Podcasts about intracerebral

There has been tremendous progress in recent decades in the management of ischemic strokes. Meanwhile, hemorrhagic strokes have stubbornly resisted this progress. Interventions for these types of strokes have failed again and again to show a benefit over standard medical management, until this year. The recently published ENRICH trial is the first to show that minimally invasive neurosurgery may improve functional outcomes for patients with hemorrhagic stroke. Study lead author, Dr. Gustavo Pradilla joins us today to talk about the differences between ENRICH and previous negative trials, and future neurosurgical approaches for spontaneous intracerebral hemorrhage. Dr. Pradilla is a Professor of Neurosurgery, Otolaryngology, and Head and Neck Surgery at Emory University School of Medicine and Chief of Neurosurgery at Grady Memorial Hospital. He spoke to Dr. Masoom J. Desai, neurointensivist and Assistant Professor of Neurology at the University of New Mexico. Series 5, Episode 9 Featuring: Guest: Dr. Gustavo Pradilla, Emory University School of Medicine & Grady Memorial Hospital Interviewer: Dr. Masoom Desai, University of New Mexico

What is the Human Brain Project and how might it advance epilepsy research? Dr. Maryam Nouri speaks with Dr. Philippe Ryvlin about the project in terms of the Human Intracerebral EEG Platform and how compiling these unique data from around the world could lead to new breakthroughs and understanding of epilepsy.The Human Intracerebral EEG Platform is an open-source platform designed for collecting, managing, analyzing, and sharing iEEG data at an international level. Its primary mission is to promote the development of large-scale iEEG research projects by facilitating international collaborations in the field.Links:Human Brain ProjectHuman Intracerebral EEG PlatformThe Virtual Brain Registration is now open for the 15th European Epilepsy Congress, held September 7th through 11th in Rome, Italy. Join your colleagues for five days of teaching courses, symposia, platform sessions, career development sessions, and more! To receive a discount on registration fees, register by May 10. Visit the ILAE website for more information, or register directly at bit.ly/ilaerome. That's

CME credits: 1.50 Valid until: 27-02-2025 Claim your CME credit at https://reachmd.com/programs/cme/implementation-of-the-2022-ahaasa-guideline-for-the-management-of-patients-with-spontaneous-intracerebral-hemorrhageare-you-doing-enough/18126/ Join experts and explore an exciting new frontier of care for patients on direct oral anticoagulants who present with an intracranial hemorrhage. Three factors can be used to optimize treatment: emerging data on anticoagulation reversal, artificial intelligence utilization, and evidence-based ABC care bundling. Learn how these developments transform clinical practice, deepen institutional expertise, and ultimately improve patient outcomes.

We've spent countless hours (rightfully so) discussing ischemic stroke management over the past several years. Sometimes, the other 20% of strokes, the hemorrhagic version, can get neglected. No, we don't have stroke-mobiles at MCHD to diagnose an ICH in the field, but there are some patient care keys to emphasize for EMS when we suspect non-traumatic, acute intracranial bleeding. REFERENCES 1. Qureshi AI, Palesch YY, Barsan WG, Hanley DF, Hsu CY, Martin RL, Moy CS, Silbergleit R, Steiner T, Suarez JI, Toyoda K, Wang Y, Yamamoto H, Yoon BW; ATACH-2 Trial Investigators and the Neurological Emergency Treatment Trials Network. Intensive Blood-Pressure Lowering in Patients with Acute Cerebral Hemorrhage. N Engl J Med. 2016 Sep 15;375(11):1033-43. 2. Zeiler FA, Sader N, West M, Gillman LM. Sodium Bicarbonate for Control of ICP: A Systematic Review. J Neurosurg Anesthesiol. 2018 Jan;30(1):2-9.

From the Institute for Stroke and Cerebrovascular Diseases at UTHealth Houston, today, we delve into a fascinating study exploring the intriguing concept known as the "obesity paradox" in patients with spontaneous intracerebral hemorrhage (ICH). Joining us are two esteemed guests, Dr. Jared Chen and Dr. Andrea Gaitan, who played integral roles in this research.  You are in for a treat as we unpack the study's background, objectives, and compelling results. The study, aiming to understand the association between body mass index (BMI) and functional outcomes in patients with ICH, also explores the role of race/ethnicity in this relationship. Their research article can be found at https://www.neurology.org/doi/10.1212/WNL.0000000000208014

Allie Curran, PharmD reviews blood pressure management strategies in intracerebral hemorrhage. For more pharmacy content, follow Mayo Clinic Pharmacy Residency Programs @MayoPharmRes. You can also connect with the Mayo Clinic's School of Continuous Professional Development online at https://ce.mayo.edu/ or on Twitter @MayoMedEd. 

Neurology Today Editor-in-chief Joseph E. Safdieh, MD, FAAN, discusses new research on the risk of spontaneous intracerebral hemorrhages after blood transfusions; the burden of long distance travel to see neurologists; and two promising biomarkers for early diagnosis of Parkinson's disease.

MedLink Neurology Podcast is delighted to feature selected episodes from BrainWaves, courtesy of James E Siegler MD, its originator and host. BrainWaves is an academic audio podcast whose mission is to educate medical providers through clinical cases and topical reviews in neurology, medicine, and the humanities, and episodes originally aired from 2016 to 2021. Originally released: July 18, 2017 Trauma and hypertension account for the overwhelming majority of cases of intracerebral hemorrhage. Today, we address the minority. In this week's episode, Dr. Steven Messe discusses the atypical causes of intracerebral hemorrhage and how they are managed. BrainWaves podcasts and online content are intended for medical education only and should not be used to guide medical decision-making in routine clinical practice. REFERENCES Biffi A, Greenberg SM. Cerebral amyloid angiopathy: a systematic review. J Clin Neurol 2011;7(1):1-9. PMID 21519520Gilden D, Cohrs RJ, Mahalingam R, Nagel MA. Varicella zoster virus vasculopathies: diverse clinical manifestations, laboratory features, pathogenesis, and treatment. Lancet Neurol 2009;8(8):731-40. PMID 19608099Mast H, Young WL, Koennecke HC, et al. Risk of spontaneous haemorrhage after diagnosis of cerebral arteriovenous malformation. Lancet 1997;350(9084):1065-8. PMID 10213548Ruíz-Sandoval JL, Cantú C, Barinagarrementeria F. Intracerebral hemorrhage in young people: analysis of risk factors, location, causes, and prognosis. Stroke 1999;30(3):537-41. PMID 10066848Siegler JE, Ichord RN. Teaching neuroimages: multicompartmental intracranial hemorrhage in a pediatric patient. Neurology 2016;87(23):e284. PMID 27920292  We believe that the principles expressed or implied in the podcast remain valid, but certain details may be superseded by evolving knowledge since the episode's original release date.

Welcome back Rounds Table Listeners! In this throwback episode, Mike and John discuss two papers exploring pharmacotherapy-based interventions for agitation experienced by individuals with dementia and when to start or restart antiplatelet therapy after stroke caused by intracerebral hemorrhage. Check it out below! Effects of Antiplatelet Therapy After Stroke Caused by Intracerebral Hemorrhage (0:00 – 7:14). ...The post TBT – Agitation in Dementia and Antiplatelet Therapy after Intracerebral Hemorrhage appeared first on Healthy Debate.

Welcome back Rounds Table Listeners! In this throwback episode, Mike and John discuss two papers exploring pharmacotherapy-based interventions for agitation experienced by individuals with dementia and when to start or restart antiplatelet therapy after stroke caused by intracerebral hemorrhage. Check it out below! Effects of Antiplatelet Therapy After Stroke Caused by Intracerebral Hemorrhage (0:00 – 7:14). ... The post TBT – Agitation in Dementia and Antiplatelet Therapy after Intracerebral Hemorrhage first appeared on Healthy Debate. The post TBT – Agitation in Dementia and Antiplatelet Therapy after Intracerebral Hemorrhage appeared first on Healthy Debate.

Dr. David Roh is an Assistant Professor of Neurology at Columbia University where he is an attending neurointensivist. In this lecture, Dr. Roh reviews the currently implemented diagnostic and treatment approaches for hemorrhage control in intracerebral hemorrhage and discusses novel approaches being investigated.

The ENRICH trial compared the outcomes between early surgical intervention using the BrainPath® Approach (i.e., MIPS) and a medically managed cohort. The integrated surgical approach included a combination of available technologies, including the FDA-cleared NICO BrainPath® for non-disruptive access and NICO Myriad® to achieve the goal of maximum clot evacuation. Alex Reynolds is joined by the ENRICH trial PIs, Gustavo Pradilla, Jonathan Ratcliff, and Alex Hall plus guests Chris Kellner and Kara Melmed to discuss the findings of the ENRICH clinical trial.  

Listen to the fifth episode of NCS' INSIGHTS series, this time on Intracerebral Hemorrhage. The INSIGHTS series is hosted by Casey Albin, MD and Salia Farrokh, PharmD, and covers different topics from Neurocritical Care ON CALL®, the only up-to-date, comprehensive resource to offer content exclusively dedicated to the practice of neurocritical care. Learn more about ON CALL®. This episode is sponsored by ceribell. Time is brain when it comes to seizures. Ceribell Point of Care EEG empowers the bedside team to detect or rule out seizure activity in minutes. To learn more, visit ceribell.com. The NCS Podcast is the official podcast of the Neurocritical Care Society.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.08.01.551291v1?rss=1 Authors: Hamilton, L. K., Mbra, P. E. H., Mailloux, S., Galoppin, M., Aumont, A., Fernandes, K. J. L. Abstract: Evidence from genetic and epidemiological studies point to lipid metabolism defects in both the brain and periphery being at the core of Alzheimer's disease (AD) pathogenesis. Previously, we reported that central inhibition of the rate-limiting enzyme in monounsaturated fatty acid synthesis, Stearoyl-CoA Desaturase (SCD), improves brain structure and function in the 3xTg mouse model of AD. Here, we tested whether these beneficial central effects involve recovery of peripheral metabolic defects, such as fat accumulation and glucose and insulin handling. As early as 3 months of age, 3xTg-AD mice exhibited obesity-like phenotypes including increased body weight and visceral and subcutaneous white adipose tissue deposition, as well as diabetic-like peripheral gluco-regulatory abnormalities. Intracerebral infusion of an SCD inhibitor that normalizes brain fatty acid metabolism, synapse loss and learning and memory deficits in middle-aged symptomatic 3xTg-AD mice did not affect peripheral phenotypes. This suggests that the beneficial effects of central SCD inhibition on cognitive function are not mediated by recovery of peripheral metabolic abnormalities. Given the widespread side-effects of systemically administered SCD inhibitors, these data suggest that selective inhibition of SCD in the brain may represent a clinically safer and more effective strategy for AD. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Welcome to the Master Class Series where we will learn from the masters in Neurocritical Care. On this episode, learn from Stephan Mayer, MD, FCCM, FNCS Director of Neurocritical Care and Emergency Neurology Services for Westchester Medical Center Health System and Professor of Neurology and Neurosurgery at New York Medical College as he discusses Hyperacute Management of Intracerebral Hemorrhage. NCS offers free CE credits for the NCS Podcast Series episodes. Listen to any of the posted episodes, complete a five-question survey, and claim your credits here! Credits are available for physicians, pharmacists, nurses, and non-physicians. The NCS Podcast is the official podcast of the Neurocritical Care Society. 

Dr. Seemant Chaturvedi discusses two trials in the field of intracerebral hemorrhage: INTERACT-3 trial and the ENRICH trial. This podcast is sponsored by argenx. Visit www.vyvgarthcp.com for more information.  

