Podcasts about acute ischemic stroke

Rapid advances in acute ischemic stroke care have expanded treatment windows and improved patient outcomes through thrombolysis, mechanical thrombectomy, and optimized antithrombotic strategies. This episode highlights evolving approaches to patient selection, the growing role of tenecteplase, and the importance of team-based systems of care in delivering timely, effective treatment. In this episode, Casey S. Albin, MD, FAAN, speaks with Christopher R. Leon Guerrero, MD, author of the article "Thrombolysis, Thrombectomy, and Antithrombotic Therapy for Acute Ischemic Stroke" in the Continuum® June 2026 Cerebrovascular Disease issue. Dr. Albin is a Continuum® Audio interviewer, associate editor of media engagement, and an assistant professor of neurology and neurosurgery at Emory University School of Medicine in Atlanta, Georgia. Dr. Leon Guerrero is an associate professor of neurology and the adult neurology residency program director at Atrium Health Carolinas Medical Center in Charlotte, North Carolina, where he also serves as outpatient stroke director. Additional Resources Read the article: Thrombolysis, Thrombectomy, and Antithrombotic Therapy for Acute Ischemic Stroke Subscribe to Continuum®: shop.lww.com/Continuum Earn CME (available only to AAN members): continpub.com/AudioCME Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): continpub.com/Aloud More about the American Academy of Neurology: aan.com Social Media facebook.com/continuumcme @ContinuumAAN Host: @caseyalbin Full episode transcript available here Dr Albin: In stroke care, every minute kills nearly two million neurons. But today, we're going to unpack all the details about the latest treatments that can give those neurons back.  Dr Jones: This is Dr. Lyell Jones, Editor-in-Chief of Continuum. Thank you for listening to Continuum Audio. Be sure to visit the links in the episode notes for information about earning CME, subscribing to the journal, and exclusive access to interviews not featured on the podcast.  Dr Albin: Hello and welcome. This is Dr. Casey Albin. Today, I'm interviewing Dr. Christopher Leon-Guerrero about his article on Thrombolysis, Thrombectomy, and Antithrombotic Therapy for Acute Ischemic Stroke. This article appears in the April 2026 Continuum issue on cerebrovascular disease. Welcome to the podcast. I always like to start by just having you introduce yourself so our listeners know a little bit about you.  Dr Leon-Guerrero: Thanks for the introduction, Dr. Albin. Really glad to be here today. My name is Chris Leon-Guerrero. I'm a vascular neurologist at Atrium Health in Charlotte, North Carolina, at Carolinas Medical Center. I'm an associate professor in the Department of Neurology. I serve as our Neurology Residency Program Director, and I also wear the hat of an outpatient stroke director in our clinics.  Dr Albin: So, you are wearing a lot of hats and balancing a lot of things, and it's a really exciting time to be talking about this. For our listeners, we are recording this right after the launch of the American Heart Association, American Stroke Association just released their new guidelines on acute ischemic care. So, no better time to kind of dive into some of this. And really, when I think about acute ischemic stroke care, it's dramatically transformed in the last two to three decades. I mean, from lengthening time windows for IV thrombolysis to expanded thrombectomy eligibility, this is really, I think, some of the most exciting stuff in neurology. And your article did a fantastic job of distilling those rapid advancements and clarifying some of the evidence behind some of these new evolving treatment selections and imaging modalities, and it's exciting. So, let's just start with thrombolysis. Where are we now with IV thrombolytics and the time windows there?  Dr Leon-Guerrero: So, a lot has changed in the last decade, since that initial trial with NINDS, nearly thirty years ago. We're still giving intravenous thrombolysis in the traditional time window up to 4.5 hours, and really emphasizing we should be selecting patients for treatment early and quickly as possible. In most of those cases, a non-con head CT is sufficient to rule out bleeding and initiate treatment as quickly as possible. Where things have gotten really exciting is using advanced neuroimaging to help select patients beyond that traditional 4.5 hour window, and we're able to treat patients even up to twenty-four hours from symptom onset.  Dr Albin: Which is really exciting. It has really totally shifted the paradigm here. You know, I think most listeners are going to be pretty familiar with three to four and a half hours. Like, that's sort of our standard. What can you tell us about some of the advanced imaging we're using for that later selection period?  Dr Leon-Guerrero: It's around the principle of you want to be able to, uh, rescue significant salvageable tissue without a lot of core. So, this large profusion deficit and small core is really how you're trying to select out these patients. And two types of modalities are used. One is going to be MRI, and a lot of those imaging protocols, you know, are outlined in the WAKE UP trial and basically are looking for patients with DWI hyperintense lesions and FLAIR negative lesions to suggest that patients in an early time window that's treatable for thrombolysis. And then in the other category, we'll be using profusion imaging, whether that's CT profusion or MR profusion, to look for patients with large salvageable tissue.  Dr Albin: Yeah. And I think that this has been one of the things that, to me, has been really impactful is I think when WAKE UP came out, it was exciting. It was fun to sort of think about, "Hey, we're going to be able to use MRI." But MRI can be very challenging to get acutely, especially in community centers where they don't have the capabilities to get someone from the emergency department into an MRI rapidly enough to make thrombolysis decisions. So, to see some of that expand to CT profusion has been really exciting. How are you going about sort of counseling patients or thinking about their risk when you're using some of those, like, advanced imaging techniques?  Dr Leon-Guerrero: Yeah. I think it's similar to the conversations we've had with patients even within the traditional 4.5 hour window. The risk for intravenous thrombolysis is hemorrhage, and counseling patients on the, you know, the risk and benefits of hemorrhage and the potential clinical benefit of receiving thrombolytics is important. And then providing patients with that information to make an informed decision, so that they can make the best decision for their own care.  Dr Albin: Totally. And it's, again, time sensitive, but trying to give families enough information and enough time to sort of process those, especially when it's a little bit beyond the standard that we're so used to consenting for. The other big area that's really changed is that tenecteplase has become the star of the show. It's really gained momentum, so what should clinicians understand about this?  Dr Leon-Guerrero: Yeah. There's been an explosion of data over the last decade on tenecteplase supporting its use for clinical practice. You know, there was recent updates even from the neurology journal with a large meta-analysis with all of the data showing good clinical outcomes and perhaps even lower risk of bleeding. And so, I think you're seeing a lot of centers across the country switching from alteplase to tenecteplase. There's some practical advantages. So tenecteplase is a one-time bolus dose. And then biologically, it seems to have better fibrin specificity, longer half-life, which may ultimately make it a more attractive drug and may make it even more effective. But I think the practical aspects of tenecteplase are not to be understated. I think there's a lot of advantages for speed and efficiency and for centers to make that switch.  Dr Albin: Yeah. I remember when our health system made the pivot from alteplase to tenecteplase. Like any changes, that obviously created some adjustments with the new workflow. But, the fact that this could be given just as a one-time dose and not with the "we got to calculate the bolus, and now we got to get the infusion on board," like really simplified workflow. So, I think that's been pragmatically one of the nicest things we've done in stroke care. Really exciting.  Dr Leon-Guerrero: Yeah. And, you know, it's a doable thing. I think you have to be, very deliberate about it at whatever center you're at to make sure that all stakeholders are aware of that change. I think that's helpful to get everybody involved and have a lot of planning to avoid wrong dosing errors or inadvertently dosing as alteplase versus tenecteplase. But it's certainly doable, and I think in the long term, centers that have switched have been pretty satisfied with tenecteplase.  Dr Albin: And you know, initially when this came out, there really was sort of a debate about, is it gonna be 0.25? Was it gonna be 0.4? Where have we landed with that debate?  Dr Leon-Guerrero: So, I think we found the correct dose is 0.25 milligrams per kilogram is the recommended dose with a max out of 25 milligrams. There's some within the American Heart Association guidelines that were just published. They mentioned even tier dosing based on 10 kilograms, so intervals. So, that may be an easier way for centers to do it. But that cap out dose of 25 milligrams at 0.25 milligrams per kilogram, I think, is the sweet spot.  Dr Albin: Yeah. That's great, and I think that that has helped, you know, say, "This is what we're doing. There's not a debate that's happening anymore." And that really just got codified in the new ASA guidelines, so really exciting there. So, there is a lot of guidance for these patients, but I think one of the things that your article really tackled is the fact that there are some special populations, where we really still don't have a lot of guidance. And so, I think just to kind of distill those for the listeners, thinking about our pregnant patients, thinking about children, how are we approaching thrombolysis decisions in these special populations?  Dr Leon-Guerrero: These are always tough cases. For example, for pregnant women, they've often been excluded in the thrombolytic trials. But there's still evidence. You know, there's some inference based on the evidence we do have, and there's a lot of registry and case reports suggesting potential safe treatment for pregnant women. And I think when you're approaching those cases, again, it's gonna be patient-centered and really should be multidisciplinary. These are the types of cases you really need to lean on your maternal fetal medicine colleagues, your high-risk OBGYNs, your obstetricians to help with that decision-making. And I think, a multidisciplinary approach is the way to go for these cases. It's the same thing with the pediatric population. We had some data. There was one trial, randomized control trial, called TIPS trial that looked at using intravenous alteplase for acute ischemic stroke in patients under the age of 18. It had difficulty with enrollment. But I think most experts would argue that patients with pediatric stroke should be considered for intravenous thrombolysis if appropriate. Again, same thing. You want to make it a multidisciplinary approach, really getting your pediatric neurologists, your pediatricians involved early to make the best decision for the patient.  Dr Albin: Yeah. That's just really an important takeaway, just thinking about this as a multidisciplinary decision, because there are going to be other stakeholders to the patient's care who may have some different information than what we as neurologists are bringing to the approach. And obviously, our perspective really matters. But trying to work in everyone's unique vantage point of the patient really helps to make the most effective decision. When we talk about acute ischemic stroke care, I really don't think that you could do justice to the topic without pivoting to mechanical thrombectomy, which, you know, as we think about how the medical field as a whole, not just neurology, how the medical field has evolved. I mean, there's probably no bigger impact than mechanical thrombectomy has made in terms of reducing not just morbidity, but mortality from stroke. I mean both. So, thrombectomy has been around for a while, but just walk our listeners through what's the core that we for sure know that these are the patients that this works for?  