ischemic area [remote parenchymal hemorrhage, PHr]), and poor 3- to 6-month functional outcome (modified Rankin score >2). In 1973 patients from 8 centers, the crude prevalence of CMBs was 526 of 1973 (26.7%). A total of 77 of 1973 (3.9%) patients experienced symptomatic ICH, 210 of 1806 (11.6%) experienced PH, and 56 of 1720 (3.3%) experienced PHr. In adjusted analyses, patients with CMBs (compared with those without CMBs) had increased risk of PH (odds ratio: 1.50; 95% confidence interval: 1.09-2.07; P =0.013) and PHr (odds ratio: 3.04; 95% confidence interval: 1.73-5.35; P <0.001) but not symptomatic ICH. Both cerebral amyloid angiopathy and noncerebral amyloid angiopathy patterns of CMBs were associated with PH and PHr. Increasing CMB burden category was associated with the risk of symptomatic ICH ( P =0.014), PH ( P =0.013), and PHr ( P <0.00001). Five or more and >10 CMBs independently predicted poor 3- to 6-month outcome (odds ratio: 1.85; 95% confidence interval: 1.10-3.12; P =0.020; and odds ratio: 3.99; 95% confidence interval: 1.55-10.22; P =0.004, respectively). Increasing CMB burden is associated with increased risk of ICH (including PHr) and poor

CT Evolution of Hematoma and Surrounding Hypodensity in a Cadaveric Model of Intracerebral Hemorrhage.

PubMed

Majidi, Shahram; Rahim, Basit; Gilani, Sarwat I; Gilani, Waqas I; Adil, Malik M; Qureshi, Adnan I

2016-05-01

The evolution of intracerebral hematoma and perihematoma edema in the ultra-early period on computed tomographic (CT) scans in patients with intracerebral hemorrhage (ICH) is not well understood. We aimed to investigate hematoma and perihematoma changes in "neutral brain" models of ICH. One human and five goat cadaveric heads were used as "neutral brains" to provide physical properties of brain without any biological activity or new bleeding. ICH was induced by slow injection of 4 ml of fresh human blood into the right basal ganglia of the goat brains. Similarly, 20 ml of fresh blood was injected deep into the white matter of the human cadaver head in each hemisphere. Serial CT scans of the heads were obtained immediately after hematoma induction and then 1, 3, and 5 hours afterward. Analyze software (AnalyzeDirect, Overland Park, KS, USA) was used to measure hematoma and perihematoma hypodensity volumes in the baseline and follow-up CT scans. The initial hematoma volumes of 11.6 ml and 10.5 ml in the right and left hemispheres of the cadaver brains gradually decreased to 6.6 ml and 5.4 ml at 5 hours, showing 43% and 48% retraction of hematoma, respectively. The volume of the perihematoma hypodensity in the right and left hemisphere increased from 2.6 ml and 2.2 ml in the 1-hour follow-up CT scans to 4.9 ml and 4.4 ml in the 5-hour CT scan, respectively. Hematoma retraction was also observed in all five goat brains ICH models with the mean ICH volume decreasing from 1.49 ml at baseline scan to 1.01 ml at the 5-hour follow-up CT scan (29.6% hematoma retraction). Perihematoma hypodensity was visualized in 70% of ICH in goat brains, with an increasing mean hypodensity volume of 0.4 ml in the baseline CT scan to 0.8 ml in the 5-hour follow-up CT scan. Our study demonstrated that substantial hematoma retraction and perihematoma hypodensity occurs in ICH in the absence of any new bleeding or biological activity of surrounding brain. Such observations suggest that active

The health loss from ischemic stroke and intracerebral hemorrhage: evidence from the North East Melbourne Stroke Incidence Study (NEMESIS).

PubMed

Cadilhac, Dominique A; Dewey, Helen M; Vos, Theo; Carter, Rob; Thrift, Amanda G

2010-05-14

People suffering different types of stroke have differing demographic characteristics and survival. However, current estimates of disease burden are based on the same underlying assumptions irrespective of stroke type. We hypothesized that average Quality Adjusted Life Years (QALYs) lost from stroke would be different for ischemic stroke and intracerebral hemorrhage (ICH). We used 1 and 5-year data collected from patients with first-ever stroke participating in the North East Melbourne Stroke Incidence Study (NEMESIS). We calculated case fatality rates, health-adjusted life expectancy, and quality-of-life (QoL) weights specific to each age and gender category. Lifetime 'health loss' for first-ever ischemic stroke and ICH surviving 28-days for the 2004 Australian population cohort was then estimated. Multivariable uncertainty analyses and sensitivity analyses (SA) were used to assess the impact of varying input parameters e.g. case fatality and QoL weights. Paired QoL data at 1 and 5 years were available for 237 NEMESIS participants. Extrapolating NEMESIS rates, 31,539 first-ever strokes were expected for Australia in 2004. Average discounted (3%) QALYs lost per first-ever stroke were estimated to be 5.09 (SD 0.20; SA 5.49) for ischemic stroke (n = 27,660) and 6.17 (SD 0.26; SA 6.45) for ICH (n = 4,291; p < 0.001). QALYs lost also differed according to gender for both subtypes (ischemic stroke: males 4.69 SD 0.38, females 5.51 SD 0.46; ICH: males 5.82 SD 0.67, females 6.50 SD 0.40). People with ICH incurred greater loss of health over a lifetime than people with ischemic stroke. This is explained by greater stroke related case fatality at a younger age, but longer life expectancy with disability after the first 12 months for people with ICH. Thus, studies of disease burden in stroke should account for these differences between subtype and gender. Otherwise, in countries where ICH is more common, health loss for stroke may be underestimated. Similar to other studies

Current Practice Trends for Use of Early Venous Thromboembolism Prophylaxis After Intracerebral Hemorrhage.

PubMed

Cherian, Laurel J; Smith, Eric E; Schwamm, Lee H; Fonarow, Gregg C; Schulte, Phillip J; Xian, Ying; Wu, Jingjing; Prabhakaran, Shyam K

2018-01-01

Venous thromboembolism (VTE) is common after intracerebral hemorrhage (ICH). Guidelines recommend early VTE prophylaxis. To determine characteristics associated with early chemoprophylaxis (CP) after ICH in the Get With The Guidelines-Stroke registry. In this observational cohort study, we identified patients with ICH between January 1, 2009 and September 30, 2013, who (1) were non-ambulatory and/or not comfort care measures by hospital day 2; (2) were not transferred to another acute care facility; and (3) had known VTE prophylaxis status at end of hospital day 2. Categories for VTE prophylaxis were as follows: (1) mechanical non-CP or (2) CP with or without mechanical prophylaxis. Early prophylaxis was defined as occurring by hospital day 2. Using multivariable logistic regression, we assessed patient, hospital, and geographic factors independently associated with early CP use. Among 74 283 patients with ICH from 1358 hospitals, 5929 (7.9%) received early CP, 66 444 (89.4%) received early mechanical/non-CP, and 1910 (2.6%) had no prophylaxis, mechanical or CP, within the first 2 days. There was no increase in early CP use over the study period; 60% of hospitals provided early CP to <9% of patients. In multivariable analysis, female sex, atrial fibrillation, diabetes, coronary, carotid, and peripheral artery disease, prior ischemic stroke or transient ischemic attack, hospital size >500 beds, and geographic region were independently associated with early vs no early CP use. Nationwide, the large majority of ICH patients receive early mechanical VTE prophylaxis only, without CP. Patient comorbidities and hospital characteristics such as geographic location are determinants of higher use of early CP. Copyright © 2017 by the Congress of Neurological Surgeons

Common Variants within Oxidative Phosphorylation Genes Influence Risk of Ischemic Stroke and Intracerebral Hemorrhage

PubMed Central

Anderson, Christopher D.; Biffi, Alessandro; Nalls, Michael A.; Devan, William J.; Schwab, Kristin; Ayres, Alison M.; Valant, Valerie; Ross, Owen A.; Rost, Natalia S.; Saxena, Richa; Viswanathan, Anand; Worrall, Bradford B.; Brott, Thomas G.; Goldstein, Joshua N.; Brown, Devin; Broderick, Joseph P.; Norrving, Bo; Greenberg, Steven M.; Silliman, Scott L.; Hansen, Björn M.; Tirschwell, David L.; Lindgren, Arne; Slowik, Agnieszka; Schmidt, Reinhold; Selim, Magdy; Roquer, Jaume; Montaner, Joan; Singleton, Andrew B.; Kidwell, Chelsea S.; Woo, Daniel; Furie, Karen L.; Meschia, James F.; Rosand, Jonathan

2013-01-01

Background and Purpose Prior studies demonstrated association between mitochondrial DNA variants and ischemic stroke (IS). We investigated whether variants within a larger set of oxidative phosphorylation (OXPHOS) genes encoded by both autosomal and mitochondrial DNA were associated with risk of IS and, based on our results, extended our investigation to intracerebral hemorrhage (ICH). Methods This association study employed a discovery cohort of 1643 individuals, a validation cohort of 2432 individuals for IS, and an extension cohort of 1476 individuals for ICH. Gene-set enrichment analysis (GSEA) was performed on all structural OXPHOS genes, as well as genes contributing to individual respiratory complexes. Gene-sets passing GSEA were tested by constructing genetic scores using common variants residing within each gene. Associations between each variant and IS that emerged in the discovery cohort were examined in validation and extension cohorts. Results IS was associated with genetic risk scores in OXPHOS as a whole (odds ratio (OR)=1.17, p=0.008) and Complex I (OR=1.06, p=0.050). Among IS subtypes, small vessel (SV) stroke showed association with OXPHOS (OR=1.16, p=0.007), Complex I (OR=1.13, p=0.027) and Complex IV (OR 1.14, p=0.018). To further explore this SV association, we extended our analysis to ICH, revealing association between deep hemispheric ICH and Complex IV (OR=1.08, p=0.008). Conclusions This pathway analysis demonstrates association between common genetic variants within OXPHOS genes and stroke. The associations for SV stroke and deep ICH suggest that genetic variation in OXPHOS influences small vessel pathobiology. Further studies are needed to identify culprit genetic variants and assess their functional consequences. PMID:23362085

Polybutylcyanoacrylate nanoparticles for delivering hormone response element-conjugated neurotrophin-3 to the brain of intracerebral hemorrhagic rats.

PubMed

Chung, Chiu-Yen; Yang, Jen-Tsung; Kuo, Yung-Chih

2013-12-01

Hypertensive intracerebral hemorrhage (ICH) is a rapidly evolutional pathology, inducing necrotic cell death followed by apoptosis, and alters gene expression levels in surrounding tissue of an injured brain. For ICH therapy by controlled gene release, the development of intravenously administrable delivery vectors to promote the penetration across the blood-brain barrier (BBB) is a critical challenge. To enhance transfer efficiency of genetic materials under hypoxic conditions, polybutylcyanoacrylate (PBCA) nanoparticles (NPs) were used to mediate the intracellular transport of plasmid neurotrophin-3 (NT-3) containing hormone response element (HRE) with a cytomegalovirus (cmv) promoter and to differentiate induced pluripotent stem cells (iPSCs). The differentiation ability of iPSCs to neurons was justified by various immunological stains for protein fluorescence. The effect of PBCA NP/cmvNT-3-HRE complexes on treating ICH rats was studied by immunostaining, western blotting and Nissl staining. We found that the treatments with PBCA NP/cmvNT-3-HRE complexes increased the capability of differentiating iPSCs to express NT-3, TrkC and MAP-2. Moreover, PBCA NPs could protect cmvNT-3-HRE against degradation with EcoRI/PstI and DNase I in vitro and raise the delivery across the BBB in vivo. The administration of PBCA NP/cmvNT-3-HRE complexes increased the expression of NT-3, inhibited the expression of apoptosis-inducing factor, cleaved caspase-3 and DNA fragmentation, and reduced the cell death rate after ICH in vivo. PBCA NPs are demonstrated as an appropriate delivery system for carrying cmvNT-3-HRE to the brain for ICH therapy. Copyright © 2013 Elsevier Ltd. All rights reserved.

Is β-blocker (atenolol) a preferred antihypertensive in acute intracerebral hemorrhage?

PubMed

Kalita, Jayantee; Misra, Usha Kant; Kumar, Bishwanath

2013-07-01

The mortality in intracerebral hemorrhage (ICH) is mainly due to raised intracranial pressure, and its complications mediated by sympathetic overactivity. There is paucity of studies evaluating the role of β-blockers in the outcome of ICH. This study reports the role of atenolol in reducing mortality, pneumonia, systemic inflammatory response syndrome (SIRS), and 3 months outcome in the patients with hypertensive ICH. 138 consecutive patients with hypertensive ICH were included and their stroke risk factors and clinical details were recorded. Consciousness was assessed by Glasgow Coma Scale and severity of stroke by Canadian Neurological Scale. Volume of hematoma was measures on CT scan and occurrence of SIRS and pneumonia were noted. 3 months outcome was categorized into good (Barthel index >12) and poor (BI < 12). The patients were categorized into those receiving atenolol and nonatenolol. The effects of atenolol on stroke outcome parameters were evaluated. Seventy-nine patients received atenolol and 59 did not and they mainly received amlodipine. There was no difference in the base line clinical characteristics between the two groups except smoking (P = 0.01) and baseline blood pressure (P = 0.007). Atenolol significantly reduced the mortality (11.4 vs 37.3 %, P < 0.0001), SIRS (16.4 vs 40.9 %, P = 0.007), and pneumonia (8.9 vs 30.5 %, P = 0.002) compared to those not receiving atenolol. At 3 months, patients with atenolol had insignificantly better outcome compared to nonatenolol group (49.1 vs 31.9 %, P = 0.11). Use of atenolol in hypertensive ICH results in reduction in mortality, SIRS, and pneumonia which may be due to its β-adrenergic blocking effect.

[Perspectives of cell therapy in sequelae from cerebrovascular accidents].

PubMed

Otero, Laura; Zurita, Mercedes; Bonilla, Celia; Aguayo, Concepción; Rico, Miguel Angel; Vaquero, Jesús

2012-09-01

Spontaneous intracerebral hemorrhage (ICH) is associated with mortality between 40 and 50% of cases. Among the survivors, only 10% are independent after one month, there is no effective treatment of sequelae, except for the limited possibilities providing for rehabilitation. We review the current experience with intracerebral transplantation of mesenchymal stem cells (MSCs) obtained from bone marrow as a potential treatment of neurological sequelae occurring after experimental ICH. We describe the model of ICH by intracerebral administration of collagenaseIV at basal ganglia level in Wistar rats. Neurological deficits caused by ICH can be quantified through a variety of functional assessment test (NMSS, Rota-rod, VTB-test). 5×10allogeneic MSCs in 10μl of saline were administered intracerebrally in 10 animals, 2 months after ICH. In another 10 animals (controls) the same volume of saline was administered. Changes in the functional deficits were assessed during the next 6 months in both experimental groups. The results suggested therapeutic efficacy of MSCs transplantation and showed that transplanted stem cells can survive in the injured brain, transforming into neurons and glial cells. This form of cell therapy induces reactivation of endogenous neurogenesis at the subventricular zone (SVZ) and achieves antiapoptotic protective effect in the injured brain. Cell therapy represents an important field of research with potential clinical application to treatment of neurological sequels, currently considered irreversible. Neurosurgeons should become involved in the development of these new techniques that are likely to shape the future of this specialty. Copyright © 2011 Sociedad Española de Neurocirugía. Published by Elsevier España. All rights reserved.

Evaluation of Oral Anticoagulant-Associated Intracranial Parenchymal Hematomas Using CT Findings.

PubMed

Gökçe, E; Beyhan, M; Acu, B

2015-06-01

Intracranial hemorrhage (ICH) is one of the most serious and lethal complications of anticoagulants with a reported incidence of 5-18.5 %. Computed tomographic (CT) findings, should be carefully studied because early diagnosis and treatment of oral anticoagulant use-associated hematomas are vitally important. In the present study, CT findings of intraparenchymal hematomas associated with anticoagulant and antihypertensive use are presented. This study included 45 patients (25 men, 20 women) under anticoagulant (21 patients) or antihypertensive (24 patients) treatment who had brain CT examinations due to complaints and findings suggesting cerebrovascular disease during July 2010-October 2013 period. CT examinations were performed to determine hematoma volumes and presence of swirl sign, hematocrit effect, mid-line shift effect, and intraventricular extension. The patients were 40-89 years of age. In four cases, a total of 51 intraparenchymal hematomas (42 cerebral, 7 cerebellar and 2 brain stem) were detected in multiple foci. Hematoma volumes varied from 0.09 to 284.00 ml. Swirl sign was observed in 87.5 and 63.0 % of OAC-associated ICHs and non-OAC-associated ICHs, respectively. In addition, hematocrit effect was observed in 41.6 % of OAC-associated and in 3.7 % of non-OAC-associated ICHs. Volume increases were observed in all 19 hematomas where swirl sign was detected, and follow-up CT scanning was conducted. Mortality of OAC-associated ICHs was correlated with initial volumes of hematoma, mid-line shift amount, and intraventricular extension. Detection of hematocrit effect by CT scanning of intracranial hematomas should be cautionary in oral anticoagulant use, while detection of swirl sign should be suggestive of active hemorrhage.

Estimating the long-term costs of ischemic and hemorrhagic stroke for Australia: new evidence derived from the North East Melbourne Stroke Incidence Study (NEMESIS).

PubMed

Cadilhac, Dominique A; Carter, Rob; Thrift, Amanda G; Dewey, Helen M

2009-03-01

Stroke is associated with considerable societal costs. Cost-of-illness studies have been undertaken to estimate lifetime costs; most incorporating data up to 12 months after stroke. Costs of stroke, incorporating data collected up to 12 months, have previously been reported from the North East Melbourne Stroke Incidence Study (NEMESIS). NEMESIS now has patient-level resource use data for 5 years. We aimed to recalculate the long-term resource utilization of first-ever stroke patients and compare these to previous estimates obtained using data collected to 12 months. Population structure, life expectancy, and unit prices within the original cost-of-illness models were updated from 1997 to 2004. New Australian stroke survival and recurrence data up to 10 years were incorporated, as well as cross-sectional resource utilization data at 3, 4, and 5 years from NEMESIS. To enable comparisons, 1997 costs were inflated to 2004 prices and discounting was standardized. In 2004, 27 291 ischemic stroke (IS) and 4291 intracerebral hemorrhagic stroke (ICH) first-ever events were estimated. Average annual resource use after 12 months was AU$6022 for IS and AU$3977 for ICH. This is greater than the 1997 estimates for IS (AU$4848) and less than those for ICH (previously AU$10 692). The recalculated average lifetime costs per first-ever case differed for IS (AU$57 106 versus AU$52 855 [1997]), but differed more for ICH (AU$49 995 versus AU$92 308 [1997]). Basing lifetime cost estimates on short-term data overestimated the costs for ICH and underestimated those for IS. Patterns of resource use varied by stroke subtype and, overall, the societal cost impact was large.

Ambient Temperature and Stroke Occurrence: A Systematic Review and Meta-Analysis.

PubMed

Wang, Xia; Cao, Yongjun; Hong, Daqing; Zheng, Danni; Richtering, Sarah; Sandset, Else Charlotte; Leong, Tzen Hugh; Arima, Hisatomi; Islam, Shariful; Salam, Abdul; Anderson, Craig; Robinson, Thompson; Hackett, Maree L

2016-07-12

Biologically plausible associations exist between climatic conditions and stroke risk, but study results are inconsistent. We aimed to summarize current evidence on ambient temperature and overall stroke occurrence, and by age, sex, and variation of temperature. We performed a systematic literature search across MEDLINE, Embase, PsycINFO, CINAHL, Web of Science, and GEOBASE, from inception to 16 October 2015 to identify all population-based observational studies. Where possible, data were pooled for meta-analysis with Odds ratios (OR) and corresponding 95% confidence intervals (CI) by means of the random effects meta-analysis. We included 21 studies with a total of 476,511 patients. The data were varied as indicated by significant heterogeneity across studies for both ischemic stroke (IS) and intracerebral hemorrhage (ICH). Pooled OR (95% CI) in every 1 degree Celsius increase in ambient temperature was significant for ICH 0.97 (0.94-1.00), but not for IS 1.00 (0.99-1.01) and subarachnoid hemorrhage (SAH) 1.00 (0.98-1.01). Meta-analysis was not possible for the pre-specified subgroup analyses by age, sex, and variation of temperature. Change in temperature over the previous 24 h appeared to be more important than absolute temperature in relation to the risk of stroke, especially in relation to the risk of ICH. Older age appeared to increase vulnerability to low temperature for both IS and ICH. To conclude, this review shows that lower mean ambient temperature is significantly associated with the risk of ICH, but not with IS and SAH. Larger temperature changes were associated with higher stroke rates in the elderly.

The REstart or STop Antithrombotics Randomised Trial (RESTART) after stroke due to intracerebral haemorrhage: study protocol for a randomised controlled trial.

PubMed

Al-Shahi Salman, Rustam; Dennis, Martin S; Murray, Gordon D; Innes, Karen; Drever, Jonathan; Dinsmore, Lynn; Williams, Carol; White, Philip M; Whiteley, William N; Sandercock, Peter A G; Sudlow, Cathie L M; Newby, David E; Sprigg, Nikola; Werring, David J

2018-03-05

For adults surviving stroke due to spontaneous (non-traumatic) intracerebral haemorrhage (ICH) who had taken an antithrombotic (i.e. anticoagulant or antiplatelet) drug for the prevention of vaso-occlusive disease before the ICH, it is unclear whether starting antiplatelet drugs results in an increase in the risk of recurrent ICH or a beneficial net reduction of all serious vascular events compared to avoiding antiplatelet drugs. The REstart or STop Antithrombotics Randomised Trial (RESTART) is an investigator-led, randomised, open, assessor-blind, parallel-group, randomised trial comparing starting versus avoiding antiplatelet drugs for adults surviving antithrombotic-associated ICH at 122 hospital sites in the United Kingdom. RESTART uses a central, web-based randomisation system using a minimisation algorithm, with 1:1 treatment allocation to which central research staff are masked. Central follow-up includes annual postal or telephone questionnaires to participants and their general (family) practitioners, with local provision of information about adverse events and outcome events. The primary outcome is recurrent symptomatic ICH. The secondary outcomes are: symptomatic haemorrhagic events; symptomatic vaso-occlusive events; symptomatic stroke of uncertain type; other fatal events; modified Rankin Scale score; adherence to antiplatelet drug(s). The magnetic resonance imaging (MRI) sub-study involves the conduct of brain MRI according to a standardised imaging protocol before randomisation to investigate heterogeneity of treatment effect according to the presence of brain microbleeds. Recruitment began on 22 May 2013. The target sample size is at least 720 participants in the main trial (at least 550 in the MRI sub-study). Final results of RESTART will be analysed and disseminated in 2019. ISRCTN71907627 ( www.isrctn.com/ISRCTN71907627 ). Prospectively registered on 25 April 2013.

Correlation between subacute sensorimotor deficits and brain edema in two mouse models of intracerebral hemorrhage.

PubMed

Krafft, Paul R; McBride, Devin W; Lekic, Tim; Rolland, William B; Mansell, Charles E; Ma, Qingyi; Tang, Jiping; Zhang, John H

2014-05-01

Formation of brain edema after intracerebral hemorrhage (ICH) is highly associated with its poor outcome. However, the relationship between cerebral edema and behavioral deficits has not been thoroughly examined in the preclinical setting. Hence, this study aimed to evaluate the ability of common sensorimotor tests to predict the extent of brain edema in two mouse models of ICH. One hundred male CD-1 mice were subjected to sham surgery or ICH induction via intrastriatal injection of either autologous blood (30 μL) or bacterial collagenase (0.0375U or 0.075U). At 24 and 72 h after surgery, animals underwent a battery of behavioral tests, including the modified Garcia neuroscore (Neuroscore), corner turn test (CTT), forelimb placing test (FPT), wire hang task (WHT) and beam walking (BW). Brain edema was evaluated via the wet weight/dry weight method. Intrastriatal injection of autologous blood or bacterial collagenase resulted in a significant increase in brain water content and associated sensorimotor deficits (p<0.05). A significant correlation between brain edema and sensorimotor deficits was observed for all behavioral tests except for WHT and BW. Based on these findings, we recommend implementing the Neuroscore, CTT and/or FPT in preclinical studies of unilateral ICH in mice. Copyright © 2014 Elsevier B.V. All rights reserved.

Up-regulation of Vps4A promotes neuronal apoptosis after intracerebral hemorrhage in adult rats.

PubMed

Ren, Jianbing; Yuan, Debin; Xie, Lili; Tao, Xuelei; Duan, Chenwei; Bao, Yifeng; He, Yunfeng; Ge, Jianbin; Lu, Hongjian

2017-04-01

Vps4, vacuolar protein sorting 4, belongs to ATPases Associated with diverse cellular Activities (AAA) protein family which is made up of Vps4A and Vps4B. Previous studies demonstrated that Vps4A plays vital roles in diverse aspects such as virus budding, the efficient transport of H-Ras to the PM (plasma membrane) and the involvement in the MVB (multivesiculate bodies) pathway. Interestingly, Vps4A is also expressed in the brain. However, the distribution and function of Vps4A in ICH diseases remain unclear. In this study, we show that Vps4A may be involved in neuronal apoptosis during pathophysiological processes of intracerebral hemorrhage (ICH). Based on the results of Western blot and immunohistochemistry, we found a remarkable up-regulation of Vps4A expression surrounding the hematoma after ICH. Double labeled immunofluorescence showed that Vps4A was co-expressed with NeuN but rarely with astrocytes and microglia. Morever, we detected that neuronal apoptosis marker active caspase-3 had co-localizations with Vps4A. Additionaly, Vps4A knockdown in vitro specifically leads to decreasing neuronal apoptosis coupled with increased Akt phosphorylation. All datas suggested that Vps4A was involved in promoting neuronal apoptosis via inhibiting Akt phosphorylation after ICH.

Performance of blend sign in predicting hematoma expansion in intracerebral hemorrhage: A meta-analysis.

PubMed

Yu, Zhiyuan; Zheng, Jun; Guo, Rui; Ma, Lu; Li, Mou; Wang, Xiaoze; Lin, Sen; Li, Hao; You, Chao

2017-12-01

Hematoma expansion is independently associated with poor outcome in intracerebral hemorrhage (ICH). Blend sign is a simple predictor for hematoma expansion on non-contrast computed tomography. However, its accuracy for predicting hematoma expansion is inconsistent in previous studies. This meta-analysis is aimed to systematically assess the performance of blend sign in predicting hematoma expansion in ICH. A systematic literature search was conducted. Original studies about predictive accuracy of blend sign for hematoma expansion in ICH were included. Pooled sensitivity, specificity, positive and negative likelihood ratios were calculated. Summary receiver operating characteristics curve was constructed. Publication bias was assessed by Deeks' funnel plot asymmetry test. A total of 5 studies with 2248 patients were included in this meta-analysis. The pooled sensitivity, specificity, positive and negative likelihood ratios of blend sign for predicting hematoma expansion were 0.28, 0.92, 3.4 and 0.78, respectively. The area under the curve (AUC) was 0.85. No significant publication bias was found. This meta-analysis demonstrates that blend sign is a useful predictor with high specificity for hematoma expansion in ICH. Further studies with larger sample size are still necessary to verify the accuracy of blend sign for predicting hematoma expansion. Copyright © 2017 Elsevier B.V. All rights reserved.

Differences in Spontaneous Intracerebral Hemorrhage Cases between Urban and Rural Regions of Taiwan: Big Data Analytics of Government Open Data.

PubMed

Ting, Hsien-Wei; Chien, Ting-Ying; Lai, K Robert; Pan, Ren-Hao; Wu, Kuan-Hsien; Chen, Jun-Min; Chan, Chien-Lung

2017-12-10

This study evaluated the differences in spontaneous intracerebral hemorrhage (sICH) between rural and urban areas of Taiwan with big data analysis. We used big data analytics and visualization tools to examine government open data, which included the residents' health medical administrative data, economic status, educational status, and relevant information. The study subjects included sICH patients of Taipei region (29,741 cases) and Eastern Taiwan (4565 cases). The incidence of sICH per 100,000 population per year in Eastern Taiwan (71.3 cases) was significantly higher than that of the Taipei region (42.3 cases). The mean coverage area per hospital in Eastern Taiwan (452.4 km²) was significantly larger than the Taipei region (24 km²). The residents educational level in the Taipei region was significantly higher than that in Eastern Taiwan. The mean hospital length of stay in the Taipei region (17.9 days) was significantly greater than that in Eastern Taiwan (16.3 days) ( p < 0.001). There were no significant differences in other medical profiles between two areas. Distance and educational barriers were two possible reasons for the higher incidence of sICH in the rural area of Eastern Taiwan. Further studies are necessary in order to understand these phenomena in greater depth.

Differences in Spontaneous Intracerebral Hemorrhage Cases between Urban and Rural Regions of Taiwan: Big Data Analytics of Government Open Data

PubMed Central

Ting, Hsien-Wei; Chien, Ting-Ying; Lai, K. Robert; Wu, Kuan-Hsien; Chen, Jun-Min

2017-01-01

This study evaluated the differences in spontaneous intracerebral hemorrhage (sICH) between rural and urban areas of Taiwan with big data analysis. We used big data analytics and visualization tools to examine government open data, which included the residents’ health medical administrative data, economic status, educational status, and relevant information. The study subjects included sICH patients of Taipei region (29,741 cases) and Eastern Taiwan (4565 cases). The incidence of sICH per 100,000 population per year in Eastern Taiwan (71.3 cases) was significantly higher than that of the Taipei region (42.3 cases). The mean coverage area per hospital in Eastern Taiwan (452.4 km2) was significantly larger than the Taipei region (24 km2). The residents educational level in the Taipei region was significantly higher than that in Eastern Taiwan. The mean hospital length of stay in the Taipei region (17.9 days) was significantly greater than that in Eastern Taiwan (16.3 days) (p < 0.001). There were no significant differences in other medical profiles between two areas. Distance and educational barriers were two possible reasons for the higher incidence of sICH in the rural area of Eastern Taiwan. Further studies are necessary in order to understand these phenomena in greater depth. PMID:29232864

Meta-Analysis of Predictive Significance of the Black Hole Sign for Hematoma Expansion in Intracerebral Hemorrhage.

PubMed

Zheng, Jun; Yu, Zhiyuan; Guo, Rui; Li, Hao; You, Chao; Ma, Lu

2018-04-27

Hematoma expansion is related to unfavorable prognosis in intracerebral hemorrhage (ICH). The black hole sign is a novel marker on non-contrast computed tomography for predicting hematoma expansion. However, its predictive values are different in previous studies. Thus, this meta-analysis was conducted to evaluate the predictive significance of the black hole sign for hematoma expansion in ICH. A systematic literature search was performed. Original researches on the association between the black hole sign and hematoma expansion in ICH were included. Sensitivity and specificity were pooled to assess the predictive accuracy. Summary receiver operating characteristics curve (SROC) was developed. Deeks' funnel plot asymmetry test was used to assess the publication bias. Five studies with a total of 1495 patients were included in this study. The pooled sensitivity and specificity of the black hole sign for predicting hematoma expansion were 0.30 and 0.91, respectively. The area under the curve was 0.78 in SROC curve. There was no significant publication bias. This meta-analysis shows that the black hole sign is a helpful imaging marker for predicting hematoma expansion in ICH. Although the black hole sign has a relatively low sensitivity, its specificity is relatively high. Copyright © 2018 Elsevier Inc. All rights reserved.

Recombinant activated factor VII for bleeding in patients without inherited bleeding disorders.

PubMed

Selin, S; Tejani, A

2006-03-01

(1) Recombinant activated factor VII (rFVIIa) is licensed in Canada for the prevention and treatment of bleeding in hemophiliacs, but it is increasingly used to control bleeding in non-hemophilic patients during surgery, or during treatment for severe trauma or intracerebral hemorrhage (ICH). (2) In one clinical trial, there was a significant reduction in mortality among patients with ICH treated with rFVIIa. In another trial, administration of rFVIIa significantly reduced the number of trauma patients needing massive blood transfusions although there was no significant difference in mortality. (3) Adequately powered randomized controlled trials are needed to clarify the efficacy and safety of rFVIIa for non-bleeding disorder indications. Phase III trials in ICH and trauma are underway. (4) There is potential for non-hemophilic use, particularly if clinical efficacy and cost effectiveness are established.

78 FR 20926 - Draft Guidance for Industry on Providing Postmarket Periodic Safety Reports in the International...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-08

...The Food and Drug Administration (FDA) is announcing the availability of a draft guidance for industry entitled ``Providing Postmarket Periodic Safety Reports in the ICH E2C(R2) Format (Periodic Benefit-Risk Evaluation Report).'' This guidance is intended to inform applicants of the conditions under which FDA will exercise its waiver authority to permit applicants to submit an International Conference on Harmonisation (ICH) E2C(R2) Periodic Benefit-Risk Evaluation Report (PBRER) in place of the ICH E2C(R1) Periodic Safety Update Report (PSUR), U.S. periodic adverse drug experience report (PADER), or U.S. periodic adverse experience report (PAER), to satisfy the periodic safety reporting requirements in FDA regulations. The guidance describes the steps applicants can take to submit the PBRER, and discusses the format, content, submission deadline, and frequency of reporting for the PBRER.