"...stroke is characterized by having poor blood flow to part of the brain leading to cell death they are grossly divided into ischemic and hemorrhagic with around 15 to 20 percent of Strokes being hemorrhagic a hemorrhagic stroke results from the rupture of a blood vessel leading to bleeding compared ischemic stroke that have a sudden occlusion of a blood vessel within hemorrhagic Strokes there are two main types intracerebral meaning bleeding within the brain itself which can be intraparenchymal Hemorrhage weather is bleeding within the brain tissue or an intraventricular Hemorrhage where there is bleeding within the ventricular system of the brain around one intracerebral hemorrhage into the ventricles intracerebral Hemorrhage is most commonly caused by hypertension and age-related cerebral amyloid angiopathy which is where deposition of Lloyd Peter peptide in the vessels leads to a weaker vessel structure which is then therefore more likely to bleed the other main type is a subarachnoid with the bleed occurs between the arachnoid Mater and the Pia Mater subarachnoid hemorrhages can be due to trauma or can be spontaneous in 85% of cases in taneous subarachnoid hemorrhage is caused by rupture of a cerebral aneurysm with the most common locations being the anterior communicating artery in 35 percent of cases internal carotid artery in 30% and middle cerebral artery in 22% in 30% of cases there are multiple aneurysms the remaining maybe caused by rupture of an arteriovenous malformation coagulopathy or extension of an intraparenchymal bleed note that both of these types of hemorrhagic I considered intracranial bleeds however other types of intracranial bleeds such as epidural and subdural hemorrhages are not considered hemorrhagic stroke we take this few seconds off to inform you are valued loyal listener about the best health and fitness podcast shows from the Nez pod Studios join us as we give you the best of the best health and wellness updates you can rely on for the treatment of chronic classic functional medicine Back to Basics health tips and special updates from the best doctors in the United States of America check out this health and wellness podcast shows explore Health talk healthy lifestyle matters excellent Health digest healthy and free daily and last but not least weekly health and fitness Corner also check out nasty Boise see the truest story never told Fiction podcast for that real life on the go experience with the 27 year old Golden boy..." Learn more about your ad choices. Visit megaphone.fm/adchoices

"...stroke is characterized by having poor blood flow to part of the brain leading to cell death they are grossly divided into ischemic and hemorrhagic with around 15 to 20 percent of Strokes being hemorrhagic a hemorrhagic stroke results from the rupture of a blood vessel leading to bleeding compared ischemic stroke that have a sudden occlusion of a blood vessel within hemorrhagic Strokes there are two main types intracerebral meaning bleeding within the brain itself which can be intraparenchymal Hemorrhage weather is bleeding within the brain tissue or an intraventricular Hemorrhage where there is bleeding within the ventricular system of the brain around one intracerebral hemorrhage into the ventricles intracerebral Hemorrhage is most commonly caused by hypertension and age-related cerebral amyloid angiopathy which is where deposition of Lloyd Peter peptide in the vessels leads to a weaker vessel structure which is then therefore more likely to bleed the other main type is a subarachnoid with the bleed occurs between the arachnoid Mater and the Pia Mater subarachnoid hemorrhages can be due to trauma or can be spontaneous in 85% of cases in taneous subarachnoid hemorrhage is caused by rupture of a cerebral aneurysm with the most common locations being the anterior communicating artery in 35 percent of cases internal carotid artery in 30% and middle cerebral artery in 22% in 30% of cases there are multiple aneurysms the remaining maybe caused by rupture of an arteriovenous malformation coagulopathy or extension of an intraparenchymal bleed note that both of these types of hemorrhagic I considered intracranial bleeds however other types of intracranial bleeds such as epidural and subdural hemorrhages are not considered hemorrhagic stroke we take this few seconds off to inform you are valued loyal listener about the best health and fitness podcast shows from the Nez pod Studios join us as we give you the best of the best health and wellness updates you can rely on for the treatment of chronic classic functional medicine Back to Basics health tips and special updates from the best doctors in the United States of America check out this health and wellness podcast shows explore Health talk healthy lifestyle matters excellent Health digest healthy and free daily and last but not least weekly health and fitness Corner also check out nasty Boise see the truest story never told Fiction podcast for that real life on the go experience with the 27 year old Golden boy..." Learn more about your ad choices. Visit megaphone.fm/adchoices

"...stroke is characterized by having poor blood flow to part of the brain leading to cell death they are grossly divided into ischemic and hemorrhagic with around 15 to 20 percent of Strokes being hemorrhagic a hemorrhagic stroke results from the rupture of a blood vessel leading to bleeding compared ischemic stroke that have a sudden occlusion of a blood vessel within hemorrhagic Strokes there are two main types intracerebral meaning bleeding within the brain itself which can be intraparenchymal Hemorrhage weather is bleeding within the brain tissue or an intraventricular Hemorrhage where there is bleeding within the ventricular system of the brain around one intracerebral hemorrhage into the ventricles intracerebral Hemorrhage is most commonly caused by hypertension and age-related cerebral amyloid angiopathy which is where deposition of Lloyd Peter peptide in the vessels leads to a weaker vessel structure which is then therefore more likely to bleed the other main type is a subarachnoid with the bleed occurs between the arachnoid Mater and the Pia Mater subarachnoid hemorrhages can be due to trauma or can be spontaneous in 85% of cases in taneous subarachnoid hemorrhage is caused by rupture of a cerebral aneurysm with the most common locations being the anterior communicating artery in 35 percent of cases internal carotid artery in 30% and middle cerebral artery in 22% in 30% of cases there are multiple aneurysms the remaining maybe caused by rupture of an arteriovenous malformation coagulopathy or extension of an intraparenchymal bleed note that both of these types of hemorrhagic I considered intracranial bleeds however other types of intracranial bleeds such as epidural and subdural hemorrhages are not considered hemorrhagic stroke we take this few seconds off to inform you are valued loyal listener about the best health and fitness podcast shows from the Nez pod Studios join us as we give you the best of the best health and wellness updates you can rely on for the treatment of chronic classic functional medicine Back to Basics health tips and special updates from the best doctors in the United States of America check out this health and wellness podcast shows explore Health talk healthy lifestyle matters excellent Health digest healthy and free daily and last but not least weekly health and fitness Corner also check out nasty Boise see the truest story never told Fiction podcast for that real life on the go experience with the 27 year old Golden boy..." Learn more about your ad choices. Visit megaphone.fm/adchoices

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.02.13.528249v1?rss=1 Authors: Jing, J., Chen, S., Wu, X., Yang, J., Liu, X., Wang, J., Wang, J., Li, Y., Zhang, P., Tang, Z. Abstract: Intracerebral hemorrhage (ICH) is an acute cerebrovascular disease with high disability and mortality rates. Recombinant tissue plasminogen activator (rtPA) is commonly applied for hematoma evacuation in minimally invasive surgery (MIS) after ICH. However, rtPA may contact directly with brain tissue during MIS procedure, which makes it necessary to discuss the safety of rtPA. We found that, in the in vivo ICH model induced by VII-type collagenase, rtPA treatment improved the neurological function of ICH mice, alleviated the pathological damage and decreased the apoptosis and autophagy level of the peri-hematoma tissue. In the in-vitro model of ICH induced by hemin, the administration of rtPA down-regulated neuronal apoptosis, autophagy, and endoplasmic reticulum stress of neurons. Transcriptome sequencing analysis showed that rtPA treatment upregulated the PI3K/AKT/mTOR pathway in neurons, and PI3K inhibitor (LY294002) can reverse the protective effects of rtPA in inhibiting excessive apoptosis, autophagy and ER-stress. Epidermal growth factor receptor inhibitor (AG-1487) reversed the effect of rtPA on PI3K/AKT/mTOR pathway, which might indicate that the EGF domain played an important role in the activation of PI3K/AKT/mTOR pathway. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.01.13.523921v1?rss=1 Authors: Alonso, F., Mercadal, B., Salvador, R., Ruffini, G., Bartolomei, F., Wendling, F., Modolo, J. Abstract: Intracranial electrodes are used clinically for diagnostic or therapeutic purposes, notably in drug-refractory epilepsy (DRE) among others. Visualization and quantification of the energy delivered through such electrodes is key to understanding how the resulting electric fields modulate neuronal excitability, i.e. the ratio between excitation and inhibition. Quantifying the electric field induced by electrical stimulation in a patient-specific manner is challenging, because these electric fields depend on a number of factors: electrode trajectory with respect to folded brain anatomy, biophysical (electrical conductivity / permittivity) properties of brain tissue and stimulation parameters such as electrode contacts position and intensity. Here, we aimed to evaluate various biophysical models for characterizing the electric fields induced by electrical stimulation in DRE patients undergoing stereoelectroencephalography (SEEG) recordings in the context of pre-surgical evaluation. This stimulation was performed with multiple-contact intracranial electrodes used in routine clinical practice. We introduced realistic 3D models of electrode geometry and trajectory in the neocortex. For the electrodes, we compared point (0D) and line (1D) sources approximations. For brain tissue, we considered three configurations of increasing complexity: a 6-layer spherical model, a toy model with a sulcus representation, replicating results from previous approaches; and went beyond the state-of-the-art by using a realistic head model geometry. Electrode geometry influenced the electric field distribution at close distances (~3 mm) from the electrode axis. For larger distances, the volume conductor geometry and electrical conductivity dominated electric field distribution. These results are the first step towards accurate and computationally tractable patient-specific models of electric fields induced by neuromodulation and neurostimulation procedures. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

We have another Grand Rounds follow up interview for you today, and a special one at that! Dr. Jared Chen has joined the Stroke Institute here at UTHealth Houston and we were so thankful not only for his time spent on his Grand Rounds presentation, but for sticking around for an in-depth look into his research and new faculty position. One of this year's Stroke Institute fellows, Mohammad Rauf, discussed Intracerebral Hemorrhage Therapies with Dr. Chen, past, present, and future, and we hope you enjoy, and share with colleagues. ____________________________________ Twitter: @UTHealthStroke Instagram: @UTHealthStroke Facebook: facebook.com/uthealthstroke Ideas and opinions are our own and this podcast is not a substitute for expert medical advice. About StrokeBusters is a podcast series of recorded conversations on the topic of stroke and cerebrovascular disease. Based in the Texas Medical Center, the largest medical center in the world, we tap into our local network of astonishing leaders in healthcare and medicine to discuss the latest and most exciting news on stroke. Throughout this ten-episode series, we connect with UTHealth physicians and researchers, many of who are experts in their field, to discuss their practice, cutting-edge research, and medical care. Who We Are The Institute for Stroke and Cerebrovascular Disease, better known as the Stroke Institute, serves as a multi-disciplinary hub for research and best practices in stroke recovery, stroke prevention, services, population health, and vascular dementia. We are one of the most active research and clinical programs in the country, the first Comprehensive Stroke Center in the state, and launched the first Mobile Stroke Unit in the nation. Our stroke program, founded by Dr. James Grotta in 1979, specializes in stroke epidemiology, clinical trial design, and basic science. We train the next generation of revolutionary academics and leaders in cerebrovascular disease through our NINDS-funded fellowship programs. Contact For more information or if you have any questions, please contact us at info.uthiscd@gmail.com

The post Episode 88. Review of the AHA 2022 Guideline for the Management of Patients With Spontaneous Intracerebral Hemorrhage appeared first on The Pharm So Hard Podcast.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.11.02.513525v1?rss=1 Authors: Lopez-Madrona, V. J., Trebuchon, A., Mindruta, I., Barbeau, E. J., Barborica, A., Pistol, C., Oane, I., ALARIO, F.- X., Benar, C. G. Abstract: The role of the hippocampal formation in memory recognition has been well studied in animals, with different pathways and structures linked to specific memory processes. In contrast, the hippocampus is commonly analyzed as a unique responsive area in most electrophysiological studies in humans, and the specific activity of its subfields remains unexplored. We combined intracerebral electroencephalogram recordings from epileptic patients with independent component analysis (ICA) during a memory recognition task involving the recognition of old and new images to disentangle the activities of multiple neuronal sources within the hippocampus. We identified two sources with different responses emerging from the hippocampus: a fast one (maximum at ~250 ms) that could not be directly identified from raw recordings, and a later one, peaking at ~400 ms. The earliest component was found in 12 out of 15 electrodes, with different amplitudes for old and new items in half of the electrodes. The latter component, identified in 13 out of 15 electrodes, had different delays for each condition, with a faster activation (~290 ms after stimulus onset) for recognized items. We hypothesize that both sources represent two steps of hippocampal memory recognition, the faster reflecting the input from other structures and the latter the hippocampal internal processing. Recognized images evoking early activations would facilitate neural computation in the hippocampus, accelerating memory retrieval of complementary information. Overall, our results suggest that hippocampal activity is composed by several sources, including an early system for memory recognition, that can be disentangled with ICA methods. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

In this week's podcast, Neurology Today's editor-in-chief discusses new findings on chronic kidney disease and risk for intracerebral hemorrhage, the potential of  gonadotropic replacement for improving cognition in Down syndrome, and distinguishing polio from acute flaccid myelitis and other viruses.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.09.06.506660v1?rss=1 Authors: Akeret, K., Buzzi, R. M., Thomson, B. R., Schwendinger, N., Klohs, J., Schulthess, N., Baselgia, L., Hansen, K., Regli, L., Vallelian, F., Hugelshofer, M., Schaer, D. Abstract: The functional neurological outcome of patients with intracerebral hemorrhage (ICH) strongly relates to the degree of secondary brain injury (ICH SBI) evolving within days after the initial bleeding. Different mechanisms including the incitement of inflammatory pathways, dysfunction of the blood brain barrier (BBB), activation of resident microglia, and an influx of blood-borne immune cells, have been hypothesized to contribute to ICH SBI. Yet, the spatiotemporal interplay of specific inflammatory processes within different brain compartments has not been sufficiently characterized, limiting potential therapeutic interventions to prevent and treat ICH SBI. Using a whole-blood injection model in mice, we systematically characterized the spatial and temporal dynamics of inflammatory processes after ICH using 7 Tesla magnetic resonance imaging (MRI), spatial RNA sequencing (spRNAseq), functional BBB assessment, and immunofluorescence average intensity mapping. We identified a pronounced early response of the choroid plexus (CP) peaking at 12 to 24h, that was characterized by inflammatory cytokine expression, epithelial and endothelial expression of leukocyte adhesion molecules, and the accumulation of leukocytes. In contrast, we observed a delayed secondary reaction pattern at the injection site (striatum) peaking at 96h, defined by gene expression corresponding to perilesional leukocyte infiltration and correlating to the delayed signal alteration seen on MRI. Pathway analysis revealed a dependence of the early inflammatory reaction in the CP on toll-like receptor 4 (TLR4) signaling via myeloid differentiation factor 88 (MyD88). TLR4 and MyD88 knockout mice corroborated this observation, lacking the early upregulation of adhesion molecules and leukocyte infiltration within the CP 24h after whole-blood injection. In conclusion, we report a biphasic brain reaction pattern after ICH with a MyD88 TLR4 dependent early inflammatory response of the CP, preceding inflammation, edema and leukocyte infiltration at the lesion site. Pharmacological targeting of the early CP activation might harbor the potential to modulate the development of ICH SBI. Copy rights belong to original authors. Visit the link for more info Podcast created by PaperPlayer

Moderator: Prof. Barbara Tettenborn (St. Gallen, Switzerland) Guest: Prof. Dr. Thorsten Steiner (Frankfurt, Germany) Prof. Barbara Tettenborn speaks with Prof. Dr. Thorsten Steiner about the etiology, diagnosis and management of intracerebral hemorrhages.