Dr Leon-Guerrero: The types of patients we should be selecting for intervention are patients with large vessel occlusions. And those initial trials that were published in 2015 really demonstrated that this is a quite an effective treatment for patients with large vessel occlusion ischemic strokes in the anterior circulation. When that smattering of publications occurred in 2015, the general consensus, we should be treating all patients up to six hours from symptom onset if they do have a large vessel occlusion. And then, Dr. Albin, as you know, the, the windows continue to expand. So, we were using advanced neuroimaging with MR selection and perfusion selection based on DAWN and DEFUSE 3 trial protocols to select patients all the way out to the 24 window, and it's even expanded beyond that over the last few years.  Dr Albin: I think that when we think about trials that really, totally, changed the game, when we think about DAWN and DEFUSE 3, and we switched from that time-based window to more of that, like we talked about for thrombolysis, that tissue-based clock and, like, looking at what is salvageable and where can we make an impact on salvageable tissue, truly moved the needle in terms of just bringing this therapy for people who, you know, it's hard to get in within six hours. When we moved the needle to 24, it made a huge difference. But people were still coming in with a lot of ischemic damage already done, and they would have traditionally been excluded from being enrolled in thrombectomy trials. But that's changing too. So where are we there?  Dr Leon-Guerrero: Yeah. I think there were lessons learned from DEFUSE and DAWN that we were probably over-selecting. Perhaps too stringent. You know, we had number needed to treat in the range of two to three for good outcome based on those trials. And so, I think those were lessons learned to move forward, and we, and, and people started looking at large core infarctions. And in the last few years, we've seen a multitude of randomized control trials examining large core infarctions. These are patients with ASPECT scores all the way down to zeros. A lot of the trials relied on three to six as their score, but there was at least one large core study that looked at ASPECT scores down to zero to two, and all of these studies showing benefit.  Dr Albin: Yeah. And we've really moved into if there's some tissue to spare there, probably getting clot out really makes a big difference in impact. You know, it was really surprising to me as a neurointensivist looking at these trials, that the trials had such low rates of hemorrhage, and pretty low rates of dramatic cerebral edema after thrombectomy. I don't know that we've seen all of that in sort of real world applications, but again, we are still seeing some of these patients come in, that really would've been devastated having some amount of functional recovery regained, which is incredible. In terms of another patient population that I think gives a lot of people pause or stickiness, is those basilar artery occlusions, right? Another large vessel, but one that we've had a little bit harder of a time enrolling in trials and having well-selected trials. Where are we now on whether or not basilar artery occlusion should go to mechanical thrombectomy?  Dr Leon-Guerrero: So, a lot of excitement in this area, too. There's at least two studies that were published in the last five years that were showing benefit in doing thrombectomy for patients with basilar artery occlusion up to 24 hours, and these were patients with moderate to severe deficits with NIH Stroke Scale scores greater than 10. And then making sure that they don't have large core, so using a newer scoring algorithm on the CAT scan called PC ASPECT, so basically a posterior circulation ASPECT score, to kind of make sure that patients don't have large core infarctions that are being considered for thrombectomy. All of those things collectively in those two recent studies, the ATTENTION trial and the BAOCHI trial, I think is what ended up making those studies positive, is that we were selecting the right types of patients, uh, without large core, early core, and patients with moderate to severe deficits that made the difference from previous trials.  Dr Albin: Yeah. I think that that's so important. Those trials to me, and like how long it took to get those enrolled, really emphasized to me that there really was a selection bias. Like, we believed this worked, which made it hard to then do a trial. But I'm so glad to hear that we have the data now to support moving forward in a more rigorous way.  Dr Leon-Guerrero: You're absolutely right. I think that was some of the challenges with the initial trials. In fact, the authors had commented on that. There's a lot of difficulties with lack of clinical equipoise, or experts wanting to take these patients anyways out of clinical trial and treat them, and so that's always been an issue. And then, you know, we all remember basilar artery occlusion cases. They can be severe, devastating cases in our career, but the reality is they're not that common. So, if you look at large vessel occlusions, they only account for about 10%, and if you look at all stroke patients presenting to most centers, they represent about 1% of cases. So really hard clinical trials to do just because there's thankfully not a lot of patients walking around with basilar artery occlusions, but certainly makes for challenges when you're trying to conduct randomized controlled trials on this subset of patients.  Dr Albin: Absolutely. But we did it, and I think that, like, really if, if the listeners take nothing else, it's that the field of vascular neurology is really moving forward with evidence-based, doing very rigorously controlled clinical trials, which is, I think, is what makes this field so exciting. Finally, closing out, cause we could talk all day, but we don't have all day. You know, it seems to me that more and more we are just using dual antiplatelet therapy all the time. And maybe that is, uh, a little bit of a hyperbole, cause I don't think it's all the time, but let's walk through— when is there good evidence for dual antiplatelet therapy?  Dr Leon-Guerrero: Yeah. So, there's strong evidence for early initiation of dual antiplatelet therapy or DAPT in patients with minor stroke or high-risk TIAs, and it's been studied using both clopidogrel as an add-on to aspirin and ticagrelor. Both seem like they're viable options in patients. I think one of the key things is the duration of therapy. So, in these cases with minor stroke and high-risk TIAs, we really should be confining the treatment of early DAPT for 21 days. The risk profile changes, so the risk of recurrent stroke starts to decline with time, and that risk of hemorrhage complications increases with time. And so that sweet spot of 21 days, or even some centers will do 30 days for just practical purposes, you know, really is what we should be doing in most of those cases. Other instances where DAPT can be considered, is in patients with intracranial atherosclerosis that's symptomatic, extrapolating from the SAMMPRIS trial that in the, in the medical management arm alone, used dual antiplatelet therapy with aspirin and clopidogrel for up to 90 days. So, you'll see that as well in clinical practice. Some people will opt for a 90-day duration for those patients with symptomatic intracranial atherosclerosis and stroke.  Dr Albin: Just so I emphasize, this is not set it and forget it. You can stay on DAPT forever. It is you're going to have a definitive time course, 21 days, 90 days. We have directed instructions where we're doing more benefit than harm because of that risk of hemorrhage.  Dr Leon-Guerrero: That's correct. In most cases, we really should be confining the duration of DAPT either to 21 days or 90 days. This is a challenging clinical practice. Centers really have been making an emphasis on stroke follow-up, so making sure these patients get appropriate and timely stroke follow-up to address these issues and to make sure that DAPT is discontinued if appropriate.  Dr Albin: Yeah. I love that, and I want to pull on that a little bit because you as someone who is helping direct a stroke center– A lot of this really does rely on systems of care. When we think about early lysis decisions or mechanical thrombectomy, it's how do we get the patient to one of those capable centers as quickly as possible? And then on the back end, when you're discharging a patient, how do you make sure that they are getting follow-up, making sure that they're getting their Holter monitor if they need it? You know, all the stuff that goes into kind of figuring out, why did the stroke happen? What are some of the things that you, in your role, are really excited about, that will move the needle over the next five or 10 years?  Dr Leon-Guerrero: Yeah. I think a lot of centers are doing it just like we're doing it. It really has to be a team-based approach, and you really want to reach the patient where they are in terms of the continuum of care. And so making sure if it's the in the field that you've reached out to your EMS and first responders to make sure they understand triage protocols to get patients where they need to be, to get the acute treatments that they need for the type of stroke that they're presenting with, to the actual centers that you work at, making sure your whole team, nurses, emergency physicians, APPs that are involved in care are all aware of the stroke protocols and how we're selecting these patients, making sure that your imaging protocols are up to date, and so that it's seamless when patients come in, that we're not adding on perfusion if we should have gotten that up front– We already know, have made decisions before that patient gets there. And then thinking about the patient after that hospital stay, I think, is critical. We really want to reduce their risk of recurrence, making sure that we're leveraging transitions of care, getting those patients seen in our stroke clinics for follow-up, and then make sure we're passing that baton to the long term. All of their long-term comorbidities that may be increasing their risk of stroke are managed and reduced as best as possible.  Dr Albin: From the Continuum journal to the continuum of stroke care.  Dr Leon-Guerrero: That's right.  Dr Albin: I mean, we have it all. I think that that really is so important. I'll just close with what's one thing that is your favorite part about being a vascular neurologist?  Dr Leon-Guerrero: I think it's what attracted to me to this field. As a medical student at that time, all we had was intravenous thrombolysis, and there was so much promise. There was so much promise that there was going to be widespread advancements in acute stroke, and here we are. There's been a tremendous amount of advancements and improvements for patients. I'm really excited to see what unfolds in the next few years, and I'm really excited that we've been able to increase the number of patients we're able to treat with acute ischemic stroke. I hope that we continue to expand the time window, the inclusion criteria, all of those things that we can treat more stroke patients effectively.  Dr Albin: It is really a very exciting time to be a vascular neurologist. Again, today, I've been interviewing Dr. Christopher Leon-Guerrero about his article on Thrombolysis, Thrombectomy, and Antithrombotic Therapy for Acute Ischemic Stroke. This article appears in the April 2026 Continuum issue on cerebrovascular disease. Be sure to check out Continuum Audio episodes from this and other issues, and thank you again, Dr. Leon Guerrero and our listeners for joining today.  Dr Leon-Guerrero: Thanks for having me.  Dr Monteith: This is Dr. Teshamae Monteith, associate editor of Continuum Audio. If you've enjoyed this episode, you'll love the journal, which is full of in-depth and clinically relevant information important for neurology practitioners. Use the link in the episode notes to learn more and subscribe. AAN members, you can get CME for listening to this interview by completing the evaluation at continpub.com/audioCME. Thank you for listening to Continuum Audio.