Association Between Hypodensities Detected by Computed Tomography and Hematoma Expansion in Patients With Intracerebral Hemorrhage

PubMed Central

Boulouis, Gregoire; Morotti, Andrea; Brouwers, H. Bart; Charidimou, Andreas; Jessel, Michael J.; Auriel, Eitan; Pontes-Neto, Octávio; Ayres, Alison; Vashkevich, Anastasia; Schwab, Kristin M.; Rosand, Jonathan; Viswanathan, Anand; Gurol, Mahmut E.; Greenberg, Steven M.; Goldstein, Joshua N.

2017-01-01

IMPORTANCE Hematoma expansion is a potentially modifiable predictor of poor outcome following an acute intracerebral hemorrhage (ICH). The ability to identify patients with ICH who are likeliest to experience hematoma expansion and therefore likeliest to benefit from expansion-targeted treatments remains an unmet need. Hypodensities within an ICH detected by noncontrast computed tomography (NCCT) have been suggested as a predictor of hematoma expansion. OBJECTIVE To determine whether hypodense regions, irrespective of their specific patterns, are associated with hematoma expansion in patients with ICH. DESIGN, SETTING, AND PARTICIPANTS We analyzed a large cohort of 784 patients with ICH (the development cohort; 55.6% female), examined NCCT findings for any hypodensity, and replicated our findings on a different cohort of patients (the replication cohort; 52.7% female). Baseline and follow-up NCCT data from consecutive patients with ICH presenting to a tertiary care hospital between 1994 and 2015 were retrospectively analyzed. Data analyses were performed between December 2015 and January 2016. MAIN OUTCOMES AND MEASURES Hypodensities were analyzed by 2 independent blinded raters. The association between hypodensities and hematoma expansion (>6 cm3 or 33% of baseline volume) was determined by multivariable logistic regression after controlling for other variables associated with hematoma expansion in univariate analyses with P ≤ .10. RESULTS A total of 1029 patients were included in the analysis. In the development and replication cohorts, 222 of 784 patients (28.3%) and 99 of 245 patients (40.4%; 321 of 1029 patients [31.2%]), respectively, had NCCT scans that demonstrated hypodensities at baseline (κ = 0.87 for interrater reliability). In univariate analyses, hypodensities were associated with hematoma expansion (86 of 163 patients with hematoma expansion had hypodensities [52.8%], whereas 136 of 621 patients without hematoma expansion had hypodensities [21

Identification of six polymorphisms as novel susceptibility loci for ischemic or hemorrhagic stroke by exome-wide association studies

PubMed Central

Yamada, Yoshiji; Sakuma, Jun; Takeuchi, Ichiro; Yasukochi, Yoshiki; Kato, Kimihiko; Oguri, Mitsutoshi; Fujimaki, Tetsuo; Horibe, Hideki; Muramatsu, Masaaki; Sawabe, Motoji; Fujiwara, Yoshinori; Taniguchi, Yu; Obuchi, Shuichi; Kawai, Hisashi; Shinkai, Shoji; Mori, Seijiro; Arai, Tomio; Tanaka, Masashi

2017-01-01

In this study, we performed exome-wide association studies (EWASs) to identify genetic variants that confer susceptibility to ischemic stroke, intracerebral hemorrhage (ICH), or subarachnoid hemorrhage (SAH). EWAS for ischemic stroke was performed using 1,575 patients with this condition and 9,210 controls, and EWASs for ICH and SAH were performed using 673 patients with ICH, 265 patients with SAH and 9,158 controls. Analyses were performed with Illumina HumanExome-12 DNA Analysis BeadChip or Infinium Exome-24 BeadChip arrays. The relation of allele frequencies for 41,339 or 41,332 single nucleotide polymorphisms (SNPs) that passed quality control to ischemic or hemorrhagic stroke, respectively, was examined with Fisher's exact test. Based on Bonferroni's correction, a P-value of <1.21×10−6 was considered statistically significant. EWAS for ischemic stroke revealed that 77 SNPs were significantly associated with this condition. Multivariable logistic regression analysis with adjustment for age, sex and the prevalence of hypertension and diabetes mellitus revealed that 4 of these SNPs [rs3212335 of GABRB3 (P=0.0036; odds ratio, 1.29), rs147783135 of TMPRSS7 (P=0.0024; odds ratio, 0.37), rs2292661 of PDIA5 (P=0.0054; odds ratio, 0.35) and rs191885206 of CYP4F12 (P=0.0082; odds ratio, 2.60)] were related (P<0.01) to ischemic stroke. EWASs for ICH or SAH revealed that 48 and 12 SNPs, respectively, were significantly associated with these conditions. Multivariable logistic regression analysis with adjustment for age, sex and the prevalence of hypertension revealed that rs138533962 of STYK1 (P<1.0×10−23; odds ratio, 111.3) was significantly (P<2.60×10−4) associated with ICH and that rs117564807 of COL17A1 (P=0.0009; odds ratio, 2.23×10−8) was significantly (P<0.0010) associated with SAH. GABRB3, TMPRSS7, PDIA5 and CYP4F12 may thus be novel susceptibility loci for ischemic stroke, whereas STYK1 and COL17A1 may be such loci for ICH and SAH, respectively. PMID

Clinical outcomes and management associated with major bleeding in patients with atrial fibrillation treated with apixaban or warfarin: insights from the ARISTOTLE trial.

PubMed

Held, Claes; Hylek, Elaine M; Alexander, John H; Hanna, Michael; Lopes, Renato D; Wojdyla, Daniel M; Thomas, Laine; Al-Khalidi, Hussein; Alings, Marco; Xavier, Dennis; Ansell, Jack; Goto, Shinya; Ruzyllo, Witold; Rosenqvist, Mårten; Verheugt, Freek W A; Zhu, Jun; Granger, Christopher B; Wallentin, Lars

2015-05-21

In the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial, apixaban compared with warfarin reduced the risk of stroke, major bleed, and death in patients with atrial fibrillation. In this ancillary study, we evaluated clinical consequences of major bleeds, as well as management and treatment effects of warfarin vs. apixaban. Major International Society on Thrombosis and Haemostasis bleeding was defined as overt bleeding accompanied by a decrease in haemoglobin (Hb) of ≥2 g/dL or transfusion of ≥2 units of packed red cells, occurring at a critical site or resulting in death. Time to event [death, ischaemic stroke, or myocardial infarction (MI)] was evaluated by Cox regression models. The excess risk associated with bleeding was evaluated by separate time-dependent indicators for intracranial (ICH) and non-intracranial haemorrhage. Major bleeding occurred in 848 individuals (4.7%), of whom 126 (14.9%) died within 30 days. Of 176 patients with an ICH, 76 (43.2%) died, and of the 695 patients with major non-ICH, 64 (9.2%) died within 30 days of the bleeding. The risk of death, ischaemic stroke, or MI was increased roughly 12-fold after a major non-ICH bleeding event within 30 days. Corresponding risk of death following an ICH was markedly increased, with HR 121.5 (95% CI 91.3-161.8) as was stroke or MI with HR 21.95 (95% CI 9.88-48.81), respectively. Among patients with major bleeds, 20.8% received vitamin K and/or related medications (fresh frozen plasma, coagulation factors, factor VIIa) to stop bleeding within 3 days, and 37% received blood transfusion. There was no interaction between apixaban and warfarin and major bleeding on the risk of death, stroke, or MI. Major bleeding was associated with substantially increased risk of death, ischaemic stroke, or MI, especially following ICH, and this risk was similarly elevated regardless of treatment with apixaban or warfarin. These results underscore the

Major bleeding and intracranial hemorrhage risk prediction in patients with atrial fibrillation: Attention to modifiable bleeding risk factors or use of a bleeding risk stratification score? A nationwide cohort study.

PubMed

Chao, Tze-Fan; Lip, Gregory Y H; Lin, Yenn-Jiang; Chang, Shih-Lin; Lo, Li-Wei; Hu, Yu-Feng; Tuan, Ta-Chuan; Liao, Jo-Nan; Chung, Fa-Po; Chen, Tzeng-Ji; Chen, Shih-Ann

2018-03-01

While modifiable bleeding risks should be addressed in all patients with atrial fibrillation (AF), use of a bleeding risk score enables clinicians to 'flag up' those at risk of bleeding for more regular patient contact reviews. We compared a risk assessment strategy for major bleeding and intracranial hemorrhage (ICH) based on modifiable bleeding risk factors (referred to as a 'MBR factors' score) against established bleeding risk stratification scores (HEMORR 2 HAGES, HAS-BLED, ATRIA, ORBIT). A nationwide cohort study of 40,450 AF patients who received warfarin for stroke prevention was performed. The clinical endpoints included ICH and major bleeding. Bleeding scores were compared using receiver operating characteristic (ROC) curves (areas under the ROC curves [AUCs], or c-index) and the net reclassification index (NRI). During a follow up of 4.60±3.62years, 1581 (3.91%) patients sustained ICH and 6889 (17.03%) patients sustained major bleeding events. All tested bleeding risk scores at baseline were higher in those sustaining major bleeds. When compared to no ICH, patients sustaining ICH had higher baseline HEMORR 2 HAGES (p=0.003), HAS-BLED (p<0.001) and MBR factors score (p=0.013) but not ATRIA and ORBIT scores. When HAS-BLED was compared to other bleeding scores, c-indexes were significantly higher compared to MBR factors (p<0.001) and ORBIT (p=0.05) scores for major bleeding. C-indexes for the MBR factors score was significantly lower compared to all other scores (De long test, all p<0.001). When NRI was performed, HAS-BLED outperformed all other bleeding risk scores for major bleeding (all p<0.001). C-indexes for ATRIA and ORBIT scores suggested no significant prediction for ICH. All contemporary bleeding risk scores had modest predictive value for predicting major bleeding but the best predictive value and NRI was found for the HAS-BLED score. Simply depending on modifiable bleeding risk factors had suboptimal predictive value for the prediction of major

Management of intracranial hemorrhage in patients with left ventricular assist devices.

PubMed

Wilson, Thomas J; Stetler, William R; Al-Holou, Wajd N; Sullivan, Stephen E; Fletcher, Jeffrey J

2013-05-01

The authors conducted a study to review outcomes and management in patients in whom intracranial hemorrhage (ICH) develops during left ventricular assist device (LVAD) therapy. This retrospective cohort study included all adult patients (18 years of age or older) at a single institution who underwent placement of an LVAD between January 1, 2003, and March 1, 2012. The authors conducted a detailed medical chart review, and data were abstracted to assess outcomes in patients in whom ICH developed compared to those in patients in whom ICH did not develop; to compare management of antiplatelet agents and anticoagulation with outcomes; to describe surgical management employed and outcomes achieved; to compare subtypes of ICH (intraparenchymal, subdural, and subarachnoid hemorrhage) and their outcomes; and to determine any predictors of outcome. During the study period, 330 LVADs were placed and 36 patients developed an ICH (traumatic subarachnoid hemorrhage in 10, traumatic subdural hematoma in 8, spontaneous intraventricular hemorrhage in 1, and spontaneous intraparenchymal hemorrhage in 17). All patients were treated with aspirin and warfarin at the time of presentation. With suspension of these agents, no thromboembolic events or pump failures were seen and no delayed rehemorrhages occurred after resuming these medications. Intraparenchymal hemorrhages had the worst outcomes, with a 30-day mortality rate in 59% compared with a 30-day mortality rate of 0% in patients with traumatic subarachnoid hemorrhages and 13% in those with traumatic subdural hematomas. Five patients with intraparenchymal hemorrhages were managed with surgical intervention, 4 of whom died within 60 days. The only factor found to be predictive of outcome was initial Glasgow Coma Scale score. No patients with a Glasgow Coma Scale score less than 11 survived beyond 30 days. Overall, the development of an ICH significantly reduced survival compared with the natural history of patients on LVAD therapy

Development and clinical translation of a cone-beam CT scanner for high-quality imaging of intracranial hemorrhage

NASA Astrophysics Data System (ADS)

Sisniega, A.; Xu, J.; Dang, H.; Zbijewski, W.; Stayman, J. W.; Mow, M.; Koliatsos, V. E.; Aygun, N.; Wang, X.; Foos, D. H.; Siewerdsen, J. H.

2017-03-01

Purpose: Prompt, reliable detection of intracranial hemorrhage (ICH) is essential for treatment of stroke and traumatic brain injury, and would benefit from availability of imaging directly at the point-of-care. This work reports the performance evaluation of a clinical prototype of a cone-beam CT (CBCT) system for ICH imaging and introduces novel algorithms for model-based reconstruction with compensation for data truncation and patient motion. Methods: The tradeoffs in dose and image quality were investigated as a function of analytical (FBP) and model-based iterative reconstruction (PWLS) algorithm parameters using phantoms with ICH-mimicking inserts. Image quality in clinical applications was evaluated in a human cadaver imaged with simulated ICH. Objects outside of the field of view (FOV), such as the head-holder, were found to introduce challenging truncation artifacts in PWLS that were mitigated with a novel multi-resolution reconstruction strategy. Following phantom and cadaver studies, the scanner was translated to a clinical pilot study. Initial clinical experience indicates the presence of motion in some patient scans, and an image-based motion estimation method that does not require fiducial tracking or prior patient information was implemented and evaluated. Results: The weighted CTDI for a nominal scan technique was 22.8 mGy. The high-resolution FBP reconstruction protocol achieved < 0.9 mm full width at half maximum (FWHM) of the point spread function (PSF). The PWLS soft-tissue reconstruction showed <1.2 mm PSF FWHM and lower noise than FBP at the same resolution. Effects of truncation in PWLS were mitigated with the multi-resolution approach, resulting in 60% reduction in root mean squared error compared to conventional PWLS. Cadaver images showed clear visualization of anatomical landmarks (ventricles and sulci), and ICH was conspicuous. The motion compensation method was shown in clinical studies to restore visibility of fine bone structures

The comparative method of language acquisition research: a Mayan case study.

PubMed

Pye, Clifton; Pfeiler, Barbara

2014-03-01

This article demonstrates how the Comparative Method can be applied to cross-linguistic research on language acquisition. The Comparative Method provides a systematic procedure for organizing and interpreting acquisition data from different languages. The Comparative Method controls for cross-linguistic differences at all levels of the grammar and is especially useful in drawing attention to variation in contexts of use across languages. This article uses the Comparative Method to analyze the acquisition of verb suffixes in two Mayan languages: K'iche' and Yucatec. Mayan status suffixes simultaneously mark distinctions in verb transitivity, verb class, mood, and clause position. Two-year-old children acquiring K'iche' and Yucatec Maya accurately produce the status suffixes on verbs, in marked distinction to the verbal prefixes for aspect and agreement. We find evidence that the contexts of use for the suffixes differentially promote the children's production of cognate status suffixes in K'iche' and Yucatec.

Management of Acute Hypertensive Response in Intracerebral Hemorrhage Patients After ATACH-2 Trial.

PubMed

Majidi, Shahram; Suarez, Jose I; Qureshi, Adnan I

2017-10-01

Acute hypertensive response is elevation of systolic blood pressure (SBP) in the first 24 h after symptom onset which is highly prevalent in patients with intracerebral hemorrhage (ICH). Observational studies suggested association between acute hypertensive response and hematoma expansion, peri-hematoma edema and death and disability, and possible reduction in these adverse outcomes with treatment of acute hypertensive response. Recent clinical trials have focused on determining the clinical efficacy of early intensive SBP reduction in ICH patients. The Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH-2) trial was the latest phase 3 randomized controlled multicenter clinical trial aimed to study the efficacy of early intensive reduction of SBP in ICH patients. In this review article, we summarize the results of recent clinical trials, treatment principles based on the latest guidelines, and the anticipated interpretation and incorporation of ATACH-2 trial results in clinical practice.

Associations with health-related quality of life after intracerebral haemorrhage: pooled analysis of INTERACT studies.

PubMed

Delcourt, Candice; Zheng, Danni; Chen, Xiaoying; Hackett, Maree; Arima, Hisatomi; Hata, Jun; Heeley, Emma; Al-Shahi Salman, Rustam; Woodward, Mark; Huang, Yining; Robinson, Thompson; Lavados, Pablo M; Lindley, Richard I; Stapf, Christian; Davies, Leo; Chalmers, John; Anderson, Craig S; Sato, Shoichiro

2017-01-01

Limited data exist on health-related quality of life (HRQoL) after intracerebral haemorrhage (ICH). We aimed to determine baseline factors associated with HRQoL among participants of the pilot and main phases of the Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage Trials (INTERACT 1 and 2). The INTERACT studies were randomised controlled trials of early intensive blood pressure (BP) lowering in patients with ICH (<6 hours) and elevated systolic BP (150-220 mm Hg). HRQoL was determined using the European Quality of Life Scale (EQ-5D) at 90 days, completed by patients or proxy responders. Binary logistic regression analyses were performed to identify factors associated with poor overall HRQoL. 2756 patients were included. Demographic, clinical and radiological factors associated with lower EQ-5D utility score were age, randomisation outside of China, antithrombotic use, high baseline National Institutes of Health Stroke Scale (NIHSS) score, larger ICH, presence of intraventricular extension and use of proxy responders. High (≥14) NIHSS score, larger ICH and proxy responders were associated with low scores in all five dimensions of the EQ-5D. The NIHSS score had a strong association with poor HRQoL (p<0.001). Female gender and antithrombotic use were associated with decreased scores in dimensions of pain/discomfort and usual activity, respectively. Poor HRQoL was associated with age, comorbidities, proxy source of assessment, clinical severity and ICH characteristics. The strongest association was with initial clinical severity defined by high NIHSS score. NCT00226096 and NCT00716079; Post-results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

STARTING-SICH Nomogram to Predict Symptomatic Intracerebral Hemorrhage After Intravenous Thrombolysis for Stroke.

PubMed

Cappellari, Manuel; Turcato, Gianni; Forlivesi, Stefano; Zivelonghi, Cecilia; Bovi, Paolo; Bonetti, Bruno; Toni, Danilo

2018-02-01

Symptomatic intracerebral hemorrhage (sICH) is a rare but the most feared complication of intravenous thrombolysis for ischemic stroke. We aimed to develop and validate a nomogram for individualized prediction of sICH in intravenous thrombolysis-treated stroke patients included in the multicenter SITS-ISTR (Safe Implementation of Thrombolysis in Stroke-International Stroke Thrombolysis Register). All patients registered in the SITS-ISTR by 179 Italian centers between May 2001 and March 2016 were originally included. The main outcome measure was sICH per the European Cooperative Acute Stroke Study II definition (any type of intracerebral hemorrhage with increase of ≥4 National Institutes of Health Stroke Scale score points from baseline or death <7 days). On the basis of multivariate logistic model, the nomogram was generated. We assessed the discriminative performance by using the area under the receiver-operating characteristic curve and calibration of risk prediction model by using the Hosmer-Lemeshow test. A total of 15 949 patients with complete data for generating the nomogram was randomly dichotomized into training (3/4; n=12 030) and test (1/4; n=3919) sets. After multivariate logistic regression, 10 variables remained independent predictors of sICH to compose the STARTING-SICH (systolic blood pressure, age, onset-to-treatment time for thrombolysis, National Institutes of Health Stroke Scale score, glucose, aspirin alone, aspirin plus clopidogrel, anticoagulant with INR ≤1.7, current infarction sign, hyperdense artery sign) nomogram. The area under the receiver-operating characteristic curve of STARTING-SICH was 0.739. Calibration was good ( P =0.327 for the Hosmer-Lemeshow test). The STARTING-SICH is the first nomogram developed and validated in a large SITS-ISTR cohort for individualized prediction of sICH in intravenous thrombolysis-treated stroke patients. © 2018 American Heart Association, Inc.

Running exercise enhances motor functional recovery with inhibition of dendritic regression in the motor cortex after collagenase-induced intracerebral hemorrhage in rats.

PubMed

Takamatsu, Yasuyuki; Tamakoshi, Keigo; Waseda, Yuya; Ishida, Kazuto

2016-03-01

Rehabilitative approaches benefit motor functional recovery after stroke and relate to neuronal plasticity. We investigated the effects of a treadmill running exercise on the motor functional recovery and neuronal plasticity after collagenase-induced striatal intracerebral hemorrhage (ICH) in rats. Male Wistar rats were injected with type IV collagenase into the left striatum to induce ICH. Sham-operated animals were injected with saline instead of collagenase. The animals were randomly assigned to the sham control (SC), the sham exercise (SE), the ICH control (IC), or the ICH exercise (IE) group. The exercise groups were forced to run on a treadmill at a speed of 9 m/min for 30 min/day between days 4 and 14 after surgery. Behavioral tests were performed using a motor deficit score, a beam-walking test and a cylinder test. At fifteen days after surgery, the animals were sacrificed, and their brains were removed. The motor function of the IE group significantly improved compared with the motor function of the IC group. No significant differences in cortical thickness were found between the groups. The IC group had fewer branches and shorter dendrite lengths compared with the sham groups. However, dendritic branches and lengths were not significantly different between the IE and the other groups. Tropomyosin-related kinase B (TrkB) expression levels increased in the IE compared with IC group, but no significant differences in other protein (brain-derived neurotrophic factor, BDNF; Nogo-A; Rho-A/Rho-associated protein kinase 2, ROCK2) expression levels were found between the groups. These results suggest that improved motor function after a treadmill running exercise after ICH may be related to the prevention of dendritic regression due to TrkB upregulation. Copyright © 2015. Published by Elsevier B.V.

Lost potential of kidney and liver donors amongst deceased intracerebral hemorrhage patients.

PubMed

Sairanen, T; Koivisto, A; Koivusalo, A-M; Rantanen, K; Mustanoja, S; Meretoja, A; Putaala, J; Strbian, D; Kaste, M; Isoniemi, H; Tatlisumak, T

2014-01-01

Intracerebral hemorrhage (ICH) has high acute mortality. The number of potential kidney and liver donors amongst deceased ICH patients was estimated to improve our institutional guidelines on acute care of neurocritical patients to increase organ donation. A chart review was carried out by a multi-professional team for consecutive ICH patients admitted to the emergency department at Helsinki University Central Hospital and dying within 14 days between 2005 and 2010. In all, 955 patients had follow-up data, of whom 254 (27%) died within 14 days and eight ended up as organ donors. An additional 51 potentially suitable donors not different from actual donors were identified: nine suitable for kidney donation, 11 for liver and 31 for both. In 49/51 (96%) cases prognosis seemed non-existent and do-not-resuscitate orders were issued early, which led to refrainment from intensive care in 76.5%. These potential donors differed from those ICH patients surviving a whole year (n = 529) by male preponderance, more severe symptoms (median National Institutes of Health Stroke Scale 25 vs. 6 and Glasgow Coma Scale 7 vs. 15), larger hematoma volumes of 24.8 cm(3) (vs. 6.7), and frequent finding of midline shift and intraventricular rupture of the hemorrhage in admission brain CT. Based on the results, our guidelines were revised towards more active treatment including mechanical ventilation for neurocritical patients at the emergency department for at least 48 h, resulting in an increase in organ donations in 2012. A considerable number of ICH patients are potential organ donors if the evaluation takes place on arrival and organ donation is considered as part of usual end-of-life care. © 2013 The Author(s) European Journal of Neurology © 2013 EFNS.

Vortex depinning as a nonequilibrium phase transition phenomenon: Scaling of current-voltage curves near the low and the high critical-current states in 2 H -Nb S2 single crystals

NASA Astrophysics Data System (ADS)

Bag, Biplab; Sivananda, Dibya J.; Mandal, Pabitra; Banerjee, S. S.; Sood, A. K.; Grover, A. K.

2018-04-01

The vortex depinning phenomenon in single crystals of 2 H -Nb S2 superconductors is used as a prototype for investigating properties of the nonequilibrium (NEQ) depinning phase transition. The 2 H -Nb S2 is a unique system as it exhibits two distinct depinning thresholds, viz., a lower critical current Icl and a higher one Ich. While Icl is related to depinning of a conventional, static (pinned) vortex state, the state with Ich is achieved via a negative differential resistance (NDR) transition where the velocity abruptly drops. Using a generalized finite-temperature scaling ansatz, we study the scaling of current (I)-voltage (V) curves measured across Icl and Ich. Our analysis shows that for I >Icl , the moving vortex state exhibits Arrhenius-like thermally activated flow behavior. This feature persists up to a current value where an inflexion in the IV curves is encountered. While past measurements have often reported similar inflexion, our analysis shows that the inflexion is a signature of a NEQ phase transformation from a thermally activated moving vortex phase to a free flowing phase. Beyond this inflection in IV, a large vortex velocity flow regime is encountered in the 2 H -Nb S2 system, wherein the Bardeen-Stephen flux flow limit is crossed. In this regime the NDR transition is encountered, leading to the high Ich state. The IV curves above Ich we show do not obey the generalized finite-temperature scaling ansatz (as obeyed near Icl). Instead, they scale according to the Fisher's scaling form [Fisher, Phys. Rev. B 31, 1396 (1985), 10.1103/PhysRevB.31.1396] where we show thermal fluctuations do not affect the vortex flow, unlike that found for depinning near Icl.

Preadmission Use of Glucocorticoids and 30-Day Mortality After Stroke.

PubMed

Sundbøll, Jens; Horváth-Puhó, Erzsébet; Schmidt, Morten; Dekkers, Olaf M; Christiansen, Christian F; Pedersen, Lars; Bøtker, Hans Erik; Sørensen, Henrik T

2016-03-01

The prognostic impact of glucocorticoids on stroke mortality remains uncertain. We, therefore, examined whether preadmission use of glucocorticoids is associated with short-term mortality after ischemic stroke, intracerebral hemorrhage (ICH), or subarachnoid hemorrhage (SAH). We conducted a nationwide population-based cohort study using medical registries in Denmark. We identified all patients with a first-time inpatient diagnosis of stroke between 2004 and 2012. We categorized glucocorticoid use as current use (last prescription redemption ≤90 days before admission), former use, and nonuse. Current use was further classified as new or long-term use. We used Cox regression to compute 30-day mortality rate ratios with 95% confidence intervals (CIs), controlling for confounders. We identified 100 042 patients with a first-time stroke. Of these, 83 735 patients had ischemic stroke, 11 779 had ICH, and 4528 had SAH. Absolute mortality risk was higher for current users compared with nonusers for ischemic stroke (19.5% versus 10.2%), ICH (46.5% versus 34.4%), and SAH (35.0% versus 23.2%). For ischemic stroke, the adjusted 30-day mortality rate ratio was increased among current users compared with nonusers (1.58, 95% CI: 1.46-1.71), driven by the effect of glucocorticoids among new users (1.80, 95% CI: 1.62-1.99). Current users had a more modest increase in the adjusted 30-day mortality rate ratio for hemorrhagic stroke (1.26, 95% CI: 1.09-1.45 for ICH and 1.40, 95% CI: 1.01-1.93 for SAH) compared with nonusers. Former use was not substantially associated with mortality. Preadmission use of glucocorticoids was associated with increased 30-day mortality among patients with ischemic stroke, ICH, and SAH. © 2016 American Heart Association, Inc.

Incidence, risk factors, etiology, severity and short-term outcome of non-traumatic intracerebral hemorrhage in young adults.

PubMed

Koivunen, R-J; Satopää, J; Meretoja, A; Strbian, D; Haapaniemi, E; Niemelä, M; Tatlisumak, T; Putaala, J

2015-01-01

Intracerebral hemorrhage (ICH) is a common and severe form of stroke but is scarcely studied in young adults. Our aim was to study risk factors, clinical presentation and early mortality of ICH in the young and compare these features with older patients. All consecutive patients aged between 16 and 49 diagnosed with a first-ever ICH at the Departments of Neurology or Neurosurgery of the Helsinki University Central Hospital between January 2000 and March 2010 (n = 336) were analyzed retrospectively. Comparisons were performed amongst demographic subgroups and with patients over 49 years of age enrolled between January 2005 and March 2010 (n = 921). In the young patients, median age was 42 years (interquartile range 34-47), 59.5% were male, and annual incidence was 4.9 (95% confidence interval 4.5-5.3) per 100 000. The most prevalent risk factors were hypertension (29.8%) and smoking (22.3%). Compared with older patients hypertensive microangiopathy was less common (25.0% vs. 34.3%, P = 0.002) and structural lesions more common (25.0% vs. 4.9%, P < 0.001) assumed etiologies of ICH. The cause remained elusive in 32.1% of all young patients and in 22.5% of those who underwent magnetic resonance imaging and any angiography (n = 89, P = 0.023). Three-month mortality rate was lower in young patients compared with older ones (17.0% vs. 32.7%, P < 0.001). Hematoma volumes were similar across all ages (P = 0.324) and independently predicted mortality in older patients but not in the young. Intracerebral hemorrhage (ICH) in the young appears less fatal and has a different spectrum of causes and factors associated with short-term mortality than for the elderly. © 2014 EAN.

Clinical Course and Outcomes of Small Supratentorial Intracerebral Hematomas.

PubMed

Behrouz, Réza; Misra, Vivek; Godoy, Daniel A; Topel, Christopher H; Masotti, Luca; Klijn, Catharina J M; Smith, Craig J; Parry-Jones, Adrian R; Slevin, Mark A; Silver, Brian; Willey, Joshua Z; Masjuán Vallejo, Jaime; Nzwalo, Hipólito; Popa-Wagner, Aurel; Malek, Ali R; Hafeez, Shaheryar; Di Napoli, Mario

2017-06-01

Intracerebral hemorrhage (ICH) volume, particularly if ≥30 mL, is a major determinant of poor outcome. We used a multinational ICH data registry to study the characteristics, course, and outcomes of supratentorial hematomas with volumes <30 mL. Basic characteristics, clinical and radiological course, and 30-day outcomes of these patients were recorded. Outcomes were categorized as early neurological deterioration (END), hematoma expansion, Glasgow Outcome Scale (GOS), and in-hospital death. Poor outcome was defined as composite of in-hospital death and severe disability (GOS ≤ 3). Comparison was conducted based on hemorrhage location. Logistic regression using dichotomized outcome scales was applied to determine predictors of poor outcome. Among 375 cases of supratentorial ICH with volumes <30 mL, expansion and END rates were 19.2% and 7.5%, respectively. Hemorrhage growth was independently associated with END (odds ratio: 28.7, 95% confidence interval [CI]: 8.51-96.5; P < .0001). Expansion rates did not differ according to ICH location. Overall, 13.9% (exact binomial 95% CI: 10.5-17.8) died in the hospital and 29.1% (CI: 24.5-34.0) had severe disability at 30 days; there was a cumulative poor outcome rate of 42.9% (CI: 37.9-48.1). Age, admission Glasgow Coma Scale, intraventricular extension, and END were independently associated with poor outcome. There was no difference in poor outcome rates between lobar and deep locations (40.2% versus 43.8%, P = .56). Patients with supratentorial ICH <30 mL have high rates of poor outcome at 30 days, regardless of location. Nearly 1 in 5 hematomas <30 mL expands, leading to END or death. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Protective role of free and quercetin-loaded nanoemulsion against damage induced by intracerebral haemorrhage in rats.

PubMed

Galho, A R; Cordeiro, M F; Ribeiro, S A; Marques, M S; Antunes, M F D; Luz, D C; Hädrich, G; Muccillo-Baisch, A L; Barros, D M; Lima, J V; Dora, C L; Horn, A P

2016-04-29

Intracerebral haemorrhage (ICH) is a worldwide public health problem. Experimental studies have shown that oxidative stress plays an important role in the pathogenesis of ICH and could represent a target for its treatment. However, the blood-brain barrier is an obstacle to be overcome, as it hampers the administration of compounds to the central nervous system. In this study, we compared the effects of a quercetin-loaded nanoemulsion (QU-N) with the free form of the drug (QU-SP) in a collagenase-induced ICH rat model. Quercetin (QU) is a polyphenol that has an antioxidant effect in vitro, but due to its high lipophilicity, it has low bioavailability in vivo. In this study, animals submitted or not to ICH were treated with a single intraperitoneal QU dose (free or nanoemulsion) of 30 mg kg(-1). Motor assessment was evaluated by the open field, foot fault and beam walking behavioural tests. 72 h after surgery the haematoma size was evaluated and biochemical measurements were performed. Animals treated with QU-N had a significant improvement in the beam walking and open field tests. Also, QU-N was able to reduce the size of the haematoma, preserving the activity of glutathione S-transferase (GST), increasing GSH content, and the total antioxidant capacity. QU-SP recovered locomotor activity and increased the GSH content and the total antioxidant capacity. Thus, it can be observed that QU presented antioxidant activity in both formulations, but the incorporation into nanoemulsions increased its antioxidant effect, which was reflected in the improvement of the motor skills and in the haematoma size decrement. These results suggest that the nanoemulsion containing QU developed in this study could be promising for future studies on treatments for ICH.

Cost-effectiveness of recombinant activated factor VII in the treatment of intracerebral hemorrhage.