On Episode 18 of the Stroke Alert Podcast, host Dr. Negar Asdaghi highlights two articles from the July 2022 issue of Stroke: “Impact of Shunting Practice Patterns During Carotid Endarterectomy for Symptomatic Carotid Stenosis” and “Socioeconomic Inequalities in Reperfusion Therapy for Acute Ischemic Stroke.” She also interviews Dr. Magdy Selim about his article “Effect of Deferoxamine on Trajectory of Recovery After Intracerebral Hemorrhage: A Post Hoc Analysis of the i-DEF Trial.” Dr. Negar Asdaghi:         Let's start with some questions. 1) Is deferoxamine mesylate yet another failed agent for treatment of patients with intracerebral hemorrhage, or is deferoxamine getting us closer than ever to an approved therapy for this deadly form of stroke? 2) Are different strokes happening to different folks due to their disadvantaged socioeconomic status? 3) And finally, how does a surgeon's personal practice preference to either routinely or selectively use carotid shunting during carotid endarterectomy impact the recurrent risk of stroke or death in patients with symptomatic carotid disease? We'll tackle these questions and a lot more in today's podcast as we continue to cover the cerebrovascular world's latest and greatest because, without a doubt, this is the best in Stroke. Dr. Negar Asdaghi:         Welcome back to the July issue of the Stroke Alert Podcast. My name is Negar Asdaghi. I'm an Associate Professor of Neurology at the University of Miami Miller School of Medicine and your host for the monthly Stroke Alert Podcast. The July 2022 issue of Stroke contains a range of really interesting papers that I'd like to highlight here. As part of our Cochrane Corner articles, giving us short summaries of the long systematic review of a given topic, we have two short articles, one on the issue of local versus general anesthesia for carotid endarterectomy, where we learn that based on the current evidence, there's no convincing difference between local versus general anesthesia in the risk of stroke and death within 30 days after the procedure. In the second Cochrane Corner article, titled "Information Provision for Stroke Survivors and Their Carers," we learn that stroke survivors and their caregivers routinely report dissatisfaction with information provided to them by their clinicians about their condition and how active approaches to information provision is superior to its passive forms in improving patients' involvement in their care, their satisfaction, and, ultimately and not surprisingly, their stroke outcome. Dr. Negar Asdaghi:         As part of our original contributions in this issue of the journal, we have an important paper titled "The Risk of Early Versus Later Rebleeding From Dural AV Fistulas With Cortical Venous Drainage." We are reminded in this paper that cranial dural arteriovenous fistulas are classified based on their venous drainage into those with or those without cortical venous drainage, or CVD. Dural AV fistulas without CVD rarely cause intracranial bleeding, while those with CVD may cause hemorrhage. In this study, the authors show that the risk of rebleeding of dural AV fistulas with CVD presenting with hemorrhage is increased in the first two weeks after ICH, emphasizing the importance of early detection of these malformations by vascular imaging and early treatment of AV fistulas with cortical drainage. This paper is another analysis from the CONDOR registry. Our devoted Stroke Alert listeners recall that we covered this registry in more detail when we interviewed Dr. Amin-Hanjani last October on the outcomes of intracerebral hemorrhage patients found to have dural AV fistulas. I encourage you to review these articles in addition to listening to our podcast today. Dr. Negar Asdaghi:         Later in the podcast, I have the distinct honor of interviewing Dr. Magdy Selim from Harvard Medical School on a critical analysis from i-DEF trial to examine the long-term outcome of patients with ICH who were randomized to receive deferoxamine versus placebo. As an expert in the field of intracerebral hemorrhage and a member of the recently published American Heart Association Guidelines Committee, Dr. Selim was not fazed at all about the neutral results of the trial. "The future of ICH is bright," he says, and in the interview, he tells us why. But first, with these two articles. Dr. Negar Asdaghi:         Since its first reported successful surgery in 1953, carotid endarterectomy, or CEA, has become a common surgical procedure to prevent ischemic stroke in patients with carotid disease. CEA requires a temporary clamping of the carotid artery that is being worked on. During this time, the ipsilateral hemisphere is, of course, dependent on collateral flow from the posterior circulation or from the contralateral anterior circulation to maintain its perfusion pressure. Intraoperatively, various methods are used to monitor cerebral perfusion, and the risk of clamping-induced hypoperfusion is obviously variable for each patient depending on the patient's specific anatomy, their collateral status, and other risk factors. One way to protect the brain against possible clamp-induced ischemia is to do carotid shunting. The problem is that carotid shunting also comes with its own set of risks and problems. There's the risk of causing carotid dissection, embolization of pieces of the plaque during shunt insertion, or the risk of causing air embolism. Dr. Negar Asdaghi:         There are also other shunt-related local complications that should be noted, such as possibility of causing injuries to the cranial nerves or development of neck hematoma related to the more extensive surgical exposure required for shunting. So, it's not surprising that the practice patterns with regards to shunting is quite variable amongst different surgeons. There are surgeons that are considered routine shunters, and those who are considered selective shunters, meaning that the shunt is inserted only in cases with a particular indication. The question is whether the surgeon's preference for shunting can impact the CEA outcomes. In the current issue of the journal, we have an interesting study led by Dr. Randall DeMartino from the Division of Vascular and Endovascular Surgery at Mayo Clinic, Rochester, where the authors look at the impact of shunting practice patterns during carotid endarterectomy on the following post-CEA outcomes: number one, in-hospital stroke and in-hospital death rates, and number two, combined stroke and death in patients with a recent symptomatic carotid disease, that is, carotid stenosis associated with a history of either ipsilateral stroke or TIA within the past 14 days of endarterectomy. Dr. Negar Asdaghi:         So, the data for the study came from the ongoing Vascular Quality Initiative database, which comprises a network of more than 600 North American academic and community hospitals, and collects data on 12 different vascular procedures, one of which is CEA. The study included over 13,000 carotid endarterectomies performed from 2010 to 2019 for symptomatic carotid patients. This number came after they applied their exclusion criteria to all CEAs performed in the database during this timeframe, importantly excluding any asymptomatic carotid surgeries or those in whom surgery was performed after the two-week mark post qualifying TIA or stroke. Now, before we go over the results, let's go over some definitions used in the study. They had to classify surgeons to be able to do the study into two categories of routine versus selective shunters. So, what they did was to analyze all consecutive CEAs, whether they were done on symptomatic or asymptomatic carotids, in this database, aggregated at the surgeon level. Surgeons routinely shunting in over 95% of their procedures were gauged as routine shunters. Otherwise, they were classified as selective shunters. Dr. Negar Asdaghi:         Now, coming to each case included in this study, each surgical case was, in turn, classified into four categories based on whether or not a shunt was actually used for that particular case: category one, no shunt used; category two, shunt used as a routine procedure; number three, shunt used for a preoperative, mostly anatomical indication; number four, shunt was used for an intraoperative indication, which, as we mentioned before, these are mostly intraoperative hemodynamic compromised situations. And here are the results: In total, 3,186 of surgeries, that is 24% of surgeries, were performed by routine shunters versus 76% by selective shunters. So, most surgeons were selective shunters in this study. The demographic of patients operated by the routine versus selective shunters were more or less similar with regards to the age of the patients, most of their vascular risk factors, and the degree of ipsilateral or contralateral carotid stenosis or occlusion, with a few notable exceptions, in that patients undergoing surgery by routine shunters were more likely White, more likely to have had a prior CABG, more likely to undergo the operation while taking a P2Y12 inhibitor antiplatelet agent, and these patients were more likely to have had a TIA rather than a stroke as their qualifying event, which probably explains why they were more likely to be operated on within 48 hours of symptom onset as well. So, the authors accounted for these differences when they did their multivariate analysis. Dr. Negar Asdaghi:         The other thing to note was that overall, routine shunters used a shunt in 98.1% of their cases, whereas selective shunters used them in 46% of their cases. Now, in terms of their study outcomes, the shunting practice pattern did not impact the primary outcomes of in-hospital stroke or death, or a combination of these two outcomes, or even the odds of development of cranial nerve injuries or hemorrhage in the adjusted model, which is really good news here. But interestingly, in the final adjusted model, whether or not an actual shunt was placed during surgery did significantly increase the risk of postoperative stroke, with the odds ratio of 1.29, an effect that was entirely driven by the use of shunt by a surgeon classified as a selective shunter in this study. Dr. Negar Asdaghi:         So, in simple terms, if a shunt was placed during CEA, it did increase the risk of stroke only if that surgeon was a selective shunter. Another interesting association was that amongst selective shunters, placing a shunt for a patient with a very recent ischemic event, that is, TIA or stroke within the past 48 hours prior to surgery, and placing a shunt for an intraoperative indication, meaning shunt placement was not pre-surgically planned, also significantly increased the risk of postoperative stroke. So, what we learned from the study is that, though a surgeon's shunting practice pattern did not have an impact on the overall postoperative risk of stroke or death, the placement of a shunt did indeed increase the risk of postoperative stroke only if it was placed by a surgeon who is a selective shunter, especially for an intraoperative indication in a patient with a recent ischemic event. Dr. Negar Asdaghi:         So, shunts can be tricky, especially if they're done by a surgeon who doesn't place them routinely. So, my take-home message is that ultimately, like every other procedure in medicine, clinical outcomes are as much operator dependent as they are patient dependent, and for every procedure, it's fair to say that practice makes perfect. Dr. Negar Asdaghi:         It is now more than 25 years since intravenous thrombolytic therapy has been approved for treatment of patients with acute ischemic stroke and more than seven years since randomized control trials demonstrated the efficacy of mechanical thrombectomy to improve clinical outcome in ischemic stroke patients with large vessel occlusions. To date, reperfusion therapies are the only available acute treatments for select patients with ischemic stroke. What do we mean by "select"? "Select" meaning that not all patients will benefit from these therapies, making it absolutely necessary for clinicians to be up to date with various indications and contraindications to use these therapies. Needless to say that the criteria for reperfusion therapies do not and should not consider the socioeconomic status of patients, but sadly, socioeconomic inequalities seem to impact the use of reperfusion therapies. Dr. Negar Asdaghi:         In this issue of the journal, in the study titled "Socioeconomic Inequalities in Reperfusion Therapy for Acute Ischemic Stroke," Dr. Øgendahl Buus from Aarhus University Hospital in Denmark and colleagues studied the impact of the socioeconomic status of stroke patients on the odds of receiving reperfusion therapies in the large nationwide Danish Stroke Registry, or DSR. Now a bit about the registry: DSR contains prospectively collected nationwide data on all stroke patients admitted to Danish hospitals. It's interesting to note that in Denmark, stroke patients are exclusively admitted to public hospitals, and all departments treating stroke patients are obligated to report data to DSR. Now, for this study, they included over 63,000 stroke patients from 2013 to 2018. After excluding hemorrhagic stroke, TIAs, and other exclusion criteria of the study, they arrived at their sample size of 37,187 patients that were included in this study. Dr. Negar Asdaghi:         Now, a few definitions. The socioeconomic status of each patient was determined based on three parameters. Parameter number one, their educational level. It was categorized into three levels of low, medium, or high levels of education. Category number two, income level. This was calculated based on the average family equivalent disposable income, or FED income, during five years prior to stroke onset, again classified into three categories of high, medium, or low income. And the third factor was the employment status of the patient during the calendar year prior to the stroke onset, also categorized into three categories of employed, unemployed, and retired. And, of course, the authors used various definitions to be able to fit special situations into these categories. For instance, a person who is temporarily unemployed due to illness or other special situation was still categorized under the employed category. So, that gave them, in total, nine groups to analyze across these three categories. Dr. Negar Asdaghi:         And here are their findings. The median age of total stroke patients in the cohort was 73.2 years, 44.1% were women, 41% categorized under low educational level, 68% retired, and 33.3% had low income levels. Not surprisingly, patients and hospital characteristics varied tremendously across these nine groups of education, employment, and income, and a univariate analysis in general, low socioeconomic status was associated with more severe strokes, living alone, living at an assisted living residency, having had prior stroke, high comorbidity index score, hypertension, and late hospital arrival. So, they accounted for these differences in their multivariate analysis. Dr. Negar Asdaghi:         Now, overall, the treatment rates of IV thrombolysis was 17.6%, which is actually considered a very high percentage as compared to other registry-based studies, but the percentage of IV thrombolytic use dramatically varied based on the different socioeconomic designation. So, let's look at this. In the univariate analysis, for education, intravenous thrombolysis rates were 19.3% among patients with high educational level compared to 16.2% among patients with low educational level. Let's look at income. For income, IV thrombolytic treatment rates reach 20.7% for high-income patients compared to 14.8% for low-income patients. For employment status, thrombolytic rates were 23.7% among employed patients compared to 15.7% for unemployed patients. In their fully adjusted models, unemployed patients were less likely to receive IV lytics as compared to their employed counterparts. Dr. Negar Asdaghi:         Now, for thrombectomy, socioeconomic gradients were also noted for these three categories. For education, thrombectomy rates were 4.5% among patients with high education level compared to 3.6% among patients with low educational level. For income, treatment rates were 3.2% among low-income patients compared to 4.7% among high-income patients. But arguably, the most robust differences were noted again across the category of employment. Employed patients were nearly twice more likely to receive thrombectomy as compared to unemployed patients, rates being 5.1% versus 2.8%, respectively. Now, when they adjusted their analysis to only those patients presenting within the reperfusion time windows in the fully adjusted models, unemployment and low income remain significant negative predictors of receiving both of these reperfusion therapies. So, what we learned from this study is that stroke patients who were unemployed, earned a relatively low income, or had fewer years of formal education were less likely to receive life-saving reperfusion therapies despite potentially being eligible for these treatments. Dr. Negar Asdaghi:         Now, let's take a moment to really understand that data presented here are in the context of a tax-funded, universal healthcare offered across Denmark, where we can at least make the assumption that financial constraints potentially preventing access to therapies are likely minimized. There are many countries around the globe where patients or family members have to pay for these therapies before even receiving them. So, these findings from the current study from Denmark are alarming in that they point to possibly more robust inequalities across the globe in other healthcare systems. Dr. Negar Asdaghi:         Intracerebral hemorrhage, or ICH, is an aggressive form of stroke, typically carrying a higher morbidity and mortality than its ischemic counterpart. Yet much of the research in the field of intracerebral hemorrhage has followed the ischemic stroke footsteps, including defining the optimal primary outcome for the randomized trials of ICH. For ischemic stroke, the 90-day functional outcome, as measured by the modified Rankin Scale, is commonly used as a primary outcome in clinical trials. There are many reasons for this selection, including the ease of use and the fact that the majority of functional recovery post-ischemic stroke occurs during the first 90-day time period. But time to maximum recovery and, importantly, the trajectory of recovery may be different in hemorrhagic as compared to ischemic stroke. Defining the long-term outcomes and longitudinal trajectory of recovery in ICH is, therefore, important to better understand its prognosis and, of course, selecting the appropriate primary outcome measure for future randomized trials of ICH. Dr. Negar Asdaghi:         In the recent years, the safety and efficacy of various agents to improve ICH outcomes have been tested. Deferoxamine mesylate, an iron-chelating agent, is one such agent that was recently studied as part of the i-DEF multicenter randomized trial, and the main results of the study were published in Lancet Neurology in 2019. In the current issue of the journal, in the study titled "Effect of Deferoxamine on Trajectory of Recovery After Intracerebral Hemorrhage," we learn about the results of a post hoc analysis of i-DEF that looks at the trajectory of functional outcome in patients enrolled in the trial with a special attention on their continued recovery after the 90-day post-ICH mark. Dr. Negar Asdaghi:         Joining me now is the senior author of this paper, Dr. Magdy Selim, who's also one of the primary investigators of i-DEF trial. Dr. Selim is a Professor of Neurology at Harvard Medical School and Chief of Stroke Division at Beth Israel Deaconess Medical Center in Boston. He's a world renowned researcher in the field of cerebrovascular disorders with special focus on treatment of patients with intracerebral hemorrhage. Dr. Selim has led and currently leads multiple National Institutes of Health-funded clinical trials of intracerebral hemorrhage, including the ongoing SATURN trial. I'm delighted to welcome him to our podcast today. Good afternoon, Magdy. Thank you for joining us today. Dr. Magdy Selim:             Thank you, Dr. Asdaghi. It's really my pleasure to be here with you, and I'm certainly honored to do this today. Dr. Negar Asdaghi:         That's great. Thank you. So, let's start with some background on deferoxamine and the literature supporting the use of deferoxamine before i-DEF. Dr. Magdy Selim:             So, as you mentioned, deferoxamine is an iron chelator; it binds to iron and removes excess iron from the body. The unique thing about it is that it has other neuroprotective properties, which are good for hemorrhagic stroke and ischemic stroke. It also has anti-inflammatory and anti-apoptotic effects. It even lowers the blood pressure, which we know sometimes is helpful in intracerebral hemorrhage. The rationale behind this or why this would be effective really comes from animal studies. After you have a hemorrhage, there is hemolysis of the red blood cells, there is a release of hemoglobin degradation products, in particular, iron, and the accumulation of iron in the hematoma and the surrounding tissue triggers a cascade of molecular and cellular events that lead to what we call secondary injury, characterized by inflammation, hydroxyl radical formation, and cell death. And many animal studies, animal models of intracerebral hemorrhage, whether in pigs or in rats, young or aged rats, have shown that treatment with deferoxamine can reduce iron in the brain after intracerebral hemorrhage and also results in improved performance on behavioral tests. And that was the reason why we moved into clinical testing. Dr. Negar Asdaghi:         So, a lot of encouraging data before the trial. Can we hear a little bit about the trial, its design, and inclusion criteria, please? Dr. Magdy Selim:             Sure. So i-DEF was a phase 2 study, and actually it started as Hi-DEF, which was high dose deferoxamine, and then became i-DEF, which intermediate dose deferoxamine. So, it's a randomized, double blind, placebo control trial. We used something called futility design, which is actually sort of new in the stroke field. And we had 294 patients who had supratentorial hemorrhage that were randomized within 24 hours to either get placebo or deferoxamine. And deferoxamine initially was given at 62 mg per day for three days, but then we ran into some safety issues with this high dose, and that's why we lowered it to 32, and that became the intermediate dose, or the i-DEF. So, the only kind of thing unique about inclusion/exclusion criteria was that there was an age cutoff, patients had to be 80 or younger. They needed to have some deficit on the exam, so their NIH Stroke Scale had to be 6 or greater, and their GCS had to be greater than 6, and their modified Rankin before the onset of the hemorrhage had to be less than 1. Dr. Negar Asdaghi:         And so, what were the primary and secondary outcomes in i-DEF? Dr. Magdy Selim:             The primary outcome was twofold actually. One of them was safety. One of the issues we ran into with the high dose is that the drug is associated with increased risk for adult respiratory distress syndrome, ARDS. So, we wanted to make sure that this lower dose was safe, and it does not increase the instance of ARDS. The second thing was, as I said, we used something called the futility design, and we wanted to compare the outcome of patients treated with deferoxamine versus placebo to determine whether it's futile to move to a large phase 3 trial or not. And what we were looking at is a difference in outcome and modified Rankin 0 to 2 at 90 days, and the difference would be at least 12% in favor of deferoxamine in order for us to move forward. You asked about the secondary outcomes as well? Dr. Negar Asdaghi:         Yes. Dr. Magdy Selim:             So, actually, the secondary outcomes, they're relevant because they're relevant to the study that we just published. So, the secondary outcomes was also to look at modified Rankin 0 to 3, instead of 0 to 2, at 90 days and the difference between the two treatment groups. We wanted to look at the ordinal distribution of the Rankin at the same time point. And we also wanted to look at all the outcomes at six months, 180 days. And that came a little bit later in the course of the study because there was some evidence emerging at that time that maybe assessment of outcome later in intracerebral hemorrhage would be more accurate than assessing it early on. Dr. Negar Asdaghi:         So, I want to come back to the secondary outcome, of course, that's sort of the topic of your current paper in this issue of the journal, but can you just briefly tell us, please, the primary outcome and the sort of results of what was published in 2019 with i-DEF before we move on to the current paper? Dr. Magdy Selim:             Yeah. So, as I said, the primary outcome was the difference in the proportion of patients that achieved modified Rankin 0 to 2 at 90 days, and what we wanted to see is a difference of around 12%. Unfortunately, the primary outcome was neutral, we did not see that. But what we saw actually, almost all the secondary outcomes were positive, except for the primary outcome. So, when we looked at the secondary outcome using modified Rankin 0 to 3, instead of 0 to 2, the difference was 12.1%. When we looked at the difference in the modified Rankin 0 to 2 at six months, the difference was 15.6% in favor of deferoxamine, but these were secondary outcomes and not the primary outcomes. Dr. Negar Asdaghi:         So, the trial is almost positive. It just depends on how you define the primary outcome, which is really a nice segue to your current study. In the current study, you looked at this secondary outcome in a longitudinal way and looked at the mRS of 0 to 2 at six months from ICH. Can you please tell us about this current paper? Dr. Magdy Selim:             Yeah. So, one of the things that we did with i-DEF is that we were checking the modified Rankin at different time points for all the patients. So, we had it after one week, after one month, after two months, after three months, and after six months. And what we wanted really was a couple of things, just in patients with intracerebral hemorrhage without any treatment, what's the natural course of recovery? And the interesting thing we found out is that patients actually continue to improve over time, and that's what you expect, but what we didn't expect is that they even continue to improve after 90 days. Dr. Magdy Selim:             We always used to think that maximum recovery is around 90 days from ischemic stroke literature, but we saw a lot of patients getting better after 90 days. And this turns out to be also the case with deferoxamine, but the interesting thing is that the percentage of patients that had a good outcome, modified Rankin 0 to 2, was higher with deferoxamine at day seven, at day 30, at day 60, not at 90 days, but again at six months. So, actually, it was higher at all time points except our primary endpoint. Dr. Negar Asdaghi:         So, Magdy, you've already answered my next question, which is exactly what you alluded to, deferoxamine seemed to have improved the outcomes at all of those time points, except for the 90 day, which was the primary outcome of your trial. Why do you think the magic was lost at 90 days? Dr. Magdy Selim:             This is really the million-dollar question. I think we obviously struggled over this. And we went back, we thought maybe there was misrating of the modified Rankin in some of the patients. We tried to correct for this. The difference was bigger, but still not significant. So, we don't really have a good reason to tell you why, at this particular time point, we didn't see the difference except bad luck, I think. But I mean, there are reasons, I think, the question that people actually ask me is the opposite, is why do you think a drug that you give for three days early on is going to make a difference after six months? And I think there are biological reasons to explain this. Dr. Magdy Selim:             So, what happened is that those hemorrhage patients have a lot of other problems. They have increased ICP, they have hydrocephalus, they have intraventricular hemorrhage, and actually iron has been implicated in the development of hydrocephalus in chronic white matter injury. So, my explanation is that you start early on with the treatment, it does help, but it takes a while for it to kick in and for this kind of medical complication to resolve until actually you see the true effect of the drug. And maybe that's why you see the unmasking at the end between the two groups. Dr. Negar Asdaghi:         Yeah, I think I want to recap this for our listeners. Very important to, again, think about those things that some of the acute therapies that we offer the patients may not have a measurable improvement outcome difference early on, certainly with intravenous thrombolysis, we saw that, whereas we saw measurable outcome difference at 90 days, or maybe in this case at six months, but not quite early on. So, it doesn't mean that they don't work. We just are unable to measure that difference and improvement early on. So, what do you think the future holds for deferoxamine? Are we going to see another trial? Dr. Magdy Selim:             Well, I certainly hope so. We're working on some few ideas for that. A lot of people think that maybe we should just do the same thing, but look at six months as the primary outcome. But I think we're actually, that's probably not our primary thinking at this point in time. So, we have published other papers, other analysis, to show that the effect of deferoxamine actually relates to the volume of the hemorrhage. So, if the hemorrhage is very small, there is very minimal benefit. If the hemorrhage is very large, also there is very minimal benefit. And that's really to get kind of the big bang for your buck. You really want people who have mild-to-moderate size hemorrhages. So, we're thinking of a couple of ways to go about deferoxamine with this, whether alone or in combination with other interventions. So, hopefully, we'll have some stuff to share with you in the coming few years, two or three. Dr. Negar Asdaghi:         We'll definitely look forward to reading about those or being involved in the trials as a site, but there's a great way of just actually talking about my next question. It's just completely different than the current paper. I wanted to digress a bit and talk about the recently published intracerebral hemorrhage guidelines, which just published a few months ago. You were part of the guidelines committee. Can you give us a little bit of your point of view of what are the top two most important updates from the guidelines in ICH treatment? Dr. Magdy Selim:             Actually, the guidelines, for the first time this year, in the first page, they have the top 10 take-home messages or top 10 new ones. So, in my opinion, the most important ones, we usually tell you what to do, but here we tell you what not to do because we think it's not good for the patients. So, for example, using steroids just as a prophylactic therapy is actually not recommended. The same thing, we see a lot of people put patients with hemorrhage on hypertonic saline, hyperosmolar therapy, just prophylactically. I don't think there's any benefit that this helps as well, and the same thing for antiepileptic drugs. So, that was one important point. The second one was blood pressure lowering, and there is emphasis now that whatever you use to lower the blood pressure, you want to make sure that the blood pressure variability is very minimal and that there is a smooth kind of control over blood pressure that has been shown to be actually important in terms of help. I'm going to make them three, not two, because I think the third one is important. Dr. Negar Asdaghi:         Okay. I'll give you one more then. Dr. Magdy Selim:             Which is the first time we include this in the guideline, and with emphasis on the role of the home caregiver for hemorrhage patients and the psychological support, the education that they need, and the training that they need to actually care for these patients and how to improve their quality of life. So, I think that's an important aspect that we didn't touch upon before, and obviously very important. Dr. Negar Asdaghi:         Very important points. Let me just review them again for our listeners. So, don't do steroids, hypertonics, and preemptive antiepileptic therapies. They don't work. The second point that you raise is reduction of blood pressure, important to keep that in mind, but paying attention to blood pressure variability. And the third one, the importance of social aspect of care of patients with intracerebral hemorrhage. That's great for us. Let me just end with one last question. Magdy, thank you so much for all of this wonderful take-home messages from the current study from i-DEF and also the guidelines. There's been a lot of excitement in the field of ischemic stroke with the success of reperfusion therapies, and yet not much for intracerebral hemorrhage. What is your hope in terms of future therapies for ICH? Dr. Magdy Selim:             So, I happen to be one of the people who is very optimistic about the future of ICH. I think it's just a matter of time. But I think we need to make some changes. We need to really treat ICH as an emergency, so time is really important. And I think right now, you see a hemorrhage patient, they just put them on the side because they think that there's nothing to do. But the way I see the future evolving, and probably the breaking point to be, is that we can diagnose ICH in the field. You immediately lower the blood pressure, reverse coagulopathy if you can, and even kind of use hemostatic agents, if the FASTEST trial shows evidence to support that, and then you take them to the hospital where there might be some role for hematoma reduction using minimally invasive therapy and some other treatments like deferoxamine, or there are a lot of other agents to target the secondary injury at the same time. So, I think it's going to be a combination of things, and they need to happen in tandem and continuously, but we need to start quickly on these patients. Dr. Negar Asdaghi:         Dr. Magdy Selim, it's been a pleasure interviewing you on the podcast. We look forward to having you back and covering more of your work. Thank you for joining us. Dr. Magdy Selim:             Thank you very much for having me. Dr. Negar Asdaghi:         And this concludes our podcast for the July 2022 issue of Stroke. Please be sure to check out this month's table of contents for a full list of publications, including a series of Focus Updates on the very topic of, you guessed it, intracerebral hemorrhage. These updates are great complements to the newly published American Heart Association guidelines for the management of patients with spontaneous intracerebral hemorrhage in May 2022. Dr. Negar Asdaghi:         And with this, we end our July podcast and draw inspiration from one particular July story, which unfolded on July 20. In 1969, on this day, Commander Neil Armstrong and lunar module pilot Buzz Aldrin landed on the moon, and Armstrong became the first person to walk on the moon. The crew of Apollo 11 changed the course of history, landing humanity on another celestial body for the first time and later safely returning everyone back to earth. Armstrong, an experienced naval aviator, a test pilot, a decorated veteran, astronaut, and university professor, passed away in 2012 from complications of coronary artery disease, reminding us that every step we take in understanding, diagnosing, and treating vascular disorders is truly part of that giant leap to save the mankind. And what better way to do this than to stay alert with Stroke Alert. Dr. Negar Asdaghi:         This program is copyright of the American Heart Association, 2022. The opinions expressed by speakers in this podcast are their own and not necessarily those of the editors or of the American Heart Association. For more, visit AHAjournals.org.