In this episode, we review key updates from the 2026 AHA/ASA Guideline for the Early Management of Patients With Acute Ischemic Stroke, including changes to IV thrombolysis, antiplatelet therapy, endovascular treatment, blood pressure goals, and glycemic goals. Key Concepts Tenecteplase (TNKase) is now equally preferred to alteplase (Activase) by the 2026 AHA/ASA guidelines. Tenecteplase has several advantages related to administration and the risk of medication errors. IV thrombolysis can be given in selected patients up to 9 hours after stroke symptom onset depending on brain imaging findings. Patients with symptom onset less than 4.5 hours are still eligible for IV thrombolysis regardless of brain imaging findings. IV thrombolysis should not be given for mild, non-disabling stroke symptoms. A "non-disabling" stroke means the symptoms do not impair activities of daily living or ability to return to work. The criteria for dual antiplatelet therapy (DAPT) has been updated. DAPT can be given for NIHSS of 4 or 5 (not just 3 or less) and can be started up to 72 hours after stroke onset (not just within 24 hours). References Prabhakaran S, Gonzalez NR, Zachrison KS, et al. 2026 Guideline for the Early Management of Patients With Acute Ischemic Stroke: A Guideline From the American Heart Association/American Stroke Association. Stroke. Published online January 26, 2026. doi:10.1161/STR.0000000000000513

Dr. Andy Southerland and Dr. Shyam Prabhakaran explain the significance of these guidelines and why they are important.  Show citation:  Prabhakaran S, Gonzalez NR, Zachrison KS, et al. 2026 Guideline for the Early Management of Patients With Acute Ischemic Stroke: A Guideline From the American Heart Association/American Stroke Association. Stroke. Published online January 26, 2026. doi:10.1161/STR.0000000000000513  Show transcript:  Dr. Andy Southerland: Hello everyone. This is Andy Southerland from the University of Virginia. And for this week's Neurology Minute, I've just been speaking with my colleague, Shyam Prabhakaran, from the University of Chicago, who was the Chair of the 2026 AHA/ASA guidelines for the early management of patients with Acute Ischemic stroke published in the January 2026 online version of the journal, Stroke. So Shyam, in our brief Neurology Minute today, why don't you just give a plea about why these guidelines are so important? Dr. Shyam Prabhakaran: Thanks, Andy. These guidelines are the first guidelines since 2019, so a lot has happened. So when you look at these guidelines, you'll see a lot of new recommendations. In fact, I think the majority have been revised in some way or another. And I'd point to the actual guideline document, which is in the journal Stroke online January '26, and the print version will be for the March edition of the journal Stroke. In addition to that, I'd say because you want to have interpretability and ease of practice, there are a bunch of derivatives on the AHA website that are very useful. They include case studies, they include figures and workflows that could be really useful for you to have these conversations. And there's even a slide deck that was prepared by our AHA ambassadors. There are these young whippersnappers that did a great job putting together a slide deck for anyone to use. They can use that to have conversations locally or anywhere they want. I encourage people, read the guidelines, but then also use the derivative products that people spent a lot of time on developing. Dr. Andy Southerland: Thank you, Shyam. I think that's a great message from the Chair of the writing group, that when you look at these guidelines, they can seem daunting. But the way you all have provided all these additional resources and analogs for people to interpret it and apply it in their own stroke centers and practice, I think folks definitely will be running out to do that, just to seek out the full guideline, and let's apply all this great new evidence to better care for our patients. So Shyam, thanks again for joining us for this week's Neurology Minute. 