PubMed

Earnshaw, Stephanie R; Joshi, Ashish V; Wilson, Michele R; Rosand, Jonathan

2006-11-01

Intracerebral hemorrhage (ICH) is among the most costly and debilitating forms of stroke. Results from a recent Phase IIb clinical trial demonstrate that administration of recombinant activated factor VII (rFVIIa) reduces ICH mortality and improves functional outcome. In the current analysis, we examine the cost-effectiveness of early treatment with rFVIIa for ICH in the United States. A decision-analytic model was developed to estimate the lifetime costs and outcomes associated with rFVIIa treatment at doses of 40, 80 and 160 microg/kg compared with current standard of care in treating ICH, from a US third-party payer perspective. The patient population was similar to that of the Phase IIb clinical trial. Model structure and inputs were obtained from published literature, clinical trial data, claims databases, and expert opinion. All costs are presented in 2005 US dollars. Outcomes included incremental cost per life-year (LY) saved and incremental cost per quality-adjusted life-year (QALY) gained. Costs and outcomes were discounted at 3% annually. Univariate and multivariate sensitivity analyses were conducted to assess model robustness. Compared with standard care, treatment with rFVIIa 40 microg/kg, and 160 microg/kg results in total lifetime cost-effectiveness ratios of 6308 dollars/QALY and 3152 dollars/QALY, respectively. Treatment with rFVIIa 80 microg/kg was found to be cost saving and a gain of 1.67 QALYs is achieved over a patient's lifetime. These results are robust to changes in input parameters. Treatment of ICH with rFVIIa 40 microg/kg and 160 microg/kg appears to be cost-effective (

Systemic thrombolysis in acute ischemic stroke patients with unruptured intracranial aneurysms

PubMed Central

Goyal, Nitin; Tsivgoulis, Georgios; Zand, Ramin; Sharma, Vijay K.; Barlinn, Kristian; Male, Shailesh; Katsanos, Aristeidis H.; Bodechtel, Ulf; Iftikhar, Sulaiman; Arthur, Adam; Elijovich, Lucas; Alexandrov, Anne W.

2015-01-01

Objective: We sought to determine the safety of IV thrombolysis (IVT) in acute ischemic stroke (AIS) patients harboring unruptured intracranial aneurysm (UIA) in a multicenter study and a comprehensive meta-analysis of available case series. Methods: We analyzed prospectively collected data from consecutive AIS patients treated with IVT during a 4-year period at 4 tertiary-care stroke centers. All patients routinely underwent CT or magnetic resonance angiography during hospitalization. The presence of UIA was documented on the basis of neuroradiology reports. Symptomatic intracranial hemorrhage (sICH) was defined as imaging evidence of ICH combined with an increase in NIH Stroke Scale score of ≥4 points. A systematic meta-analysis of case series reporting safety of IVT in AIS with concomitant UIA was conducted according to PRISMA recommendations. Results: Among 1,398 AIS patients treated with IVT, we identified 42 cases (3.0%) harboring a total of 48 UIAs. The rates of symptomatic and asymptomatic ICH were 2.4% (95% confidence interval [CI] by adjusted Wald method: 0%–12.6%) and 7.1% (95% CI: 1.8%–19.7%), respectively. A total of 5 case series met our inclusion criteria for meta-analysis, and the pooled rate of sICH among 120 IVT-treated AIS patients harboring UIA was 6.7% (95% CI: 3.1%–13.7%). In the overall analysis of 5 case-series studies, the risk ratio of sICH did not differ between AIS patients with and without UIA (risk ratio = 1.60; 95% CI: 0.54–4.77; p = 0.40) with no evidence of heterogeneity across included studies (I2 = 22% and p = 0.27 for Cochran Q test). Conclusions: Our prospectively collected multicenter data, coupled with the findings of the meta-analysis, indicate the potential safety of IVT in AIS patients with UIA. PMID:26408492

Systemic thrombolysis in acute ischemic stroke patients with unruptured intracranial aneurysms.

PubMed

Goyal, Nitin; Tsivgoulis, Georgios; Zand, Ramin; Sharma, Vijay K; Barlinn, Kristian; Male, Shailesh; Katsanos, Aristeidis H; Bodechtel, Ulf; Iftikhar, Sulaiman; Arthur, Adam; Elijovich, Lucas; Alexandrov, Anne W; Alexandrov, Andrei V

2015-10-27

We sought to determine the safety of IV thrombolysis (IVT) in acute ischemic stroke (AIS) patients harboring unruptured intracranial aneurysm (UIA) in a multicenter study and a comprehensive meta-analysis of available case series. We analyzed prospectively collected data from consecutive AIS patients treated with IVT during a 4-year period at 4 tertiary-care stroke centers. All patients routinely underwent CT or magnetic resonance angiography during hospitalization. The presence of UIA was documented on the basis of neuroradiology reports. Symptomatic intracranial hemorrhage (sICH) was defined as imaging evidence of ICH combined with an increase in NIH Stroke Scale score of ≥4 points. A systematic meta-analysis of case series reporting safety of IVT in AIS with concomitant UIA was conducted according to PRISMA recommendations. Among 1,398 AIS patients treated with IVT, we identified 42 cases (3.0%) harboring a total of 48 UIAs. The rates of symptomatic and asymptomatic ICH were 2.4% (95% confidence interval [CI] by adjusted Wald method: 0%-12.6%) and 7.1% (95% CI: 1.8%-19.7%), respectively. A total of 5 case series met our inclusion criteria for meta-analysis, and the pooled rate of sICH among 120 IVT-treated AIS patients harboring UIA was 6.7% (95% CI: 3.1%-13.7%). In the overall analysis of 5 case-series studies, the risk ratio of sICH did not differ between AIS patients with and without UIA (risk ratio = 1.60; 95% CI: 0.54-4.77; p = 0.40) with no evidence of heterogeneity across included studies (I(2) = 22% and p = 0.27 for Cochran Q test). Our prospectively collected multicenter data, coupled with the findings of the meta-analysis, indicate the potential safety of IVT in AIS patients with UIA. © 2015 American Academy of Neurology.

Intracranial hemorrhage in anticoagulated patients with mild traumatic brain injury: significant differences between direct oral anticoagulants and vitamin K antagonists.

PubMed

Cipriano, Alessandro; Pecori, Alessio; Bionda, Alessandra Eugenia; Bardini, Michele; Frassi, Francesca; Leoli, Francesco; Lami, Valentina; Ghiadoni, Lorenzo; Santini, Massimo

2018-03-08

Prognosis after mild traumatic brain injury (MTBI) on oral anticoagulant therapy (OAT) is uncertain. We evaluated the rate of immediate and delayed traumatic intracranial hemorrhage (ICH) comparing vitamin K antagonists (VKAs) to direct oral anticoagulants (DOACs) and the safety of a clinical management protocol. In this single-center prospective observational study, we enrolled 220 patients on OAT with MTBI. After a first negative CT scan, asymptomatic patients underwent a close neurological observation; if neurologically stable, they were discharged without a second CT scan and followed up for 1 month. Out of the 220 patients, 206 met the inclusion criteria. 23 of them (11.2%) had a positive first CT scan for ICH. Only 1 (0.5%, 95% CI 0.0-1.4%) died because of ICH; no one required neurosurgical intervention. The observed prevalence rate of immediate ICH resulted statistically higher in VKAs-treated patients compared to those treated with DOACs (15.7 vs. 4.7%, RR 3.34, 95% CI 1.18-9.46, P < 0.05). In the 1-month follow-up, 5 out of the 183 patients with a negative CT scan were lost. Out of the remaining 178 patients, only 3 showed a delayed ICH (1.7%, 95% CI 0.0-3.6%), 1 of them died (0.6%, 95% CI 0.5-1.7%) and the others did not require neurosurgical intervention. DOACs resulted safer than VKAs also in the setting of MTBI. In our observation, the rate of delayed hemorrhage was relatively low. Patients presenting with a negative first CT scan and without neurological deterioration could be safely discharged after a short period of in-ward observation with a low rate of complications and without a second CT scan.

Safety and Feasibility of a Neuroscience Critical Care Program to Mobilize Patients With Primary Intracerebral Hemorrhage.

PubMed

Bahouth, Mona N; Power, Melinda C; Zink, Elizabeth K; Kozeniewski, Kate; Kumble, Sowmya; Deluzio, Sandra; Urrutia, Victor C; Stevens, Robert D

2018-06-01

To measure the impact of a progressive mobility program on patients admitted to a neurocritical critical care unit (NCCU) with intracerebral hemorrhage (ICH). The early mobilization of critically ill patients with spontaneous ICH is a challenge owing to the potential for neurologic deterioration and hemodynamic lability in the acute phase of injury. Patients admitted to the intensive care unit have been excluded from randomized trials of early mobilization after stroke. An interdisciplinary working group developed a formalized NCCU Mobility Algorithm that allocates patients to incremental passive or active mobilization pathways on the basis of level of consciousness and motor function. In a quasi-experimental consecutive group comparison, patients with ICH admitted to the NCCU were analyzed in two 6-month epochs, before and after rollout of the algorithm. Mobilization and safety endpoints were compared between epochs. NCCU in an urban, academic hospital. Adult patients admitted to the NCCU with primary intracerebral hemorrhage. Progressive mobilization after stroke using a formalized mobility algorithm. Time to first mobilization. The 2 groups of patients with ICH (pre-algorithm rolllout, n=28; post-algorithm rollout, n=29) were similar on baseline characteristics. Patients in the postintervention group were significantly more likely to undergo mobilization within the first 7 days after admission (odds ratio 8.7, 95% confidence interval 2.1, 36.6; P=.003). No neurologic deterioration, hypotension, falls, or line dislodgments were reported in association with mobilization. A nonsignificant difference in mortality was noted before and after rollout of the algorithm (4% vs 24%, respectively, P=.12). The implementation of a progressive mobility algorithm was safe and associated with a higher likelihood of mobilization in the first week after spontaneous ICH. Research is needed to investigate methods and the timing for the first mobilization in critically ill stroke

Race/Ethnic differences in the risk of hemorrhagic complications among patients with ischemic stroke receiving thrombolytic therapy.

PubMed

Mehta, Rajendra H; Cox, Margueritte; Smith, Eric E; Xian, Ying; Bhatt, Deepak L; Fonarow, Gregg C; Peterson, Eric D

2014-08-01

Race/ethnic-related differences in safety of intravenous thrombolytic therapy have been shown in patients with myocardial infarction, but not studied in ischemic stroke. Using data from the Get With The Guidelines (GWTG)-Stroke program (n=54 334), we evaluated differences in risk-adjusted bleeding rates (any, symptomatic intracerebral hemorrhage [sICH], serious life-threatening [excluding sICH], or other) and mortality in white (n=40 411), black (n=8243), Hispanic (n=4257), and Asian (n=1523) patients receiving intravenous tissue-type plasminogen activator (tPA) for acute ischemic stroke. Compared with white patients, overall adjusted hemorrhagic complications after tPA were higher in black (odds ratio, 1.14, 95% confidence interval, 1.04-1.28) and Asian (odds ratio, 1.36, 95% confidence interval, 1.14-1.61) patients. Overall adjusted bleeding complications in Hispanics were similar to those of whites. Increased risk of overall bleeding in Asians was related to higher risk of adjusted sICH (odds ratio, 1.47, 95% confidence interval, 1.19-1.82), whereas in blacks, it was related to higher risk of other bleeding. No significant race-related difference was noted in risk of serious or life-threatening bleeding or in overall mortality or death in patients with sICH or any hemorrhagic complications. In patients with stroke receiving tPA, hemorrhagic complications were slightly higher in blacks and Asians, but not in Hispanics compared with whites. Asians also faced significantly higher risk for sICH relative to other race/ethnic groups. Future studies are needed to evaluate whether reduction in tPA dose similar to that used in many Asian countries could improve the safety of tPA therapy in Asians in the United States with acute ischemic strokes while maintaining efficacy. © 2014 American Heart Association, Inc.

Protective role of free and quercetin-loaded nanoemulsion against damage induced by intracerebral haemorrhage in rats

NASA Astrophysics Data System (ADS)

Galho, A. R.; Cordeiro, M. F.; Ribeiro, S. A.; Marques, M. S.; Antunes, M. F. D.; Luz, D. C.; Hädrich, G.; Muccillo-Baisch, A. L.; Barros, D. M.; Lima, J. V.; Dora, C. L.; Horn, A. P.

2016-04-01

Intracerebral haemorrhage (ICH) is a worldwide public health problem. Experimental studies have shown that oxidative stress plays an important role in the pathogenesis of ICH and could represent a target for its treatment. However, the blood-brain barrier is an obstacle to be overcome, as it hampers the administration of compounds to the central nervous system. In this study, we compared the effects of a quercetin-loaded nanoemulsion (QU-N) with the free form of the drug (QU-SP) in a collagenase-induced ICH rat model. Quercetin (QU) is a polyphenol that has an antioxidant effect in vitro, but due to its high lipophilicity, it has low bioavailability in vivo. In this study, animals submitted or not to ICH were treated with a single intraperitoneal QU dose (free or nanoemulsion) of 30 mg kg-1. Motor assessment was evaluated by the open field, foot fault and beam walking behavioural tests. 72 h after surgery the haematoma size was evaluated and biochemical measurements were performed. Animals treated with QU-N had a significant improvement in the beam walking and open field tests. Also, QU-N was able to reduce the size of the haematoma, preserving the activity of glutathione S-transferase (GST), increasing GSH content, and the total antioxidant capacity. QU-SP recovered locomotor activity and increased the GSH content and the total antioxidant capacity. Thus, it can be observed that QU presented antioxidant activity in both formulations, but the incorporation into nanoemulsions increased its antioxidant effect, which was reflected in the improvement of the motor skills and in the haematoma size decrement. These results suggest that the nanoemulsion containing QU developed in this study could be promising for future studies on treatments for ICH.

The Good Clinical Practice guideline and its interpretation - perceptions of clinical trial teams in sub-Saharan Africa.

PubMed

Vischer, N; Pfeiffer, C; Joller, A; Klingmann, I; Ka, A; Kpormegbe, S K; Burri, C

2016-08-01

To explore the advantages and challenges of working with the Good Clinical Practice (GCP)-International Conference of Harmonization (ICH) E6 guideline and its interpretation from the perspective of clinical trial teams based in sub-Saharan Africa. We conducted 60 key informant interviews with clinical trial staff at different levels in clinical research centres in Kenya, Ghana, Burkina Faso and Senegal and thematically analysed the responses. Clinical trial teams perceived working with ICH-GCP as highly advantageous and regarded ICH-GCP as applicable to their setting and efficiently applied. Only for informed consent did some clinical trial staff (one-third) perceive the guideline as insufficiently applicable. Specific challenges included meeting the requirements for written and individual consent, conditions for impartial witnesses for illiterates or legally acceptable representatives for children, guaranteeing voluntary participation and ensuring full understanding of the consent given. It was deemed important to have ICH-GCP compliance monitored by relevant ethics committees and regulatory authorities, without having guidelines applied overcautiously. Clinical trial teams in sub-Saharan Africa perceived GCP as a helpful guideline, despite having been developed by northern organisations and despite the high administrative burden of implementing it. To mitigate consent challenges, we suggest adapting GCP and making use of the flexibility it offers. © 2016 The Authors. Tropical Medicine & International Health Published by John Wiley & Sons Ltd.

Correlation between subacute sensorimotor deficits and brain edema in two mouse models of intracerebral hemorrhage

PubMed Central

Krafft, Paul R.; McBride, Devin W.; Lekic, Tim; Rolland, William B.; Mansell, Charles E.; Ma, Qingyi; Tang, Jiping; Zhang, John H.

2014-01-01

Formation of brain edema after intracerebral hemorrhage (ICH) is highly associated with its poor outcome, thus it is clinically important to understand the effect brain edema has on outcome. However, the relationship between cerebral edema and behavioral deficits has not been thoroughly examined in the preclinical setting. Hence, this study aimed to evaluate the ability of common sensorimotor tests to predict the extent of brain edema in two mouse models of ICH. One hundred male CD-1 mice were subjected to sham surgery or ICH induction via intrastriatal injection of either autologous blood (30 μL) or bacterial collagenase (0.0375 U or 0.075 U). At 24 and 72 hours after surgery, animals underwent a battery of behavioral tests, including the modified Garcia neuroscore (Neuroscore), corner turn test (CTT), forelimb placing test (FPT), wire hang task (WHT) and beam walking (BW). Brain edema was evaluated via the wet weight/dry weight method. Intrastriatal injection of autologous blood or bacterial collagenase resulted in a significant increase in brain water content and associated sensorimotor deficits (p<0.05). A significant correlation between brain edema and sensorimotor deficits was observed for all behavioral tests except for WHT and BW. Based on these findings, we recommend implementing the Neuroscore, CTT and/or FPT in preclinical studies of unilateral ICH in mice. PMID:24518201

Measurements of ion energies during plasma heating of the Proto-MPEX High Intensity Plasma Source

NASA Astrophysics Data System (ADS)

Caughman, J. B. O.; Goulding, R. H.; Biewer, T. M.; Bigelow, T. S.; Caneses, J.; Diem, S. J.; Green, D. L.; Isler, R. C.; Rapp, J.; Piotrowicz, P.; Beers, C. J.; Kafle, N.; Showers, M. A.

2017-10-01

The Prototype Materials Plasma Exposure eXperiment (Proto-MPEX) is a linear high-intensity RF plasma source that combines a high-density helicon plasma generator with ion and electron heating sections. It is being used to study the physics of heating over-dense plasmas in a linear configuration with the goal of delivering a plasma heat flux of 10 MW/m2 at a target. The helicon plasma is produced by coupling 13.56 MHz RF power at levels >100 kW. Additional heating is provided by ion cyclotron heating (ICH) ( 25 kW) and electron Bernstein wave (EBW) heating ( 25 kW) at 28 GHz. Measurements of the ion energy distribution with a retarding field energy analyzer (RFEA) show an increase in ion energies in the edge of the plasma when ICH is applied, which is consistent with COMSOL modeling of the power deposition from the antenna. Views of the target plate with an infrared camera show an increase in the surface temperature at large radii during ICH, and these areas map back to magnetic field lines near the antenna. The change in the power deposition at the target during ICH is compared with Thomson Scattering and RFEA measurements near the target. ORNL is managed by UT-Battelle, LLC, for the U.S. DOE under contract DE-AC-05-00OR22725.

Reliability of intracerebral hemorrhage classification systems: A systematic review.

PubMed

Rannikmäe, Kristiina; Woodfield, Rebecca; Anderson, Craig S; Charidimou, Andreas; Chiewvit, Pipat; Greenberg, Steven M; Jeng, Jiann-Shing; Meretoja, Atte; Palm, Frederic; Putaala, Jukka; Rinkel, Gabriel Je; Rosand, Jonathan; Rost, Natalia S; Strbian, Daniel; Tatlisumak, Turgut; Tsai, Chung-Fen; Wermer, Marieke Jh; Werring, David; Yeh, Shin-Joe; Al-Shahi Salman, Rustam; Sudlow, Cathie Lm

2016-08-01

Accurately distinguishing non-traumatic intracerebral hemorrhage (ICH) subtypes is important since they may have different risk factors, causal pathways, management, and prognosis. We systematically assessed the inter- and intra-rater reliability of ICH classification systems. We sought all available reliability assessments of anatomical and mechanistic ICH classification systems from electronic databases and personal contacts until October 2014. We assessed included studies' characteristics, reporting quality and potential for bias; summarized reliability with kappa value forest plots; and performed meta-analyses of the proportion of cases classified into each subtype. We included 8 of 2152 studies identified. Inter- and intra-rater reliabilities were substantial to perfect for anatomical and mechanistic systems (inter-rater kappa values: anatomical 0.78-0.97 [six studies, 518 cases], mechanistic 0.89-0.93 [three studies, 510 cases]; intra-rater kappas: anatomical 0.80-1 [three studies, 137 cases], mechanistic 0.92-0.93 [two studies, 368 cases]). Reporting quality varied but no study fulfilled all criteria and none was free from potential bias. All reliability studies were performed with experienced raters in specialist centers. Proportions of ICH subtypes were largely consistent with previous reports suggesting that included studies are appropriately representative. Reliability of existing classification systems appears excellent but is unknown outside specialist centers with experienced raters. Future reliability comparisons should be facilitated by studies following recently published reporting guidelines. © 2016 World Stroke Organization.

Il’ich’s Native Land Today,

DTIC Science & Technology

1982-09-28

riil t". r1*1e.re taft fat 2vv**,cvq 4 t"~ ~J1 of labor by 22 April 1970. for industrial enterprises to inerease the profit in 1970 in camparios with...two minuts another vehicle moves out to carry out the exerolte. The tank which was driven n the route by a third course student, Acosoal wsaer Turly...should we meet the great date with new successes in labor , but also with serious deeds in the communist upbringing of the youth. We are living in the

People’s Republic of China Scientific Abstracts No. 179

DTIC Science & Technology

1977-11-08

No 2, April 1977 7 CHIH-WU HSUEH-PAO [ACTA BOTANICA SINICA] No 2, June 1977 22 I-CH’UAN HSUEH-PAO [ACTA GENETICA SINICA] No 1...photorespirators. 8650 C50J 4009 29 ACTA GENETICA SINICA AUTHOR: WU An-chiu [0702 1344 0036] ORG: Technique Staff of San-t’ai Commune Fu County...Liaoning Province TITLE: ’TProceed in Struggle, Bring up Superior Seeds for the Revolution" SOURCE: Peking I-CH’UAN HSUEH-PAO [ACTA GENETICA

Real-time imaging and detection of intracranial haemorrhage by electrical impedance tomography in a piglet model.

PubMed

Xu, C H; Wang, L; Shi, X T; You, F S; Fu, F; Liu, R G; Dai, M; Zhao, Z W; Gao, G D; Dong, X Z

2010-01-01

The aim of this study was to use electrical impedance tomography (EIT) to detect and image acute intracranial haemorrhage (ICH) in an animal model. Blood was infused into the frontal lobe of the brains of anaesthetized piglets and impedance was measured using 16 electrodes placed in a circle on the scalp. The EIT images were constructed using a filtered back-projection algorithm. The mean of all the pixel intensities within a region of interest--the mean resistivity value (MRV)--was used to evaluate the relative impedance changes in the target region. A symmetrical index (SI), reflecting the relative impedance on both sides of the brain, was also calculated. Changes in MRV and SI were associated with the injection of blood, demonstrating that EIT can successfully detect ICH in this animal model. The unique features of EIT may be beneficial for diagnosing ICH early in patients after cranial surgery, thereby reducing the risk of complications and mortality.

Intracerebral hemorrhage with intraventricular extension and no hydrocephalus may not increase mortality or severe disability.

PubMed

Mahta, Ali; Katz, Paul M; Kamel, Hooman; Azizi, S Ausim

2016-08-01

This paper aimed to test the hypothesis that intraventricular extension of spontaneous intracerebral hemorrhage (ICH) in the absence of hydrocephalus is not associated with increased mortality or severe disability. We performed a retrospective consecutive cohort study of patients with primary spontaneous ICH who were admitted to a single institution. Multivariate logistic regression analysis was used to assess the association of each variable with functional outcome as measured by the modified Rankin Scale (mRS). A total of 164 patients met our inclusion criteria and were included in the study. Only hydrocephalus (p=0.002) and hematoma volume (p=0.006) were significantly associated with mortality or poor functional outcome (mRS of 3 to 6). In contrast, the presence of intraventricular hematoma was not independently associated with poor functional outcome. The presence of intraventricular extension of ICH in the absence of hydrocephalus may not increase mortality or disability. Copyright © 2016 Elsevier Ltd. All rights reserved.

Zahlen und Rechenvorgänge auf unterschiedlichen Abstraktionsniveaus

NASA Astrophysics Data System (ADS)

Rödler, Klaus

"Das Verständnis geht langsam vor sich!" Diesen wichtigen Satz hörte ich bei einem Vortrag von Martin Lowsky. Auf die hier behandelte Fragestellung übertragen heißt das: Was eine Zahl ist und wie ich sie im Rechenvorgang einsetzen und interpretieren kann, das erschließt sich erst allmählich. Die Zahl des Rechenanfängers ist nicht dieselbe wie die des kompetenten Rechners und es ist nicht die Zahl des Lehrers oder der Lehrerin. Die Zahlen sind nur auf der Oberfläche der Worte und Zeichen gleich. Im Innern, im Verständnis, sind sie völlig verschieden! Ich glaube, dass die Missachtung dieser Divergenz dazu führt, dass manche Kinder in für den Lehrer und Lehrerin nicht nachvollziehbaren Routinen stecken bleiben, einfachste Informationen nicht wirklich integrieren. Die auf beiden Seiten wachsende Verunsicherung durch die nicht erkannte und daher nicht kommunizierbare Diskrepanz im inneren Zahlkonzept stört den allmählichen Aufbau strukturierter Zahlvorstellungen.

Das Prinzip Bewegung - Herz und Gehirn als Metaphern des menschlichen Lebens

NASA Astrophysics Data System (ADS)

Otis, Laura

In diesem Jahr, in dem wir Charles Darwins gedenken, möchte ich etwas riskieren und eine Frage erörtern, die für die Literatur ebenso wie für die Biologie zentral ist: Was ist das Leben? Die Antwort auf diese Frage finden wir nicht in der Bibliothek und nicht im Labor, zumindest nicht an diesen erkenntnisproduzierenden Stellen allein. Als Literaturwissenschaftlerin und ehemalige Naturwissenschaftlerin glaube ich, dass wir das Leben nur verstehen werden, wenn wir seinen Wirkungen überall nachforschen, inklusive in der Literatur.

People’s Republic of China Scientific Abstracts No. 164.

DTIC Science & Technology

1977-02-23

3, Sep 76 15 I-CH’UAN HSUEH-PAO /ÄCTA GENETICA SINICA/ Vol 3, No 3, Sep 76 20 CHUNG-HUA I-HSUEH TSA-CHIH /CHINESE MEDICAL JOURNAL/ No 10...This is the preparatory work for cell hybridization in further experiments. 6168 CSO: ^4-009 19 ACTA GENETICA SINICA AUTHOR: None ORG...Peking I-CH’UAN HSUEH-PAO [ACTA GENETICA SINICA] in Chinese Vol 3 No 3, Sep 76 pp 203-209 TEXT OF ENGLISH ABSTRACT: This paper deals with the

"MOONSTROKE": Lunar patterns of stroke occurrence combined with circadian and seasonal rhythmicity--A hospital based study.

PubMed

Mao, Yiting; Schnytzer, Yisrael; Busija, Lucy; Churilov, Leonid; Davis, Stephen; Yan, Bernard

2015-01-01

Both time of the day and season have been shown to have a significant effect on stroke incidence. In contrast, the role played by the moon has been little studied. We aimed to investigate the potential association of the lunar phase with the incidence of stroke subtypes [intracerebral hemorrhage (ICH), transient ischemic attack (TIA) and ischemic stroke (IS)], adjusted by circadian and seasonal variations. Consecutive stroke admissions to the Royal Melbourne Hospital (RMH) were analyzed from 2004-2011. Of 6252 patients, 4085 (65.3%) had confirmed dates and hour of the day. Of these, 632 (15.5%) had ICH, 658 (16.1%) presented with TIA and 2202 (53.9%) had IS. There were also 593 (14.5%) stroke mimics. We measured the association of stroke incidence with a particular lunar phase using an incidence rate ratio (IRR) with 95% confidence intervals (CI) using Poisson regression model (new moon set as reference). Compared with new moon phase, ICHs occurred significantly more during the first quarter (IRR, 1.55; 95%CI, 1.04 to 2.30; p = 0.03). More TIAs were observed during the first quarter and full moon than in new moon (IRR, 1.69; 95%CI, 1.16 to 2.46; p = 0.01; IRR, 1.52; 95%CI, 0.00 to 2.31; p = 0.05; respectively). Both ICH and TIA occurrence slightly decreased as lunar illumination increased (IRR, 0.99; 95%CI, 0.99 to 1.00; p = 0.01; IRR, 0.99; 95%CI, 0.99 to 1.00; p = 0.04; respectively). No association was found between lunar phase or illumination and IS. All stroke subtypes were less likely to happen between 12AM and 6AM than the remaining 18 h of the day. IS occurrence was significantly higher during the spring than summer (IRR, 1.14; 95%CI, 1.02 to 1.28; p = 0.03). For the patients older than 65 years, incidence of both ICH and IS was higher in spring than in summer (IRR, 1.33; 95%CI, 1.01 to 1.74; p = 0.04; IRR, 1.22; 95%CI, 1.06 to 1.39; p = 0.005; respectively). The lunar phase and illumination are associated with both ICH and TIA incidence. These findings

S100b and BNP predict functional neurological outcome after intracerebral hemorrhage

PubMed Central

James, Michael L.; Blessing, Robert; Phillips-Bute, Barbara G.; Bennett, Ellen; Laskowitz, Daniel T.

2009-01-01

Objective To determine the predictive value of S100b and brain natriuretic peptide (BNP) to accurately and quickly determine discharge prognosis after primary supratentorial intracerebral hemorrhage (ICH). Methods After IRB approval and informed consent, blood samples were obtained and analyzed from 28 adult patients consecutively admitted to the neuroscience intensive care unit with computed tomography-proven supratentorial ICH from June 2003 and December 2004 within the first 24 h after symptom onset for S100b and BNP. Functional outcomes on discharge were dichotomized to favorable (mRS<3) or unfavorable. Results BNP (a neurohormone) and S100b (a marker of glial activation) were found to be independently highly predictive of functional neurological outcome at the time of discharge as measured by modified Rankin Score (BNP:p<0.01, r=0.46; S100b: p<0.01, r=0.42) and Barthel Index (BNP:p<0.01, r=0.54; s100b:p<0.01, r=0.50). Although inclusion of either biomarker produced additive value when included with traditional clinical prognostic variables, such as the ICH Score (Barthel index: p<0.01, r=0.66; mRS:p<0.01, r=0.96), little predictive power is added with inclusion of both biomarkers in a regression model for neurological outcome. Conclusions Serum S100b and BNP levels in the first 24 h after injury accurately predict neurological function at discharge after supratentorial ICH. PMID:19505208

Intra- and extracranial atherosclerotic disease in acute spontaneous intracerebral hemorrhage.

PubMed

Sato, Shoichiro; Uehara, Toshiyuki; Hayakawa, Mikito; Nagatsuka, Kazuyuki; Minematsu, Kazuo; Toyoda, Kazunori

2013-09-15

There is little information about intracranial atherosclerotic disease (ICAD) and extracranial atherosclerotic disease (ECAD) in patients with acute spontaneous intracerebral hemorrhage (ICH). The purpose of the present study was to elucidate the prevalence of and the factors that correlate with ICAD and ECAD in patients with ICH. A total of 274 patients with acute spontaneous ICH were enrolled. ICAD and ECAD (moderate to severe stenosis or occlusion) were mainly assessed by intracranial magnetic resonance angiography and carotid duplex sonography, respectively. Fifty-one patients (19%) had ICAD or ECAD; 32 had ICAD, and 21 had ECAD. On multivariable analyses, age (OR, 1.52; 95% CI, 1.06-2.28 for every 10 years), monocyte count (OR, 1.37; 95% CI, 1.02-1.87 for every 100/mm(3)), hemoglobin A1c (OR, 2.25; 95% CI, 1.08-5.15 for every 1%), and low-density lipoprotein cholesterol levels (OR, 1.23; 95% CI, 1.08-1.42 for every 10mg/dL) were independently associated with ICAD. Age (OR, 2.20; 95% CI, 1.20-4.38 for 10 years) and dyslipidemia (OR, 3.95; 95% CI, 1.01-15.97) were independently associated with ECAD. ICAD and ECAD were detected in approximately one-fifth of patients with spontaneous ICH. Age and dyslipidemia (or lipid profile) were associated with both ICAD and ECAD. Monocyte count and hemoglobin A1c were associated with ICAD. © 2013. Published by Elsevier B.V. All rights reserved.

Surgical Evacuation of Spontaneous Supratentorial Lobar Intracerebral Hemorrhage: Comparison of Safety and Efficacy of Stereotactic Aspiration, Endoscopic Surgery, and Craniotomy.

PubMed

Li, Yuqian; Yang, Ruixin; Li, Zhihong; Yang, Yanping; Tian, Bo; Zhang, Xingye; Wang, Bao; Lu, Dan; Guo, Shaochun; Man, Minghao; Yang, Yang; Luo, Tao; Gao, Guodong; Li, Lihong

2017-09-01

The safety and efficacy of craniotomy, endoscopic surgery, and stereotactic aspiration for surgical evacuation of spontaneous supratentorial lobar intracerebral hemorrhage (ICH) is yet uncertain. The present study analyzed the clinical and radiographic data from 99 patients with spontaneous supratentorial lobar ICH, retrospectively, to address this issue. Patients who underwent craniotomy, endoscopy surgery, or stereotactic aspiration were assigned to the craniotomy group (n = 31), endoscopy surgery group (n = 32), or stereotactic aspiration group (n = 36), respectively. The characteristics of all the enrolled patients at the time of admission were assimilated. Also, the therapeutic effects of the three surgical procedures were evaluated based on short-term outcomes within 30 days and long-term outcomes at 6 months after the ictus. The results showed that stereotactic aspiration and endoscopic surgery were associated with a superior clinical therapeutic effect in both short-term and long-term outcomes than craniotomy for the treatment of spontaneous supratentorial lobar ICH. Notably, severely affected patients with hematoma volume > 60 mL or Glasgow Coma Scale score 4-8 may benefit more from endoscopic surgery than the two other surgical procedures. The current findings demonstrate that both stereotactic aspiration and endoscopic surgery possess an apparent advantage over craniotomy for the evacuation of spontaneous supratentorial lobar ICH. The endoscopic surgery might be more safe and effective with higher evacuation rate, better functional neurological outcomes, and lower complication and mortality rates. Copyright © 2017 Elsevier Inc. All rights reserved.

Ambient temperature and volume of perihematomal edema in acute intracerebral haemorrhage: the INTERACT1 study.