Joanne apresenta um caso de AVC Hemorrágico para o Kaue e José Marcos, com um foco mais em abordagem, falamos um pouco sobre manifestações clínicas, etiologias, qual imagem pedir para o diagnóstico e como manejar. Tem interesse em ser nosso estagiário? Inscreva-se aqui: http://gg.gg/estagiotdc Referências: 1. Hemphill JC 3rd, Greenberg SM, Anderson CS, et al. Guidelines for the Management of Spontaneous Intracerebral Hemorrhage: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke 2015; 46:2032. 2. Gross BA, Jankowitz BT, Friedlander RM. Cerebral Intraparenchymal Hemorrhage: A Review. JAMA 2019; 321:1295. 3. Baharoglu MI, Cordonnier C, Al-Shahi Salman R, et al. Platelet transfusion versus standard care after acute stroke due to spontaneous cerebral haemorrhage associated with antiplatelet therapy (PATCH): a randomised, open-label, phase 3 trial. Lancet 2016; 387:2605. 4. Brott T, Broderick J, Kothari R, et al. Early hemorrhage growth in patients with intracerebral hemorrhage. Stroke 1997; 28:1. 5. Manning L, Hirakawa Y, Arima H, et al. Blood pressure variability and outcome after acute intracerebral haemorrhage: a post-hoc analysis of INTERACT2, a randomised controlled trial. Lancet Neurol 2014; 13:364. 6. Qureshi AI, Palesch YY, Foster LD, et al. Blood Pressure-Attained Analysis of ATACH 2 Trial. Stroke 2018; 49:1412. 7. Cordonnier C, Demchuk A, Ziai W, Anderson CS. Intracerebral haemorrhage: current approaches to acute management. Lancet 2018; 392:1257. 8. Kuramatsu JB, Biffi A, Gerner ST, et al. Association of Surgical Hematoma Evacuation vs Conservative Treatment With Functional Outcome in Patients With Cerebellar Intracerebral Hemorrhage. JAMA 2019; 322:1392. 9. Hanley DF, Thompson RE, Rosenblum M, et al. Efficacy and safety of minimally invasive surgery with thrombolysis in intracerebral haemorrhage evacuation (MISTIE III): a randomised, controlled, open-label, blinded endpoint phase 3 trial. Lancet 2019; 393:1021. 10. Mendelow AD, Gregson BA, Rowan EN, et al. Early surgery versus initial conservative treatment in patients with spontaneous supratentorial lobar intracerebral haematomas (STICH II): a randomised trial. Lancet 2013; 382:397.