Dr. Andy Southerland talks with Dr. Shyam Prabhakaran about the 2026 AHA/ASA guidelines for the early management of acute ischemic stroke, highlighting key recommendations, the role of advanced imaging, and the importance of thrombolysis and thrombectomy.  Read the related article in the journal Stroke.  Disclosures can be found at Neurology.org. 

Welcome to this special episode of the NeurologyLive® Mind Moments® podcast. Tune in to hear leaders in neurology sound off on topics that impact your clinical practice. For major FDA decisions in the field of neurology, we release short special episodes to offer a snapshot of the news, including the main takeaways for the clinical community, as well as highlights of the efficacy and safety profile of the agent in question.In this special edition of Mind Moments, Shyam Prabhakaran, MD, MS, the James Nelson and Anna Louise Raymond Professor of Neurology and chair of the Department of Neurology at the University of Chicago Medicine, joined the show to discuss the recent updates to the American Heart Association/American Stroke Association's guideline for the early management of acute ischemic stroke.  Prabhakaran clarified the main takeaways for clinicians and touched on details around endovascular thrombectomy care in pediatrics as well as treatment within and outside of the golden window.For NeurologyLive's coverage of ISC 2026, head here: International Stroke Conference (ISC) To read the new guidelines, head here: 2026 Guideline for the Early Management of Patients With Acute Ischemic Stroke: A Guideline From the American Heart Association/American Stroke AssociationThanks for listening to the NeurologyLive Mind Moments podcast. To support the show, be sure to rate, review, and subscribe wherever you listen to podcasts. For more neurology news and expert-driven content, visit neurologylive.com.

This INSIGHTS episode revisits a core topic from Neurocritical Care ON CALL®, originally released in August 2023.  Listen to the fourth episode of the NCS INSIGHTS series on acute ischemic stroke (part 2 of 2). The INSIGHTS series is hosted by Casey Albin, MD, and Salia Farrokh, PharmD, and covers topics from Neurocritical Care ON CALL®, the only up-to-date, comprehensive resource dedicated exclusively to the practice of neurocritical care. Learn more about ON CALL®. This episode is sponsored by Biogen. Science that transforms patient lives. Science that seeks to solve societal problems. Science that acts with purpose. Science that is inspired by the diversity and passion of our people. Discover where science meets humanity at Biogen. The NCS Podcast is the official podcast of the Neurocritical Care Society. The views expressed on the NCS Podcast are solely those of the hosts and guests and do not necessarily reflect the opinions or official positions of the Neurocritical Care Society.

This INSIGHTS episode revisits a core topic from Neurocritical Care ON CALL®, originally released in August 2023.  Listen to the third episode of the NCS INSIGHTS series on acute ischemic stroke (part 1 of 2). The INSIGHTS series is hosted by Casey Albin, MD, and Salia Farrokh, PharmD, and covers topics from Neurocritical Care ON CALL®, the only up-to-date, comprehensive resource dedicated exclusively to the practice of neurocritical care. Learn more about ON CALL®. This episode is sponsored by Biogen. Science that transforms patient lives. Science that seeks to solve societal problems. Science that acts with purpose. Science that is inspired by the diversity and passion of our people. Discover where science meets humanity at Biogen. The NCS Podcast is the official podcast of the Neurocritical Care Society. The views expressed on the NCS Podcast are solely those of the hosts and guests and do not necessarily reflect the opinions or official positions of the Neurocritical Care Society.

In this AJNR Fellows' Journal Club article summary, Dr. Francis Deng and Dr. Amir Khadivi discuss the article by Proner et al., "Impact of Clinical and Radiologic Factors on CTP Timing in Acute Ischemic Stroke." They discuss the authors' findings that cardiac arrhythmias and older age are independent predictors of nondiagnostic CTP exams. Specifically, these factors often lead to the truncation of reference vessel time-attenuation curves that fail to reach equilibrium within a 45-second acquisition window.