PubMed

Zheng, Danni; Arima, Hisatomi; Heeley, Emma; Karpin, Anne; Yang, Jie; Chalmers, John; Anderson, Craig S

2015-01-01

As no human data exist, we aimed to determine the relation between ambient temperature and volume of perihematomal 'cerebral' edema in acute spontaneous intracerebral haemorrhage (ICH) among Chinese participants of the pilot phase, Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial (INTERACT1). INTERACT1 was a multicenter, open, blind outcome assessed, randomized controlled trial of intensive (systolic target <140 mmHg) vs. guideline-recommended (systolic target <180 mmHg) blood pressure (BP) lowering in 404 patients with acute ICH. Data on ambient temperature (mean, minimum, maximum, and range) on the day of each participant's ICH obtained from China Meteorological Data Sharing Service System were linked to other data including edema volumes. Multivariable regression analyses were performed to evaluate association between ambient temperature and edema volumes. A generalized linear regression model with a generalized estimating equations approach (GEE) was used to assess any association of ambient temperature and change in edema volume over 72 h. A total of 250 of all 384 Chinese participants had complete data that showed positive associations between ambient temperature (mean and minimum temperatures) and edema volumes at each time point over 72 h after hospital admission (all P < 0·05). All temperature parameters except diurnal temperature range were positively associated with edema volume after adjustment for confounding variables (all P < 0·02). An apparent positive association exists between ambient temperature and perihematomal edema volume in acute spontaneous ICH. © 2014 World Stroke Organization.

Timing of anticoagulant re-initiation following intracerebral hemorrhage in mechanical heart valves: Survey of neurosurgeons and thrombosis experts.

PubMed

AlKherayf, Fahad; Xu, Yan; Westwick, Harrison; Moldovan, Ioana Doina; Wells, Philip S

2017-03-01

While oral anticoagulation (OAC) is universally indicated for patients with mechanical heart valves (MHVs), OAC resumption following anticoagulant-associated intracerebral hemorrhage (ICH) is an area of uncertainty. We sought to determine the practice preferences of North American neurosurgeons and thrombosis experts on optimal timing of OAC re-initiation. A cross-sectional survey was disseminated to North American members of the American Association of Neurological Surgeons and the International Society for Thrombosis and Haemostasis. Demographic factors, as well as a clinical scenario with 14 modifiable clinical risk factors were included in the survey. 504 physicians completed our survey (response rate 34.3%). Majority of participants were affiliated with academic centres, and managed≤10 ICH patients with MHV per year. There was wide distribution in response in optimal timing for OAC resumption following an ICH: 59% and 60% preferred to re-start OAC between 3 and 14 days following the hemorrhagic event (median of 6-7 days). Smaller hemorrhages (<30cm 2 ). CHADS 2 score ≥2, concomitant venous thromboembolism, mitral valve prosthesis, caged-ball valves and multiple valves prompted earlier OAC resumption. Wide variation in the current practice of neurosurgeons and thrombosis specialists exist when they encounter patients with ICH and MHV, though decisions were influenced by patient- and valve-related factors. As our observed variation likely reflects the immense gap in current evidence, prospective randomized trials in this population are therefore urgently needed. Copyright © 2017 Elsevier B.V. All rights reserved.

Progress, innovation and regulatory science in drug development: the politics of international standard-setting.

PubMed

Abraham, John; Reed, Tim

2002-06-01

This paper examines international standard-setting in the toxicology of pharmaceuticals during the 1990s, which has involved both the pharmaceutical industry and regulatory agencies in an organization known as the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). The analysis shows that the relationships between innovation, regulatory science and 'progress' may be more complex and controversial than is often assumed. An assessment of the ICH's claims about the implications of 'technical' harmonization of drug-testing standards for the maintenance of drug safety, via toxicological testing, and the delivery of therapeutic progress, via innovation, is presented. By demonstrating that there is not a technoscientific validity for these claims, it is argued that, within the ICH, a discourse of technological innovation and scientific progress has been used by regulatory agencies and prominent parts of the transnational pharmaceutical industry to legitimize the lowering and loosening of toxicological standards for drug testing. The mobilization and acceptance of this discourse are shown to be pivotal to the ICH's transformation of reductions in safety standards, which are apparently against the interests of patients and public health, into supposed therapeutic benefits derived from promises of greater access to more innovative drug products. The evidence suggests that it is highly implausible that these reductions in the standards of regulatory toxicology are consistent with therapeutic progress for patients, and highlights a worrying aspect embedded in the 'technical trajectories' of regulatory science.

A method for normalizing pathology images to improve feature extraction for quantitative pathology.

PubMed

Tam, Allison; Barker, Jocelyn; Rubin, Daniel

2016-01-01

With the advent of digital slide scanning technologies and the potential proliferation of large repositories of digital pathology images, many research studies can leverage these data for biomedical discovery and to develop clinical applications. However, quantitative analysis of digital pathology images is impeded by batch effects generated by varied staining protocols and staining conditions of pathological slides. To overcome this problem, this paper proposes a novel, fully automated stain normalization method to reduce batch effects and thus aid research in digital pathology applications. Their method, intensity centering and histogram equalization (ICHE), normalizes a diverse set of pathology images by first scaling the centroids of the intensity histograms to a common point and then applying a modified version of contrast-limited adaptive histogram equalization. Normalization was performed on two datasets of digitized hematoxylin and eosin (H&E) slides of different tissue slices from the same lung tumor, and one immunohistochemistry dataset of digitized slides created by restaining one of the H&E datasets. The ICHE method was evaluated based on image intensity values, quantitative features, and the effect on downstream applications, such as a computer aided diagnosis. For comparison, three methods from the literature were reimplemented and evaluated using the same criteria. The authors found that ICHE not only improved performance compared with un-normalized images, but in most cases showed improvement compared with previous methods for correcting batch effects in the literature. ICHE may be a useful preprocessing step a digital pathology image processing pipeline.

Neuronal Death After Hemorrhagic Stroke In Vitro and In Vivo Shares Features of Ferroptosis and Necroptosis

PubMed Central

Zille, Marietta; Karuppagounder, Saravanan S.; Chen, Yingxin; Gough, Peter J.; Phil, D.; Bertin, John; Finger, Joshua; Milner, Teresa A.; Jonas, Elizabeth A.; Ratan, Rajiv R.

2017-01-01

Background and Purpose Intracerebral hemorrhage (ICH) leads to disability or death with few established treatments. Adverse outcomes following ICH result from irreversible damage to neurons resulting from primary and secondary injury. Secondary injury has been attributed to hemoglobin and its oxidized product hemin from lysed red blood cells. The aim of this study was to identify the underlying cell death mechanisms attributable to secondary injury by hemoglobin and hemin to broaden treatment options. Methods We investigated cell death mechanisms in cultured neurons exposed to hemoglobin or hemin. Chemical inhibitors implicated in all known cell death pathways were employed. Identified cell death mechanisms were confirmed using molecular markers and electron microscopy. Results Chemical inhibitors of ferroptosis and necroptosis protected against hemoglobin- and hemin-induced toxicity. By contrast, inhibitors of caspase-dependent apoptosis, protein or mRNA synthesis, autophagy, mitophagy or parthanatos had no effect. Accordingly, molecular markers of ferroptosis and necroptosis were increased following ICH in vitro and in vivo. Electron microscopy showed that hemin induced a necrotic phenotype. Necroptosis and ferroptosis inhibitors each abrogated death by greater than 80% and had similar therapeutic windows in vitro. Conclusion Experimental ICH shares features of ferroptotic and necroptotic cell death, but not caspase-dependent apoptosis or autophagy. We propose that ferroptosis or necroptotic signaling induced by lysed blood is sufficient to reach a threshold of death that leads to neuronal necrosis and that inhibition of either one of these pathways can bring cells below that threshold to survival. PMID:28250197

Telemedicine-assisted treatment of patients with intracerebral hemorrhage.

PubMed

Angileri, Filippo F; Cardali, Salvatore; Conti, Alfredo; Raffa, Giovanni; Tomasello, Francesco

2012-04-01

Telemedicine provides a new approach to improve stroke care in community settings, delivering acute stroke expertise to hospitals in rural areas. Given the controversies in many aspects of the treatment of intracerebral hemorrhage (ICH) and the lack of guidelines, a prompt neurosurgical second opinion may facilitate the treatment of patients with ICH. Here, the authors' 8-year experience with the use of telemedicine in the management of ICH is reported. The medical records of patients with ICH treated through a telemedicine system in the district of Messina, Italy, between June 2003 and June 2011 were retrospectively reviewed. Neuroradiological and clinical data for patients were transmitted through a high-technology "hub-and-spoke" telemedicine network. Neurosurgical teleconsulting (at the hub) was available for 7 peripheral hospitals (spokes) serving about 700,000 people. The authors analyzed 1) the time between peripheral hospital admission and the specialized second opinion consultation, 2) primary and secondary transfers to the authors' neurosurgery department, and 3) the treatments (surgical or medical) of patients transferred to the hub. The telemedicine network was used to treat more than 2800 patients, 733 with ICH. A neurosurgical consultation was provided in 38 minutes versus 160 minutes for a consultation without telemedicine. One hundred seventy-six (24%) of 733 patients were primarily transferred to the hub. Ninety-five patients (13%) underwent surgical treatment. The remaining 81 patients (11%) underwent neurointensive care. Eight (1.4%) of 557 patients treated at the spokes needed a secondary transfer for surgical treatment because of a worsening clinical condition and/or CT findings. Considering secondary and inappropriate transfers, the interpretation of data was correct in 96.5% of cases. Telemedicine allowed rapid visualization of neuroradiological and clinical data, providing neurosurgical expertise to community hospitals on demand and within

CM352 Reduces Brain Damage and Improves Functional Recovery in a Rat Model of Intracerebral Hemorrhage.

PubMed

Rodríguez, José A; Sobrino, Tomás; López-Arias, Esteban; Ugarte, Ana; Sánchez-Arias, Juan A; Vieites-Prado, Alba; de Miguel, Irene; Oyarzabal, Julen; Páramo, José A; Campos, Francisco; Orbe, Josune; Castillo, José

2017-06-01

Intracerebral hemorrhage (ICH) is an acute neurological disorder with high mortality and no effective treatment. In addition to the initial bleeding event, rebleeding and hematoma expansion are associated with poor outcome in these patients. We studied the effectiveness of the new antifibrinolytic agent CM352, a short-half-life matrix metalloproteinase inhibitor, for achieving early hemostasis and improving functional recovery in a rat model of collagenase-induced ICH. ICH was induced by striatal injection of collagenase, and 1 hour later, rats received an intravenous injection of saline (n=6) or CM352 (1 mg/kg, n=6). Hematoma (basal and after 3 and 24 hours) and lesion (14 days) volumes were quantified on T2-weighted (T2) magnetic resonance images. Neurological and functional recovery was evaluated by using Bederson score and a cylinder test (basal, 24 hours, and 14 days). Early treatment (1 hour) with CM352 was efficient reducing hematoma expansion at 3 hours ( P <0.01) and, more markedly, at 24 hours ( P <0.01). Decreased bleeding after antifibrinolytic treatment was accompanied by reduced interleukin-6 levels at 3 hours ( P <0.05) and smaller lesion volume at 14 days ( P <0.01). CM352 drastically reduced sensorimotor impairment (cylinder test) after ICH in rats at 24 hours ( P <0.01) and 14 days ( P <0.01). Similarly, it also attenuated neurological deficit (Bederson scale) at 24 hours ( P <0.01) and 14 days ( P <0.01). Interestingly, late (3 hours) CM352 administration also resulted in reduced lesion size and better functional outcome. CM352, a new antifibrinolytic agent and matrix metalloproteinase inhibitor, effectively prevented hematoma growth and reduced lesion size in ICH in association with improved functional and neurological recovery. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Spontaneous Intracerebral Hemorrhage in a Plateau Area: A Study Based on the Tibetan Population.

PubMed

Chen, Ruiqi; Xiao, Anqi; You, Chao; Ma, Lu

2018-05-19

To reveal characteristics of spontaneous intracerebral hemorrhage (sICH) in a plateau area based on the Tibetan population. Data of Tibetan and Han patients (control group) with sICH treated at our center from January 2013 to April 2017 were retrospectively reviewed. A total of 122 Tibetan and 927 Han patients were included. Compared with Han patients, Tibetan patients were older (54.7±11.2 VS 50.9±18.3 years, P=0.027), exhibited higher ratios of males (73.8% VS 55.0%, P<0.001), overweight patients (22.1% VS 13.1%, P=0.007) and smokers (36.9% VS 20.5%, P<0.001), had a higher concentration of hemoglobin (163.7±17.6 VS 134.8±20.2 g/L, P<0.001) and included a higher number of patients with hypertension (83.6% VS 60.5%, P<0.001), diabetes mellitus (19.2% VS 9.3%, P=0.002) and prior hemorrhagic stroke (9.0% VS 2.0%, P<0.001). Tibetan patients also experienced more brain stem hemorrhage (11.5% VS 5.1%, P=0.039) in the infratentorial region and had a higher risk of in-hospital complications due to hematoma enlargement (20.5% VS 10.4%, P=0.002) and cerebral infarction (59.0% VS 9.7%, P<0.001). During a 6-month follow-up period, they had higher rates of unfavorable outcomes and case mortality (P<0.05). A multivariable analysis adjusted for confounding factors revealed that the Tibetan race was positively associated with unfavorable clinical outcomes in sICH patients (P<0.05). Tibetan sICH patients from the plateau area presented unique characteristics in their baseline measurements, incidence of comorbidities, hematoma location, risk of in-hospital complications and clinical outcomes compared with Han patients. The Tibetan race was positively associated with unfavorable 6-month outcomes in ICH patients. Copyright © 2018 Elsevier Inc. All rights reserved.

Safety of Intravenous Thrombolytic Use in Four Emergency Departments without Acute Stroke Teams

PubMed Central

Scott, Phillip A.; Frederiksen, Shirley M.; Kalbfleisch, John D.; Xu, Zhenzhen; Meurer, William J.; Caveney, Angela F.; Sandretto, Annette; Holden, Ann B.; Haan, Mary N.; Hoeffner, Ellen G.; Ansari, Sameer A.; Lambert, David P.; Jaggi, Michael; Barsan, William G.; Silbergleit, Robert

2010-01-01

Objectives To evaluate safety of intravenous tissue plasminogen activator (tPA) delivered without dedicated thrombolytic stroke teams. Methods This was a retrospective, observational study of patients treated between 1996 and 2005 at four southeastern Michigan hospital emergency departments (EDs) with a prospectively defined comparison to the National Institute of Neurological Disorders and Stroke (NINDS) tPA stroke study cohort. Main outcome measures were mortality, intracerebral hemorrhage (ICH), systemic hemorrhage, neurologic recovery, and guideline violations. Results Two hundred seventy-three consecutive stroke patients were treated by 95 emergency physicians using guidelines and local neurology resources. One-year mortality was 27.8%. Unadjusted Cox model relative risk of mortality compared to the NINDS tPA treatment and placebo groups was 1.20 (95% confidence interval [CI] = 0.87 to 1.64) and 1.04 (95% CI = 0.76 to 1.41), respectively. Rate of significant ICH by computed tomography criteria was 6.6% (OR 1.03, 95% CI = 0.56 to 1.90 compared to NINDS tPA treatment group). The proportion of symptomatic ICH by two other pre-specified sets of clinical criteria was 4.8% and 7.0%. Rate of any ICH within 36 hours of treatment was 9.9% (relative risk [RR] 0.94, 95% CI = 0.58 to 1.51 compared to NINDS tPA group). Occurrence of major systemic hemorrhage (requiring transfusion) was 1.1%. Functional recovery by the modified Rankin Scale score (mRS 0 to 2) at discharge occurred in 38% of patients with a premorbid disability mRS < 2. Guideline deviations occurred in the ED in 26% of patients and in 25% of patients following admission. Conclusions In these EDs there was no evidence of increased risk with respect to mortality, ICH, systemic hemorrhage, or worsened functional outcome when tPA was administered without dedicated thrombolytic stroke teams. Additional effort is needed to improve guideline compliance. PMID:21040107

Impact of body mass index on outcome in stroke patients treated with intravenous thrombolysis.

PubMed

Gensicke, H; Wicht, A; Bill, O; Zini, A; Costa, P; Kägi, G; Stark, R; Seiffge, D J; Traenka, C; Peters, N; Bonati, L H; Giovannini, G; De Marchis, G M; Poli, L; Polymeris, A; Vanacker, P; Sarikaya, H; Lyrer, P A; Pezzini, A; Vandelli, L; Michel, P; Engelter, S T

2016-12-01

The impact of body mass index (BMI) on outcome in stroke patients treated with intravenous thrombolysis (IVT) was investigated. In a multicentre IVT-register-based observational study, BMI with (i) poor 3-month outcome (i.e. modified Rankin Scale scores 3-6), (ii) death and (iii) symptomatic intracranial haemorrhage (sICH) based on criteria of the ECASS II trial was compared. BMI was used as a continuous and categorical variable distinguishing normal weight (reference group 18.5-24.9 kg/m 2 ) from underweight (<18.5 kg/m 2 ), overweight (25-29.9 kg/m 2 ) and obese (≥30 kg/m 2 ) patients. Univariable and multivariable regression analyses with adjustments for age and stroke severity were done and odds ratios with 95% confidence intervals [OR (95% CI)] were calculated. Of 1798 patients, 730 (40.6%) were normal weight, 55 (3.1%) were underweight, 717 (39.9%) overweight and 295 (16.4%) obese. Poor outcome occurred in 38.1% of normal weight patients and did not differ significantly from underweight (45.5%), overweight (36.1%) and obese (32.5%) patients. The same was true for death (9.5% vs. 14.5%, 9.6% and 7.5%) and sICH (3.9% vs. 5.5%, 4.3%, 2.7%). Neither in univariable nor in multivariable analyses did the risks of poor outcome, death or sICH differ significantly between BMI groups. BMI as a continuous variable was not associated with poor outcome, death or sICH in unadjusted [OR (95% CI) 0.99 (0.97-1.01), 0.98 (0.95-1.02), 0.98 (0.94-1.04)] or adjusted analyses [OR (95% CI) 1.01 (0.98-1.03), 0.99 (0.95-1.05), 1.01 (0.97-1.05)], respectively. In this largest study to date, investigating the impact of BMI in IVT-treated stroke patients, BMI had no prognostic meaning with regard to 3-month functional outcome, death or occurrence of sICH. © 2016 EAN.

Day-night variability of hematoma expansion in patients with spontaneous intracerebral hemorrhage.

PubMed

Yao, Xiaoying; Wu, Bo; Xu, Ye; Siwila-Sackman, Erica; Selim, Magdy

2015-06-01

The levels of several coagulation factors, able to influence hemostatic balance, display circadian variations. We hypothesized that the onset and extent of hematoma expansion (HE) following intracerebral hemorrhage (ICH) also display diurnal patterns. We reviewed clinical, laboratory, and radiological data from 111 consecutive patients with spontaneous ICH who had baseline head computed tomography (CT) scans within 3 h of ICH onset and follow-up CT during the following 72 h. We defined any HE (AHE) as any increase in hematoma volume from baseline to follow-up CT and significant HE (SHE) as an absolute increase in hematoma volume >6 mL or relative increase >33%. We categorized the patients into 2 groups based on the timing of the initial CT scans--day group (from 0800 to 2000 h) and night group (from 2000 to 0800 h)--and performed logistic regression analyses. We also analyzed the differences in the rates of HE between the groups during six 4-h periods spanning 24 h, using χ(2) tests. We found that the rates of AHE and SHE were higher in the day versus night group (75% vs. 48%; p = 0.009 for AHE and 47.6% vs. 25.9%; p = 0.047 for SHE). On multivariable logistic regression, day group assignment was independently associated with AHE (adjusted odds ratio = 3.53; p = 0.008) but not with SHE. Both AHE and SHE peaked in the early afternoon (1200-1600 h) and reached a nadir during the 2000 to 2400 h time period, and they were significantly different between the time periods (0000-0400, 0400-0800, 0800-1200, 1200-1600, 1600-2000, and 2000-2400 h); p = 0.002 and 0.029, respectively. These exploratory findings support the presence of a daily pattern in the occurrence of HE, with a higher risk during the day hours. Our results could have implications for future therapeutic efforts targeting HE in ICH and for the triage of ICH patients. They require further validation. © 2015 The Author(s).

Estimated GFR and the Effect of Intensive Blood Pressure Lowering After Acute Intracerebral Hemorrhage.

PubMed

Zheng, Danni; Sato, Shoichiro; Arima, Hisatomi; Heeley, Emma; Delcourt, Candice; Cao, Yongjun; Chalmers, John; Anderson, Craig S

2016-07-01

The kidney-brain interaction has been a topic of growing interest. Past studies of the effect of kidney function on intracerebral hemorrhage (ICH) outcomes have yielded inconsistent findings. Although the second, main phase of the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT2) suggests the effectiveness of early intensive blood pressure (BP) lowering in improving functional recovery after ICH, the balance of potential benefits and harms of this treatment in those with decreased kidney function remains uncertain. Secondary analysis of INTERACT2, which randomly assigned patients with ICH with elevated systolic BP (SBP) to intensive (target SBP<140mmHg) or contemporaneous guideline-based (target SBP<180mmHg) BP management. 2,823 patients from 144 clinical hospitals in 21 countries. Admission estimated glomerular filtration rates (eGFRs) of patients were categorized into 3 groups based on the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) creatinine equation: normal or high, mildly decreased, and moderately to severely decreased (>90, 60-90, and <60mL/min/1.73m(2), respectively). The effect of admission eGFR on the primary outcome of death or major disability at 90 days (defined as modified Rankin Scale scores of 3-6) was analyzed using a multivariable logistic regression model. Potential effect modification of intensive BP lowering treatment by admission eGFR was assessed by interaction terms. Of 2,623 included participants, 912 (35%) and 280 (11%) had mildly and moderately/severely decreased eGFRs, respectively. Patients with moderately/severely decreased eGFRs had the greatest risk for death or major disability at 90 days (adjusted OR, 1.82; 95% CI, 1.28-2.61). Effects of early intensive BP lowering were consistent across different eGFRs (P=0.5 for homogeneity). Generalizability issues arising from a clinical trial population. Decreased eGFR predicts poor outcome in acute ICH. Early intensive BP lowering provides

Substrate transport and anion permeation proceed through distinct pathways in glutamate transporters

PubMed Central

Cheng, Mary Hongying; Torres-Salazar, Delany; Gonzalez-Suarez, Aneysis D; Amara, Susan G; Bahar, Ivet

2017-01-01

Advances in structure-function analyses and computational biology have enabled a deeper understanding of how excitatory amino acid transporters (EAATs) mediate chloride permeation and substrate transport. However, the mechanism of structural coupling between these functions remains to be established. Using a combination of molecular modeling, substituted cysteine accessibility, electrophysiology and glutamate uptake assays, we identified a chloride-channeling conformer, iChS, transiently accessible as EAAT1 reconfigures from substrate/ion-loaded into a substrate-releasing conformer. Opening of the anion permeation path in this iChS is controlled by the elevator-like movement of the substrate-binding core, along with its wall that simultaneously lines the anion permeation path (global); and repacking of a cluster of hydrophobic residues near the extracellular vestibule (local). Moreover, our results demonstrate that stabilization of iChS by chemical modifications favors anion channeling at the expense of substrate transport, suggesting a mutually exclusive regulation mediated by the movement of the flexible wall lining the two regions. DOI: http://dx.doi.org/10.7554/eLife.25850.001 PMID:28569666

Internationalization of regulatory requirements.

PubMed

Juillet, Y

2003-02-01

The aim of harmonisation of medicines regulatory requirements is to allow the patient quicker access to new drugs and to avoid animal and human duplications. Harmonisation in the European Union (EU) is now completed, and has led to the submission of one dossier in one language study leading to European marketing authorizations, thanks in particular to efficacy guidelines published at the European level. With the benefit of the European experience since 1989, more than 40 guidelines have been harmonised amongst the EU, Japan and the USA through the International Conference on Harmonisation (ICH). ICH is a unique process gathering regulators and industry experts from the three regions. Its activity is built on expertise and trust. The Common Technical Document (CTD), an agreed common format for application in the three regions, is a logical follow-up to the ICH first phase harmonising the content of the dossier. The CTD final implementation in July 2003 will have considerable influence on the review process and on the exchange of information in the three regions.

[Intracranial pressure monitoring in severe traumatic brain injury: A different perspective of the BestTrip trial].

PubMed

Murillo-Cabezas, F; Godoy, D A

2014-05-01

The present study outlines a series of questions and reflections upon the recent publication of Chesnut et al., who compared 2 approaches to the treatment of intracranial hypertension (ICH) in severe head injuries: one with and the other without intracranial pressure monitoring (ICP). The authors concluded that no improved outcome was observed in the treatment group guided by ICP monitoring. The main concerns relate to the degree of training of the physicians involved in the monitoring and management of ICH in the ICP group, as well as to the possible inter-observer variability in interpreting the CT scans, the capacity of clinical signs to guide the treatment of ICH, and the suitability of randomization. The analysis of this trial should not be taken to suggest the futility of ICP monitoring but rather the need to correctly use the information afforded by ICP monitoring, with emphasis on the importance of the definition of alternative methods for non-invasive monitoring. Copyright © 2013 Elsevier España, S.L. and SEMICYUC. All rights reserved.

Cardiac safety strategies. 25-26 October 2005, the Radisson SAS Hotel, Nice, France.

PubMed

Hanton, Gilles; Tilbury, Lorraine

2006-03-01

This meeting was organised by IIR Life Sciences. It was chaired by Brian Guth, (head of General Pharmacology at Boehringer Ingelheim Pharma) and brought together scientists and clinicians from the pharmaceutical industry, university and regulatory agencies. The meeting presented emerging trends in cardiac safety, including its regulatory context pertaining to ICH S7A, S7B and E14. ICH S7A and S7B highlight the importance of the hERG test and telemetric studies in non-rodents. ICH E14 describes the clinical 'thorough QT study' that is required by the FDA for any new drug. Marked physiological variability in QT interval over time can be observed, partly as a result of fluctuation in autonomic tone. Beat-to-beat QT variability and T-wave morphology should be considered as a part of an integrated estimate of proarrhythmic risk. A case study illustrated the predictivity of preclinical data for proarrhythmic risk in humans, showing the importance of evaluating QT effects in patients to establish a safety margin.

The Structural Basis of IKs Ion-Channel Activation: Mechanistic Insights from Molecular Simulations.

PubMed

Ramasubramanian, Smiruthi; Rudy, Yoram

2018-06-05

Relating ion channel (iCh) structural dynamics to physiological function remains a challenge. Current experimental and computational techniques have limited ability to explore this relationship in atomistic detail over physiological timescales. A framework associating iCh structure to function is necessary for elucidating normal and disease mechanisms. We formulated a modeling schema that overcomes the limitations of current methods through applications of artificial intelligence machine learning. Using this approach, we studied molecular processes that underlie human IKs voltage-mediated gating. IKs malfunction underlies many debilitating and life-threatening diseases. Molecular components of IKs that underlie its electrophysiological function include KCNQ1 (a pore-forming tetramer) and KCNE1 (an auxiliary subunit). Simulations, using the IKs structure-function model, reproduced experimentally recorded saturation of gating-charge displacement at positive membrane voltages, two-step voltage sensor (VS) movement shown by fluorescence, iCh gating statistics, and current-voltage relationship. Mechanistic insights include the following: 1) pore energy profile determines iCh subconductance; 2) the entire protein structure, not limited to the pore, contributes to pore energy and channel subconductance; 3) interactions with KCNE1 result in two distinct VS movements, causing gating-charge saturation at positive membrane voltages and current activation delay; and 4) flexible coupling between VS and pore permits pore opening at lower VS positions, resulting in sequential gating. The new modeling approach is applicable to atomistic scale studies of other proteins on timescales of physiological function. Copyright © 2018 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Immediate, early and late seizures after primary intracerebral hemorrhage.

PubMed

Qian, Cheng; Löppönen, Pekka; Tetri, Sami; Huhtakangas, Juha; Juvela, Seppo; Turtiainen, Hanna-Maria E; Bode, Michaela K; Hillbom, Matti

2014-05-01

Seizures after primary intracerebral hemorrhage (PICH) are significant and treatable complications, but the factors predicting immediate, early and late seizures are poorly known. We investigated characteristics and outcome with special reference to occurrence and timing of a first seizure among consecutive subjects with PICH. A population-based study was conducted in Northern Ostrobothnia, Finland, in 1993-2008 that included all patients with a first-ever primary ICH without any prior diagnosis of epilepsy. Immediate (<24h after admission), early (1-14 days) and late (>2 weeks) seizures were considered separately. Out of a total of 935 ICH patients, 51 had immediate, 21 early and 58 late seizures. The patients with seizures were significantly younger than the others and more often had a subcortical hematoma location (p<0.05). Lifestyle factors did not differ between the groups. The risk factors for immediate seizures in multivariable analysis were a low Glasgow coma scale score (GCS) on admission, subcortical location and age inversely (p<0.01). The only independent risk factor for early seizures was subcortical location (p<0.001), whereas subcortical location (p<0.001), age inversely (p<0.01) and hematoma evacuation (p<0.05) independently predicted late seizures. Immediate and early seizures predicted infectious complications (p<0.05). Patients with subcortical hematoma and of younger age are at risk for immediate seizures after primary ICH irrespective of hematoma size. Patients with immediate and early seizures more often had infectious complications. Surgery increases the risk of a late seizure after ICH. Copyright © 2014 Elsevier B.V. All rights reserved.

A risk score for in-hospital death in patients admitted with ischemic or hemorrhagic stroke.

PubMed

Smith, Eric E; Shobha, Nandavar; Dai, David; Olson, DaiWai M; Reeves, Mathew J; Saver, Jeffrey L; Hernandez, Adrian F; Peterson, Eric D; Fonarow, Gregg C; Schwamm, Lee H

2013-01-28

We aimed to derive and validate a single risk score for predicting death from ischemic stroke (IS), intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH). Data from 333 865 stroke patients (IS, 82.4%; ICH, 11.2%; SAH, 2.6%; uncertain type, 3.8%) in the Get With The Guidelines-Stroke database were used. In-hospital mortality varied greatly according to stroke type (IS, 5.5%; ICH, 27.2%; SAH, 25.1%; unknown type, 6.0%; P<0.001). The patients were randomly divided into derivation (60%) and validation (40%) samples. Logistic regression was used to determine the independent predictors of mortality and to assign point scores for a prediction model in the overall population and in the subset with the National Institutes of Health Stroke Scale (NIHSS) recorded (37.1%). The c statistic, a measure of how well the models discriminate the risk of death, was 0.78 in the overall validation sample and 0.86 in the model including NIHSS. The model with NIHSS performed nearly as well in each stroke type as in the overall model including all types (c statistics for IS alone, 0.85; for ICH alone, 0.83; for SAH alone, 0.83; uncertain type alone, 0.86). The calibration of the model was excellent, as demonstrated by plots of observed versus predicted mortality. A single prediction score for all stroke types can be used to predict risk of in-hospital death following stroke admission. Incorporation of NIHSS information substantially improves this predictive accuracy.

Magnetic Resonance Imaging Profile of Blood–Brain Barrier Injury in Patients With Acute Intracerebral Hemorrhage

PubMed Central

Aksoy, Didem; Bammer, Roland; Mlynash, Michael; Venkatasubramanian, Chitra; Eyngorn, Irina; Snider, Ryan W.; Gupta, Sandeep N.; Narayana, Rashmi; Fischbein, Nancy; Wijman, Christine A. C.

2013-01-01

Background Spontaneous intracerebral hemorrhage (ICH) is associated with blood–brain barrier (BBB) injury, which is a poorly understood factor in ICH pathogenesis, potentially contributing to edema formation and perihematomal tissue injury. We aimed to assess and quantify BBB permeability following human spontaneous ICH using dynamic contrast‐enhanced magnetic resonance imaging (DCE MRI). We also investigated whether hematoma size or location affected the amount of BBB leakage. Methods and Results Twenty‐five prospectively enrolled patients from the Diagnostic Accuracy of MRI in Spontaneous intracerebral Hemorrhage (DASH) study were examined using DCE MRI at 1 week after symptom onset. Contrast agent dynamics in the brain tissue and general tracer kinetic modeling were used to estimate the forward leakage rate (Ktrans) in regions of interest (ROI) in and surrounding the hematoma and in contralateral mirror–image locations (control ROI). In all patients BBB permeability was significantly increased in the brain tissue immediately adjacent to the hematoma, that is, the hematoma rim, compared to the contralateral mirror ROI (P<0.0001). Large hematomas (>30 mL) had higher Ktrans values than small hematomas (P<0.005). Ktrans values of lobar hemorrhages were significantly higher than the Ktrans values of deep hemorrhages (P<0.005), independent of hematoma volume. Higher Ktrans values were associated with larger edema volumes. Conclusions BBB leakage in the brain tissue immediately bordering the hematoma can be measured and quantified by DCE MRI in human ICH. BBB leakage at 1 week is greater in larger hematomas as well as in hematomas in lobar locations and is associated with larger edema volumes. PMID:23709564

Incidence of stroke subtypes in the North East Melbourne Stroke Incidence Study (NEMESIS): differences between men and women.