Welcome back Rounds Table Listeners! We are back today with our Classic Rapid Fire Podcast! This week, Mike and John do a Rapid Fire session to discuss two recent papers exploring pharmacotherapy-based interventions for agitation experienced by individuals with dementia and when to start/restart antiplatelet therapy after stroke caused by intracerebral hemorrhage. Two papers, here ...The post Episode 32 – Agitation in Dementia and Antiplatelet Therapy after Intracerebral Hemorrhage appeared first on Healthy Debate.

Welcome back Rounds Table Listeners! We are back today with our Classic Rapid Fire Podcast! This week, Mike and John do a Rapid Fire session to discuss two recent papers exploring pharmacotherapy-based interventions for agitation experienced by individuals with dementia and when to start/restart antiplatelet therapy after stroke caused by intracerebral hemorrhage. Two papers, here ... The post Episode 32 – Agitation in Dementia and Antiplatelet Therapy after Intracerebral Hemorrhage appeared first on Healthy Debate.

Intracerebral hemorrhages are challenging to manage and patients need immediate interventions to preserve life and limit morbidity. Lessons learned from the ICU and ED shed light on how to best care for these patients.

Dr. Halley Alexander discusses the article, "Analysis Weighs Use of Prophylaxis Antiseizure Drugs in Aftermath of Spontaneous Intracerebral Hemorrhage". Show references: https://journals.lww.com/neurotodayonline/fulltext/2021/09020/analysis_weighs_use_of_prophylaxis_antiseizure.3.aspx

Interview with Lidia Moura, MD, MPH, author of Seizure Prophylaxis After Spontaneous Intracerebral Hemorrhage

Interview with Lidia Moura, MD, MPH, author of Seizure Prophylaxis After Spontaneous Intracerebral Hemorrhage

On this month's episode, Jason Siegel interviews Dr. Afshin Divani on his recent article, "The Magnitude of Blood Pressure Reduction Predicts Poor In-Hospital Outcome in Acute Intracerebral Hemorrhage". NCS offers free CE credits for the NCS Podcast Series episodes. Listen to any of the posted episodes, complete a five question survey, and claim your credits here! Credits are available for physicians, pharmacists, nurses, and non-physicians. The NCS Podcast is the official podcast of the Neurocritical Care Society. Our senior producer is Bonnie Rossow. Our host is Fawaz Almufti, and our production staff includes Tareq Saad Almaghrabi, Andrew Bauerschmidt, Leonid Groysman, Atul Kalanuria, Lauren Koffman, Kassi Kronfeld, Holly Ledyard, Lindsay Marchetti, Alexandra Reynolds, Lucia Rivera Lara, Jon Rosenberg, Jason Siegel, Zachary Threlkeld, Teddy Youn, and Chris Zammit. Our administrative staff includes Bonnie Rossow. Music by Mohan Kottapally.

Dr. Roland Faigle discusses the assessment of critical care needs for patients with spontaneous intracerebral hemorrhage.

Join Dr. Benjamin Miller as he interviews Dr. Rajeev Garg on his recent article, "The Influence of Diffusion Weighted Imaging Lesions on Outcomes in Patients with Acute Spontaneous Intracerebral Hemorrhage.” NCS offers free CE credits for the NCS Podcast Series episodes. Listen to any of the posted episodes, complete a five question survey, and claim your credits here! Credits are available for physicians, pharmacists, nurses, and non-physicians. The NCS Podcast is the official podcast of the Neurocritical Care Society. Our senior producer is Bonnie Rossow. Our host is Fawaz Almufti, and our production staff includes Tareq Saad Almaghrabi, Andrew Bauerschmidt, Leonid Groysman, Atul Kalanuria, Lauren Koffman, Kassi Kronfeld, Holly Ledyard, Lindsay Marchetti, Alexandra Reynolds, Lucia Rivera Lara, Jon Rosenberg, Jason Siegel, Zachary Threlkeld, Teddy Youn, and Chris Zammit. Our administrative staff includes Bonnie Rossow. Music by Mohan Kottapally.

Thanks to Dr John Williamson for lending us this episode that he recorded for another clinically-focused neurology podcast - Neuropodcases.   Listen in as he chats with Associated Professor Nawaf Yassi about intracerebral haemorrhage. They discuss hypertensive ICH, intraventricular extension, amyloid ICH, role of surgery, how to approach antithrombotics and ICH in younger patients. It's a fascinating conversation with plenty of clinical pearls.   We would highly encourage you to have a look at John's podcast over at https://www.neuropodcases.co.uk/ where you will also find imaging referred to in this podcast.