En este episodio abordo la farmacología en neurorrehabilitación del adulto desde una perspectiva clínica y realista, pensada especialmente para profesionales no médicos que conviven a diario con informes, pautas y nombres de fármacos sin disponer siempre de un marco claro para interpretarlos. Recorremos los principales medicamentos utilizados en patologías neurológicas frecuentes —ictus, lesión medular, esclerosis múltiple, enfermedad de Parkinson, ELA, distonías y traumatismo craneoencefálico— diferenciando entre tratamientos agudos, terapias modificadoras de la enfermedad y manejo farmacológico de secuelas. A lo largo del episodio explico de forma progresiva los mecanismos de acción, la base neurofisiológica y el estado actual de la evidencia, poniendo especial énfasis en qué fármacos realmente cambian el pronóstico y cuáles cumplen un papel fundamentalmente sintomático. El objetivo no es prescribir, sino entender mejor cómo la farmacología condiciona la recuperación, la participación en terapia y la toma de decisiones en neurorrehabilitación, con una mirada crítica y basada en la evidencia disponible. Referencias del episodio: 1.     Adams, M. M., & Hicks, A. L. (2005). Spasticity after spinal cord injury. Spinal cord, 43(10), 577–586. https://doi.org/10.1038/sj.sc.3101757 (https://pubmed.ncbi.nlm.nih.gov/15838527/). 2.     AFFINITY Trial Collaboration (2020). Safety and efficacy of fluoxetine on functional outcome after acute stroke (AFFINITY): a randomised, double-blind, placebo-controlled trial. The Lancet. Neurology, 19(8), 651–660. https://doi.org/10.1016/S1474-4422(20)30207-6 (https://pubmed.ncbi.nlm.nih.gov/32702334/). 3.     Angeli, C. A., Edgerton, V. R., Gerasimenko, Y. P., & Harkema, S. J. (2014). Altering spinal cord excitability enables voluntary movements after chronic complete paralysis in humans. Brain : a journal of neurology, 137(Pt 5), 1394–1409. https://doi.org/10.1093/brain/awu038 (https://pubmed.ncbi.nlm.nih.gov/24713270/). 4.     Bracken, M. B., Shepard, M. J., Collins, W. F., Holford, T. R., Young, W., Baskin, D. S., Eisenberg, H. M., Flamm, E., Leo-Summers, L., & Maroon, J. (1990). A randomized, controlled trial of methylprednisolone or naloxone in the treatment of acute spinal-cord injury. Results of the Second National Acute Spinal Cord Injury Study. The New England journal of medicine, 322(20), 1405–1411. https://doi.org/10.1056/NEJM199005173222001 (https://pubmed.ncbi.nlm.nih.gov/2278545/). 5.     Bracken, M. B., Shepard, M. J., Holford, T. R., Leo-Summers, L., Aldrich, E. F., Fazl, M., Fehlings, M., Herr, D. L., Hitchon, P. W., Marshall, L. F., Nockels, R. P., Pascale, V., Perot, P. L., Jr, Piepmeier, J., Sonntag, V. K., Wagner, F., Wilberger, J. E., Winn, H. R., & Young, W. (1997). Administration of methylprednisolone for 24 or 48 hours or tirilazad mesylate for 48 hours in the treatment of acute spinal cord injury. Results of the Third National Acute Spinal Cord Injury Randomized Controlled Trial. National Acute Spinal Cord Injury Study. JAMA, 277(20), 1597–1604 (https://pubmed.ncbi.nlm.nih.gov/9168289/). 6.     Cardenas, D. D., Ditunno, J. F., Graziani, V., McLain, A. B., Lammertse, D. P., Potter, P. J., Alexander, M. S., Cohen, R., & Blight, A. R. (2014). Two phase 3, multicenter, randomized, placebo-controlled clinical trials of fampridine-SR for treatment of spasticity in chronic spinal cord injury. Spinal cord, 52(1), 70–76. https://doi.org/10.1038/sc.2013.137 (https://pubmed.ncbi.nlm.nih.gov/24216616/). 7.     Chollet, F., Tardy, J., Albucher, J. F., Thalamas, C., Berard, E., Lamy, C., Bejot, Y., Deltour, S., Jaillard, A., Niclot, P., Guillon, B., Moulin, T., Marque, P., Pariente, J., Arnaud, C., & Loubinoux, I. (2011). Fluoxetine for motor recovery after acute ischaemic stroke (FLAME): a randomised placebo-controlled trial. The Lancet. Neurology, 10(2), 123–130. https://doi.org/10.1016/S1474-4422(10)70314-8 (https://pubmed.ncbi.nlm.nih.gov/21216670/). 8.     Dávalos, A., Alvarez-Sabín, J., Castillo, J., Díez-Tejedor, E., Ferro, J., Martínez-Vila, E., Serena, J., Segura, T., Cruz, V. T., Masjuan, J., Cobo, E., Secades, J. J., & International Citicoline Trial on acUte Stroke (ICTUS) trial investigators (2012). Citicoline in the treatment of acute ischaemic stroke: an international, randomised, multicentre, placebo-controlled study (ICTUS trial). Lancet (London, England), 380(9839), 349–357. https://doi.org/10.1016/S0140-6736(12)60813-7 (https://pubmed.ncbi.nlm.nih.gov/22691567/). 9.     EFFECTS Trial Collaboration (2020). Safety and efficacy of fluoxetine on functional recovery after acute stroke (EFFECTS): a randomised, double-blind, placebo-controlled trial. The Lancet. Neurology, 19(8), 661–669. https://doi.org/10.1016/S1474-4422(20)30219-2 (https://pubmed.ncbi.nlm.nih.gov/32702335/). 10.  Fehlings, M. G., Theodore, N., Harrop, J., Maurais, G., Kuntz, C., Shaffrey, C. I., Kwon, B. K., Chapman, J., Yee, A., Tighe, A., & McKerracher, L. (2011). A phase I/IIa clinical trial of a recombinant Rho protein antagonist in acute spinal cord injury. Journal of neurotrauma, 28(5), 787–796. https://doi.org/10.1089/neu.2011.1765 (https://pubmed.ncbi.nlm.nih.gov/21381984/). 11.  FOCUS Trial Collaboration (2019). Effects of fluoxetine on functional outcomes after acute stroke (FOCUS): a pragmatic, double-blind, randomised, controlled trial. Lancet (London, England), 393(10168), 265–274. https://doi.org/10.1016/S0140-6736(18)32823-X (https://pubmed.ncbi.nlm.nih.gov/30528472/). 12.  Forgione, N., & Fehlings, M. G. (2014). Rho-ROCK inhibition in the treatment of spinal cord injury. World neurosurgery, 82(3-4), e535–e539. https://doi.org/10.1016/j.wneu.2013.01.009 (http://pubmed.ncbi.nlm.nih.gov/23298675/). 13.  Fournier, A. E., Takizawa, B. T., & Strittmatter, S. M. (2003). Rho kinase inhibition enhances axonal regeneration in the injured CNS. The Journal of neuroscience : the official journal of the Society for Neuroscience, 23(4), 1416–1423. https://doi.org/10.1523/JNEUROSCI.23-04-01416.2003 (https://pubmed.ncbi.nlm.nih.gov/12598630/). 14.  Giacino, J. T., Whyte, J., Bagiella, E., Kalmar, K., Childs, N., Khademi, A., Eifert, B., Long, D., Katz, D. I., Cho, S., Yablon, S. A., Luther, M., Hammond, F. M., Nordenbo, A., Novak, P., Mercer, W., Maurer-Karattup, P., & Sherer, M. (2012). Placebo-controlled trial of amantadine for severe traumatic brain injury. The New England journal of medicine, 366(9), 819–826. https://doi.org/10.1056/NEJMoa1102609 (https://pubmed.ncbi.nlm.nih.gov/22375973/). 15.  Goodman, A. D., Brown, T. R., Krupp, L. B., Schapiro, R. T., Schwid, S. R., Cohen, R., Marinucci, L. N., Blight, A. R., & Fampridine MS-F203 Investigators (2009). Sustained-release oral fampridine in multiple sclerosis: a randomised, double-blind, controlled trial. Lancet (London, England), 373(9665), 732–738. https://doi.org/10.1016/S0140-6736(09)60442-6 (https://pubmed.ncbi.nlm.nih.gov/19249634/). 16.  Goodman, A. D., Brown, T. R., Edwards, K. R., Krupp, L. B., Schapiro, R. T., Cohen, R., Marinucci, L. N., Blight, A. R., & MSF204 Investigators (2010). A phase 3 trial of extended release oral dalfampridine in multiple sclerosis. Annals of neurology, 68(4), 494–502. https://doi.org/10.1002/ana.22240 (https://pubmed.ncbi.nlm.nih.gov/20976768/). 17.  Hurlbert, R. J., Hadley, M. N., Walters, B. C., Aarabi, B., Dhall, S. S., Gelb, D. E., Rozzelle, C. J., Ryken, T. C., & Theodore, N. (2013). Pharmacological therapy for acute spinal cord injury. Neurosurgery, 72 Suppl 2, 93–105. https://doi.org/10.1227/NEU.0b013e31827765c6 (https://pubmed.ncbi.nlm.nih.gov/23417182/). 18.  Johnston, S. C., Amarenco, P., Denison, H., Evans, S. R., Himmelmann, A., James, S., Knutsson, M., Ladenvall, P., Molina, C. A., Wang, Y., & THALES Investigators (2020). Ticagrelor and Aspirin or Aspirin Alone in Acute Ischemic Stroke or TIA. The New England journal of medicine, 383(3), 207–217. https://doi.org/10.1056/NEJMoa1916870 (https://pubmed.ncbi.nlm.nih.gov/32668111/). 19.  Kheder, A., & Nair, K. P. (2012). Spasticity: pathophysiology, evaluation and management. Practical neurology, 12(5), 289–298. https://doi.org/10.1136/practneurol-2011-000155 (https://pubmed.ncbi.nlm.nih.gov/22976059/). 20.  Kirkman, M. A., Day, J., Gehring, K., Zienius, K., Grosshans, D., Taphoorn, M., Li, J., & Brown, P. D. (2022). Interventions for preventing and ameliorating cognitive deficits in adults treated with cranial irradiation. The Cochrane database of systematic reviews, 11(11), CD011335. https://doi.org/10.1002/14651858.CD011335.pub3 (https://pubmed.ncbi.nlm.nih.gov/36427235/). 21.  Martinsson L, Hårdemark H, Eksborg S. Amphetamines for improving recovery after stroke. Cochrane Database Syst Rev. 2007 Jan 24;2007(1):CD002090. doi: 10.1002/14651858.CD002090.pub2. PMID: 17253474; PMCID: PMC12278358 (https://pubmed.ncbi.nlm.nih.gov/17253474/). 22.  Miller, T. M., Cudkowicz, M. E., Genge, A., Shaw, P. J., Sobue, G., Bucelli, R. C., Chiò, A., Van Damme, P., Ludolph, A. C., Glass, J. D., Andrews, J. A., Babu, S., Benatar, M., McDermott, C. J., Cochrane, T., Chary, S., Chew, S., Zhu, H., Wu, F., Nestorov, I., … VALOR and OLE Working Group (2022). Trial of Antisense Oligonucleotide Tofersen for SOD1 ALS. The New England journal of medicine, 387(12), 1099–1110. https://doi.org/10.1056/NEJMoa2204705 (https://pubmed.ncbi.nlm.nih.gov/36129998/). 23.  Mueller, B. K., Mack, H., & Teusch, N. (2005). Rho kinase, a promising drug target for neurological disorders. Nature reviews. Drug discovery, 4(5), 387–398. https://doi.org/10.1038/nrd1719 (https://pubmed.ncbi.nlm.nih.gov/15864268/). 24.  Nourbakhsh, B., Revirajan, N., & Waubant, E. (2018). Treatment of fatigue with methylphenidate, modafinil and amantadine in multiple sclerosis (TRIUMPHANT-MS): Study design for a pragmatic, randomized, double-blind, crossover clinical trial. Contemporary clinical trials, 64, 67–76. https://doi.org/10.1016/j.cct.2017.11.005 (https://pubmed.ncbi.nlm.nih.gov/29113955/). 25.  Paganoni, S., Hendrix, S., Dickson, S. P., Knowlton, N., Macklin, E. A., Berry, J. D., Elliott, M. A., Maiser, S., Karam, C., Caress, J. B., Owegi, M. A., Quick, A., Wymer, J., Goutman, S. A., Heitzman, D., Heiman-Patterson, T. D., Jackson, C. E., Quinn, C., Rothstein, J. D., Kasarskis, E. J., … Cudkowicz, M. E. (2021). Long-term survival of participants in the CENTAUR trial of sodium phenylbutyrate-taurursodiol in amyotrophic lateral sclerosis. Muscle & nerve, 63(1), 31–39. https://doi.org/10.1002/mus.27091 (https://pubmed.ncbi.nlm.nih.gov/33063909/). 26.  Schwab M. E. (2004). Nogo and axon regeneration. Current opinion in neurobiology, 14(1), 118–124. https://doi.org/10.1016/j.conb.2004.01.004 (https://pubmed.ncbi.nlm.nih.gov/15018947/). 27.  Shneider, N. A., Harms, M. B., Korobeynikov, V. A., Rifai, O. M., Hoover, B. N., Harrington, E. A., Aziz-Zaman, S., Singleton, J., Jamil, A., Madan, V. R., Lee, I., Andrews, J. A., Smiley, R. M., Alam, M. M., Black, L. E., Shin, M., Watts, J. K., Walk, D., Newman, D., Pascuzzi, R. M., … Bennett, C. F. (2025). Antisense oligonucleotide jacifusen for FUS-ALS: an investigator-initiated, multicentre, open-label case series. Lancet (London, England), 405(10494), 2075–2086. https://doi.org/10.1016/S0140-6736(25)00513-6 (https://pubmed.ncbi.nlm.nih.gov/40414239/). 28.  Stocchi, F., Bravi, D., Emmi, A., & Antonini, A. (2024). Parkinson disease therapy: current strategies and future research priorities. Nature reviews. Neurology, 20(12), 695–707. https://doi.org/10.1038/s41582-024-01034-x (https://pubmed.ncbi.nlm.nih.gov/39496848/).