PubMed

Thrift, Amanda G; Dewey, Helen M; Sturm, Jonathan W; Srikanth, Velandai K; Gilligan, Amanda K; Gall, Seana L; Macdonell, Richard A L; McNeil, John J; Donnan, Geoffrey A

2009-01-01

Incidence rates of stroke subtypes may be imprecise when samples are small. We aimed to determine the incidence of stroke subtypes in a large geographically defined population. Multiple overlapping sources were used to ascertain all strokes occurring in 22 postcodes (population of 306,631) of Melbourne, Australia, between 1997 and 1999. Stroke subtypes were defined by CT, MRI and autopsy. The Mantel-Haenszel age-adjusted rate ratio (MH RR) was used to compare incidence rates between men and women. We identified 1,421 strokes among 1,337 residents, 1,035 (72.8%) being first-ever strokes. Incidence (number/100,000 population/year), adjusted to the European population 45-84 years, was 197 (95% confidence interval, CI, 169-224) for ischemic stroke (IS), 47 (95% CI 33-60) for intracerebral haemorrhage (ICH) and 19 (95% CI 10-27) for subarachnoid haemorrhage (SAH). Compared with women, men in this age group had a greater incidence of IS (MH RR 1.65, 95% CI 1.39-1.96, p < 0.0001) and ICH (MH RR 1.46, 95% CI 1.01-2.10, p = 0.0420), but lesser rates of SAH (MH RR 0.34, 95% CI 0.16-0.69, p = 0.0031). In this population-based study, the incidence of IS and ICH was greater among men than women, while women had a greater incidence of SAH. More effort may need to be directed at modifying risk factors for IS and ICH in men. 2008 S. Karger AG, Basel

A method for normalizing pathology images to improve feature extraction for quantitative pathology

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tam, Allison; Barker, Jocelyn; Rubin, Daniel

Purpose: With the advent of digital slide scanning technologies and the potential proliferation of large repositories of digital pathology images, many research studies can leverage these data for biomedical discovery and to develop clinical applications. However, quantitative analysis of digital pathology images is impeded by batch effects generated by varied staining protocols and staining conditions of pathological slides. Methods: To overcome this problem, this paper proposes a novel, fully automated stain normalization method to reduce batch effects and thus aid research in digital pathology applications. Their method, intensity centering and histogram equalization (ICHE), normalizes a diverse set of pathology imagesmore » by first scaling the centroids of the intensity histograms to a common point and then applying a modified version of contrast-limited adaptive histogram equalization. Normalization was performed on two datasets of digitized hematoxylin and eosin (H&E) slides of different tissue slices from the same lung tumor, and one immunohistochemistry dataset of digitized slides created by restaining one of the H&E datasets. Results: The ICHE method was evaluated based on image intensity values, quantitative features, and the effect on downstream applications, such as a computer aided diagnosis. For comparison, three methods from the literature were reimplemented and evaluated using the same criteria. The authors found that ICHE not only improved performance compared with un-normalized images, but in most cases showed improvement compared with previous methods for correcting batch effects in the literature. Conclusions: ICHE may be a useful preprocessing step a digital pathology image processing pipeline.« less

Intravenous thrombolysis and endovascular therapy for acute ischemic stroke with internal carotid artery occlusion: a systematic review of clinical outcomes.

PubMed

Mokin, Maxim; Kass-Hout, Tareq; Kass-Hout, Omar; Dumont, Travis M; Kan, Peter; Snyder, Kenneth V; Hopkins, L Nelson; Siddiqui, Adnan H; Levy, Elad I

2012-09-01

Strokes secondary to acute internal carotid artery (ICA) occlusion are associated with extremely poor prognosis. The best treatment approach to acute stroke in this setting is unknown. We sought to determine clinical outcomes in patients with acute ischemic stroke attributable to ICA occlusion treated with intravenous (IV) systemic thrombolysis or intra-arterial endovascular therapy. Using the PubMed database, we searched for studies that included patients with acute ischemic stroke attributable to ICA occlusion who received treatment with IV thrombolysis or intra-arterial endovascular interventions. Studies providing data on functional outcomes beyond 30 days and mortality and symptomatic intracerebral hemorrhage (sICH) rates were included in our analysis. We compared the proportions of patients with favorable functional outcomes, sICH, and mortality rates in the 2 treatment groups by calculating χ(2) and confidence intervals for odds ratios. We identified 28 studies with 385 patients in the IV thrombolysis group and 584 in the endovascular group. Rates of favorable outcomes and sICH were significantly higher in the endovascular group than the IV thrombolysis-only group (33.6% vs 24.9%, P=0.004 and 11.1% vs 4.9%, P=0.001, respectively). No significant difference in mortality rate was found between the groups (27.3% in the IV thrombolysis group vs 32.0% in the endovascular group; P=0.12). According to our systematic review, endovascular treatment of acute ICA occlusion results in improved clinical outcomes. A higher rate of sICH after endovascular treatment does not result in increased overall mortality rate.

Technology that achieves the Triple Aim: an economic analysis of the BrainPath™ approach in neurosurgery.

PubMed

Norton, Sidney P; Dickerson, Evan M; Kulwin, Charles G; Shah, Mitesh V

2017-01-01

The Triple Aim is defined as: improving the patient experience of care, improving the health of populations, and reducing the per capita cost of health care. The purpose of this analysis was to evaluate the economic value of a new neurosurgical technique, the BrainPath™ approach, for use in patients with subcortical tumors and intracerebral hemorrhage (ICH). Inpatient length of stay (LOS) data were collected for ICH and brain tumor surgical patient cases between August 2013 and November 2015. Patient cases were separated into two groups; BrainPath approach (n = 28) and conventional techniques, such as craniotomy, (n = 208). The average intensive care unit (ICU) LOS was calculated for each group by diagnosis-related group and compared between groups. The new surgical technology resulted in surgical intervention in 14 ICH cases which otherwise would have been medically managed due to the hemorrhage location or size of the ICH. A reduction in ICU LOS was seen in this group. Based on the variable direct cost per day in the neuro critical care unit at this academic medical center, 14 patient cases incurred ~ US$210,000 less in direct ICU costs. Surgical resection was possible in two tumor patient cases which would have been biopsied, rather than surgically resected, also due to location of the abnormalities. A total net value of > US$329,000 is attributable to the analyzed approach over a 28-month period. This analysis shows positive economic value for the new technology group when ICU LOS and reimbursement are considered against equipment costs, thus achieving Triple Aim objectives.

Salinity of the Little Colorado River in Grand Canyon confers anti-parasitic properties on a native fish

USGS Publications Warehouse

Ward, David L.

2012-01-01

Water in the Little Colorado River within Grand Canyon is naturally high in salt (NaCl), which is known to prohibit development of external fish parasites such as Ich (Ichthyophthirius multifiliis). The naturally high salinity (>0.3%) of the Little Colorado River at baseflow may be one factor allowing survival and persistence of larval and juvenile humpback chub (Gila cypha) and other native fishes in Grand Canyon. We compared salinity readings from the Little Colorado River to those reported in the literature as being effective at removing protozoan parasites from fish. In laboratory tests, 10 juvenile roundtail chub (Gila robusta; 61–90 mm TL) were randomly placed into each of 12, 37-L aquaria filled with freshwater, water obtained from the Little Colorado River (0.3% salinity), or freshwater with table salt added until the salinity reached 0.3%. Roundtail chub was used as a surrogate for humpback chub in this study because the species is not listed as endangered but is morphologically and ecologically similar to humpback chub. All roundtail chub infected with Ich recovered and survived when placed in water from the Little Colorado River or water with 0.3% salinity, but all experimental fish placed in freshwater died because of Ich infection. The naturally high salinity of the Little Colorado River at baseflow (0.22%–0.36%), appears sufficiently high to interrupt the life cycle of Ich and may allow increased survival of larval and juvenile humpback chub relative to other areas within Grand Canyon.

Observations of single-pass ion cyclotron heating in a trans-sonic flowing plasma

NASA Astrophysics Data System (ADS)

Bering, E. A.; Díaz, F. R. Chang; Squire, J. P.; Glover, T. W.; Carter, M. D.; McCaskill, G. E.; Longmier, B. W.; Brukardt, M. S.; Chancery, W. J.; Jacobson, V. T.

2010-04-01

The VAriable Specific Impulse Magnetoplasma Rocket (VASIMR®) is a high power electric spacecraft propulsion system, capable of Isp/thrust modulation at constant power [F. R. Chang Díaz et al., Proceedings of the 39th AIAA Aerospace Sciences Meeting and Exhibit, Reno, NV, 8-11 Jan. 2001]. The VASIMR® uses a helicon discharge to generate plasma. This plasma is energized by an rf booster stage that uses left hand polarized slow mode waves launched from the high field side of the ion cyclotron resonance. In the experiments reported in this paper, the booster uses 2-4 MHz waves with up to 50 kW of power. This process is similar to the ion cyclotron heating (ICH) in tokamaks, but in the VASIMR® the ions only pass through the resonance region once. The rapid absorption of ion cyclotron waves has been predicted in recent theoretical studies. These theoretical predictions have been supported with several independent measurements in this paper. The single-pass ICH produced a substantial increase in ion velocity. Pitch angle distribution studies showed that this increase took place in the resonance region where the ion cyclotron frequency was roughly equal to the frequency on the injected rf waves. Downstream of the resonance region the perpendicular velocity boost should be converted to axial flow velocity through the conservation of the first adiabatic invariant as the magnetic field decreases in the exhaust region of the VASIMR®. This paper will review all of the single-pass ICH ion acceleration data obtained using deuterium in the first VASIMR® physics demonstrator machine, the VX-50. During these experiments, the available power to the helicon ionization stage increased from 3 to 20+ kW. The increased plasma density produced increased plasma loading of the ICH coupler. Starting with an initial demonstration of single-pass ion cyclotron acceleration, the experiments demonstrate significant improvements in coupler efficiency and in ion heating efficiency. In

Stroke Incidence by Major Pathological Type and Ischemic Subtypes in the Auckland Regional Community Stroke Studies: Changes Between 2002 and 2011.

PubMed

Krishnamurthi, Rita V; Barker-Collo, Suzanne; Parag, Varsha; Parmar, Priyakumari; Witt, Emma; Jones, Amy; Mahon, Susan; Anderson, Craig S; Barber, P Alan; Feigin, Valery L

2018-01-01

Major pathological stroke types (ischemic stroke [IS], primary intracerebral hemorrhage [ICH], and subarachnoid hemorrhage) and IS subtypes, have differing risk factors, management, and prognosis. We report changes in major stroke types and IS subtypes incidence during 10 years using data from the ARCOS (Auckland Regional Community Stroke Study) III performed during 12 months in 2002 to 2003 and the fourth ARCOS study (ARCOS-IV) performed in 2011 to 2012. ARCOS-III and ARCOS-IV were population-based registers of all new strokes in the greater Auckland region (population aged >15 years, 1 119 192). Strokes were classified into major pathological types (IS, ICH, subarachnoid hemorrhage, and undetermined type). Crude annual age-, sex-, and ethnic-specific stroke incidence with 95% confidence intervals was calculated. ISs were subclassified using TOAST (Trial of ORG 10172 in Acute Stroke Treatment) criteria into 5 etiologic groups. Rate ratios with 95% confidence intervals were calculated for differences in age-standardized rates between the 2 studies. In ARCOS-IV, there were 1329 (81%) ISs, 211 (13%) ICHs, 79 (5%) subarachnoid hemorrhages, and 24 (1%) undetermined type strokes. The proportional distribution of IS subtypes was 29% cardioembolism, 21% small-vessel occlusion, 15% large-artery atherosclerosis, 5% other determined etiology, and 31% undetermined type. Between 2002 and 2011, age-standardized incidence decreased for subarachnoid hemorrhage (rate ratios, 0.73; 95% confidence intervals, 0.54-0.99) and undetermined type (rate ratios, 0.14; 95% confidence intervals, 0.09-0.22). Rates were stable for IS and ICH. Among IS subtypes, large-artery atherosclerosis and small-vessel occlusion rates increased significantly. The frequency of all risk factors increased in IS. Ethnic differences were observed for both stroke subtype rates and their risk factor frequencies. A lack of change in IS and ICH incidence may reflect a trend toward increased incidence of younger

WE-AB-207A-03: A CBCT Head Scanner for Point-Of-Care Imaging of Intracranial Hemorrhage

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xu, J; Sisniega, A; Zbijewski, W

Purpose: This work reports the design, development, and first technical assessment of a cone-beam CT (CBCT) scanner developed specifically for imaging of acute intracranial hemorrhage (ICH) at the point of care, with target applications in diagnosis and monitoring of traumatic brain injury, stroke, and postsurgical hemorrhage. Methods: System design employed a task-based image quality model to quantify the influence of factors such as additive noise and high-gain (HG) detector readout on ICH detectability. Three bowtie filters with varying bare-beam attenuation strength and curvature were designed to enable HG readout without detector saturation, and a polyenergetic gain correction was developed tomore » minimize artifacts from bowtie flood-field calibration. Image reconstruction used an iterative penalized weighted least squares (PWLS) method with artifact correction including Monte Carlo scatter estimation, Joseph-Spital beam hardening correction, and spatiotemporal deconvolution of detector glare and lag. Radiation dose was characterized for half-scan and full-scan protocols at various kV, and imaging performance was assessed in a head phantom presenting simulated ICH with diameter ranging 2–12 mm. Results: The image quality model guided system design and was validated by measurements on a CBCT imaging bench. Compared to low-gain readout without a bowtie filter, the combination of HG readout and a modest bowtie improved the contrast-to-noise ratio (CNR per unit square-root dose) by 20% in the center of the image but degraded noise performance near the periphery (20% reduction in CNR). Low-frequency bowtie artifacts (∼100 HU magnitude) were corrected by the polyenergetic gain correction. Image reconstructions on the prototype scanner demonstrate clear visibility of the smallest ICH insert (2 mm diameter) in both HG readout (with a bowtie) and dual-gain readout (without bowtie). Conclusion: Technical assessment of the prototype scanner suggests the

Intrasylvian/Intracerebral Hematomas Associated with Ruptured Middle Cerebral Artery Aneurysms: A Single-Center Series and Literature Review.

PubMed

Zhang, Yupeng; Hu, Quan; Xue, Hao; Zhang, Mingran; Shen, Jie; Deng, Lin; Liu, Qinglin; Li, Gang

2017-02-01

Ruptured middle cerebral artery (MCA) aneurysms usually lead to subarachnoid hemorrhage (SAH), and several cases have shown concomitant intrasylvian or intracerebral hematomas. The objective of this study was to compare the clinical and radiographic characteristics with their different outcomes. The charts of 30 consecutive patients with ruptured MCA aneurysm-related intracranial hematoma were retrospectively reviewed. These patients were dichotomized into an intrasylvian hematoma (ISH) group and an intracerebral hematoma (ICH) group by the presence of intrahematomal contrast-enhancing vessel; for patients under open surgery, hematoma type was further confirmed by intraoperative observation. The characteristics were compared between these 2 groups (ie, age, gender, history of hypertension, history of smoking, systolic pressure at admission, hematoma volume, size and side of aneurysms, the angle between the pointing direction of the aneurysm and the MCA trunk [denoted as α], middle line shifting, treatment modality, and outcome). All the angles are measured in the anterior-posterior projection. In our series, only hematoma volume, the angle α, and the middle line shift showed statistical significance regarding prognosis between 2 hematoma groups. An angle α between 109.0°and 216.0° is associated with ISH, whereas aneurysm with an angle beyond this range indicates ICH. In our series, patients in the ICH group had a larger hematoma volume compared with the ISH patients (33.3 ± 17.6 vs. 11.5 ± 10.5; P = 0.002). There exists no statistical difference regarding prognosis between these 2 groups, even although there is a trend toward worse recovery for patients in the ISH group (Glasgow Outcome Scale score, 3.0 ± 1.3 vs. 3.8 ± 1.9; P = 0.07). In our series, the prognosis of patients with ICH was worse than that of patients with ISH. Early discrimination of these 2 types of hematoma helps to predict future outcome; an angle (between the pointing direction of

The H-ATOMIC Criteria for the Etiologic Classification of Patients with Intracerebral Hemorrhage

PubMed Central

Prats-Sánchez, Luis; Martínez-Domeño, Alejandro; Camps-Renom, Pol; Marín, Rebeca; Jiménez-Xarrié, Elena; Fuentes, Blanca; Dorado, Laura; Purroy, Francisco; Arias-Rivas, Susana; Delgado-Mederos, Raquel

2016-01-01

Background and Purpose There are no generally accepted criteria for the etiologic classification of intracerebral hemorrhage (ICH). For this reason, we have developed a set of etiologic criteria and have applied them to a large number of patients to determine their utility. Methods The H-ATOMIC classification includes 7 etiologic categories: Hypertension, cerebral Amyloid angiopathy, Tumour, Oral anticoagulants, vascular Malformation, Infrequent causes and Cryptogenic. For each category, the etiology is scored with three degrees of certainty: Possible(3), Probable(2) and Definite(1). Our aim was to perform a basic study consisting of neuroimaging, blood tests, and CT-angio when a numerical score (SICH) suggested an underlying structural abnormality. Combinations of >1 etiologic category for an individual patient were acceptable. The criteria were evaluated in a multicenter and prospective study of consecutive patients with spontaneous ICH. Results Our study included 439 patients (age 70.8 ± 14.5 years; 61.3% were men). A definite etiology was achieved in 176 (40.1% of the patients: Hypertension 28.2%, cerebral Amyloid angiopathy 0.2%, Tumour 0.2%, Oral anticoagulants 2.2%, vascular Malformation 4.5%, Infrequent causes 4.5%). A total of 7 patients (1.6%) were cryptogenic. In the remaining 58.3% of the patients, ICH was attributable to a single (n = 56, 12.7%) or the combination of ≥2 (n = 200, 45.5%) possible/probable etiologies. The most frequent combinations of etiologies involved possible hypertension with possible CAA (H3A3, n = 38) or with probable CAA (H3A2, n = 29), and probable hypertension with probable OA (H2O2, n = 27). The most frequent category with any degree of certainty was hypertension (H1+2+3 = 80.6%) followed by cerebral amyloid angiopathy (A1+2+3 = 30.9%). Conclusions According to our etiologic criteria, only about 40% patients received a definite diagnosis, while in the remaining patients ICH was attributable to a single possible

Mode of delivery and risk of intracranial haemorrhage in newborns with severe haemophilia A: a multicentre study in Gulf region.

PubMed

Nazir, H F; Al Lawati, T; Beshlawi, I; AlSharidah, S; Elshinawy, M; Alkasim, F; Khanani, M F; Tarawa, A; Al Subhi, T; Alrawas, A; Al Riyami, W; Al Kindi, S; Al Saadi, K; Al-Lamki, S; Wali, Y

2016-05-01

The optimum mode of delivery in a known carrier of a haemophilia A is still an issue of debate. This study was conducted to report a multicentre experience in Gulf Cooperation Council (GCC) on the incidence of intracranial haemorrhage (ICH) in newborns with severe haemophilia A delivered by different modalities. We have conducted a retrospective/prospective multicentre cohort study including a total of seven hospitals distributed in four GCC countries between 1998 and Jan 2015. A total of 163 patient with severe haemophilia A (factor VIII <1%) were enrolled in this study, age ranged between 2 weeks to 18 years. Most of the patients were born by spontaneous vaginal delivery (SVD) (131, 80.4%), whereas 26 patients (16%) were born by CS and only six patients were born by instrumental delivery (3.7%), five of them by vacuum and one was delivered using forceps. Five out of 163 patients developed ICH during the first 2 weeks of life (3.1%). Two of them were born by SVD (2/131; 1.5%) and two were born by instrumental delivery (2/6; 33.3%). Only one patient among those who were born by caesarean section developed ICH (1/26; 3.8%). Assisted vaginal delivery was associated with a significant risk of ICH, in comparison to SVD and CS (P = 0.0093). Normal vaginal delivery is still considered a safe journey through the birth canal for haemophilic newborns particularly in this area of the world. Larger prospective studies might be needed to define an evidence-based optimal mode of delivery for the haemophilia carrier expecting an affected child. © 2015 John Wiley & Sons Ltd.

The effect of the stroke etiology on functional improvement in our geriatric hemiplegic patients.

PubMed

Nakipoğlu-Yüzer, Güldal F; Doğan-Aslan, Meryem; Doğan, Asuman; Ozgirgin, Neşe

2010-05-01

We aimed to determine the effect of the cerebrovascular accident etiology in the geriatric patients with hemiplegia included in our physical medicine and rehabilitation program on functional improvement. A total of 46 geriatric patients with hemiplegia attending the inpatient physical medicine and rehabilitation program were included in the study. The patients were divided into two groups-thromboembolic vessel disease (TEVD) and intracerebral hemorrhage (ICH)-depending on the cerebrovascular accident etiology. The daily living activities of the patients in both groups were evaluated using the Barthel Index (BI) and the ambulation levels were evaluated using the Functional Ambulation Classification (FAC) at admittance and at discharge from hospital. There was a statistically significant difference between admission and discharge BI values in both groups. There was no significant difference between the admission and discharge BI scores of the TEVD and ICH groups. For both groups, on admission there were 19 (82.5%) patients at the FAC 0, 1, and 2 levels, and 4 (17.3%) patients at the FAC 3 and 4 levels. On discharge there were 11 (47.8%) patients in the TEVD group at the FAC 0 and 2 levels, and 12 (52.1%) patients at the FAC 3, 4, and 5 levels; whereas in the ICH group there were 8 (34.7%) patients at the FAC 0, 1, and 2 levels, and 15 (65.2%) patients at the FAC 3, 4, and 5 levels. We found that the disease etiology did not influence the rehabilitation results for our geriatric patients with hemiplegia attending a physical medicine and rehabilitation program following TEVD or ICH. Copyright (c) 2010 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Early introduction of direct oral anticoagulants in cardioembolic stroke patients with non-valvular atrial fibrillation.

PubMed

Cappellari, Manuel; Carletti, Monica; Danese, Alessandra; Bovi, Paolo

2016-10-01

Direct oral anticoagulants (DOACs) are superior to warfarin in reduction of the intracranial bleeding risk. The aim of the present study was to assess whether early DOAC introduction (1-3 days after onset) in stroke patients with non-valvular atrial fibrillation (nVAF) may be safe and effective, compared with DOAC introduction after 4-7 days. We conducted a prospective analysis based on data collected from 147 consecutive nVAF patients who started DOAC within 7 days after stroke onset. In all patients, we performed pre-DOAC CT scan 24-36 h after onset and follow-up CT scan at 7 days after DOAC introduction. Outcome measures were post-DOAC intracranial bleeding (new any intracerebral hemorrhage (ICH) in patients with pre-DOAC infarct without hemorrhagic transformation (HT) or expansion of ICH in patients with pre-DOAC infarct with asymptomatic HT) and post-DOAC recurrent ischemic stroke (any new ischemic infarct) on follow-up CT scan. 97 patients started DOAC after 1-3 days and 50 patients started DOAC after 4-7 days. On pre-DOAC CT scan, 132 patients had an infarct without HT and 15 an infarct with asymptomatic HT. On follow-up CT scan, new any ICH was noted in seven patients (asymptomatic in 6) and asymptomatic expansion of ICH in one patient. We found no association between early DOAC introduction and intracranial bleeding. Large infarct remained the only independent predictor of post-DOAC intracranial bleeding. No patients suffered recurrent ischemic stroke after DOAC introduction. Early DOAC introduction might be safe in carefully selected patients with nVAF who experience small- and medium-sized cardioembolic ischemic strokes. Further investigation will be needed.

Restarting antiplatelet therapy after spontaneous intracerebral hemorrhage: Functional outcomes.

PubMed

Chen, Ching-Jen; Ding, Dale; Buell, Thomas J; Testai, Fernando D; Koch, Sebastian; Woo, Daniel; Worrall, Bradford B

2018-05-30

To compare the functional outcomes and health-related quality of life metrics of restarting vs not restarting antiplatelet therapy (APT) in patients presenting with intracerebral hemorrhage (ICH) in the ERICH (Ethnic/Racial Variations of Intracerebral Hemorrhage) study. Adult patients aged 18 years and older who were on APT before ICH and were alive at hospital discharge were included. Patients were dichotomized based on whether or not APT was restarted after hospital discharge. The primary outcome was a modified Rankin Scale score of 0-2 at 90 days. Secondary outcomes were excellent outcome (modified Rankin Scale score 0-1), mortality, Barthel Index, and health status (EuroQol-5 dimensions [EQ-5D] and EQ-5D visual analog scale scores) at 90 days. The APT and no APT cohorts comprised 127 and 732 patients, respectively. Restarting APT was associated with lower rates of good functional outcome (36.5% vs 40.8%; p = 0.021) and lower Barthel Index scores at 90 days ( p = 0.041). The 2 cohorts were then matched in a 1:1 ratio, and the matched cohorts each comprised 107 patients. No difference in primary outcome was observed between restarting vs not restarting APT (35.5% vs 43.9%; p = 0.105). There were also no differences between the secondary outcomes of the 2 cohorts. Restarting APT in patients with ICH of mild to moderate severity after acute hospitalization is not associated with worse functional outcomes or health-related quality of life at 90 days. In patients with significant cardiovascular risk factors who experience an ICH, restarting APT remains the decision of the treating practitioner. © 2018 American Academy of Neurology.

Neurovascular Cell Sheet Transplantation in a Canine Model of Intracranial Hemorrhage

PubMed Central

Lee, Woo-Jin; Lee, Jong Young; Jung, Keun-Hwa; Lee, Soon-Tae; Kim, Hyo Yeol; Park, Dong-Kyu; Yu, Jung-Suk; Kim, So-Yun; Jeon, Daejong; Kim, Manho; Lee, Sang Kun; Roh, Jae-Kyu; Chu, Kon

2017-01-01

Cell-based therapy for intracerebral hemorrhage (ICH) has a great therapeutic potential. However, methods to effectively induce direct regeneration of the damaged neural tissue after cell transplantation have not been established, which, if done, would improve the efficacy of cell-based therapy. In this study, we aimed to develop a cell sheet with neurovasculogenic potential and evaluate its usefulness in a canine ICH model. We designed a composite cell sheet made of neural progenitors derived from human olfactory neuroepithelium and vascular progenitors from human adipose tissue-derived stromal cells. We also generated a physiologic canine ICH model by manually injecting and then infusing autologous blood under arterial pressure. We transplanted the sheet cells (cell sheet group) or saline (control group) at the cortex over the hematoma at subacute stages (2 weeks from ICH induction). At 4 weeks from the cell transplantation, cell survival, migration, and differentiation were evaluated. Hemispheric atrophy and neurobehavioral recovery were also compared between the groups. As a result, the cell sheet was rich in extracellular matrices and expressed neurotrophic factors as well as the markers for neuronal development. After transplantation, the cells successfully survived for 4 weeks, and a large portion of those migrated to the perihematomal site and differentiated into neurons and pericytes (20% and 30% of migrated stem cells, respectively). Transplantation of cell sheets alleviated hemorrhage-related hemispheric atrophy (p = 0.042) and showed tendency for improving functional recovery (p = 0.062). Therefore, we concluded that the cell sheet transplantation technique might induce direct regeneration of neural tissue and might improve outcomes of intracerebral hemorrhage. PMID:28713638

MIS Score: Prediction Model for Minimally Invasive Surgery.

PubMed

Hu, Yuanyuan; Cao, Jingwei; Hou, Xianzeng; Liu, Guangcun

2017-03-01

Reports suggest that patients with spontaneous intracerebral hemorrhage (ICH) can benefit from minimally invasive surgery, but the inclusion criterion for operation is controversial. This article analyzes factors affecting the 30-day prognoses of patients who have received minimally invasive surgery and proposes a simple grading scale that represents clinical operation effectiveness. The records of 101 patients with spontaneous ICH presenting to Qianfoshan Hospital were reviewed. Factors affecting their 30-day prognosis were identified by logistic regression. A clinical grading scale, the MIS score, was developed by weighting the independent predictors based on these factors. Univariate analysis revealed that the factors that affect 30-day prognosis include Glasgow coma scale score (P < 0.01), age ≥80 years (P < 0.05), blood glucose (P < 0.01), ICH volume (P < 0.01), operation time (P < 0.05), and presence of intraventricular hemorrhage (P < 0.001). Logistic regression revealed that the factors that affect 30-day prognosis include Glasgow coma scale score (P < 0.05), age (P < 0.05), ICH volume (P < 0.01), and presence of intraventricular hemorrhage (P < 0.05). The MIS score was developed accordingly; 39 patients with 0-1 MIS scores had favorable prognoses, whereas only 9 patients with 2-5 MIS scores had poor prognoses. The MIS score is a simple grading scale that can be used to select patients who are suited for minimal invasive drainage surgery. When MIS score is 0-1, minimal invasive surgery is strongly recommended for patients with spontaneous cerebral hemorrhage. The scale merits further prospective studies to fully determine its efficacy. Copyright © 2016 Elsevier Inc. All rights reserved.

Racial and ethnic disparities in the use of intravenous recombinant tissue plasminogen activator and outcomes for acute ischemic stroke.

PubMed

Nasr, Deena M; Brinjikji, Waleed; Cloft, Harry J; Rabinstein, Alejandro A

2013-02-01

Racial and ethnic disparities in acute stroke care in the United States have been previously reported. This study investigated possible racial and ethnic disparities in the administration and outcome of recombinant tissue plasminogen activator (rtPA) therapy for acute ischemic stroke in whites, blacks, Hispanics, and Asian/Pacific Islanders. Using the National Inpatient Sample for 2001-2008, we selected patients with a primary diagnosis of acute ischemic stroke who received treatment with rtPA. Patient data were stratified by race (white, black, Hispanic, and Asian/Pacific Islander). We analyzed the association of patient race on rtPA utilization rate, in-hospital morbidity (ie, discharge to long-term facility), intracranial hemorrhage (ICH) rate, and in-hospital mortality. We performed a multivariate logistic regression analysis to determine independent predictors of poor outcomes. White patients had a higher rate of tPA utilization than black and Hispanic patients (2.3% vs 1.8% and 2.0%, respectively; P < .0001 for both groups). There was no difference in the rate of tPA utilization between whites and Asian/Pacific Islanders (2.3% vs 2.2% P = .07). Multivariate analysis of morbidity, mortality, and ICH rates found that Asian/Pacific Islanders had significantly higher rates of mortality (odds ratio, 1.22, 95% confidence interval, 1.03-1.44; P = .02) and ICH (odds ratio, 2.01; 95% confidence interval, 1.91-2.11; P < .0001) compared with whites. rtPA utilization was greater in white and Asian/Pacific Islander patients than in black and Hispanic patients. Asian/Pacific Islander race was associated with increased risk of ICH and mortality after rtPA administration. Copyright © 2013. Published by Elsevier Inc.

Low free triiodothyronine levels are related to symptomatic intracranial hemorrhage and poor functional outcomes after intravenous thrombolysis in acute ischemic stroke patients.

PubMed

Liu, Junfeng; Wang, Deren; Xiong, Yao; Yuan, Ruozhen; Tao, Wendan; Liu, Ming

2016-05-01

Low free triiodothyronine (fT3) levels have been associated with increased mortality and poor functional outcomes in patients with stroke. However, the research of relationship between fT3 levels and acute ischemic stroke (AIS) patients with intravenous thrombolysis (IVT) is scarce. We aimed to investigate the association of fT3 levels with symptomatic intracranial hemorrhage (sICH) and functional outcomes at discharge in AIS patients with IVT. Patients with AIS admitted to West China hospital, Sichuan University, who had underwent IVT treatment, were consecutively and retrospectively included. Demographic and clinical information were collected and analyzed according to the levels of fT3. We used logistic regression analysis to estimate the multivariable adjusted association of fT3 levels and post-IVT sICH, and functional outcomes at discharge. Among the 46 patients (26 males; mean age, 63.6 years) in the final analysis, 17 patients (37.0%) had fT3 levels lower than the reference range. After adjustment for age, gender, and statistically important variables (NIHSS on admission, urea levels and creatinine levels), low fT3 levels were significantly associated with post-IVT sICH (p = 0.01, OR = 0.27, 95% CI 0.10-0.77) and poor functional outcomes at discharge (p = 0.04 OR = 2.58, 95% CI 1.05-6.35). We found that lower free T3 levels are independently related to post-IVT sICH and poor functional outcomes at discharge in AIS patients with IVT, which should be verified and extended in large cohorts in the future.

Poor Long-Term Blood Pressure Control after Intracerebral Hemorrhage

PubMed Central

Zahuranec, Darin B.; Wing, Jeffrey J.; Edwards, Dorothy F.; Menon, Ravi S.; Fernandez, Stephen J.; Burgess, Richard E.; Sobotka, Ian A.; German, Laura; Trouth, Anna J.; Shara, Nawar M.; Gibbons, M. Chris; Boden-Albala, Bernadette; Kidwell, Chelsea S.

2012-01-01

Background and Purpose Hypertension is the most important risk factor associated with intracerebral hemorrhage (ICH). We explored racial differences in blood pressure (BP) control after ICH and assessed predictors of BP control at presentation, 30 days, and 1 year in a prospective cohort study. Methods Subjects with spontaneous ICH were identified from the DiffErenCes in the Imaging of Primary Hemorrhage based on Ethnicity or Race (DECIPHER) Project. Blood pressure was compared by race at each time point. Multivariable linear regression was used to determine predictors of presenting mean arterial pressure (MAP), and longitudinal linear regression was used to assess predictors of MAP at follow-up. Results A total of 162 patients were included (mean age 59, 53% male, 77% black). MAP at presentation was 9.6 mmHg higher in blacks than whites despite adjustment for confounders (p=0.065). Fewer than 20% of patients had normal blood pressure (<120/80 mmHg) at 30 days or 1 year. While there was no difference at 30 days (p=0.331), blacks were more likely than whites to have Stage I/II hypertension at one year (p=0.036). Factors associated with lower MAP at follow-up in multivariable analysis were being married at baseline (p=0.032) and living in a facility (versus personal residence) at the time of BP measurement (p=0.023). Conclusions Long-term blood pressure control is inadequate in patients following ICH, particularly in blacks. Further studies are needed to understand the role of social support and barriers to control to identify optimal approaches to improve blood pressure in this high-risk population. PMID:22903494

Severe bleeding events in adults and children with primary immune thrombocytopenia: a systematic review.