In this episode we are joined by Associate Professor Nawaf Yassi to discuss his approach to the investigation and management of a patient presenting with intracerebral haemorrhage. We discuss boht common and rarer causes for the presentation alongside the evidence base behind treatment decisions. Music: Good Starts - Jingle Punks https://youtu.be/NstTz8iyl-c

In this episode from the ACEP-EQUAL series, guest Dr. Bruce Lo reviews several common intracerebral hemorrhage scoring systems, the components, and tips on how to use them in real world practice. Guests: Bruce Lo, MD, MBA, FACEP Chief, Department of Emergency Medicine, Sentara Norfolk General Hospital Professor of Emergency Medicine, Eastern Virginia Medical School Host: Jason Woods, MD Audio Editor: Kellen Vu www.acep.org/equal References Hemphill JC 3rd, Bonovich DC, Besmertis L, Manley GT, Johnston SC. The ICH score: a simple, reliable grading scale for intracerebral hemorrhage. Stroke. 2001 Apr;32(4):891-7. doi: 10.1161/01.str.32.4.891. PMID: 11283388. Clarke JL, Johnston SC, Farrant M, Bernstein R, Tong D, Hemphill JC 3rd. External validation of the ICH score. Neurocrit Care. 2004;1(1):53-60. doi: 10.1385/NCC:1:1:53. PMID: 16174898. Gregório T, Pipa S, Cavaleiro P, Atanásio G, Albuquerque I, Chaves PC, Azevedo L. Assessment and Comparison of the Four Most Extensively Validated Prognostic Scales for Intracerebral Hemorrhage: Systematic Review with Meta-analysis. Neurocrit Care. 2019 Apr;30(2):449-466. doi: 10.1007/s12028-018-0633-6. PMID: 30426449. Pinho J, Costa AS, Araújo JM, Amorim JM, Ferreira C. Intracerebral hemorrhage outcome: A comprehensive update. J Neurol Sci. 2019 Mar 15;398:54-66. doi: 10.1016/j.jns.2019.01.013. Epub 2019 Jan 14. PMID: 30682522. Øie LR, Madsbu MA, Solheim O, Jakola AS, Giannadakis C, Vorhaug A, Padayachy L, Jensberg H, Dodick D, Salvesen Ø, Gulati S. Functional outcome and survival following spontaneous intracerebral hemorrhage: A retrospective population-based study. Brain Behav. 2018 Oct;8(10):e01113. doi: 10.1002/brb3.1113. Epub 2018 Sep 21. PMID: 30240164; PMCID: PMC6192392. Hemphill JC 3rd, Greenberg SM, Anderson CS, Becker K, Bendok BR, Cushman M, Fung GL, Goldstein JN, Macdonald RL, Mitchell PH, Scott PA, Selim MH, Woo D; American Heart Association Stroke Council; Council on Cardiovascular and Stroke Nursing; Council on Clinical Cardiology. Guidelines for the Management of Spontaneous Intracerebral Hemorrhage: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2015 Jul;46(7):2032-60. doi: 10.1161/STR.0000000000000069. Epub 2015 May 28. PMID: 26022637. Houben R, Schreuder FHBM, Bekelaar KJ, Claessens D, van Oostenbrugge RJ, Staals J. Predicting Prognosis of Intracerebral Hemorrhage (ICH): Performance of ICH Score Is Not Improved by Adding Oral Anticoagulant Use. Front Neurol. 2018 Feb 28;9:100. doi: 10.3389/fneur.2018.00100. PMID: 29541054; PMCID: PMC5836590.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.15.339184v1?rss=1 Authors: Wang, H., Faw, T. D., Lin, Y., Huang, S., Venkatraman, T. N., Cantillana, V., Lascola, C. D., James, M. L., Laskowitz, D. T. Abstract: Background: Intracerebral hemorrhage (ICH) is a devastating form of cerebrovascular disease for which there are no approved pharmacological interventions that improve outcomes. Apolipoprotein E (apoE) has emerged as a promising therapeutic target given its neuroprotective properties and ability to modify neuroinflammatory responses. We developed a 5-amino acid peptide, CN-105, that mimics the polar face of the apoE helical domain involved in receptor interactions, readily crosses the blood-brain barrier, and improves outcomes in well-established preclinical ICH models. In the current study, we investigated the therapeutic potential of CN-105 in translational ICH models that account for hypertensive comorbidity, sex, species, and age. Methods: In three separate experiments, we delivered three intravenous doses of CN-105 (up to 0.20 mg/kg) or vehicle to hypertensive male BPH/2J mice, spontaneously hypertensive female rats, or 11-month old male mice within 24-hours of ICH. Neuropathological and neurobehavioral outcomes were determined over 3, 7, and 9 days, respectively. Results: In spontaneously hypertensive male mice, there was a significant dose-dependent effect of CN-105 on vestibulomotor function at 0.05 and 0.20 mg/kg doses (p < 0.05; 95% CI: 0.91 - 153.70 and p < 0.001; 95% CI: 49.54 - 205.62), while 0.20 mg/kg also improved neuroseverity scores (p < 0.05; 95% CI: 0.27 - 11.00) and reduced ipsilateral brain edema (p < 0.05; 95% CI: -0.037 - -0.001). In spontaneously hypertensive female rats, CN-105 (0.05 mg/kg) had a significant effect on vestibulomotor function (p < 0.01; {eta}2 = 0.093) and neuroseverity scores (p < 0.05; {eta}2 = 0.083), and reduced contralateral edema expansion (p < 0.01; 95% CI: -1.41 - -0.39). In 11-month old male mice, CN-105 had a significant effect on vestibulomotor function (p < 0.001; {eta}2 = 0.111) but not neuroseverity scores (p > 0.05; {eta}2 = 0.034). Conclusions: Acute treatment with CN-105 improves outcomes in translational ICH models independent of sex, species, age, or hypertensive comorbidity. Copy rights belong to original authors. Visit the link for more info

Artikel: Alvikas et al. (2020) A systematic review and meta-analysis of traumatic intracranial hemorrhage in patients taking prehospital antiplatelet therapy: Is there a role for platelet transfusions? J. Trauma Acute Care Surg. 88:847–854. PMID: 32118818

Interview with Adnan I. Qureshi, MD, author of Outcomes of Intensive Systolic Blood Pressure Reduction in Patients With Intracerebral Hemorrhage and Excessively High Initial Systolic Blood Pressure: Post Hoc Analysis of a Randomized Clinical Trial

Interview with Adnan I. Qureshi, MD, author of Outcomes of Intensive Systolic Blood Pressure Reduction in Patients With Intracerebral Hemorrhage and Excessively High Initial Systolic Blood Pressure: Post Hoc Analysis of a Randomized Clinical Trial

The conclusion of our scenario of severe intraparenchymal hemorrhage with resulting herniation, with a closer look at neurological exams, prognostication, and the flow of care after initial stabilization, as well as our mindset as caregivers in these psychologically challenging cases. Takeaway lessons Early tracheostomy may not hold concrete benefits for neuro patients (i.e. improved mortality), … Continue reading "Episode 14: Intracerebral hemorrhage and elevated ICP (part 2)"

A typical case of severe intraparenchymal hemorrhage with resulting herniation. Takeaway lessons DOACs like apixaban (Eliquis), although not usually monitored using routine coagulation assays, tend to elevate the INR only slightly (e.g. 1.0–1.3 or so). A strikingly INR in warfarin-like ranges should raise suspicion for an additional occult cause of coagulopathy. Manage elevated ICPs using … Continue reading "Episode 13: Intracerebral hemorrhage and elevated ICP (part 1)"

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.06.11.145433v1?rss=1 Authors: Gueguen, M. C., Billeke, P., Lachaux, J.-P., Rheims, S., Kahane, P., Minotti, L., David, O., pessiglione, m., Bastin, J. Abstract: Whether maximizing rewards and minimizing punishments rely on distinct brain systems remains debated, inconsistent results coming from human neuroimaging and animal electrophysiology studies. Bridging the gap across species and techniques, we recorded intracerebral activity from twenty patients with epilepsy while they performed an instrumental learning task. We found that both reward and punishment prediction errors (PE), estimated from computational modeling of choice behavior, correlated positively with broadband gamma activity (BGA) in several brain regions. In all cases, BGA increased with both outcome (reward or punishment versus nothing) and surprise (how unexpected the outcome is). However, some regions (such as the ventromedial prefrontal and lateral orbitofrontal cortex) were more sensitive to reward PE, whereas others (such as the anterior insula and dorsolateral prefrontal cortex) were more sensitive to punishment PE. Thus, opponent systems in the human brain might mediate the repetition of rewarded choices and the avoidance of punished choices. Copy rights belong to original authors. Visit the link for more info

On this episode, Dr. Jim Siegler is joined by Dr. Rustam Al-Shahi Salman to discuss his recent article, "Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial." The NCS Podcast is the official podcast of the Neurocritical Care Society. Our senior producer is Bonnie Rossow. Our host is Fawaz Almufti, and our production staff includes Ramani Balu, Michael Brogan, Joshua Levine, Sarah Stern-Nezer, Benjamin Miller, Starane Shepherd, and Chris Zammit. Our administrative staff includes Bonnie Rossow and Angel Gindele. Music by Mohan Kottapally.

Commentary by Dr. Valentin Fuster

Dr. Kevin Sheth discusses his article, "Racial/Ethnic Disparities in the Risk of Intracerebral Hemorrhage Recurrence". Read the article here: https://n.neurology.org/content/94/3/e314

On this episode, Dr. Starane Shepherd is joined by Dr. Santosh Murthy to discuss his recent article, "Risk of Arterial Ischemic Events After Intracerebral Hemorrhage." This podcast is sponsored by the TTM Academy program at Penn Medicine, an educational initiative to improve care for patients following cardiac arrest and other eurocritical illness using targeted temperature management. This includes live CME workshops, an on-line video educational program, and a free podcast program. Find out more at www.pennttm.com. The NCS Podcast is the official podcast of the Neurocritical Care Society. Our senior producer is Bonnie Rossow. Our host is Fawaz Almufti, and our production staff includes Ramani Balu, Michael Brogan, Joshua Levine, Sarah Stern-Nezer, Benjamin Miller, Starane Shepherd, and Chris Zammit. Our administrative staff include Bonnie Rossow and Angel Gindele. Music by Mohan Kottapally.

Andrew Dixon from Radiopaedia covers the common pathology seen on CT scans in critical care. He covers basic anatomy and important areas not to miss, strokes, trauma, herniation syndromes, hypoxic brain injury and diffuse axonal injury

In the first segment, Dr. Jason Crowell talks with Dr. Casey Halpern about his paper on a three-year follow-up of a prospective trial of focused ultrasound thalamotomy for essential tremor. In the second part of the podcast, Will Rondeau talks with Dr. Jared Chen and Dr. Andrew Southerland about statins for neuroprotection in spontaneous intracerebral hemorrhage. Disclosures can be found at Neurology.org. CME Opportunity: Listen to this week’s Neurology Podcast and earn 0.5 AMA PRA Category 1 CME Credits™ by answering the multiple-choice questions in the online Podcast quiz.

Intracerebral hemorrhage (ICH) affects more than one million people annually, worldwide, and is the deadliest and most disabling type of stroke. In this episode of Critical Matters we will discuss the critical care management of ICH. Our guest is Dr. Sayona John, Associate Professor in the Department of Neurological Sciences at Rush Medical College. She is a practicing neurointensivist and also serves as the Head of the Section of Critical Care Neurology and Medical Director of the Neuroscience Intensive Care Unit & Neuroemergency Transfer programs at Rush University Medical Center in Chicago. Additional Resources: AHA 2015 Guidelines for the Management of Spontaneous Intracerebral Hemorrhage: http://bit.ly/33ovvZo The ICH score: a simple, reliable grading scale for intracerebral hemorrhage: http://bit.ly/2rsRh0G ICH Score Calculator: http://bit.ly/2OotfNx Music Mentioned in this Episode: Brother in Arms by Dire Straits: https://amzn.to/34pMxYj Money for Nothing by Dire Straits: http://bit.ly/34pAWZ9

Dr. Fawaz Al-Mufti is joined by Dr. Daniel Hanley and Dr. Issam Awad to discuss Dr. Hanley's recent article, "Efficacy and safety of minimally invasive surgery with thrombolysis in intracerebral haemorrhage evacuation (MISTIE III): a randomised, controlled, open-label, blinded endpoint phase 3 trial." This podcast is sponsored by the TTM Academy program at Penn Medicine, an educational initiative to improve care for patients following cardiac arrest and other eurocritical illness using targeted temperature management. This includes live CME workshops, an on-line video educational program, and a free podcast program. Find out more at www.pennttm.com. The NCS Podcast is the official podcast of the Neurocritical Care Society. Our senior producer is Bonnie Rossow. Our host is Fawaz Almufti, and our production staff includes Ramani Balu, Michael Brogan, Joshua Levine, Sarah Stern-Nezer, Benjamin Miller, Starane Shepherd, and Chris Zammit. Our administrative staff include Becca Stickney, Sara Memmen, and Angel Gindele. Music by Mohan Kottapally. Hanley DF, Thompson RE, Rosenblum M, Yenokyan G, et al. Efficacy and safety of minimally invasive surgery with thrombolysis in intracerebral haemorrhage evacuation (MISTIE III): a randomised, controlled, open-label, blinded endpoint phase 3 trial. Lancet. 2019 Mar 9;393(10175):1021-1032.

This month on the NCS Podcast, Dr. Chris Zammit interviews Dr. David Roh on their retrospective evaluation of ABO blood type on the risk of hematoma expansion in intracerebral hemorrhage. The NCS Podcast is the official podcast of the Neurocritical Care Society. Our senior producer is Jim Siegler. Our host is Fawaz Almufti, and our production staff includes Ramani Balu, Michael Brogan, Joshua Levine, Sarah Stern-Nezer, Benjamin Miller, Starane Shepherd, and Chris Zammit. Our administrative staff include Becca Stickney, Sara Memmen, and Angel Gindele. Music by Lee Roosevere. Roh D, Martin A, Sun CH, Eisenberger A, Boehme A, Elkind MSV, Pucci JU, Murthy S, Kamel H, Sansing L, Park S, Agarwal S, Connolly ES, Claassen J, Hod E and Francis RO. ABO Blood Type and Hematoma Expansion After Intracerebral Hemorrhage: An Exploratory Analysis. Neurocritical care. 2019;31:66-71.