Theodoros Mavridis (Dublin, Ireland) Ana Catarina Fonseca (Lisbon, Portugal) In this episode, Theodoros Mavridis speaks with Ana Catarina Fonseca about the updated European guidelines for acute ischemic stroke. They discuss advances in reperfusion therapy, including extended time windows for thrombolysis using advanced imaging, broader eligibility criteria, and evidence supporting thrombectomy in patients with low ASPECTS scores, mild deficits, and posterior circulation strokes. The conversation also highlights the continued importance of stroke unit care and emerging pre-hospital technologies aimed at speeding diagnosis and improving outcomes.

Editor's Summary by Kirsten Bibbins-Domingo, PhD, MD, MAS, Editor in Chief, and Preeti Malani, MD, MSJ, Deputy Editor of JAMA, the Journal of the American Medical Association, for articles published from August 2-8, 2025.

Commentary by Dr. Jian'an Wang.

Welcome to this special episode of the NeurologyLive® Mind Moments® podcast. Tune in to hear leaders in neurology sound off on topics that impact your clinical practice. For major FDA decisions in the field of neurology, we release short special episodes to offer a snapshot of the news, including the main takeaways for the clinical community, as well as highlights of the efficacy and safety profile of the agent in question. In this episode, we cover the recent approval of Genentech's tenecteplase, marketed as TNKase, as a new treatment for adults with acute ischemic stroke (AIS). The thrombolytic medicine is an intravenous tissue plasminogen activator that is clot-dissolving, administered as a single 5-second intravenous bolus. Tenecteplase is only the second such approval for this indication, following the 2015 approval of alteplase (Activase; Genentech); however, tenecteplase is considered faster and more simply administered than alteplase. To better understand the implications of this approval, NeurologyLive sat down with stroke expert Bijoy Menon, MD, MSc, FRCPC, a professor of neurology at the University of Calgary. In the interview, Menon talked about the downstream impacts of having another approved therapy, how tenecteplase differs from other thrombolytic agents, and the efficacy and safety that supported its approval. Furthermore, he provided commentary on how the approval continues to chip away toward the idea of precision medicine and personalizing treatments for patients with AIS.  For more of NeurologyLive's coverage of sodium oxybate's (Lumryz) expanded indication, head here: FDA Approves Tenecteplase for Acute Ischemic Stroke Episode Breakdown: 1:40 – Immediate reaction and significance of tenecteplase approval 5:30 – Safety considerations and administration when prescribing tenecteplase 10:20 – Supportive efficacy and safety, phase 3 AcT trial, and other supplementary studies 14:50 – Advancing precision medicine, treatment personalization with new approval Thanks for listening to the NeurologyLive Mind Moments podcast. To support the show, be sure to rate, review, and subscribe wherever you listen to podcasts. For more neurology news and expert-driven content, visit neurologylive.com.