PubMed

Neunert, C; Noroozi, N; Norman, G; Buchanan, G R; Goy, J; Nazi, I; Kelton, J G; Arnold, D M

2015-03-01

The burden of severe bleeding in adults and children with immune thrombocytopenia (ITP) has not been established. To describe the frequency and severity of bleeding events in patients with ITP, and the methods used to measure bleeding in ITP studies. We performed a systematic review of all prospective ITP studies that enrolled 20 or more patients. Two reviewers searched Medline, Embase, CINAHL and the Cochrane registry up to May 2014. Overall weighted proportions were estimated using a random effects model. Measurement properties of bleeding assessment tools were evaluated. We identified 118 studies that reported bleeding (n = 10 908 patients). Weighted proportions for intracerebral hemorrhage (ICH) were 1.4% for adults (95% confidence interval [CI], 0.9-2.1%) and 0.4% for children (95% CI, 0.2-0.7%; P < 0.01), most of whom had chronic ITP. The weighted proportion for severe (non-ICH) bleeding was 9.6% for adults (95% CI, 4.1-17.1%) and 20.2% for children (95% CI, 10.0-32.9%; P < 0.01) with newly-diagnosed or chronic ITP. Methods of reporting and definitions of severe bleeding were highly variable in primary studies. Two bleeding assessment tools (Buchanan 2002 for children; Page 2007 for adults) demonstrated adequate inter-rater reliability and validity in independent assessments. ICH was more common in adults and tended to occur during chronic ITP; other severe bleeds were more common in children and occurred at all stages of disease. Reporting of non-ICH bleeding was variable across studies. Further attention to ITP-specific bleeding measurement in clinical trials is needed to improve standardization of this important outcome for patients. © 2014 International Society on Thrombosis and Haemostasis.

Influence of Bleeding Pattern on Ischemic Lesions After Spontaneous Hypertensive Intracerebral Hemorrhage with Intraventricular Hemorrhage.

PubMed

Rivera-Lara, Lucia; Murthy, Santosh B; Nekoovaght-Tak, Saman; Ali, Hasan; McBee, Nichol; Dlugash, Rachel; Ram, Malathi; Thompson, Richard; Awad, Issam A; Hanley, Daniel F; Ziai, Wendy C

2018-03-27

Concomitant acute ischemic lesions are detected in up to a quarter of patients with spontaneous intracerebral hemorrhage (ICH). Influence of bleeding pattern and intraventricular hemorrhage (IVH) on risk of ischemic lesions has not been investigated. Retrospective study of all 500 patients enrolled in the CLEAR III randomized controlled trial of thrombolytic removal of obstructive IVH using external ventricular drainage. The primary outcome measure was radiologically confirmed ischemic lesions, as reported by the Safety Event Committee and confirmed by two neurologists. We assessed predictors of ischemic lesions including analysis of bleeding patterns (ICH, IVH and subarachnoid hemorrhage) on computed tomography scans (CT). Secondary outcomes were blinded assessment of mortality and modified Rankin scale (mRS) at 30 and 180 days. Ischemic lesions occurred in 23 (4.6%) during first 30 days after ICH. Independent risk factors associated with ischemic lesions in logistic regression models adjusted for confounders were higher IVH volume (p = 0.004) and persistent subarachnoid hemorrhage on CT scan (p = 0.03). Patients with initial IVH volume ≥ 15 ml had five times the odds of concomitant ischemic lesions compared to IVH volume < 15 ml. Patients with ischemic lesions had significantly higher odds of death at 1 and 6 months (but not poor outcome; mRS 4-6) compared to patients without concurrent ischemic lesions. Occurrence of ischemic lesions in the acute phase of IVH is not uncommon and is significantly associated with increased early and late mortality. Extra-parenchymal blood (larger IVH and visible subarachnoid hemorrhage) is a strong predictor for development of concomitant ischemic lesions after ICH.

Multimodality Monitoring for Cerebral Perfusion Pressure Optimization in Comatose Patients with Intracerebral Hemorrhage

PubMed Central

Ko, Sang-Bae; Choi, H. Alex; Parikh, Gunjan; Helbok, Raimund; Schmidt, J. Michael; Lee, Kiwon; Badjatia, Neeraj; Claassen, Jan; Connolly, E. Sander; Mayer, Stephan A.

2011-01-01

Background and Purpose Limited data exists to recommend specific cerebral perfusion pressure (CPP) targets in patients with intracerebral hemorrhage (ICH). We sought to determine the feasibility of brain multimodality monitoring (MMM) for optimizing CPP and potentially reducing secondary brain injury after ICH. Methods We retrospectively analyzed brain MMM data targeted at perihematomal brain tissue in 18 comatose ICH patients (median monitoring: 164 hours). Physiological measures were averaged over one-hour intervals corresponding to each microdialysis sample. Metabolic crisis (MC) was defined as a lactate/pyruvate ratio (LPR) >40 with a brain glucose concentration <0.7 mmol/L. Brain tissue hypoxia (BTH) was defined as PbtO2 <15 mm Hg. Pressure reactivity index (PRx) and oxygen reactivity index (ORx) were calculated. Results Median age was 59 years, median GCS score 6, and median ICH volume was 37.5 ml. The risk of BTH, and to a lesser extent MC, increased with lower CPP values. Multivariable analyses showed that CPP <80 mm Hg was associated with a greater risk of BTH (OR 1.5, 95% CI 1.1–2.1, P=0.01) compared to CPP >100 mm Hg as a reference range. Six patients died (33%). Survivors had significantly higher CPP and PbtO2 and lower ICP values starting on post-bleed day 4, whereas LPR and PRx values were lower, indicating preservation of aerobic metabolism and pressure autoregulation. Conclusions PbtO2 monitoring can be used to identify CPP targets for optimal brain tissue oxygenation. In patients who do not undergo MMM, maintaining CPP >80 mm Hg may reduce the risk of BTH. PMID:21852615

Added value of delayed computed tomography angiography in primary intracranial hemorrhage and hematoma size for predicting spot sign.

PubMed

Wu, Te Chang; Chen, Tai Yuan; Shiue, Yow Ling; Chen, Jeon Hor; Hsieh, Tsyh-Jyi; Ko, Ching Chung; Lin, Ching Po

2018-04-01

Background The computed tomography angiography (CTA) spot sign represents active contrast extravasation within acute primary intracerebral hemorrhage (ICH) and is an independent predictor of hematoma expansion (HE) and poor clinical outcomes. The spot sign could be detected on first-pass CTA (fpCTA) or delayed CTA (dCTA). Purpose To investigate the additional benefits of dCTA spot sign in primary ICH and hematoma size for predicting spot sign. Material and Methods This is a retrospective study of 100 patients who underwent non-contrast CT (NCCT) and CTA within 24 h of onset of primary ICH. The presence of spot sign on fpCTA or dCTA, and hematoma size on NCCT were recorded. The spot sign on fpCTA or dCTA for predicting significant HE, in-hospital mortality, and poor clinical outcomes (mRS ≥ 4) are calculated. The hematoma size for prediction of CTA spot sign was also analyzed. Results Only the spot sign on dCTA could predict high risk of significant HE and poor clinical outcomes as on fpCTA ( P < 0.05). With dCTA, there is increased sensitivity and negative predictive value (NPV) for predicting significant HE, in-hospital mortality, and poor clinical outcomes. The XY value (product of the two maximum perpendicular axial dimensions) is the best predictor (area under the curve [AUC] = 0.82) for predicting spot sign on fpCTA or dCTA in the absence of intraventricular and subarachnoid hemorrhage. Conclusion This study clarifies that dCTA imaging could improve predictive performance of CTA in primary ICH. Furthermore, the XY value is the best predictor for CTA spot sign.

CT Angiography Spot Sign, Hematoma Expansion, and Outcome in Primary Pontine Intracerebral Hemorrhage.

PubMed

Morotti, Andrea; Jessel, Michael J; Brouwers, H Bart; Falcone, Guido J; Schwab, Kristin; Ayres, Alison M; Vashkevich, Anastasia; Anderson, Christopher D; Viswanathan, Anand; Greenberg, Steven M; Gurol, M Edip; Romero, Javier M; Rosand, Jonathan; Goldstein, Joshua N

2016-08-01

The computed tomography angiography (CTA) spot sign is a validated predictor of hematoma expansion and poor outcome in supratentorial intracerebral hemorrhage (ICH), but patients with brainstem ICH have typically been excluded from the analyses. We investigated the frequency of spot sign and its relationship with hematoma expansion and outcome in patients with primary pontine hemorrhage (PPH). We performed a retrospective analysis of PPH cases obtained from a prospectively collected cohort of consecutive ICH patients who underwent CTA. CTA first-pass readings for spot sign presence were analyzed by two trained readers. Baseline and follow-up hematoma volumes on non-contrast CT scans were assessed by semi-automated computer-assisted volumetric analysis. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive and negative likelihood ratio, and accuracy of spot sign for prediction of in-hospital mortality were calculated. 49 subjects met the inclusion criteria of whom 11 (22.4 %) showed a spot sign. In-hospital mortality was higher in spot sign-positive versus spot sign-negative subjects (90.9 vs 47.4 %, p = 0.020). Spot sign showed excellent specificity (95 %) and PPV (91 %) in predicting in-hospital mortality. Absolute hematoma growth, defined as parenchymal and intraventricular hematoma expansion of any amount, was significantly higher in spot sign-positive versus spot sign-negative subjects (13.72 ± 20.93 vs 3.76 ± 8.55 mL, p = 0.045). As with supratentorial ICH, the CTA spot sign is a common finding and is associated with higher risk of hematoma expansion and mortality in PPH. This marker may assist clinicians in prognostic stratification.

Comparison of Swirl Sign and Black Hole Sign in Predicting Early Hematoma Growth in Patients with Spontaneous Intracerebral Hemorrhage.

PubMed

Xiong, Xin; Li, Qi; Yang, Wen-Song; Wei, Xiao; Hu, Xi; Wang, Xing-Chen; Zhu, Dan; Li, Rui; Cao, Du; Xie, Peng

2018-01-29

BACKGROUND Early hematoma growth is associated with poor outcome in patients with spontaneous intracerebral hemorrhage (ICH). The swirl sign (SS) and the black hole sign (BHS) are imaging markers in ICH patients. The aim of this study was to compare the predictive value of these 2 signs for early hematoma growth. MATERIAL AND METHODS ICH patients were screened for the appearance of the 2 signs within 6 h after onset of symptoms. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the 2 signs in predicting early hematoma growth were assessed. The accuracy of the 2 signs in predicting early hematoma growth was analyzed by receiver-operator analysis. RESULTS A total of 200 patients were enrolled in this study. BHS was found in 30 (15%) patients, and SS was found in 70 (35%) patients. Of the 71 patients with early hematoma growth, BHS was found on initial computed tomography scans in 24 (33.8%) and SS in 33 (46.5%). The sensitivity, specificity, PPV, and NPV of BHS for predicting early hematoma growth were 33.8%, 95.3%, 80.0%, and 72.0%, respectively. The sensitivity, specificity, PPV, and NPV of SS were 46.5%, 71.3%, 47.0%, and 71.0%, respectively. The area under the curve was 0.646 for BHS and 0.589 for SS (P=0.08). Multivariate logistic regression showed that presence of BHS is an independent predictor of early hematoma growth. CONCLUSIONS The Black hole sign seems to be good predictor for hematoma growth. The presence of swirl sign on admission CT does not independently predict hematoma growth in patients with ICH.

Technology that achieves the Triple Aim: an economic analysis of the BrainPath™ approach in neurosurgery

PubMed Central

Norton, Sidney P; Dickerson, Evan M; Kulwin, Charles G; Shah, Mitesh V

2017-01-01

Background The Triple Aim is defined as: improving the patient experience of care, improving the health of populations, and reducing the per capita cost of health care. The purpose of this analysis was to evaluate the economic value of a new neurosurgical technique, the BrainPath™ approach, for use in patients with subcortical tumors and intracerebral hemorrhage (ICH). Methods Inpatient length of stay (LOS) data were collected for ICH and brain tumor surgical patient cases between August 2013 and November 2015. Patient cases were separated into two groups; BrainPath approach (n = 28) and conventional techniques, such as craniotomy, (n = 208). The average intensive care unit (ICU) LOS was calculated for each group by diagnosis-related group and compared between groups. Results The new surgical technology resulted in surgical intervention in 14 ICH cases which otherwise would have been medically managed due to the hemorrhage location or size of the ICH. A reduction in ICU LOS was seen in this group. Based on the variable direct cost per day in the neuro critical care unit at this academic medical center, 14 patient cases incurred ~ US$210,000 less in direct ICU costs. Surgical resection was possible in two tumor patient cases which would have been biopsied, rather than surgically resected, also due to location of the abnormalities. A total net value of > US$329,000 is attributable to the analyzed approach over a 28-month period. Conclusion This analysis shows positive economic value for the new technology group when ICU LOS and reimbursement are considered against equipment costs, thus achieving Triple Aim objectives. PMID:28894384

Incidence of Hospitalized Stroke in the Czech Republic: The National Registry of Hospitalized Patients.

PubMed

Sedova, Petra; Brown, Robert D; Zvolsky, Miroslav; Kadlecova, Pavla; Bryndziar, Tomas; Kubelka, Tomáš; Weiss, Viktor; Volný, Ondřej; Bednarik, Josef; Mikulik, Robert

2017-05-01

Contemporary stroke incidence data are not available in some countries and regions, including in Eastern Europe. Based on previous validation of the accuracy of the National Registry of Hospitalized Patients (NRHOSP), we report the incidence of hospitalized stroke in the Czech Republic (CR) using the NRHOSP. The results of the prior validation study assessing the accuracy of coding of stroke diagnoses in the NRHOSP were applied, and we calculated (1) the overall incidence of hospitalized stroke and (2) the incidence rates of hospitalized stroke for the three main stroke types: cerebral infarction (International Classification of Diseases Tenth Revision, CI I63), subarachnoid hemorrhage (SAH I60), and intracerebral hemorrhage (ICH I61). We calculated the average annual age- and sex-standardized incidence. The overall incidence of hospitalized stroke was 241 out of 100,000 individuals. The incidence of hospitalized stroke for the main stroke types was 8.2 cases in SAH, 29.5 in ICH, and 211 in CI per 100,000 individuals. The standardized annual stroke incidence adjusted to the 2000 World Health Organization population for overall stroke incidence of hospitalized stroke was 131 per 100,000 individuals. Standardized stroke incidence for stroke subtypes was 5.7 cases in SAH, 16.7 in ICH, and 113 in CI per 100,000 individuals. These studies provide an initial assessment of the burden of stroke in this part of the world. The estimates of hospitalized stroke in the CR and Eastern Europe suggest that ICH is about three times more common than SAH, and hemorrhagic stroke makes up about 18% of strokes. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Orienting-defense responses and psychophysiological reactivity in isolated clinic versus sustained hypertension.

PubMed

García-Vera, María Paz; Sanz, Jesús; Labrador, Francisco J

2007-04-01

This study sought to determine whether patients with white-coat or isolated clinic hypertension (ICH) show, in comparison to patients with sustained hypertension (SH), a defense response pattern to novel stimuli and an enhanced psychophysiological reactivity to stress. Forty-three patients with essential hypertension were divided into two groups after 16 days of self-monitoring blood pressure (BP): ICH (24 men; self-measured BP < 135/85 mmHg) and SH (19 men; self-measured BP >or= 135/85 mmHg). Defense responses were measured as the cardiac changes to phasic non-aversive auditory stimuli. Psychophysiological reactivity (heart and breath rate, blood volume pulse, electromyography, and skin conductance) was measured during mental arithmetic and video game tasks. The standard deviation of self-measured BPs and the difference between mean BPs at work and at home were used as indicators of cardiovascular reactivity to daily stress. No significant differences were seen in defense responses or psychophysiological reactivity to laboratory or naturally occurring stressors. These results do not support the hypothesis that ICH can be explained in terms of a generalized hyperreactivity to novel or stressful stimuli.

The Timing of Utterance Planning in Task-Oriented Dialogue: Evidence from a Novel List-Completion Paradigm

PubMed Central

Barthel, Mathias; Sauppe, Sebastian; Levinson, Stephen C.; Meyer, Antje S.

2016-01-01

In conversation, interlocutors rarely leave long gaps between turns, suggesting that next speakers begin to plan their turns while listening to the previous speaker. The present experiment used analyses of speech onset latencies and eye-movements in a task-oriented dialogue paradigm to investigate when speakers start planning their responses. German speakers heard a confederate describe sets of objects in utterances that either ended in a noun [e.g., Ich habe eine Tür und ein Fahrrad (“I have a door and a bicycle”)] or a verb form [e.g., Ich habe eine Tür und ein Fahrrad besorgt (“I have gotten a door and a bicycle”)], while the presence or absence of the final verb either was or was not predictable from the preceding sentence structure. In response, participants had to name any unnamed objects they could see in their own displays with utterances such as Ich habe ein Ei (“I have an egg”). The results show that speakers begin to plan their turns as soon as sufficient information is available to do so, irrespective of further incoming words. PMID:27990127

Cerebral amyloid angiopathy: diagnosis and potential therapies.

PubMed

Weber, Stewart A; Patel, Ranish K; Lutsep, Helmi L

2018-06-01

Cerebral amyloid angiopathy (CAA) is characterized by the pathologic deposition of amyloid-beta within cortical and leptomeningeal arteries, arterioles, capillaries and, in rare cases, the venules of the brain. It is often associated with the development of lobar intracerebral hemorrhages (ICHs) but may cause other neurologic symptoms or be asymptomatic. Magnetic resonance imaging characteristics, such as lobar microbleeds, support a diagnosis of CAA and assist with hemorrhage risk assessments. Immunosuppressants are used to treat rarer inflammatory forms of CAA. For the more common forms of CAA, the use of antihypertensive medications can prevent ICH recurrence while the use of antithrombotics may increase hemorrhage risk. Anti-amyloid approaches to treatment have not yet been investigated in phase 3 trials. Areas covered: A literature search was conducted using MEDLINE on the topics of imaging, biomarkers, ICH prevention and treatment trials in CAA, focusing on its current diagnosis and management and opportunities for future therapeutic approaches. Expert commentary: There is likely a significant unrecognized burden of CAA in the elderly population. Continued research efforts to discover biomarkers that allow the early diagnosis of CAA will enhance the opportunity to develop treatment interventions.

Trends in der IT-Sicherheit

NASA Astrophysics Data System (ADS)

Eckert, Claudia

Ich möchte Ihnen einen Überblick geben über Trends, Challenges, offene Fragestellungen sowie Lösungsansätze aus dem Bereich der IT-Sicherheit. Meine Vorredner haben mir schon eine wunderbare Basis dafür geschaffen, indem sie wichtige Trends im Bereich IT bereits angesprochen haben. Deshalb werde ich auf diese Trends, nämlich das Internet of Things and Services nur noch einmal kurz eingehen, um daran dann die IT-Sicherheitsthemen, die sich aus diesen IT-Trends ergeben, zu skizzieren und anschließend Lösungen vorstellen, die insbesondere im Forschungsumfeld entwickelt werden, aber schon reif sind, auch in die unternehmerische Praxis übernommen zu werden.

An update on surgical and medical management strategies for intracerebral hemorrhage.

PubMed

Kreitzer, Natalie; Adeoye, Opeolu

2013-11-01

Intracerebral hemorrhage (ICH) accounts for ∼ 10 to 15% of all strokes and is one of the major causes of stroke-related death and disability. After the initial hemorrhage, further bleeding and edema contribute to secondary damage and worsened outcomes. As such, goals of previous and ongoing trials are to prevent continued bleeding, as well as mitigate the impact of cerebral edema. Although no trials have shown a definite functional outcome benefit with a given intervention, much progress has been made recently. This review focuses on recent developments that inform the acute management of ICH. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Evaluation of a Low-risk Mild Traumatic Brain Injury and Intracranial Hemorrhage Emergency Department Observation Protocol.

PubMed

Yun, Brian J; Borczuk, Pierre; Wang, Lulu; Dorner, Stephen; White, Benjamin A; Raja, Ali S

2017-11-20

Among emergency physicians, there is wide variation in admitting practices for patients who suffered a mild traumatic brain injury (TBI) with an intracranial hemorrhage (ICH). The purpose of this study was to evaluate the effects of implementing a protocol in the emergency department (ED) observation unit for patients with mild TBI and ICH. This retrospective cohort study was approved by the institutional review board. Study subjects were patients ≥ 18 years of age with an International Classification of Diseases code corresponding to a traumatic ICH and admitted to an ED observation unit (EDOU) of an urban, academic Level I trauma center between February 1, 2015, and January 31, 2017. Patient data and discharge disposition were abstracted from the electronic health record, and imaging data, from the final neuroradiologist report. To measure kappa, two abstractors independently collected data for presence of neuro deficit from a 10% random sample of the medical charts. Using a multivariable logistic regression model with a propensity score of the probability of placement in the EDOU before and after protocol implementation as a covariate, we sought to determine the pre-post effects of implementing a protocol on the composite outcome of admission to the floor, intensive care unit, or operating room from the EDOU and the proportion of patients with worsening findings on repeat computed tomography (CT) head scan in the EDOU. A total of 379 patients were identified during the study period; 83 were excluded as they were found to have no ICH on chart review. Inter-rater reliability kappa statistic was 0.63 for 30 charts. Among the 296 patients who remained eligible and comprised the study population, 143 were in the preprotocol period and 153 after protocol implementation. The EDOU protocol was associated with an independently statistically significant decreased odds ratio (OR) for admission or worsening ICH on repeat CT scan (OR = 0.45, 95% confidence interval [CI

Identification of novel biomarker and therapeutic target candidates for acute intracerebral hemorrhage by quantitative plasma proteomics.

PubMed

Li, Guo-Chun; Zhang, Lina; Yu, Ming; Jia, Haiyu; Tian, Ting; Wang, Junqin; Wang, Fuqiang; Zhou, Ling

2017-01-01

The systematic mechanisms of acute intracerebral hemorrhage are still unknown and unverified, although many recent researches have indicated the secondary insults. This study was aimed to disclose the pathological mechanism and identify novel biomarker and therapeutic target candidates by plasma proteome. Patients with AICH (n = 8) who demographically matched healthy controls (n = 4) were prospectively enrolled, and their plasma samples were obtained. The TMT-LC-MS/MS-based proteomics approach was used to quantify the differential proteome across plasma samples, and the results were analyzed by Ingenuity Pathway Analysis to explore canonical pathways and the relationship involved in the uploaded data. Compared with healthy controls, there were 31 differentially expressed proteins in the ICH group ( P  < 0.05), of which 21 proteins increased while 10 proteins decreased in abundance. These proteins are involved in 21 canonical pathways. One network with high confidence level was selected by the function network analysis, in which 23 proteins, P38MAPK and NFκB signaling pathways participated. Upstream regulator analysis found two regulators, IL6 and TNF, with an activation z -score. Seven biomarker candidates: APCS, FGB, LBP, MGMT, IGFBP2, LYZ, and APOA4 were found. Six candidate proteins were selected to assess the validity of the results by subsequent Western blotting analysis. Our analysis provided several intriguing pathways involved in ICH, like LXR/RXR activation, acute phase response signaling, and production of NO and ROS in macrophages pathways. The three upstream regulators: IL-6, TNF, LPS, and seven biomarker candidates: APCS, APOA4, FGB, IGFBP2, LBP, LYZ, and MGMT were uncovered. LPS, APOA4, IGFBP2, LBP, LYZ, and MGMT are novel potential biomarkers in ICH development. The identified proteins and pathways provide new perspectives to the potential pathological mechanism and therapeutic targets underlying ICH.

Medication History versus Point-of-Care Platelet Activity Testing in Patients with Intracerebral Hemorrhage.

PubMed

Maas, Matthew B; Naidech, Andrew M; Kim, Minjee; Batra, Ayush; Manno, Edward M; Sorond, Farzaneh A; Prabhakaran, Shyam; Liotta, Eric M

2018-05-01

We evaluated whether reduced platelet activity detected by point-of-care (POC) testing is a better predictor of hematoma expansion and poor functional outcomes in patients with intracerebral hemorrhage (ICH) than a history of antiplatelet medication exposure. Patients presenting with spontaneous ICH were enrolled in a prospective observational cohort study that collected demographic, clinical, laboratory, and radiographic data. We measured platelet activity using the PFA-100 (Siemens AG, Germany) and VerifyNow-ASA (Accumetrics, CA) systems on admission. We performed univariate and adjusted multivariate analyses to assess the strength of association between those measures and (1) hematoma growth at 24 hours and (2) functional outcomes measured by the modified Rankin Scale (mRS) at 3 months. We identified 278 patients for analysis (mean age 65 ± 15, median ICH score 1 [interquartile range 0-2]), among whom 164 underwent initial neuroimaging within 6 hours of symptom onset. Univariate association with hematoma growth was stronger for antiplatelet medication history than POC measures, which was confirmed in multivariable models (β 3.64 [95% confidence interval [CI] 1.02-6.26], P = .007), with a larger effect size measured in the under 6-hour subgroup (β 7.20 [95% CI 3.35-11.1], P < .001). Moreover, antiplatelet medication history, but not POC measures of platelet activity, was independently associated with poor outcome at 3 months (mRS 4-6) in the under 6-hour subgroup (adjusted OR 3.6 [95% CI 1.2-11], P = .023). A history of antiplatelet medication use better identifies patients at risk for hematoma growth and poor functional outcomes than POC measures of platelet activity after spontaneous ICH. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Hospitalizations in pediatric patients with immune thrombocytopenia in the United States

PubMed Central

Tarantino, Michael D.; Danese, Mark; Klaassen, Robert J.; Duryea, Jennifer; Eisen, Melissa; Bussel, James

2016-01-01

Abstract To examine utilization and outcomes in pediatric immune thrombocytopenia (ITP) hospitalizations, we used ICD-9 code 287.31 to identify hospitalizations in patients with ITP in the 2009 HCUP KID, an all-payer sample of pediatric hospitalizations from US community hospitals. Diagnosis and procedure codes were used to estimate rates of ITP-related procedures, comorbidity prevalence, costs, length of stay (LOS), and mortality. In 2009, there were an estimated 4499 hospitalizations in children aged 6 months–17 years with ITP; 43% in children aged 1–5 years; and 47% with emergency department encounters. The mean hospitalization cost was $5398, mean LOS 2.0 days, with 0.3% mortality (n = 13). With any bleeding (15.2%, including gastrointestinal 2.0%, hematuria 1.3%, intracranial hemorrhage [ICH] 0.6%), mean hospitalization cost was $7215, LOS 2.5 days, with 1.5% mortality. For ICH (0.6%, n = 27), mean cost was $40 209, LOS 8.5 days, with 21% mortality. With infections (14%, including upper respiratory 5.2%, viral 4.9%, bacterial 1.9%), the mean cost was $6928, LOS 2.9 days, with 0.9% mortality. Septic shock was reported in 0.3% of discharges. Utilization included immunoglobulin administration (37%) and splenectomies (2.3%). Factors associated with higher costs included age >6 years, ICH, hematuria, transfusion, splenectomy, and bone marrow diagnostics (p < 0.05). In conclusion, of the 4499 hospitalizations with ITP, mortality rates of 1.5%, 21%, and 0.9% were seen with any bleeding, ICH, and infection, respectively. Higher costs were associated with clinically significant bleeding and procedures. Future analyses may reveal effects of the implementation of more recent ITP guidelines and use of additional treatments. PMID:26941022

Comparison of Spot Sign, Blend Sign and Black Hole Sign for Outcome Prediction in Patients with Intracerebral Hemorrhage.

PubMed

Sporns, Peter B; Schwake, Michael; Kemmling, André; Minnerup, Jens; Schwindt, Wolfram; Niederstadt, Thomas; Schmidt, Rene; Hanning, Uta

2017-09-01

Blend sign (BS) and black hole sign (BHS) on non-contrast computed tomography (NCCT) and spot sign (SS) on CT-angiography (CTA) are indicators of early hematoma expansion in spontaneous intracerebral hemorrhage (ICH). However, their independent contributions to outcome have not been well explored. In this retrospective study, inclusion criteria were: 1) spontaneous ICH and 2) NCCT and CTA performed on admission within 6 hours after onset of symptoms. Discharge outcome was dichotomized as good (modified Rankin Scale [mRS] 0-3) and poor (mRS 4-6) outcomes. The impacts of BHS, BS and SS on outcome were assessed in univariate and multivariable logistic regression models. Of 182 patients with spontaneous ICH, 26 (14.3%) presented with BHS, 37 (20.3%) with BS and 39 (21.4%) with SS. There was a substantial correlation between SS and BS (κ=0.701) and a moderate correlation between SS and BHS (κ=0.424). In univariable logistic regression, higher baseline hematoma volume ( P <0.001), intraventricular hemorrhage ( P =0.002) and the presence of BHS/BS/SS (all P <0.001) on admission CT scan were associated with poor outcome. Multivariable analysis identified intraventricular haemorrhage (odds ratio [OR] 2.22 per mL, P =0.022), baseline hematoma volume (OR 1.03 per mL, P <0.001) and SS on CTA (OR 11.43, P <0.001) as independent predictors of poor outcome, showing that SS compared to BS and BHS was more powerful to predict poor outcome. The NCCT BHS and BS are correlated with the CTA SS and are reliable predictors of poor outcome in patients with ICH. Of the CT variables indicating early hematoma expansion, SS on CTA was the most reliable outcome predictor. However, given their correlation with SS on CTA, BS and BHS on NCCT can be useful for predicting outcome if CTA is not obtainable.

Genetic Variations of COL4A1 Gene and Intracerebral Hemorrhage Outcome: A Cohort Study in a Chinese Han Population.

PubMed

Xia, Chao; Lin, Sen; Yang, Jie; He, Sha; Li, Hao; Liu, Ming; You, Chao

2018-05-01

To investigate the relationship between single nucleotide polymorphisms or haplotypes of COL4A1 gene and the outcome of intracerebral hemorrhage (ICH). In our study, 181 patients with hypertensive ICH were enrolled and followed up at 3 and 6 months. Outcome data included any cause of death and disability. Genomic DNA was extracted by DNA extraction kit, and the 6 single nucleotide polymorphism genotyping of the COL4A1 gene was detected through MassARRAY Analyzer. Unphased 3.1.4 and SPSS 19.0 were used to analyze the association between alleles, genotypes, and haplotypes of the COL4A1 gene and the outcomes of ICH. Of the 181 patients with hypertensive ICH, 12 were lost in follow-up, which accounted for 6.6%. Our association analysis showed that the rs532625 AA genotype of the COL4A1 gene may increase risk of disability at 3 months; the rs532625 A allele and AA genotype were association factors of the risk of disability at 6 months; the rs532625 AA genotype was an association factor of the risk of death/disability at 6 months. After adjusting for gender, age, coma, and severe neurologic deficits, only the rs532625 AA genotype was independently associated with the risk of disability at 3 and 6 months and the risk of death/disability at 6 months. Our study found that the rs532625 AA genotype in the COL4A1 gene was independently associated with the risk of disability at 3 and 6 months and death/disability at 6 months in a Chinese Han population. These conclusions need to be verified in future studies with larger samples. Copyright © 2018 Elsevier Inc. All rights reserved.

Ultraearly hematoma growth in active intracerebral hemorrhage

PubMed Central

Coscojuela, Pilar; Rubiera, Marta; Hill, Michael D.; Dowlatshahi, Dar; Aviv, Richard I.; Silva, Yolanda; Dzialowski, Imanuel; Lum, Cheemun; Czlonkowska, Anna; Boulanger, Jean-Martin; Kase, Carlos S.; Gubitz, Gord; Bhatia, Rohit; Padma, Vasantha; Roy, Jayanta; Tomasello, Alejandro; Demchuk, Andrew M.; Molina, Carlos A.

2016-01-01

Objective: To determine the association of ultraearly hematoma growth (uHG) with the CT angiography (CTA) spot sign, hematoma expansion, and clinical outcomes in patients with acute intracerebral hemorrhage (ICH). Methods: We analyzed data from 231 patients enrolled in the multicenter Predicting Haematoma Growth and Outcome in Intracerebral Haemorrhage Using Contrast Bolus CT study. uHG was defined as baseline ICH volume/onset-to-CT time (mL/h). The spot sign was used as marker of active hemorrhage. Outcome parameters included significant hematoma expansion (>33% or >6 mL, primary outcome), rate of hematoma expansion, early neurologic deterioration, 90-day mortality, and poor outcome. Results: uHG was higher in spot sign patients (p < 0.001) and in patients scanned earlier (p < 0.001). Both uHG >4.7 mL/h (p = 0.002) and the CTA spot sign (p = 0.030) showed effects on rate of hematoma expansion but not its interaction (2-way analysis of variance, p = 0.477). uHG >4.7 mL/h improved the sensitivity of the spot sign in the prediction of significant hematoma expansion (73.9% vs 46.4%), early neurologic deterioration (67.6% vs 35.3%), 90-day mortality (81.6% vs 44.9%), and poor outcome (72.8% vs 29.8%), respectively. uHG was independently related to significant hematoma expansion (odds ratio 1.06, 95% confidence interval 1.03–1.10) and clinical outcomes. Conclusions: uHG is a useful predictor of hematoma expansion and poor clinical outcomes in patients with acute ICH. The combination of high uHG and the spot sign is associated with a higher rate of hematoma expansion, highlighting the need for very fast treatment in ICH patients. PMID:27343067

The clinical effect of deferoxamine mesylate on edema after intracerebral hemorrhage.