  In this installment of the NCS Podcast, Dr. Michael Brogan interviews Dr. Andrew Naidech on their paper evaluating quality of life measures in patients who receive prophylactic levetiracetam for seizure prevention following intracerebral hemorrhage. The NCS Podcast is the official podcast of the Neurocritical Care Society. Our senior producer is Jim Siegler. Our host is Fawaz Almufti, and our production staff includes Ramani Balu, Michael Brogan, Joshua Levine, Sarah Stern-Nezer, Benjamin Miller, Starane Shepherd, and Chris Zammit. Our administrative staff include Becca Stickney, Sara Memmen, and Angel Gindele. Music by Lee Roosevere. Naidech AM, Beaumont J, Muldoon K, Liotta EM, Maas MB, Potts MB, et al. Prophylactic seizure medication and health-related quality of life after intracerebral hemorrhage. Crit Care Med. 2019;46(9):1480-1485.  

Do statins increase the risk of intracerebral haemorrhage (ICH) in patients with a previous stroke? Professor David Werring (Stroke Research Centre, UCL Institute Of Neurology, Queen Square, London, UK) joins Elizabeth Highton (JNNP podcast editor) for the first JNNP podcast of 2019. Read the full paper here: https://jnnp.bmj.com/content/90/1/75

Freddy Frost, research fellow in cystic fibrosis in Liverpool, hosts this week's episode of The Rounds Table with Alex Pickard, trainee in acute and emergency medicine in South London.  Together they cover new research on draining malignant pleural effusions and tranexamic acid in intracerebral haemorrhage. To start, Freddy walks listeners through a multicenter study looking ... The post REPLAY: Cut & Dried – Malignant Pleural Effusions and Tranexamic Acid in Intracerebral Haemorrhage appeared first on Healthy Debate.

Freddy Frost, research fellow in cystic fibrosis in Liverpool, hosts this week's episode of The Rounds Table with Alex Pickard, trainee in acute and emergency medicine in South London.  Together they cover new research on draining malignant pleural effusions and tranexamic acid in intracerebral haemorrhage. To start, Freddy walks listeners through a multicenter study looking ...The post REPLAY: Cut & Dried – Malignant Pleural Effusions and Tranexamic Acid in Intracerebral Haemorrhage appeared first on Healthy Debate.

Freddy Frost, research fellow in cystic fibrosis in Liverpool, hosts this week's episode of The Rounds Table with Alex Pickard, trainee in acute and emergency medicine in South London.  Together they cover new research on draining malignant pleural effusions and tranexamic acid in intracerebral haemorrhage. To start, Freddy walks listeners through a multicenter study looking ... The post Cut & Dried: Malignant Pleural Effusions and Tranexamic Acid in Intracerebral Haemorrhage appeared first on Healthy Debate.

Freddy Frost, research fellow in cystic fibrosis in Liverpool, hosts this week's episode of The Rounds Table with Alex Pickard, trainee in acute and emergency medicine in South London.  Together they cover new research on draining malignant pleural effusions and tranexamic acid in intracerebral haemorrhage. To start, Freddy walks listeners through a multicenter study looking ...The post Cut & Dried: Malignant Pleural Effusions and Tranexamic Acid in Intracerebral Haemorrhage appeared first on Healthy Debate.

A number of risk factors and clinical tools have been described in the literature that can accurately prognosticate outcome following intracerebral hemorrhage. But what do physicians and nurses rely on the most? Dr. David Hwang shares his experience with Dr. Starane Shepherd about which clinical and radiographic factors play a critical role in outcome prediction after ICH. The NCS Podcast is the official podcast of the Neurocritical Care Society. Our senior producer is Jim Siegler. Our production staff includes Joshua Levine, Becca Stickney, Michael Brogan, Starane Shepherd, Benjamin Miller, and Ramani Balu. Music by Lee Rosevere. Hwang DY, Chu SY, Dell CA, et al. Factors considered by clinicians when prognosticating intracerebral hemorrhage outcomes. Neurocritical Care. 2017; 27:316-325.

There exists a kind of self-fulfilling prognostic pessimism when it comes to ICH. And this pessimism sometimes leads to less than optimal care in patients who otherwise might have had a reasonably good outcome if they were managed aggressively. Despite the poor prognosis of these patients overall, there is some evidence to suggest that early aggressive medical management may improve outcomes. As such, the skill with which you manage your patient with ICH in those first few hours could be the most important determinant of their outcome. In this Golden Hour you have a chance to prevent hematoma expansion, stabilize intracerebral perfusion and give your patient the best chance of survival with neurologic recovery. The post Ep 104 Emergency Management of Intracerebral Hemorrhage – The Golden Hour appeared first on Emergency Medicine Cases.

Show description/summary:1) Intracerebral hemorrhage location and outcome among clinical trial participants 2) What's Trending: childhood amnesiaThis podcast begins and closes with Dr. Robert Gross, Editor-in-Chief, briefly discussing highlighted articles from the April 11, 2017 issue of Neurology. In the first segment, Dr. Andrew Schomer talks with Dr. Craig Anderson about his paper on intracerebral hemorrhage location and outcome among clinical trial participants. Then, for our “What's Trending” feature of the week, Dr. Ted Burns talks with Dr. Cristina Alberini about her paper on childhood amnesia. Disclosures can be found at Neurology.org.DISCLOSURES: Dr. Anderson served on scientific advisory boards for Astra Zeneca and Medtronic; receives honoraria and travel funding from Takeda China and Boehringer Ingelheim; serves on editorial boards for Stroke, Cerebrovascular Diseases, and International Journal of Stroke; and receives research support from the National Medical Research Council of Australia (grants 1052555, 1020462, and 1081356).Dr. Alberini serves on editorial boards for Neural Plasticity, Journal of Cell Science, Frontiers in Neuroscience, Neurobiology of Learning and Memory, Behavioral Neuroscience, Learning and Memory, European Brain Research Institute (EBRI) International Scientific Council (ISC), and Cellular and Molecular Neuroscience of Hippocampus. Dr. Burns serves as Podcast Editor for Neurology®; and has received research support for consulting activities with UCB, CSL Behring, Walgreens and Alexion Pharmaceuticals, Inc. All other participants report no disclosures.

Trauma and hypertension account for the overwhelming majority of cases of intracerebral hemorrhage. Today, we address the minority. In this week's episode, Dr. Steven Messe discusses the atypical causes of ICH and how they are managed. BrainWaves podcasts and online content are intended for medical education only and should not be used to guide medical decision making in routine clinical practice. REFERENCES 1. Biffi A and Greenberg SM. Cerebral amyloid angiopathy: a systematic review. J Clin Neurol. 2011;7:1-9. 2. Gilden D, Cohrs RJ, Mahalingam R and Nagel MA. Varicella zoster virus vasculopathies: diverse clinical manifestations, laboratory features, pathogenesis, and treatment. The Lancet Neurology. 2009;8:731-40. 3. Mast H, Young WL, Koennecke HC, Sciacca RR, Osipov A, Pile-Spellman J, Hacein-Bey L, Duong H, Stein BM and Mohr JP. Risk of spontaneous haemorrhage after diagnosis of cerebral arteriovenous malformation. Lancet. 1997;350:1065-8. 4. Ruiz-Sandoval JL, Cantu C and Barinagarrementeria F. Intracerebral hemorrhage in young people: analysis of risk factors, location, causes, and prognosis. Stroke; a journal of cerebral circulation. 1999;30:537-41. 5. Siegler JE and Ichord RN. Teaching NeuroImages: Multicompartmental intracranial hemorrhage in a pediatric patient. Neurology. 2016;87:e284.

Review Your brain is held inside your skull by a tri-layer membrane called the meninges.  These membranes and all the other structures in your brain are nourished by blood vessels, and different circumstances will make these vessels at risk of rupturing. *ALL BRAIN BLEEDS REQUIRE MEDICAL ATTENTION!*  Brain bleeds are classified based on the membrane they are closest to.  They can be caused by physiological malformations, stroke or aneurism from age or disease, or trauma. From the outside in Extracranial bleed: (extra = external; cranial = cranium = skull bones), between your skin and your skull.  Doesn't affect your brain, there is more room for it to stretch. Intracranial bleed: (intra = internal); bleeds inside the skull increase the intracranial pressure and requires medical intervention.  Main goal is to reduce intracranial pressure so brain cells aren't pressed on and damaged. Epidural (yep, that place they put the anesthesia for women having babies, except it's in the spinal cord): Epi = above, Dural = Dura mater, that topmost, durable layer of the meninges.  Between the skull and the dura mater. Subdural: Sub = under; blood leaks in between the dura mater and the arachnoid mater, which are normally in close contact, so the separation causes pain. Subarachnoid: under the arachnoid mater. Normally, under the arachnoid layer is the subarachnoid space which contain cerebral spinal fluid (CSF).  People who have had a subarachnoid bleed and survived, describe hearing a “thunderclap”.  Officially called a “thunderclap headache”.  It's like they can hear the blood vessel pop and experience extreme pain all over their head all at once.  Described as “the worst headache of my entire life”.  Because the pia mater under the subarachnoid space lays directly on top of the brain cells and follows all the grooves and wrinkles of the brain, this type of bleed will require emergent attention and possible surgery. Intracerebral: cerebral = cerebrum, the main part of your brain Intraparenchymal: Parenchyma = organ tissue, means it's right up against the brain cells Intraventricular: Ventricles = pockets inside the brain that make, hold, and reabsorb CSF.  The deepest part of the brain. *ALL BRAIN BLEEDS REQUIRE MEDICAL ATTENTION!*  Connect with me Support us on Patreon *NEW* Join the Pharmacist Answers Podcast Community on Facebook Subscribe: iTunes, Stitcher, GooglePlay, TuneIn Radio Like the Facebook page Music Credits:  “Radio Martini” Kevin MacLeod (incompetech.com)  Licensed under Creative Commons: By Attribution 3.0  http://creativecommons.org/licenses/by/3.0/

This is a fresh ICH discussion covering controversies in 2015: blood pressure control, reversal of anticoagulation, and prognosis.

This week we dive into the PATCH trial investigating the role of platelet transfusions in patients with spontaneous ICH on antiplatelet meds https://media.blubrry.com/coreem/content.blubrry.com/coreem/Podcast_Episode_55_0_Final_Cut.m4a Download Leave a Comment Tags: Intracerebral Hemorrhage, PATCH Trial, Platelets Show Notes Read More REBEL EM: The PATCH Trial: Hold the Platelets in Spontaneous Intracerebral Hemorrhage? St. Emlyn's: JC – Platelets for Intracranial Haemorrhage EM Lit of Note: Put the Platelets Away in ICH References

This week we dive into the PATCH trial investigating the role of platelet transfusions in patients with spontaneous ICH on antiplatelet meds https://media.blubrry.com/coreem/content.blubrry.com/coreem/Podcast_Episode_55_0_Final_Cut.m4a Download Leave a Comment Tags: Intracerebral Hemorrhage, PATCH Trial, Platelets Show Notes Read More REBEL EM: The PATCH Trial: Hold the Platelets in Spontaneous Intracerebral Hemorrhage? St. Emlyn's: JC – Platelets for Intracranial Haemorrhage EM Lit of Note: Put the Platelets Away in ICH References

This week we dive into the PATCH trial investigating the role of platelet transfusions in patients with spontaneous ICH on antiplatelet meds https://media.blubrry.com/coreem/content.blubrry.com/coreem/Podcast_Episode_55_0_Final_Cut.m4a Download Leave a Comment Tags: Intracerebral Hemorrhage, PATCH Trial, Platelets Show Notes Read More REBEL EM: The PATCH Trial: Hold the Platelets in Spontaneous Intracerebral Hemorrhage? St. Emlyn’s: JC – Platelets for Intracranial Haemorrhage EM Lit of Note: Put the Platelets Away in ICH References Baharoglu MI et al.

TBA

John B. Terry, MD from The Clinical Neuroscience Institute discusses management principles for spontaneous intracerebral hemorrhage.

After laying the foundations in the previous podcast, we dive below the dura mater in part 2 of the TBI series and take a look at subarachnoid, intraventricular, and intracerebral (parenchymal) hemorrhages as well as specific treatments for each.See omnystudio.com/listener for privacy information.

After laying the foundations in the previous podcast, we dive below the dura mater in part 2 of the TBI series and take a look at subarachnoid, intraventricular, and intracerebral (parenchymal) hemorrhages as well as specific treatments for each.