Two new trials published in JAMA evaluate the efficacy of periprocedural intra-arterial thrombolytics after successful endovascular thrombectomy for patients with acute ischemic stroke. Diederik Dippel, MD, PhD, of Erasmus University Medical Center discusses this and more with JAMA Deputy Editor Christopher C. Muth, MD. Related Content: Intra-Arterial Thrombolytics During Thrombectomy for Ischemic Stroke—End of the Story or a New Beginning? Intra-Arterial Tenecteplase Following Endovascular Reperfusion for Large Vessel Occlusion Acute Ischemic Stroke Intra-Arterial Urokinase After Endovascular Reperfusion for Acute Ischemic Stroke

Darshan H. Brahmbhatt, Podcast Editor of JACC: Advances, discusses a recently published original research paper on social vulnerability index and all-cause mortality after acute ischemic stroke for a Medicare Cohort from 2020-2023.

Dr. Linda Chu discusses the assessment of thrombectomy vs. combined thrombolysis and thrombectomy in patients with acute ischemic stroke and medium vessel occlusion with Dr. Adam Dmytriw and Dr. Adrien Guenego.   Assessment of Thrombectomy versus Combined Thrombolysis and Thrombectomy in Patients with Acute Ischemic Stroke and Medium Vessel Occlusion. The MAD-MT Consortium. Radiology 2024; 312(2):e233041. 

Can a new drug slow the progression of Alzheimer's disease? Find out about this and more in today's PeerDirect Medical News Podcast.

Show notes at pharmacyjoe.com/episode933. In this episode, I'll discuss tenecteplase for stroke from 4.5 to 24 hours after the time last know well. The post 933: Can tenecteplase be used for acute ischemic stroke beyond 4.5 hours from time last know well? appeared first on Pharmacy Joe.

Joanne e João Urbano, nosso Joca, convidam o Dr. Igor Brum para conversar sobre as últimas atualizações no manejo de AVC isquêmico. Referências: 1. Hilkens NA, Casolla B, Leung TW, de Leeuw FE. Stroke. Lancet. Published online May 14, 2024. doi:10.1016/S0140-6736(24)00642-1 2. Huo X, Ma G, Tong X, et al. Trial of Endovascular Therapy for Acute Ischemic Stroke with Large Infarct. N Engl J Med. 2023;388(14):1272-1283. doi:10.1056/NEJMoa2213379 3. Sarraj A, Hassan AE, Abraham MG, et al. Trial of Endovascular Thrombectomy for Large Ischemic Strokes [published correction appears in N Engl J Med. 2024 Jan 25;390(4):388. doi: 10.1056/NEJMx230009]. N Engl J Med. 2023;388(14):1259-1271. doi:10.1056/NEJMoa2214403 4. Strbian D, Tsivgoulis G, Ospel JM, et al. European Stroke Organisation (ESO) and European Society for Minimally Invasive Neurological Therapy (ESMINT) Guideline on Acute Management of Basilar Artery Occlusion. Eur Stroke J. Published online May 16, 2024. doi:10.1177/23969873241257223

Contributor: Travis Barlock MD Educational Pearls: Thrombolytic therapy (tPA or TNK) is often used in the ED for strokes Use of anticoagulants with INR > 1.7 or  PT >15 Warfarin will reliably increase the INR Current use of Direct thrombin inhibitor or Factor Xa inhibitor  aPTT/PT/INR are insufficient to assess the degree of anticoagulant effect of Factor Xa inhibitors like apixaban (Eliquis) and rivaroxaban (Xarelto)  Intracranial or intraspinal surgery in the last 3 months Intracranial neoplasms or arteriovenous malformations also increase the risk of bleeding Current intracranial or subarachnoid hemorrhage History of intracranial hemorrhage from thrombolytic therapy also contraindicates tPA/TNK Recent (within 21 days) or active gastrointestinal bleed Hypertension BP >185 systolic or >110 diastolic Administer labetalol before thrombolytics to lower blood pressure Timing of symptoms Onset > 4.5 hours contraindicates tPA Platelet count < 100,000 BGL < 50 Potential alternative explanation for stroke-like symptoms obviating need for thrombolytics References 1. Fugate JE, Rabinstein AA. Absolute and Relative Contraindications to IV rt-PA for Acute Ischemic Stroke. The Neurohospitalist. 2015;5(3):110-121. doi:10.1177/1941874415578532 2. Powers WJ, Rabinstein AA, Ackerson T, et al. Guidelines for the Early Management of Patients with Acute Ischemic Stroke: 2019 Update to the 2018 Guidelines for the Early Management of Acute Ischemic Stroke a Guideline for Healthcare Professionals from the American Heart Association/American Stroke Association. Vol 50.; 2019. doi:10.1161/STR.0000000000000211 Summarized by Jorge Chalit, OMSII | Edited by Jorge Chalit

Reference: Albers GW et al. TIMELESS Investigators. Tenecteplase for Stroke at 4.5 to 24 Hours with Perfusion-Imaging Selection. NEJM Feb 2024 Date: April 12, 2024 Guest Skeptic: Dr. Vasisht Srinivasan is an Emergency Medicine physician and neurointensivist at the University of Washington and Harborview Medical Center in Seattle, WA. He is an assistant professor in Emergency […] The post SGEM#436: For the Longest Time – To Give TNK for an Acute Ischemic Stroke first appeared on The Skeptics Guide to Emergency Medicine.

CME credits: 1.50 Valid until: 27-02-2025 Claim your CME credit at https://reachmd.com/programs/cme/emerging-data-in-the-management-of-acute-ischemic-stroketia/18133/ This program addresses critical gaps in healthcare professionals' knowledge and practice related to the secondary prevention of a clot-related stroke in patients with an acute ischemic stroke or at high risk for TIA. By addressing these gaps and achieving the outlined learning objectives, participants will be better equipped to provide optimal patient care, ultimately improving outcomes in managing this critical medical condition.