PubMed

Yu, Yao; Zhao, Wei; Zhu, Chunpeng; Kong, Zhiping; Xu, Yan; Liu, Guangzhi; Gao, Xuguang

2015-01-01

It has been shown that 3 days of 62 mg/kg/day deferoxamine infusion (maximum dose not to exceed 6000 mg/day) is safe and tolerated by intracerebral hemorrhage (ICH) patients. The aim of this study was to investigate the efficacy of deferoxamine mesylate for edema resolution and hematoma absorption after ICH. From February 2013 to May 2014, spontaneous ICH patients diagnosed by computed tomography (CT) within 18 hours of onset were evaluated. Patients were randomly divided into two groups: an experimental group and a control group. The treatment of the two groups was similar except that the experimental group received deferoxamine mesylate. Patients were evaluated by CT and neurology scale at the time of admission, and on the fourth, eighth, and fifteenth day (or at discharge) after admission. Patients were followed up for the first 30 days and clinical data of the two groups were compared. Forty-two patients completed 30 days of follow-up by May 2014; 21 cases in the experimental group and 21 cases in the control group. The control group's relative edema volume on the fifteenth day (or discharge) was 10.26 ± 17.54, which was higher than the experimental group (1.91 ± 1.94; P < 0.05). The control group's 1-8 day and 8-15 day relative hematoma absorption were greater than the experimental group (P < 0.05).The control group's relative edema volume on the fourth, eighth, and fifteenth day (or discharge) was higher than the experimental group (P < 0.05). Neurological scores between the two groups were not statistically different on the fifteenth day (or discharge) or on the thirtieth day. Deferoxamine mesylate may slow hematoma absorption and inhibit edema after ICH, although further investigation is required to form definitive conclusions. Chinese Clinical Trial Registry ChiCTR-TRC-14004979.

Severe bleeding events in adults and children with primary immune thrombocytopenia: a systematic review

PubMed Central

NEUNERT, C.; NOROOZI, N.; NORMAN, G.; BUCHANAN, G. R.; GOY, J.; NAZI, I.; KELTON, J. G.; ARNOLD, D. M.

2016-01-01

Summary Background The burden of severe bleeding in adults and children with immune thrombocytopenia (ITP) has not been established. Objectives To describe the frequency and severity of bleeding events in patients with ITP, and the methods used to measure bleeding in ITP studies. Patients/Methods We performed a systematic review of all prospective ITP studies that enrolled 20 or more patients. Two reviewers searched Medline, Embase, CINAHL and the Cochrane registry up to May 2014. Overall weighted proportions were estimated using a random effects model. Measurement properties of bleeding assessment tools were evaluated. Results We identified 118 studies that reported bleeding (n = 10 908 patients). Weighted proportions for intracerebral hemorrhage (ICH) were 1.4% for adults (95% confidence interval [CI], 0.9–2.1%) and 0.4% for children (95% CI, 0.2–0.7%; P < 0.01), most of whom had chronic ITP. The weighted proportion for severe (non-ICH) bleeding was 9.6% for adults (95% CI, 4.1–17.1%) and 20.2% for children (95% CI, 10.0–32.9%; P < 0.01) with newly-diagnosed or chronic ITP. Methods of reporting and definitions of severe bleeding were highly variable in primary studies. Two bleeding assessment tools (Buchanan 2002 for children; Page 2007 for adults) demonstrated adequate interrater reliability and validity in independent assessments. Conclusions ICH was more common in adults and tended to occur during chronic ITP; other severe bleeds were more common in children and occurred at all stages of disease. Reporting of non-ICH bleeding was variable across studies. Further attention to ITP-specific bleeding measurement in clinical trials is needed to improve standardization of this important outcome for patients. PMID:25495497

Localized hypothermia aggravates bleeding in the collagenase model of intracerebral hemorrhage.

PubMed

John, Roseleen F; Williamson, Michael R; Dietrich, Kristen; Colbourne, Frederick

2015-03-01

Animal studies testing whether therapeutic hypothermia is neuroprotective after intracerebral hemorrhage (ICH) have been inconclusive. In rodents, ICH is often produced in the striatum by infusing collagenase, which causes prolonged hemorrhaging from multiple vessels. Our previous data shows that this bleeding (hematoma) is worsened by systemic hypothermia given soon after collagenase infusion. In this study we hypothesized that localized brain hypothermia would also aggravate bleeding in this model (0.2 U of collagenase in 1.2 μL of saline). We also evaluated cooling after intrastriatal thrombin infusion (1 U in 30 μL of saline)-a simplified model of ICH thought to cause bleeding. Focal hypothermia was achieved by flushing cold water through an implanted cooling device attached to the skull underneath the temporalis muscle of adult rats. Previous work and data at this time shows this method cools the striatum to ∼33°C, whereas the body remains normothermic. In comparison to normothermic groups, cooling significantly worsened bleeding when instituted at 6 hours (∼94 vs. 42 μL, p=0.018) and 12 hours (79 vs. 61 μL, p=0.042) post-ICH (24-hour survival), but not after a 24-hour delay (36-hour survival). Rats were cooled until euthanasia when hematoma size was determined by a hemoglobin-based spectrophotometry assay. Cooling did not influence cerebral blood volume after just saline or thrombin infusion. The latter is explained by the fact that thrombin did not cause bleeding beyond that caused by saline infusion. In summary, local hypothermia significantly aggravates bleeding many hours after collagenase infusion suggesting that bleeding may have confounded earlier studies with hypothermia. Furthermore, these findings serve as a cautionary note on using cooling even many hours after cerebral bleeding.

Efficacy and Safety of REVIVE SE Thrombectomy Device for Acute Ischemic Stroke: River JAPAN (Reperfuse Ischemic Vessels with Endovascular Recanalization Device in Japan).

PubMed

Sakai, Nobuyuki; Ota, Shinzo; Matsumoto, Yasushi; Kondo, Rei; Satow, Tetsu; Kubo, Michiya; Tsumoto, Tomoyuki; Enomoto, Yukiko; Kataoka, Taketo; Imamura, Hirotoshi; Todo, Kenichi; Hayakawa, Mikito; Yamagami, Hiroshi; Toyoda, Kazunori; Ito, Yasushi; Sugiu, Kenji; Matsumaru, Yuji; Yoshimura, Shinichi

2018-04-15

REVIVE SE (REVIVE) is a closed-ended, self-expanding stent retriever used in the RIVER JAPAN study. We present our early experience with REVIVE for revascularization of acute ischemic stroke (AIS) in patients who have failed or are ineligible for intravenous recombinant tissue plasminogen activator treatment. This prospective, single-arm, non-randomized, multicenter registry study followed up patients undergoing mechanical thrombectomy with REVIVE for 90 days. The primary endpoint was a post-procedure Thrombolysis in Cerebral Infarction (TICI) score ≥2a. Secondary endpoints were clot migration/embolization; recanalization without symptomatic intracranial hemorrhage (ICH) at 24 h; symptomatic ICH; good neurological outcome (modified Rankin Scale score ≤2 National Institute of Health Stroke Scale (NIHSS) score decrease ≥10) at day 90; device- or procedure-related serious adverse events (SAEs) and mortality at day 90. To confirm non-inferiority of REVIVE, results were compared with historical data of the Merci Retriever. About 49 patients were enrolled (median age 73 years; males 46.9%; middle cerebral artery (MCA) occlusion 83.7%; median NIHSS score 17). A post-procedure TICI score ≥2a was observed in 73.5% (36/49, 95% confidence interval [CI] 58.9-85.1) of patients. No post-procedural clot migration/embolization events occurred. Successful recanalization without symptomatic ICH was observed in 62.5% (30/48, 95% CI 47.4-76.0). The good neurological outcome was achieved in 66.7% (32/48) patients. Symptomatic ICH and device- or procedure-related SAEs were reported in 6.3% and 12.2% of patients, respectively. Two deaths were reported. REVIVE demonstrated equivalent efficacy and safety as the Merci Retriever. Results suggest that REVIVE is effective and safe in recanalizing occluded intracranial arteries in AIS.

Efficacy and Safety of REVIVE SE Thrombectomy Device for Acute Ischemic Stroke: River JAPAN (Reperfuse Ischemic Vessels with Endovascular Recanalization Device in Japan)

PubMed Central

SAKAI, Nobuyuki; OTA, Shinzo; MATSUMOTO, Yasushi; KONDO, Rei; SATOW, Tetsu; KUBO, Michiya; TSUMOTO, Tomoyuki; ENOMOTO, Yukiko; KATAOKA, Taketo; IMAMURA, Hirotoshi; TODO, Kenichi; HAYAKAWA, Mikito; YAMAGAMI, Hiroshi; TOYODA, Kazunori; ITO, Yasushi; SUGIU, Kenji; MATSUMARU, Yuji; YOSHIMURA, Shinichi

2018-01-01

REVIVE SE (REVIVE) is a closed-ended, self-expanding stent retriever used in the RIVER JAPAN study. We present our early experience with REVIVE for revascularization of acute ischemic stroke (AIS) in patients who have failed or are ineligible for intravenous recombinant tissue plasminogen activator treatment. This prospective, single-arm, non-randomized, multicenter registry study followed up patients undergoing mechanical thrombectomy with REVIVE for 90 days. The primary endpoint was a post-procedure Thrombolysis in Cerebral Infarction (TICI) score ≥2a. Secondary endpoints were clot migration/embolization; recanalization without symptomatic intracranial hemorrhage (ICH) at 24 h; symptomatic ICH; good neurological outcome (modified Rankin Scale score ≤2 National Institute of Health Stroke Scale (NIHSS) score decrease ≥10) at day 90; device- or procedure-related serious adverse events (SAEs) and mortality at day 90. To confirm non-inferiority of REVIVE, results were compared with historical data of the Merci Retriever. About 49 patients were enrolled (median age 73 years; males 46.9%; middle cerebral artery (MCA) occlusion 83.7%; median NIHSS score 17). A post-procedure TICI score ≥2a was observed in 73.5% (36/49, 95% confidence interval [CI] 58.9–85.1) of patients. No post-procedural clot migration/embolization events occurred. Successful recanalization without symptomatic ICH was observed in 62.5% (30/48, 95% CI 47.4–76.0). The good neurological outcome was achieved in 66.7% (32/48) patients. Symptomatic ICH and device- or procedure-related SAEs were reported in 6.3% and 12.2% of patients, respectively. Two deaths were reported. REVIVE demonstrated equivalent efficacy and safety as the Merci Retriever. Results suggest that REVIVE is effective and safe in recanalizing occluded intracranial arteries in AIS. PMID:29526881

Intraoperative Active Bleeding in Endoscopic Surgery for Spontaneous Intracerebral Hemorrhage is Predicted by the Spot Sign.

PubMed

Miki, Koichi; Yagi, Kenji; Nonaka, Masani; Iwaasa, Mitsutoshi; Abe, Hiroshi; Morishita, Takashi; Arima, Hisatomi; Inoue, Tooru

2018-05-30

Endoscopic evacuation of hematoma (EEH) has recently been applied to treat patients with spontaneous intracerebral hemorrhage (sICH). Intraoperative active bleeding (IAB), which is occasionally observed in EEH, might lead to greater blood loss, further brain damage, and more postoperative recurrent hemorrhage. However, no definite predictor of IAB has been established. Because the spot sign is associated with other hemorrhagic complications, we aimed to evaluate whether it predicts IAB. We retrospectively assessed the incidence and risk factors of IAB, including the spot sign, in 127 sICH patients who underwent EEH within 6 hours after computed tomography angiography at our institution between June 2009 and December 2017. The study included 53 women and 74 men with an average age of 66.7 ± 11.8 years. IAB occurred in 40 (31.5%) of the 127 patients, and it was more frequent in patients with the spot sign than in patients without it (14/24 [58.3%] vs. 26/103 [25.2%]; P = 0.003). Multivariable regression analyses suggested that the spot sign was an independent predictor of IAB (odds ratio [OR], 3.02; 95% confidence interval [CI], 1.10-8.30; P = 0.03). In addition, earlier surgery gradually increased the risk of IAB, and surgery within 4 hours of onset was an independent risk factor (OR, 4.34; 95% CI, 1.12-16.9; P = 0.03, referring to postonset 8 hours or more). The spot sign and early surgery were independent predictors of IAB in EEH for sICH. In patients with sICH and spot sign, complete treatment of IAB by electrocoagulation might be important for minimizing surgical complications. Copyright © 2018 Elsevier Inc. All rights reserved.

Spot sign as a predictor of rebleeding after endoscopic surgery for intracerebral hemorrhage.

PubMed

Miki, Koichi; Yagi, Kenji; Nonaka, Masani; Iwaasa, Mitsutoshi; Abe, Hiroshi; Morishita, Takashi; Arima, Hisatomi; Inoue, Tooru

2018-05-25

OBJECTIVE In patients with spontaneous intracerebral hemorrhage (sICH), postoperative recurrent hemorrhage (PRH) is one of the most severe complications after endoscopic evacuation of hematoma (EEH). However, no predictors of this complication have been identified. In the present study, the authors retrospectively investigated whether PRH can be preoperatively predicted by the presence of the spot sign on CT scans. METHODS In total, 143 patients with sICH were treated by EEH between June 2009 and March 2017, and 127 patients who underwent preoperative CT angiography were included in this study. Significant correlations of PRH with the patients' baseline, clinical, and radiographic characteristics, including the spot sign, were evaluated using multivariable logistic regression models. RESULTS The incidence of and risk factors for PRH were assessed in 127 patients with available data. PRH occurred in 9 (7.1%) patients. Five (21.7%) cases of PRH were observed among 23 patients with the spot sign, whereas only 4 (3.8%) cases of PRH occurred among 104 patients without the spot sign. The spot sign was the only independent predictor of PRH (OR 5.81, 95% CI 1.26-26.88; p = 0.02). The following factors were not independently associated with PRH: age, hypertension, poor consciousness, antihemostatic factors (thrombocytopenia, coagulopathy, and use of antithrombotic drugs), the location and size of the sICH, other radiographic findings (black hole sign and blend sign), surgical duration and procedures, and early surgery. CONCLUSIONS The spot sign is likely to be a strong predictor of PRH after EEH among patients with sICH. Complete and careful control of bleeding in the operative field should be ensured when surgically treating such patients. New surgical strategies and procedures might be needed to improve these patients' outcomes.

A population-based study of the associations of stroke occurrence with weather parameters in Siberia, Russia (1982-92).

PubMed

Feigin, V L; Nikitin, Y P; Bots, M L; Vinogradova, T E; Grobbee, D E

2000-03-01

Previous studies have established a seasonal variation in stroke occurrence, but none have assessed the influence of inclement weather conditions on stroke incidence in a general population of Russia. We performed a stroke population-based study in the Oktiabrsky District of Novosibirsk, Siberia, Russia. Included in the analysis were 1929 patients with their first occurrence of ischemic stroke (IS), 215 patients with their first occurrence of intracerebral hemorrhage (ICH) and 64 patients with their first occurrence of subarachnoid hemorrhage (SAH): all patients were aged between 25 and 74 years. The cumulative daily occurrence of total strokes and stroke subtypes was evaluated in relation to aggregated daily mean values of ambient temperature, relative humidity and air pressure by means of Poisson regression analysis to estimate the rate ratio (RR) with corresponding confidence interval (CI) and to identify the weather parameters of most importance. In a multivariate analysis, with adjustment for the effects of season, solar and geomagnetic activity, and age of the patients, low ambient temperature (RR 1.32; 95% CI 1.05-1.66) and mean value of air pressure (RR 0.986; 95% CI 0.972-0.999) were important predictors of IS occurrence, while mild ambient temperature (RR 1.52; 95% CI 1. 04-2.22) was an important predictor of ICH occurrence. No relationship between SAH occurrence and any one of the weather parameters studied was revealed. There was no interaction between any meteorological variables that was statistically significant. Inclement weather conditions are associated with the occurrence of IS and ICH in Siberia, Russia. Among the meteorological parameters studied, low ambient temperature and mean air pressure are the most important predictors of IS occurrence, whereas the occurrence of ICH is associated with mild ambient temperature. There is no association between any one of the weather parameters studied and the occurrence of SAH.

Minocycline Reduces Spontaneous Hemorrhage in Mouse Models of Cerebral Amyloid Angiopathy

PubMed Central

Liao, Fan; Xiao, Qingli; Kraft, Andrew; Gonzales, Ernie; Perez, Ron; Greenberg, Steven M.; Holtzman, David; Lee, Jin-Moo

2015-01-01

Background and Purpose Cerebral Amyloid Angiopathy (CAA) is a common cause of recurrent intracerebral hemorrhage (ICH) in the elderly. Previous studies have shown that CAA induces inflammation and expression of matrix metalloproteinase-2 and -9 (gelatinases) in amyloid-laden vessels. Here, we inhibited both using minocycline in CAA mouse models to determine if spontaneous ICH could be reduced. Methods Tg2576 (n=16) and 5×FAD/ApoE4 knock-in mice (n=16), aged to 17 and 12 months, respectively, were treated with minocycline (50 mg/kg, i.p.) or saline every other day for two months. Brains were extracted and stained with X-34 (to quantify amyloid), Perl’s blue (to quantify hemorrhage), and immunostained to examined Aβ load, gliosis (GFAP, Iba-1), and vascular markers of blood-brain-barrier integrity (ZO-1 and collagen IV). Brain extracts were used to quantify mRNA for a variety of inflammatory genes. Results Minocycline treatment significantly reduced hemorrhage frequency in the brains of Tg2576 and 5×FAD/ApoE4 mice relative to the saline-treated mice, without affecting CAA load. Gliosis (GFAP and Iba-1 immunostaining), gelatinase activity, and expression of a variety of inflammatory genes (MMP-9, Nox4, CD45, S-100b, Iba-1) were also significantly reduced. Higher levels of microvascular tight junction and basal lamina proteins were found in the brains of minocycline-treated Tg2576 mice relative to saline-treated controls. Conclusions Minocycline reduced gliosis, inflammatory gene expression, gelatinase activity, and spontaneous hemorrhage in two different mouse models of CAA, supporting the importance of MMP-related and inflammatory pathways in ICH pathogenesis. As an FDA-approved drug, minocycline might be considered for clinical trials to test efficacy in preventing CAA-related ICH. PMID:25944329

Managing the therapeutic dilemma: patients with spontaneous intracerebral hemorrhage and urgent need for anticoagulation.

PubMed

Bertram, M; Bonsanto, M; Hacke, W; Schwab, S

2000-03-01

Physicians face a therapeutic dilemma in patients with acute hemorrhagic stroke requiring long-term, high-intensity anticoagulants because this treatment increases the risk of intracranial hemorrhage (ICH) 8- to 11-fold. We retrospectively studied 15 patients with ICH which occurred under anticoagulation with phenprocoumon, with an international norrmalized ratio (INR) of 2.5-6.5 on admission. Hemispheric, thalamic, cerebellar, intraventricular, or subarachnoid hemorrhage without aneurysm occurred. Absolute indications for anticoagulation were double, mitral, or aortic valve replacement, combined mitral valve failure with atrial fibrillation and atrial enlargement, internal carotid artery-jugular vein graft, frequently recurring deep vein thrombosis with risk of pulmonary embolism, and severe nontreatable ischemic heart disease. As soon as the diagnosis of ICH was established, INR normalization was attempted in all patients by administration of prothrombin complex, fresh frozen plasma, or vitamin K. After giving phenprocoumon antagonists (and neurosurgical therapy in four patients) heparin administration was started. Nine patients received full-dose intravenous and six low-dose subcutaneous heparin. The following observations were made: (a) All patients with effective, full-dose heparin treatment with a 1.5- to 2-fold elevation in partial thromboplastin time after normalization of the INR were discharged without complication. (b) Three of four of the patients with only incomplete correction of the INR (> 1.35) experienced relevant rebleeding within 3 days (all patients with an INR higher than 1.5), two of whom were on full-dose heparin. (c) Three of seven of the patients with normalized INR and without significant PTT elevation developed severe cerebral embolism. Although our data are based on a retrospective analysis, they support treatment with intravenous heparin (partial thromboplastin time 1.5-2 times baseline value) after normalization of the INR in patients

[Hospital care for stroke patients in the Valencian Region using the basic minimum data set from the International Classification of Diseases, 9th revision, clinical modification].

PubMed

Geffner-Sclarsky, D

To determine the load and characteristics of cerebrovascular diseases (CVD) admitted in the hospital network throughout the Valencian Region. The paper reports on an analysis of the information included in the basic minimum data set (BMDS) from the 26 hospitals run by the Valencian Regional Ministry of Health in the year 2001. Patients that were selected were those whose main diagnosis was codes C.430 to C.437, according to the International Classification of Diseases, 9th revision, clinical modification (ICD-9-CM). A total of 10,558 patients with CVD were discharged, which accounts for 2.6% of admissions and 3% of hospital stays. The mean age of the series was 71.03 years -standard deviation (SD): 9- and 94.8% were admitted as emergencies. By diagnoses, 3% (319) were subarachnoid haemorrhages (SAH; C.430); 13.4% (1,412) were cerebral haemorrhages (ICH; C.431); 18.5% (1,956) were transient ischemic attacks (TIA; C.435); 49.5% (5,225) were cases of cerebral infarction (CI; C.434 and C.436); and 15.6% involved other vascular processes (C.433 and C.437). Mortality rates were 30.1% in SAH; 33.9% in ICH; 11.7% in CI; and 2.7% in TIA. Mean number of days in hospital: SAH 17.4 (SD: 15); ICH 13.1 (SD: 11.8); CI 9.9 (SD: 6.4) and in cases of TIA 7.2 (SD: 4). The percentages of survivors who were discharged home were 78.9 % in SAH, 83.2% in ICH and 91.9% in the case of CI. In all, 51.3% (5,413 patients) were discharged by neurological units. In spite of possible insufficiencies analysed in this work, the use of the BMDS provides valuable epidemiological information that is very useful for health care management.

Good collaborative practice: reforming capacity building governance of international health research partnerships.

PubMed

Ward, Claire Leonie; Shaw, David; Sprumont, Dominique; Sankoh, Osman; Tanner, Marcel; Elger, Bernice

2018-01-08

In line with the policy objectives of the United Nations Sustainable Development Goals, this commentary seeks to examine the extent to which provisions of international health research guidance promote capacity building and equitable partnerships in global health research. Our evaluation finds that governance of collaborative research partnerships, and in particular capacity building, in resource-constrained settings is limited but has improved with the implementation guidance of the International Ethical Guidelines for Health-related Research Involving Humans by The Council for International Organizations of Medical Sciences (CIOMS) (2016). However, more clarity is needed in national legislation, industry and ethics guidelines, and regulatory provisions to address the structural inequities and power imbalances inherent in international health research partnerships. Most notably, ethical partnership governance is not supported by the principal industry ethics guidelines - the International Conference on Harmonization Technical Requirements for Registration of Pharmaceutical for Human Use (ICH) Good Clinical Practice (ICH-GCP). Given the strategic value of ICH-GCP guidelines in defining the role and responsibility of global health research partners, we conclude that such governance should stipulate the minimal requirements for creating an equitable environment of inclusion, mutual learning, transparency and accountability. Procedurally, this can be supported by i) shared research agenda setting with local leadership, ii) capacity assessments, and iii) construction of a memorandum of understanding (MoU). Moreover, the requirement of capacity building needs to be coordinated amongst partners to support good collaborative practice and deliver on the public health goals of the research enterprise; improving local conditions of health and reducing global health inequality. In this respect, and in order to develop consistency between sources of research governance, ICH

International Conference on Harmonisation; guidance on Q10 Pharmaceutical Quality System; availability. Notice.

PubMed

2009-04-08

The Food and Drug Administration (FDA) is announcing the availability of a guidance entitled "Q10 Pharmaceutical Quality System." The guidance was prepared under the auspices of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). The guidance describes a model for an effective quality management system for the pharmaceutical industry, referred to as the Pharmaceutical Quality System. The guidance is intended to provide a comprehensive approach to an effective pharmaceutical quality system that is based on International Organization for Standardization (ISO) concepts, includes applicable good manufacturing practice (GMP) regulations and complements ICH guidances on "Q8 Pharmaceutical Development" and "Q9 Quality Risk Management."

The importance of Good Clinical Practice guidelines and its role in clinical trials

PubMed Central

Vijayananthan, A; Nawawi, O

2008-01-01

Good Clinical Practice (GCP) is an international ethical and scientific quality standard for the design, conduct, performance, monitoring, auditing, recording, analyses and reporting of clinical trials. It also serves to protect the rights, integrity and confidentiality of trial subjects. It is very important to understand the background of the formation of the ICH-GCP guidelines as this, in itself, explains the reasons and the need for doing so. In this paper, we address the historical background and the events that led up to the formation of these guidelines. Today, the ICH-GCP guidelines are used in clinical trials throughout the globe with the main aim of protecting and preserving human rights. PMID:21614316

Regulatory aspects of oncology drug safety evaluation: past practice, current issues, and the challenge of new drugs.

PubMed

Rosenfeldt, Hans; Kropp, Timothy; Benson, Kimberly; Ricci, M Stacey; McGuinn, W David; Verbois, S Leigh

2010-03-01

The drug development of new anti-cancer agents is streamlined in response to the urgency of bringing effective drugs to market for patients with limited life expectancy. FDA's regulation of oncology drugs has evolved from the practices set forth in Arnold Lehman's seminal work published in the 1950s through the current drafting of a new International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) safety guidance for anti-cancer drug nonclinical evaluations. The ICH combines the efforts of the regulatory authorities of Europe, Japan, and the United States and the pharmaceutical industry from these three regions to streamline the scientific and technical aspects of drug development. The recent development of new oncology drug classes with novel mechanisms of action has improved survival rates for some cancers but also brings new challenges for safety evaluation. Here we present the legacy of Lehman and colleagues in the context of past and present oncology drug development practices and focus on some of the current issues at the center of an evolving harmonization process that will generate a new safety guidance for oncology drugs, ICH S9. The purpose of this new guidance will be to facilitate oncology drug development on a global scale by standardizing regional safety requirements.

Stereotactic Administration of Edaravone Ameliorates Collagenase-Induced Intracerebral Hemorrhage in Rat.

PubMed

Zhang, Yan; Yang, Yang; Zhang, Guang-Zhu; Gao, Mou; Ge, Guang-Zhi; Wang, Qin-Qin; Ji, Xin-Chao; Sun, Yi-Lin; Zhang, Hong-Tian; Xu, Ru-Xiang

2016-10-01

Edaravone is widely used for treating ischemic stroke, but it is not still confirmed in intracerebral hemorrhage (ICH) as an ideal medication targeting the brain parenchyma. We aimed to investigate the neuroprotective effects of stereotactic administration of edaravone (SI) into the brain parenchyma. Intracerebral hemorrhage rat models were established by infusion of collagenase into the caudate nucleus. Neural functional recovery was assessed using modified neurological severity scores (mNSS). A comparative study of therapeutic effects between SI and intraperitoneal injection of edaravone (IP) involved in cerebral edema, blood-brain barrier (BBB) permeability, hematoma absorption, inflammatory response and neuronal apoptosis. Compared with IP, the mNSS was significantly (P < 0.05) improved by SI; cerebral edema and BBB permeability were dramatically ameliorated (P < 0.05); IL-4 and IL-10 levels increased, but IL-1β and TNF-α levels significantly decreased; neuron apoptosis decreased markedly (P < 0.05); and caspase-3 and Bax expression significantly dropped, but Bcl-2 increased in SI group (P < 0.05). SI markedly improved neurological deficits in ICH rat models via antiinflammatory and antiapoptosis mechanisms and promoted M2-type microglia differentiation. SI was effective in rats with collagenase-induced ICH. © 2016 The Authors. CNS Neuroscience & Therapeutics Published by John Wiley & Sons Ltd.

Thrombin-induced microglial activation impairs hippocampal neurogenesis and spatial memory ability in mice.

PubMed

Yang, Yuan; Zhang, Meikui; Kang, Xiaoni; Jiang, Chen; Zhang, Huan; Wang, Pei; Li, Jingjing

2015-09-26

To investigate the effects of microglia/macrophages activation induced by intrastriatal thrombin injection on dentate gyrus neurogenesis and spatial memory ability in mice. The male C57BL/6 mice were divided into 4 groups of 10: sham, intracerebral hemorrhage (ICH), ICH + hirudin (thrombin inhibitor), and ICH + indometacin (Indo, an anti-inflammation drug). ICH model was created by intrastriatal thrombin (1U) injection. BrdU (50 mg/kg) was administrated on the same day after surgery for 6 consecutive days. Motor functions were evaluated with rotarod and beam walking tests. The spatial memory deficit was measured with Morris water maze (MWM). Cell quantification was performed for doublecortin (DCX, immature neuron), BrdU (S-phase proliferating cell population) and CD68 (activated microglia/macrophage) immune-reactive cells. Microglia/macrophages activation induced by intrastriatal thrombin injection reduced hippocampal neurogenesis and impaired spatial memory ability, but did not affect the motor function at 3 and 5 days post-injury. Both hirudin and indometacin reduced microglia/macrophages activation, enhanced hippocampal neurogenesis, and improved spatial memory ability in mice. Microglia/macrophages activation induced by intrastriatal thrombin injection might be responsible for the spatial memory deficit. Targeting both thrombin and inflammation systems in acute phase of ICH might be important in alleviating the significant spatial memory deficits.

[Pharmaceutical product quality control and good manufacturing practices].

PubMed

Hiyama, Yukio

2010-01-01

This report describes the roles of Good Manufacturing Practices (GMP) in pharmaceutical product quality control. There are three keys to pharmaceutical product quality control. They are specifications, thorough product characterization during development, and adherence to GMP as the ICH Q6A guideline on specifications provides the most important principles in its background section. Impacts of the revised Pharmaceutical Affairs Law (rPAL) which became effective in 2005 on product quality control are discussed. Progress of ICH discussion for Pharmaceutical Development (Q8), Quality Risk Management (Q9) and Pharmaceutical Quality System (Q10) are reviewed. In order to reconstruct GMP guidelines and GMP inspection system in the regulatory agencies under the new paradigm by rPAL and the ICH, a series of Health Science studies were conducted. For GMP guidelines, product GMP guideline, technology transfer guideline, laboratory control guideline and change control system guideline were written. For the GMP inspection system, inspection check list, inspection memo and inspection scenario were proposed also by the Health Science study groups. Because pharmaceutical products and their raw materials are manufactured and distributed internationally, collaborations with other national authorities are highly desired. In order to enhance the international collaborations, consistent establishment of GMP inspection quality system throughout Japan will be essential.

Changes in plasma thrombospondin-1 concentrations following acute intracerebral hemorrhage.

PubMed

Dong, Xiao-Qiao; Yu, Wen-Hua; Zhu, Qiang; Cheng, Zhen-Yu; Chen, Yi-Hua; Lin, Xiao-Feng; Ten, Xian-Lin; Tang, Xiao-Bing; Chen, Juan

2015-10-23

Angiogenesis is a fundamental process for brain development and repair. Thrombospondin-1 is the first identified endogenous angiogenesis inhibitor. Its expression in rat brain is upregulated after intracerebral hemorrhage (ICH). We determined whether plasma thrombospondin-1 concentrations are associated with injury severity and prognosis in ICH patients. This observational, prospective study recruited 110 patients and 110 age- and gender-matched healthy controls. Blood samples were collected from the patients at admission and from the healthy controls at study entry to measure plasma thrombospondin-1 concentrations. The endpoints included 1-week mortality, 6-month mortality, 6-month overall survival and 6-month unfavorable outcome (modified Rankin Scale score >2). Plasma thrombospondin-1 concentrations were markedly higher in patients than in healthy controls. Thrombospondin-1 was an independent predictive factor for all endpoints and plasma thrombospondin-1 concentrations were highly associated with injury severity reflected by hematoma volume and National Institutes of Health Stroke Scale score. Under receiver operating characteristic curves, plasma thrombospondin-1 concentrations had similar predictive values compared with hematoma volume and National Institutes of Health Stroke Scale score. Increased plasma thrombospondin-1 concentrations following ICH are independently associated with injury severity and short-term and long-term clinical outcomes. Copyright © 2015 Elsevier B.V. All rights reserved.

A combination of serum iron, ferritin and transferrin predicts outcome in patients with intracerebral hemorrhage

PubMed Central

Yang, Guang; Hu, Rong; Zhang, Chao; Qian, Christopher; Luo, Qian-Qian; Yung, Wing-Ho; Ke, Ya; Feng, Hua; Qian, Zhong-Ming

2016-01-01

Association of a high-serum ferritin with poor outcome showed that iron might play a detrimental role in the brain after intracerebral hemorrhage (ICH). Here, we investigated changes in serum iron, ferritin, transferrin (Tf) and ceruloplasmin (CP) in patients with ICH (n = 100) at day 1 (admission), 3, 7, 14 and 21 and those in control subjects (n = 75). The hematoma and edema volumes were also determined in ICH-patients on admission and at day 3. The Modified Rankin Scale (mRS) of 59 patients was ≥3 (poor outcome) and 41 < 3 (good outcome) at day 90. Serum ferritin was significantly higher and serum iron and Tf markedly lower in patients with poor-outcome than the corresponding values in patients with good-outcome at day 1 to 7 and those in the controls. There was a significant positive correlation between serum ferritin and relative edema volume or ratio at day 1 and 3 and hematoma volume at day 1 (n = 28), and a negative correlation between serum iron or Tf and hematoma volume at day 1 (n = 100). We concluded that not only increased serum ferritin but also reduced serum iron and Tf are associated with outcome as well as hematoma volume. PMID:26898550

Deaths from stroke in US young adults, 1989-2009.