A conversation with Dr. Achint Patel of Mount Sinai Hospital in New York discussing his and his colleagues research outlined in the article "A National Perspective of Do-Not-Resuscitate Order Utilization Predictors in Intracerebral Hemorrhage."  Dr. Patel discusses many factors such as demographics and patients' insurance status that lead to variations in DNR utilization.   Read the article in question here.

Bloody Oral Anticoagulants – BCC talk 2014 The use of the New Oral Anticoagulant Drugs present unique challenges for the Intensive Care practitioner 1. The NOACs now have PBS approval for non-valvular AF, below knee DVT, DVT prophylaxis and low volume PE 2. There is no specific antidote for NOAC related bleeding but don’t despair there are some things that can help 3. Routine coagulation testing does not reflect drug levels or anticoagulation activity Global sales of Dabigatran topped $1billion in 2012.  This talk outlines the pharmacodynamics and pharmacokinetics of the NOACs. Limitations and cautions of use are outlined with a review of the extensive literature. Clinical cases involving the NOACs are presented. The timing of stopping the agents before minor or major surgery, the approach to a patient with intracranial haemorrhage taking oral anticoagulants and the challenges faced when patients have an Acute Kidney Injury whilst taking these

Editor's Audio Summary by Howard Bauchner, MD, Editor in Chief of JAMA, the Journal of the American Medical Association, for the February 24, 2015 issue

This neuroRAGE Special Edition is 82 min 03 sec long and includes: Introduction, ‘What's bubbling up?' ‘Traumatic Brain Injury and a bit about the Spine' ‘ICP Monitoring' ‘Intracerebral haemorrhage and Subarachnoid Haemorrhage' A ‘smorgasbord' of other neurocritical care questions, including the ‘cranial screwtop manoeuvre' ‘A blast from the past' by Oli Flower on the origins of the EEG ‘Words of Wisdom' from Mark Wilson

[Full Audio] Oli Flower discusses the tricky issue of prognostication in neuro disasters. This includes intracerrebral haemorrhage, traumatic brain injury, subarachnoid haemorrhage and ischaemic stroke. From Bedside Critical Care 2013 in Cairns. Go to Intensive Care Network for the audio and much more.

Michael Weinstein, MD, FACS, FCCP, speaks with Jonathan Elmer, MD, lead author on an article published in the August Critical Care Medicine.

Michael Weinstein, MD, FACS, FCCP, speaks with Jonathan Elmer, MD, lead author on an article published in the August Critical Care Medicine.

Where are we with stem cell treatments for stroke and Parkinson’s disease? At the Association of British Neurologists’ recent annual meeting in Glasgow, Neil Scolding, director of the Bristol Institute of Clinical Neurosciences, spoke to Keith Muir, Institute of Neuroscience and Psychology, Univeristy of Glasgow, and Roger Barker, John van Geest Centre for Brain Repair, University of Cambridge, about current research, and the expensive, unproven treatments already on the market.And using enlarged perivascular spaces to identify arteriopathy in intracerabral haemorrhage. Nick Ward, JNNP associate editor, asks David Werring, reader in neurology, UCL Institute of Neurology, what his MRI study reveals.See also:Enlarged perivascular spaces as a marker of underlying arteriopathy in intracerebral haemorrhage: a multicentre MRI cohort study http://bit.ly/12iZWieStriatal cell transplants for Huntington’s disease: where are we now? http://bit.ly/18InWwa

Rob Tarr, JNIS editor, talks to Jennifer Frontera, Neurosurgery, Mount Sinai School of Medicine, about her study showing aneurysm coiling followed by ICH evacuation is a viable alternative to clipping and ICH evacuation, for subarachnoid hemorrhage with intracerebral hematoma.See also:Management of subarachnoid hemorrhage with intracerebral hematoma: clipping and clot evacuation versus coil embolization followed by clot evacuation http://bit.ly/XnJABz

A case-based podcast on the acute management of intra-cerebral haemorrhage by Oliver Flower, an intensive care specialist from Sydney. It accompanies a recent review article: Flower O, Smith M. The acute management of intracerebral hemorrhage. Curr Opin Crit Care. 2011 Apr;17(2):106-14.  

In this episode, Dr Cian O'Kelly covers the topic of spontaneous intracerebral hemorrhage. After listening to this episode, learners should be able to: list the risk factors for spontaneous intracerebral hemorrhage. describe the typical presentation of the patient with a spontaneous intracerebral hemorrhage. describe the prognosis of spontaneous intracerebral hemorrhage. outline the management and investigation of the patient with a spontaneous intracerebral hemorrhage. list the indications for surgery in the patient with a spontaneous intracerebral hemorrhage. Running time: 12:12

Authors Professor Yanick J Crow(Prof of Genetic Medicine, Manchester University) and Dr Vijeya Ganesan(Senior Lecturer at the Institute of Child Health, London, and Consultant at Great Ormond Street Hospital, London) discuss the bacground of Aicardi-Goutières syndrome and the most recently idenitfied gene, SAMHD1 with Editor In Chief of Developmental Medicine and Child Neurology, Dr Peter Baxter. Please see below for a link to the paper: Intracerebral large artery disease in Aicardi–Goutières syndrome implicates SAMHD1 in vascular homeostasis (p 725-732) VENKATESWARAN RAMESH, BRUNO BERNARDI, ALTIN STAFA, CATERINA GARONE, EMILIO FRANZONI, MARIO ABINUN, PATRICK MITCHELL, DIPAYAN MITRA, MARK FRISWELL, JOHN NELSON, STAVIT A SHALEV, GILLIAN I RICE, HANNAH GORNALL, MARCIN SZYNKIEWICZ, FRANÇOIS AYMARD, VIJEYA GANESAN, JULIE PRENDIVILLE, JOHN H LIVINGSTON, YANICK J CROW PDF: http://www3.interscience.wiley.com/cgi-bin/fulltext/123580141/PDFSTART

Authors Professor Yanick J Crow(Prof of Genetic Medicine, Manchester University) and Dr Vijeya Ganesan(Senior Lecturer at the Institute of Child Health, London, and Consultant at Great Ormond Street Hospital, London) discuss the bacground of Aicardi-Goutières syndrome and the most recently idenitfied gene, SAMHD1 with Editor In Chief of Developmental Medicine and Child Neurology, Dr Peter Baxter. Please see below for a link to the paper: Intracerebral large artery disease in Aicardi–Goutières syndrome implicates SAMHD1 in vascular homeostasis (p 725-732) VENKATESWARAN RAMESH, BRUNO BERNARDI, ALTIN STAFA, CATERINA GARONE, EMILIO FRANZONI, MARIO ABINUN, PATRICK MITCHELL, DIPAYAN MITRA, MARK FRISWELL, JOHN NELSON, STAVIT A SHALEV, GILLIAN I RICE, HANNAH GORNALL, MARCIN SZYNKIEWICZ, FRANÇOIS AYMARD, VIJEYA GANESAN, JULIE PRENDIVILLE, JOHN H LIVINGSTON, YANICK J CROW PDF: http://www3.interscience.wiley.com/cgi-bin/fulltext/123580141/PDFSTART

Prion diseases are a group of rare, fatal neurodegenerative diseases, also known as transmissible spongiform encephalopathies (TSEs), that affect both animals and humans and include bovine spongiform encephalopathy (BSE) in cattle, scrapie in sheep, chronic wasting disease in deer and elk and Creutzfeldt-Jakob disease (CJD) in humans. TSEs are usually rapidly progressive and clinical symptoms comprise dementia and loss of movement coordination. A common hallmark of TSEs is the accumulation of an abnormal isoform (PrPSc) of the host-encoded prion protein (PrPc) in the brains of affected animals and humans. PrPc is a highly conserved cell surface sialoglycoprotein that is expressed in several cell types, mainly neuronal cells, but its normal physiological function is still not known. However, PrPc is elementary for the acquisition and the replication of prion diseases. Several inhibitors of the PrPSc formation have been reported, but none of them showed great potency in an in vivo application. Thus, the identification of the 37kDa/67kDa laminin receptor (LRP/LR) as the cell surface receptor for prions opened a new direction for the development of a TSE therapy. Currently, no treatment to slow down or stop the disease process in humans with any form of CJD is established. However, several strategies have been investigated to find an anti-prion treatment including development of a vaccination therapy and screening for potent chemical compounds. In scrapie-infected neuronal cells, which represent a widely used and well characterized in vitro model for transmissible spongiform encephalopathies, the accumulation of PrPSc has been prevented by transfection of (i) antisense LRP RNA, (ii) small interfering RNAs targeting the LRP mRNA and (iii) incubation with the polyclonal anti-LRP antibody W3. Furthermore, the knock down of surface LRP/LR resulted in a reduction of the cellular PrP levels, suggesting an interference with the PrP internalization process. Thus, LRP/LR is required for the PrPSc propagation in vitro and involved in the PrPc metabolism.Due to the existence of several LR genes, a major step to investigate the role of the 37kDa/67kDa laminin receptor in scrapie pathogenesis in vivo is the generation of transgenic mice exhibiting a lower level of LRP/LR. Hemizygous transgenic mice that express LRP/LR antisense RNA under the control of the neuron-specific enolase (NSE) promoter were generated and showed a reduced LRP/LR protein level in the cerebellum and the hippocampus. Intracerebral inoculation of these transgenic mice with the scrapie agent will show, whether the accumulation of pathogenic PrPSc in the brain is delayed or prevented due to a reduced LRP/LR level. A further therapeutic anti-prion approach is given by LRP/LR deletion mutants that can be secreted to the cell culture medium and might act as decoys. Previously, it has been demonstrated that a transmembrane deletion mutant is able to prevent PrPc binding and internalization. In vitro studies using an N-terminally truncated LRP mutant, representing the extracellular domain of LRP/LR (LRP102-295::FLAG), revealed a reduced binding of (i) recombinant cellular PrP to mouse neuroblastoma cells, (ii) infectious moPrP 27-30 to BHK21 cells and (iii) interfered with the PrPSc propagation in chronically scrapie-infected mouse neuroblastoma cells. Furthermore, a cell free binding assay demonstrated the direct binding of the LRP102-295::FLAG mutant to both PrPc and PrPSc. These results together with the finding that that endogenous LRP levels remain unaffected by the expression of the mutant indicate that the secreted LRP102-295::FLAG mutant may act in a trans-dominant negative manner as a decoy by trapping PrP molecules. To investigate the therapeutic potential of the LRP102-295::FLAG decoy mutant in vivo transgenic mice were generated ectopically expressing LRP102-295::FLAG in the brain. Animals showed no phenotype and transgene expression was detected in cortical and cerebellar brain regions. An intracerebral prion inoculation of these mice will prove whether the expression of the LRP102-295::FLAG mutant can impair the PrPSc accumulation in the brain and can thus, act as a alternative therapeutic tool in prion diseases. The recent finding that experimental introduction of RNA can be used to interfere with the function of an endogenous gene (RNA interference) provided another tool for the development of gene-specific therapeutics. In order to evaluate a gene transfer therapeutic TSE strategy, human immunodeficiency virus (HIV)-derived vectors that express short hairpin RNA (shRNA) directed against the LRP mRNA were used. Following integration of LRP-shRNA-expressing lentiviral vectors into the genome of neuronal cells efficient LRP/LR downregulation was observed. In scrapie infected neuronal cells, downregulation of the LRP gene expression resulted in a diminishment of PrPSc propagation, providing a further therapeutic strategy in the development of a TSE treatment.

Sat, 1 Jan 2005 12:00:00 +0100 https://epub.ub.uni-muenchen.de/16800/1/10_1159_000085510.pdf Hamann, Gerhard F.; Arbusow, Viktor; Holtmannspötter, Markus; Liebetrau, Martin ddc:610, Medizin

Background: The prognosis for patients with malignant astrocytoma or brain metastases is often fatal despite intensive therapy. Therefore we wished to elucidate whether the quality of life (QoL) is a determinant of overall survival (OAS). Patients and Methods: From 1997 to 2000 153 patients with brain tumours were screened; 39 patients (26%) refused to participate and further 47 patients were excluded (cerebral impairment 14%, amaurosis/language problems 3%, Karnofsky performance score < 50% 7%, death 8%, non-compliance 7%). Thus, 57 patients were analysed (33 with primary brain tumours, 24 with brain metastases). With the FACT-G questionnaire cancer-specific aspects of health-related QoL were assessed. Results: Patients with metastases showed a lower QoL in the physical sphere than patients with astrocytoma, but there were no significant differences in OAS. Median survival of patients with good QoL was 31.3 months versus 14.2 months in patients with bad QoL. Only the two variables `living with a spouse' and FACT-G sum score had a statistically significant influence on survival (p = 0.033 and p = 0.003) modelled by the Cox-PH regression. Patients who did not live with a spouse had shorter survival times than the other patients. Conclusion: Health-related QoL can serve to identify a patient group with higher risks of death.