PubMed

Poisson, Sharon N; Glidden, David; Johnston, S Claiborne; Fullerton, Heather J

2014-12-02

To determine what the trends in stroke mortality have been over 2 decades in young adults. In this cohort study, we analyzed death certificate data for ischemic and hemorrhagic stroke (intracerebral hemorrhage [ICH] and subarachnoid hemorrhage [SAH]) in adults aged 20-44 in the United States for 1989 through 2009, covering approximately 2.2 billion person-years. Poisson regression was used to calculate and compare time trend data between groups and to compare trends in young adults to those in adults over age 45. Mortality from stroke in young adults declined by 35% over the study period, with reductions in all 3 stroke subtypes (ischemic stroke decreased by 15%, ICH by 47%, and SAH by 50%). Black race was a risk factor for all 3 stroke subtypes (relative risk 2.4 for ischemic stroke, 4.0 for ICH, and 2.1 for SAH), but declines in all stroke subtypes were more dramatic in black compared to white participants (p < 0.001 for all stroke subtypes). Although hospitalizations for stroke in young patients have been increasing, the apparent decrease in mortality rates and in racial disparities suggests that recognition and treatment in this group may be improving. © 2014 American Academy of Neurology.

Deaths from stroke in US young adults, 1989–2009

PubMed Central

Glidden, David; Johnston, S. Claiborne; Fullerton, Heather J.

2014-01-01

Objective: To determine what the trends in stroke mortality have been over 2 decades in young adults. Methods: In this cohort study, we analyzed death certificate data for ischemic and hemorrhagic stroke (intracerebral hemorrhage [ICH] and subarachnoid hemorrhage [SAH]) in adults aged 20–44 in the United States for 1989 through 2009, covering approximately 2.2 billion person-years. Poisson regression was used to calculate and compare time trend data between groups and to compare trends in young adults to those in adults over age 45. Results: Mortality from stroke in young adults declined by 35% over the study period, with reductions in all 3 stroke subtypes (ischemic stroke decreased by 15%, ICH by 47%, and SAH by 50%). Black race was a risk factor for all 3 stroke subtypes (relative risk 2.4 for ischemic stroke, 4.0 for ICH, and 2.1 for SAH), but declines in all stroke subtypes were more dramatic in black compared to white participants (p < 0.001 for all stroke subtypes). Conclusions: Although hospitalizations for stroke in young patients have been increasing, the apparent decrease in mortality rates and in racial disparities suggests that recognition and treatment in this group may be improving. PMID:25361783

Paramagnetic perfluorocarbon-filled albumin-(Gd-DTPA) microbubbles for the induction of focused-ultrasound-induced blood-brain barrier opening and concurrent MR and ultrasound imaging

NASA Astrophysics Data System (ADS)

Liao, Ai-Ho; Liu, Hao-Li; Su, Chia-Hao; Hua, Mu-Yi; Yang, Hung-Wei; Weng, Yu-Ting; Hsu, Po-Hung; Huang, Sheng-Min; Wu, Shih-Yen; Wang, Hsin-Ell; Yen, Tzu-Chen; Li, Pai-Chi

2012-05-01

This paper presents new albumin-shelled Gd-DTPA microbubbles (MBs) that can concurrently serve as a dual-modality contrast agent for ultrasound (US) imaging and magnetic resonance (MR) imaging to assist blood-brain barrier (BBB) opening and detect intracerebral hemorrhage (ICH) during focused ultrasound brain drug delivery. Perfluorocarbon-filled albumin-(Gd-DTPA) MBs were prepared with a mean diameter of 2320 nm and concentration of 2.903×109 MBs ml-1 using albumin-(Gd-DTPA) and by sonication with perfluorocarbon (C3F8) gas. The albumin-(Gd-DTPA) MBs were then centrifuged and the procedure was repeated until the free Gd3+ ions were eliminated (which were detected by the xylenol orange sodium salt solution). The albumin-(Gd-DTPA) MBs were also characterized and evaluated both in vitro and in vivo by US and MR imaging. Focused US was used with the albumin-(Gd-DTPA) MBs to induce disruption of the BBB in 18 rats. BBB disruption was confirmed with contrast-enhanced T1-weighted turbo-spin-echo sequence MR imaging. Heavy T2*-weighted 3D fast low-angle shot sequence MR imaging was used to detect ICH. In vitro US imaging experiments showed that albumin-(Gd-DTPA) MBs can significantly enhance the US contrast in T1-, T2- and T2*-weighted MR images. The r1 and r2 relaxivities for Gd-DTPA were 7.69 and 21.35 s-1mM-1, respectively, indicating that the MBs represent a positive contrast agent in T1-weighted images. In vivo MR imaging experiments on 18 rats showed that focused US combined with albumin-(Gd-DTPA) MBs can be used to both induce disruption of the BBB and detect ICH. To compare the signal intensity change between pure BBB opening and BBB opening accompanying ICH, albumin-(Gd-DTPA) MB imaging can provide a ratio of 5.14 with significant difference (p = 0.026), whereas Gd-DTPA imaging only provides a ratio of 2.13 and without significant difference (p = 0.108). The results indicate that albumin-(Gd-DTPA) MBs have potential as a US/MR dual-modality contrast agent for

Paramagnetic perfluorocarbon-filled albumin-(Gd-DTPA) microbubbles for the induction of focused-ultrasound-induced blood-brain barrier opening and concurrent MR and ultrasound imaging.

PubMed

Liao, Ai-Ho; Liu, Hao-Li; Su, Chia-Hao; Hua, Mu-Yi; Yang, Hung-Wei; Weng, Yu-Ting; Hsu, Po-Hung; Huang, Sheng-Min; Wu, Shih-Yen; Wang, Hsin-Ell; Yen, Tzu-Chen; Li, Pai-Chi

2012-05-07

This paper presents new albumin-shelled Gd-DTPA microbubbles (MBs) that can concurrently serve as a dual-modality contrast agent for ultrasound (US) imaging and magnetic resonance (MR) imaging to assist blood-brain barrier (BBB) opening and detect intracerebral hemorrhage (ICH) during focused ultrasound brain drug delivery. Perfluorocarbon-filled albumin-(Gd-DTPA) MBs were prepared with a mean diameter of 2320 nm and concentration of 2.903×10(9) MBs ml(-1) using albumin-(Gd-DTPA) and by sonication with perfluorocarbon (C(3)F(8)) gas. The albumin-(Gd-DTPA) MBs were then centrifuged and the procedure was repeated until the free Gd(3+) ions were eliminated (which were detected by the xylenol orange sodium salt solution). The albumin-(Gd-DTPA) MBs were also characterized and evaluated both in vitro and in vivo by US and MR imaging. Focused US was used with the albumin-(Gd-DTPA) MBs to induce disruption of the BBB in 18 rats. BBB disruption was confirmed with contrast-enhanced T(1)-weighted turbo-spin-echo sequence MR imaging. Heavy T(2)*-weighted 3D fast low-angle shot sequence MR imaging was used to detect ICH. In vitro US imaging experiments showed that albumin-(Gd-DTPA) MBs can significantly enhance the US contrast in T(1)-, T(2)- and T(2)*-weighted MR images. The r(1) and r(2) relaxivities for Gd-DTPA were 7.69 and 21.35 s(-1)mM(-1), respectively, indicating that the MBs represent a positive contrast agent in T(1)-weighted images. In vivo MR imaging experiments on 18 rats showed that focused US combined with albumin-(Gd-DTPA) MBs can be used to both induce disruption of the BBB and detect ICH. To compare the signal intensity change between pure BBB opening and BBB opening accompanying ICH, albumin-(Gd-DTPA) MB imaging can provide a ratio of 5.14 with significant difference (p = 0.026), whereas Gd-DTPA imaging only provides a ratio of 2.13 and without significant difference (p = 0.108). The results indicate that albumin-(Gd-DTPA) MBs have potential as a US/MR dual

Intracerebral hemorrhage and deep microbleeds associated with cnm-positive Streptococcus mutans; a hospital cohort study

PubMed Central

Tonomura, Shuichi; Ihara, Masafumi; Kawano, Tomohiro; Tanaka, Tomotaka; Okuno, Yoshinori; Saito, Satoshi; Friedland, Robert P.; Kuriyama, Nagato; Nomura, Ryota; Watanabe, Yoshiyuki; Nakano, Kazuhiko; Toyoda, Kazunori; Nagatsuka, Kazuyuki

2016-01-01

Oral infectious diseases are epidemiologically associated with stroke. We previously showed that oral Streptococcus mutans with the cnm gene encoding a collagen-binding Cnm protein induced intracerebral hemorrhage (ICH) experimentally and was also associated with cerebral microbleeds (CMBs) in our population-based cohort study. We therefore investigated the roles of cnm-positive Streptococcus mutans in this single hospital-based, observational study that enrolled 100 acute stroke subjects. The cnm gene in Streptococcus mutans isolated from saliva was screened using PCR techniques and its collagen-binding activities examined. CMBs were evaluated on T2* gradient-recalled echo MRI. One subject withdrew informed consent and 99 subjects (63 males) were analyzed, consisting of 67 subjects with ischemic stroke, 5 with transient ischemic attack, and 27 with ICH. Eleven cases showed Streptococcus mutans strains positive for cnm. The presence of cnm-positive Streptococcus mutans was significantly associated with ICH [OR vs. ischemic stroke, 4.5; 95% CI, 1.17–19.1] and increased number of deep CMBs [median (IQR), 3 (2–9) vs. 0 (0–1), p = 0.0002]. In subjects positive for Streptococcus mutans, collagen binding activity was positively correlated with the number of deep CMBs (R2 = 0.405; p < 0.0001). These results provide further evidence for the key role of oral health in stroke. PMID:26847666

Intracerebral hemorrhage and deep microbleeds associated with cnm-positive Streptococcus mutans; a hospital cohort study.

PubMed

Tonomura, Shuichi; Ihara, Masafumi; Kawano, Tomohiro; Tanaka, Tomotaka; Okuno, Yoshinori; Saito, Satoshi; Friedland, Robert P; Kuriyama, Nagato; Nomura, Ryota; Watanabe, Yoshiyuki; Nakano, Kazuhiko; Toyoda, Kazunori; Nagatsuka, Kazuyuki

2016-02-05

Oral infectious diseases are epidemiologically associated with stroke. We previously showed that oral Streptococcus mutans with the cnm gene encoding a collagen-binding Cnm protein induced intracerebral hemorrhage (ICH) experimentally and was also associated with cerebral microbleeds (CMBs) in our population-based cohort study. We therefore investigated the roles of cnm-positive Streptococcus mutans in this single hospital-based, observational study that enrolled 100 acute stroke subjects. The cnm gene in Streptococcus mutans isolated from saliva was screened using PCR techniques and its collagen-binding activities examined. CMBs were evaluated on T2* gradient-recalled echo MRI. One subject withdrew informed consent and 99 subjects (63 males) were analyzed, consisting of 67 subjects with ischemic stroke, 5 with transient ischemic attack, and 27 with ICH. Eleven cases showed Streptococcus mutans strains positive for cnm. The presence of cnm-positive Streptococcus mutans was significantly associated with ICH [OR vs. ischemic stroke, 4.5; 95% CI, 1.17-19.1] and increased number of deep CMBs [median (IQR), 3 (2-9) vs. 0 (0-1), p = 0.0002]. In subjects positive for Streptococcus mutans, collagen binding activity was positively correlated with the number of deep CMBs (R(2) = 0.405; p < 0.0001). These results provide further evidence for the key role of oral health in stroke.

Social foraging and individual consistency in following behaviour: testing the information centre hypothesis in free-ranging vultures.

PubMed

Harel, Roi; Spiegel, Orr; Getz, Wayne M; Nathan, Ran

2017-04-12

Uncertainties regarding food location and quality are among the greatest challenges faced by foragers and communal roosting may facilitate success through social foraging. The information centre hypothesis (ICH) suggests that uninformed individuals at shared roosts benefit from following informed individuals to previously visited resources. We tested several key prerequisites of the ICH in a social obligate scavenger, the Eurasian griffon vulture ( Gyps fulvus ), by tracking movements and behaviour of sympatric individuals over extended periods and across relatively large spatial scales, thereby precluding alternative explanations such as local enhancement. In agreement with the ICH, we found that 'informed' individuals returning to previously visited carcasses were followed by 'uninformed' vultures that consequently got access to these resources. When a dyad (two individuals that depart from the same roost within 2 min of each other) included an informed individual, they spent a higher proportion of the flight time close to each other at a shorter distance between them than otherwise. Although all individuals occasionally profited from following others, they differed in their tendencies to be informed or uninformed. This study provides evidence for 'following behaviour' in natural conditions and demonstrates differential roles and information states among foragers within a population. Moreover, demonstrating the possible reliance of vultures on following behaviour emphasizes that individuals in declining populations may suffer from reduced foraging efficiency. © 2017 The Author(s).

New oral anticoagulant and antiplatelet agents for neurosurgeons.

PubMed

Kimpton, George; Dabbous, Bassam; Leach, Paul

2015-01-01

Until recently, warfarin, clopidogrel and aspirin have provided the mainstay for prevention of thrombotic disease in cardiac patients. However, new classes of drugs have recently emerged that promise better clinical outcomes and lower risks. Use of such agents has increased, but increased risk and severity of intra-cranial haemorrhage (ICH) still remain. These cases of intra-cranial bleeds present as emergencies to neurosurgical units. It is of paramount importance that neurosurgical practitioners are aware of those new drugs, useful monitoring tests and available emergency reversal options in case the patient needs emergency intervention. In this review we survey newly available agents in the U.K. at the time of publication. We look at the data provided by the manufacturers, related publications and international guidelines for their use and reversal. New anticoagulants offer a lower incidence of ICH compared with warfarin. Advanced and accurate monitoring tests are emerging, as are prospective data on reversal of anticoagulation in bleeding. Some standard coagulation tests may be of use, whilst reversal agents are available and being evaluated. The trial data shows that new antiplatelet agents have similar or increased incidence and severity of intra-cranial ICH compared with clopidogrel. There is currently limited data on monitoring or reversal. We suggest they may be managed similarly to clopidogrel by using platelet reactivity assays, optimising platelet count and using platelet transfusion with adjunctive agents.

Surgery for bilateral large intracranial traumatic hematomas: evacuation in a single session.

PubMed

Kompheak, Heng; Hwang, Sun-Chul; Kim, Dong-Sung; Shin, Dong-Sung; Kim, Bum-Tae

2014-06-01

Management guidelines for single intracranial hematomas have been established, but the optimal management of multiple hematomas has little known. We present bilateral traumatic supratentorial hematomas that each has enough volume to be evacuated and discuss how to operate effectively it in a single anesthesia. In total, 203 patients underwent evacuation and/or decompressive craniectomies for acute intracranial hematomas over 5 years. Among them, only eight cases (3.9%) underwent operations for bilateral intracranial hematomas in a single session. Injury mechanism, initial Glasgow Coma Scale score, types of intracranial lesions, surgical methods, and Glasgow outcome scale were evaluated. The most common injury mechanism was a fall (four cases). The types of intracranial lesions were epidural hematoma (EDH)/intracerebral hematoma (ICH) in five, EDH/EDH in one, EDH/subdural hematoma (SDH) in one, and ICH/SDH in one. All cases except one had an EDH. The EDH was addressed first in all cases. Then, the evacuation of the ICH was performed through a small craniotomy or burr hole. All patients except one survived. Bilateral intracranial hematomas that should be removed in a single-session operation are rare. Epidural hematomas almost always occur in these cases and should be removed first to prevent the hematoma from growing during the surgery. Then, the other hematoma, contralateral to the EDH, can be evacuated with a small craniotomy.

Surgery for Bilateral Large Intracranial Traumatic Hematomas: Evacuation in a Single Session

PubMed Central

Kompheak, Heng; Kim, Dong-Sung; Shin, Dong-Sung; Kim, Bum-Tae

2014-01-01

Objective Management guidelines for single intracranial hematomas have been established, but the optimal management of multiple hematomas has little known. We present bilateral traumatic supratentorial hematomas that each has enough volume to be evacuated and discuss how to operate effectively it in a single anesthesia. Methods In total, 203 patients underwent evacuation and/or decompressive craniectomies for acute intracranial hematomas over 5 years. Among them, only eight cases (3.9%) underwent operations for bilateral intracranial hematomas in a single session. Injury mechanism, initial Glasgow Coma Scale score, types of intracranial lesions, surgical methods, and Glasgow outcome scale were evaluated. Results The most common injury mechanism was a fall (four cases). The types of intracranial lesions were epidural hematoma (EDH)/intracerebral hematoma (ICH) in five, EDH/EDH in one, EDH/subdural hematoma (SDH) in one, and ICH/SDH in one. All cases except one had an EDH. The EDH was addressed first in all cases. Then, the evacuation of the ICH was performed through a small craniotomy or burr hole. All patients except one survived. Conclusion Bilateral intracranial hematomas that should be removed in a single-session operation are rare. Epidural hematomas almost always occur in these cases and should be removed first to prevent the hematoma from growing during the surgery. Then, the other hematoma, contralateral to the EDH, can be evacuated with a small craniotomy. PMID:25237431

Intracerebral haemorrhage in Down syndrome: protected or predisposed?

PubMed Central

Buss, Lewis; Fisher, Elizabeth; Hardy, John; Nizetic, Dean; Groet, Jurgen; Pulford, Laura; Strydom, André

2016-01-01

Down syndrome (DS), which arises from trisomy of chromosome 21, is associated with deposition of large amounts of amyloid within the central nervous system. Amyloid accumulates in two compartments: as plaques within the brain parenchyma and in vessel walls of the cerebral microvasculature. The parenchymal plaque amyloid is thought to result in an early onset Alzheimer’s disease (AD) dementia, a phenomenon so common amongst people with DS that it could be considered a defining feature of the condition. The amyloid precursor protein ( APP) gene lies on chromosome 21 and its presence in three copies in DS is thought to largely drive the early onset AD. In contrast, intracerebral haemorrhage (ICH), the main clinical consequence of vascular amyloidosis, is a more poorly defined feature of DS. We review recent epidemiological data on stroke (including haemorrhagic stroke) in order to make comparisons with a rare form of familial AD due to duplication (i.e. having three copies) of the APP region on chromosome 21, here called ‘dup-APP’, which is associated with more frequent and severe ICH. We conclude that although people with DS are at increased risk of ICH, this is less common than in dup-APP, suggesting the presence of mechanisms that act protectively. We review these mechanisms and consider comparative research into DS and dup-APP that may yield further pathophysiological insight. PMID:27239286

Increased expression of Apo-J and Omi/HtrA2 after Intracerebral Hemorrage in rats.

PubMed

Li, Feng; Yang, Jing; Guo, Xiaoyan; Zheng, Xiaomei; Lv, Zhiyu; Shi, Chang Qing; Li, Xiaogang

2018-03-23

To investigate the changes of Apo-J and Omi/HtrA2 protein expression in rats with intracerebral hemorrage. 150 SD adult rats were randomly divided into 3 groups: (1) Normal Control (NC) group, (2) Sham group, (3) Intracerebral Hemorrage (ICH) group. The data were collected at 6h, 12h, 1d, 2d, 3d, 5d and 7d. Apoptosis was measured by Tunel staining. The distributions of the Apo-J and Omi/HtrA2 proteins were determined by immunohistochemical staining. The levels of Apo-J mRNA and Omi/HtrA2 mRNA expressions were examined by RT-PCR. Apoptosis in ICH group was higher than Sham and NC groups (p＜0.05). Both the Apo-J and Omi/HtrA2 expression levels were increased in the peripheral region of hemorrhage, with a peak at 3d. The Apo-J mRNA level positively correlated with HtrA2 mRNA level in ICH group (r=0.883, p＜0.001). The expressions of Apo-J and Omi/HtrA2 paralelly increased in peripheral region of rat cerebral hemorrhage. Local high expressed Apo-J in the peripheral regions might play a neuroprotective role by inhibiting apoptosis via Omi/HtrA2 pathway after hemorrhage. Copyright © 2018. Published by Elsevier Inc.

Defect Passivation of Organic–Inorganic Hybrid Perovskites by Diammonium Iodide toward High-Performance Photovoltaic Devices

DOE PAGES

Zhao, Ting; Chueh, Chu-Chen; Chen, Qi; ...

2016-09-12

The polycrystalline feature of solutionprocessed perovskite film and its ionic nature inevitably incur substantial crystallographic defects, especially at the film surface and the grain boundaries (GBs). Here, a simple defect passivation method was exploited by post-treating CH 3NH 3PbI 3 (MAPbI 3) film with a rationally selected diammonium iodide. The molecular structure of the used diammonium iodide was discovered to play a critical role in affecting the phase purity of treated MAPbI 3. Both NH 3I(CH 2) 4NH 3I and NH 3I(CH 2) 2O(CH 2) 2NH 3I (EDBE) induce three-dimensional (3D) to two-dimensional (2D) perovskite phase transformation during the treatmentmore » while only NH 3I(CH 2) 8NH 3I (C 8) successfully passivates perovskite surface and GBs without forming 2D perovskite because of the elevated activation energy arising from its unique anti-gauche isomerization. In conclusion, defect passivation of MAPbI 3 was clearly confirmed by scanning Kelvin probe microscopy (SKPM) and time-resolved photoluminescence (TRPL) studies, which results in the reduced recombination loss in derived devices. Consequently, the perovskite solar cell with C 8 passivation showed a much improved power conversion efficiency (PCE) of 17.60% compared to the control device PCE of 14.64%.« less

Identification of an itaconic acid degrading pathway in itaconic acid producing Aspergillus terreus.

PubMed

Chen, Mei; Huang, Xuenian; Zhong, Chengwei; Li, Jianjun; Lu, Xuefeng

2016-09-01

Itaconic acid, one of the most promising and flexible bio-based chemicals, is mainly produced by Aspergillus terreus. Previous studies to improve itaconic acid production in A. terreus through metabolic engineering were mainly focused on its biosynthesis pathway, while the itaconic acid-degrading pathway has largely been ignored. In this study, we used transcriptomic, proteomic, bioinformatic, and in vitro enzymatic analyses to identify three key enzymes, itaconyl-CoA transferase (IctA), itaconyl-CoA hydratase (IchA), and citramalyl-CoA lyase (CclA), that are involved in the catabolic pathway of itaconic acid in A. terreus. In the itaconic acid catabolic pathway in A. terreus, itaconic acid is first converted by IctA into itaconyl-CoA with succinyl-CoA as the CoA donor, and then itaconyl-CoA is hydrated into citramalyl-CoA by IchA. Finally, citramalyl-CoA is cleaved into acetyl-CoA and pyruvate by CclA. Moreover, IctA can also catalyze the reaction between citramalyl-CoA and succinate to generate succinyl-CoA and citramalate. These results, for the first time, identify the three key enzymes, IctA, IchA, and CclA, involved in the itaconic acid degrading pathway in itaconic acid producing A. terreus. The results will facilitate the improvement of itaconic acid production by metabolically engineering the catabolic pathway of itaconic acid in A. terreus.

Safety of tPA in stroke mimics and neuroimaging-negative cerebral ischemia(Podcast)(e–Pub ahead of print)(CME)

PubMed Central

Chernyshev, O.Y.; Martin-Schild, S.; Albright, K.C.; Barreto, A.; Misra, V.; Acosta, I.; Grotta, J.C.; Savitz, S.I.

2010-01-01

Background: Patients with acute neurologic symptoms may have other causes simulating ischemic stroke, called stroke mimics (SM), but they may also have averted strokes that do not appear as infarcts on neuroimaging, which we call neuroimaging-negative cerebral ischemia (NNCI). We determined the safety and outcome of IV thrombolysis within 3 hours of symptom onset in patients with SM and NNCI. Methods: Patients treated with IV tissue plasminogen activator (tPA) within 3 hours of symptom onset were identified from our stroke registry from June 2004 to October 2008. We collected admission NIH Stroke Scale (NIHSS) score, modified Rankin score (mRS), length of stay (LOS), symptomatic intracerebral hemorrhage (sICH), and discharge diagnosis. Results: Among 512 treated patients, 21% were found not to have an infarct on follow-up imaging. In the SM group (14%), average age was 55 years, median admission NIHSS was 7, median discharge NIHSS was 0, median LOS was 3 days, and there were no instances of sICH. The most common etiologies were seizure, complicated migraine, and conversion disorder. In the NNCI group (7%), average age was 61 years, median admission NIHSS was 7, median discharge NIHSS was 0, median LOS was 3 days, and there were no instances of sICH. Nearly all SM (87%) and NNCI (91%) patients were functionally independent on discharge (mRS 0–1). Conclusions: Our data support the safety of administering IV tissue plasminogen activator to patients with suspected acute cerebral ischemia within 3 hours of symptom onset, even when the diagnosis ultimately is found not to be stroke or imaging does not show an infarct. GLOSSARY AIS = acute ischemic stroke; CI = confidence interval; DWI = diffusion-weighted imaging; ED = emergency department; LOS = length of stay; mRS = modified Rankin score; NIHSS = NIH Stroke Scale; NNCI = neuroimaging-negative cerebral ischemia; OR = odds ratio; sICH = symptomatic intracerebral hemorrhage; SM = stroke mimics; tPA = tissue plasminogen

Fish Productivity in Open-Ocean Gyre Systems in the Late Oligocene and Miocene

NASA Astrophysics Data System (ADS)

Cuevas, J. M.; Sibert, E. C.; Norris, R. D.

2015-12-01

Understanding how marine ecosystems respond to climate change is very important as we continue to warm the climate. Fish represent a critical protein source for a significant portion of the global population, and as such, an understanding of fish production and its interactions with climate change may help better prepare for the future. Ichthyoliths, fossil fish teeth and shark scales, are a novel fossil group which can be used as an indicator for fish productivity. Several important climate events occurred during the Miocene (7 to 23 Ma), including the Middle Miocene Climatic Optimum. Here we reconstruct fish production from across the Miocene from Pacific and Atlantic Ocean gyres. South Atlantic samples, from Deep Sea Drilling Program (DSDP) Site 522 spanning from 30 to 20 Ma, show fairly variable numbers in the Oligocene (ranging from 100 to 800 ich/cm2/yr), but stabilization in the Early Miocene (around 400 ich/cm2/yr), suggesting that the beginning of the Miocene brought consistent conditions for fish production. In the North Pacific, our record from Ocean Drilling Program (ODP) Site 886 shows a distinct crash in fish productivity at 11 Ma, from 3500 ich/cm2/yr to a steady decline around 100 ich/cm2/yr for the next million years. This crash is followed by a marked increase in the presence of diatoms and biogenous opal. This is somewhat surprising, since in modern oceanic systems, an increase in diatoms and other large-celled phytoplankton is associated with shorter, more efficient food chains and higher levels of fish. It is also interesting to note that denticles remain consistently low at both sites, indicating consistently low shark populations through this time period. Together, these results suggest that the Late Oligocene and Miocene was a time of variable fish production and provide a window into understanding of dynamic ecosystem changes through the Miocene in open-ocean gyre ecosystems.

Rate of Contrast Extravasation on CT Angiography Predicts Hematoma Expansion and Mortality in Primary Intracerebral Hemorrhage

PubMed Central

Brouwers, H. Bart; Battey, Thomas W.K.; Musial, Hayley H.; Ciura, Viesha A.; Falcone, Guido J.; Ayres, Alison M.; Vashkevich, Anastasia; Schwab, Kristin; Viswanathan, Anand; Anderson, Christopher D.; Greenberg, Steven M.; Pomerantz, Stuart R.; Ortiz, Claudia J.; Goldstein, Joshua N.; Gonzalez, R. Gilberto; Rosand, Jonathan; Romero, Javier M.

2015-01-01

Background and Purpose In primary intracerebral hemorrhage (ICH), the presence of contrast extravasation following CT angiography (CTA), termed the ‘spot sign’, predicts hematoma expansion and mortality. Since the biological underpinnings of the spot sign are not fully understood, we investigated whether the rate of contrast extravasation - which may reflect the rate of bleeding - predicts expansion and mortality beyond the simple presence of the spot sign. Methods Consecutive ICH patients with first-pass CTA followed by a 90-second delayed post-contrast CT (delayed CTA) were included. CTAs were reviewed for spot sign presence by two blinded readers. Spot sign volumes on first-pass and delayed CTA and ICH volumes were measured using semi-automated software. Extravasation rates were calculated and tested for association with hematoma expansion and mortality using uni- and multivariable logistic regression. Results 162 patients were included, 48 (30%) of whom had ≥1 spot sign. Median spot sign volume was 0.04mL on first-pass CTA and 0.4mL on delayed CTA. Median extravasation rate was 0.23mL/min overall, and 0.30mL/min among expanders versus 0.07mL/min in non-expanders. Extravasation rates were also significantly higher in patients who died in hospital: 0.27mL/min versus 0.04mL/min. In multivariable analysis, the extravasation rate was independently associated with in-hospital mortality (OR1.09 [95%CI 1.04–1.18], p=0.004), 90-day mortality (OR1.15 [95%CI 1.08–1.27], p=0.0004), and hematoma expansion (OR1.03 [95%CI 1.01–1.08], p=0.047). Conclusions Contrast extravasation rate, or spot sign growth, further refines the ability to predict hematoma expansion and mortality. Our results support the hypothesis that the spot sign directly measures active bleeding in acute ICH. PMID:26243220

Comparison of the effects of 7.2% hypertonic saline and 20% mannitol on whole blood coagulation and platelet function in dogs with suspected intracranial hypertension - a pilot study.

PubMed

Yozova, Ivayla D; Howard, Judith; Henke, Diana; Dirkmann, Daniel; Adamik, Katja N

2017-06-19

Hyperosmolar therapy with either mannitol or hypertonic saline (HTS) is commonly used in the treatment of intracranial hypertension (ICH). In vitro data indicate that both mannitol and HTS affect coagulation and platelet function in dogs. The aim of this study was to compare the effects of 20% mannitol and 7.2% HTS on whole blood coagulation using rotational thromboelastometry (ROTEM®) and platelet function using a platelet function analyzer (PFA®) in dogs with suspected ICH. Thirty client-owned dogs with suspected ICH needing osmotherapy were randomized to receive either 20% mannitol (5 ml/kg IV over 15 min) or 7.2% HTS (4 ml/kg IV over 5 min). ROTEM® (EXTEM® and FIBTEM® assays) and PFA® analyses (collagen/ADP cartridges) were performed before (T 0 ), as well as 5 (T 5 ), 60 (T 60 ) and 120 (T 120 ) minutes after administration of HTS or mannitol. Data at T 5 , T 60 and T 120 were analyzed as a percentage of values at T 0 for comparison between groups, and as absolute values for comparison between time points, respectively. No significant difference was found between the groups for the percentage change of any parameter at any time point except for FIBTEM® clotting time. Within each group, no significant difference was found between time points for any parameter except for FIBTEM® clotting time in the HTS group, and EXTEM® and FIBTEM® maximum clot firmness in the mannitol group. Median ROTEM® values lay within institutional reference intervals in both groups at all time points, whereas median PFA® values were above the reference intervals at T 5 (both groups) and T 60 (HTS group). Using currently recommended doses, mannitol and HTS do not differ in their effects on whole blood coagulation and platelet function in dogs with suspected ICH. Moreover, no relevant impairment of whole blood coagulation was found following treatment with either solution, whereas a short-lived impairment of platelet function was found after both solutions.

Comparison of Spot Sign, Blend Sign and Black Hole Sign for Outcome Prediction in Patients with Intracerebral Hemorrhage

PubMed Central

Sporns, Peter B.; Schwake, Michael; Kemmling, André; Minnerup, Jens; Schwindt, Wolfram; Niederstadt, Thomas; Schmidt, Rene; Hanning, Uta

2017-01-01

Background and Purpose Blend sign (BS) and black hole sign (BHS) on non-contrast computed tomography (NCCT) and spot sign (SS) on CT-angiography (CTA) are indicators of early hematoma expansion in spontaneous intracerebral hemorrhage (ICH). However, their independent contributions to outcome have not been well explored. Methods In this retrospective study, inclusion criteria were: 1) spontaneous ICH and 2) NCCT and CTA performed on admission within 6 hours after onset of symptoms. Discharge outcome was dichotomized as good (modified Rankin Scale [mRS] 0-3) and poor (mRS 4-6) outcomes. The impacts of BHS, BS and SS on outcome were assessed in univariate and multivariable logistic regression models. Results Of 182 patients with spontaneous ICH, 26 (14.3%) presented with BHS, 37 (20.3%) with BS and 39 (21.4%) with SS. There was a substantial correlation between SS and BS (κ=0.701) and a moderate correlation between SS and BHS (κ=0.424). In univariable logistic regression, higher baseline hematoma volume (P<0.001), intraventricular hemorrhage (P=0.002) and the presence of BHS/BS/SS (all P<0.001) on admission CT scan were associated with poor outcome. Multivariable analysis identified intraventricular haemorrhage (odds ratio [OR] 2.22 per mL, P=0.022), baseline hematoma volume (OR 1.03 per mL, P<0.001) and SS on CTA (OR 11.43, P<0.001) as independent predictors of poor outcome, showing that SS compared to BS and BHS was more powerful to predict poor outcome. Conclusions The NCCT BHS and BS are correlated with the CTA SS and are reliable predictors of poor outcome in patients with ICH. Of the CT variables indicating early hematoma expansion, SS on CTA was the most reliable outcome predictor. However, given their correlation with SS on CTA, BS and BHS on NCCT can be useful for predicting outcome if CTA is not obtainable. PMID:29037015