In this episode of the BackTable Podcast, guest host Dr. Krishna Amuluru interviews Dr. Fawaz Al-Mufti about recent trials on large core strokes and how they may impact practice. Dr. Al-Mufti is a practicing neurointerventionalist and serves as the Associate Chair of Neurology for Research at New York Medical College. Dr. Al-Mufti examines the cost-effectiveness and socioeconomic implications of successful treatment of patients with large core strokes. The doctors highlight various stroke thrombectomy trials including the RESCUE-Japan, SELECT2 Trial, and TENSION trials. The discussion also covers how these findings affect thrombectomy expansion in lower resource settings and the future outlook of endovascular thrombectomy procedures. --- CHECK OUT OUR SPONSOR RADPAD® Radiation Protection https://www.radpad.com/ --- SHOW NOTES 00:00 - Introduction 02:53 - Large Ischemic Core Infarcts 06:06 - The Importance of ASPECTS 11:59 - Large Ischemic Core Trials 23:37 - Socioeconomic Implications of Thrombectomy 38:08 - The Future of Thrombectomy --- RESOURCES Mission Thrombectomy: https://missionthrombectomy.org/ The Alberta Stroke Program Early CT score (ASPECTS): A predictor of mortality in acute ischemic stroke: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8515558/ Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomized trials (HERMES Study): https://doi.org/10.1016/S0140-6736(16)00163-X Thrombectomy for Stroke at 6 to 16 Hours with Selection by Perfusion Imaging (DEFUSE III Trial): https://www.nejm.org/doi/full/10.1056/nejmoa1713973 Thrombectomy 6 to 24 Hours after Stroke with a Mismatch between Deficit and Infarct (DAWN Trial): https://www.nejm.org/doi/full/10.1056/nejmoa1706442 Endovascular Therapy for Acute Stroke with a Large Ischemic Region (RESCUE-Japan Trial): https://www.nejm.org/doi/full/10.1056/nejmoa2118191 Trial of Endovascular Thrombectomy for Large Ischemic Strokes (SELECT2 Trial): https://www.nejm.org/doi/full/10.1056/NEJMoa2214403 TESLA Trial: Rationale, Protocol, and Design: https://www.ahajournals.org/doi/10.1161/SVIN.122.000787 Endovascular thrombectomy for acute ischaemic stroke with established large infarct: multicentre, open-label, randomized trial (TENSION Trial): https://www.sciencedirect.com/science/article/pii/S0140673623020329 Evaluation of acute mechanical revascularization in large stroke (ASPECTS ⩽5) and large vessel occlusion within 7 h of last-seen-well: The LASTE multicenter, randomized, clinical trial protocol: https://pubmed.ncbi.nlm.nih.gov/37462028/ Trial of Endovascular Therapy for Acute Ischemic Stroke with Large Infarct (ANGEL-ASPECT Trial): https://www.nejm.org/doi/full/10.1056/NEJMoa2213379 Acute endovascular stroke therapy (Dr. Mike Chen Review): https://pubmed.ncbi.nlm.nih.gov/20535000/ Mechanical thrombectomy is cost-effective versus medical management alone around Europe in patients with low ASPECTS (European Cost Effectiveness Study): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10313965/ Mechanical Thrombectomy Global Access For Stroke (MT-GLASS): A Mission Thrombectomy (MT-2020 Plus) Study: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10313965/ Noncontrast Computed Tomography vs Computed Tomography Perfusion or Magnetic Resonance Imaging Selection in Late Presentation of Stroke With Large-Vessel Occlusion: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8576630/

In this episode, we review the role and indications of thrombolytics in acute ischemic stroke. The efficacy, safety, administration considerations, and cost between alteplase and tenecteplase are compared and contrasted. Key Concepts Alteplase (Activase) is a recombinant DNA version of human TPA (tissue plasminogen activator). Tenecteplase (TNKase) is similar to human TPA except it has three amino acid changes that result in a longer half-life and higher fibrin specificity. In patients with stroke, alteplase is given as a bolus followed by a 60-minute infusion. Tenecteplase is given as an IV bolus without the need for an infusion due to its longer half-life. Tenecteplase is at least as safe and effective as alteplase in acute ischemic stroke (with some studies showing greater benefit with tenecteplase). In patients with acute ischemic stroke who are candidates for mechanical thrombectomy, thrombolytics (with alteplase or tenecteplase) will still be given in patients who meet inclusion criteria and have no exclusion criteria. References Powers WJ, Rabinstein AA, Ackerson T, et al. Guidelines for the Early Management of Patients With Acute Ischemic Stroke: 2019 Update to the 2018 Guidelines for the Early Management of Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association [published correction appears in Stroke. 2019 Dec;50(12):e440-e441]. Stroke. 2019;50(12):e344-e418. doi:10.1161/STR.0000000000000211 Campbell BCV, Mitchell PJ, Churilov L, et al. Tenecteplase versus Alteplase before Thrombectomy for Ischemic Stroke. N Engl J Med. 2018;378(17):1573-1582. doi:10.1056/NEJMoa1716405 Kobeissi H, Ghozy S, Turfe B, et al. Tenecteplase vs. alteplase for treatment of acute ischemic stroke: A systematic review and meta-analysis of randomized trials. Front Neurol. 2023;14:1102463. Published 2023 Jan 23. doi:10.3389/fneur.2023.1102463

JNIS Editor-in-Chief, Dr. Felipe C. Albuquerque, is joined from Calgary by Dr. Johanna Ospel (1) to discuss "Recent developments in pre-hospital and in-hospital triage for endovascular stroke treatment", a paper detailing the many aspects of resource allocation when treating stroke patients.  Read the paper: https://jnis.bmj.com/content/early/2022/10/14/jnis-2021-018547 (1) Departments of Radiology and Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada Please subscribe to the JNIS Podcast via all podcast platforms, including Apple Podcasts, Google Podcasts, Stitcher and Spotify, to get the latest episodes. Also, please consider leaving us a review or a comment on the JNIS Podcast iTunes page: https://podcasts.apple.com/gb/podcast/jnis-podcast/id942473767  Thank you for listening! This episode was produced and edited by Brian O'Toole. 

Listen to the fourth episode of NCS's INSIGHTS series on Acute Ischemic Stroke (part 2 of 2) 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 Biogen. Science that transforms patient lives. Science that seeks to solve societal problems. Science that acts with purpose. Science that is inspired by the diversity and passion of our people. Discover where science meets humanity at Biogen. The NCS Podcast is the official podcast of the Neurocritical Care Society.

Listen to the third episode of NCS' INSIGHTS series - Acute Ischemic Stroke (part 1 of 2). 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 Biogen. Science that transforms patient lives. Science that seeks to solve societal problems. Science that acts with purpose. Science that is inspired by the diversity and passion of our people. Discover where science meets humanity at Biogen. The NCS Podcast is the official podcast of the Neurocritical Care Society.

Dr. Thanh Nguyen discusses his paper, "Dual Antiplatelet Therapy vs Alteplase for Patients With Minor Nondisabling Acute Ischemic Stroke". Show references: https://jamanetwork.com/journals/jama/article-abstract/2806532 This episode was sponsored by the ExTINGUISH Trial for NMDAR Encephalitis: Call 844-4BRAIN5 to refer patients.

Dr. Dan Ackerman talks with Dr. Thanh Nguyen about whether dual antiplatelet therapy is noninferior to intravenous thrombolysis among patients with minor nondisabling acute ischemic stroke. Read the related article in JAMA. Visit NPUb.org/Podcast for associated article links. This episode was sponsored by the ExTINGUISH Trial for NMDAR Encephalitis: Call 844-4BRAIN5 to refer patients.

"...the World Health Organization definition of stroke is rapidly developing clinical signs of focal or Global disturbance of cerebral function with symptoms lasting 24 hours or longer or leading to death with no apparent cause other than a vascular origin this means that patients with similar symptoms caused by other causes such as tumors subdural hematomas poisoning or trauma and not considered Strokes so the difference between a stroke and a TI a or a transient ischemic attack is that a TI a is a brief episode of neurological dysfunction typically less than one hour but up to 24 hours with a vascular cause and with no evidence of infarction meaning cell death on Imaging they were previously distinguished by the duration of the neurological symptoms but now a distinguished based on the absence of in fact evidence on it Jing and resolution of symptoms the two main types of stroke ischemic stroke or hemorrhagic stroke with around 80% being ischemic an ischemic stroke is caused by the blockage of blood flow while a hemorrhagic stroke is caused by a rupture and extravasation of blood in the brain or surrounding tissue also note that Strokes with ischemic areas have a risk for breeding there for ischemic stroke can undergo what is known as a hammer dragic transformation there are four main mechanisms for an ischemic stroke the first is thrombosis which is divided into large and small vessel disease large vessel disease involves the common and internal carotid 's the vertebral arteries and The Circle of Willis the main causes of thrombi here include atherosclerosis vasoconstriction dissection and vasculitis small vessel disease involves smaller she's of The Circle of Willis and arteries in the distal vertebral and battler arteries causes here include lightbulb highly gnosis which is a build-up of fatty hyelin matter secondary to hypertension and aging as well as micro after ohms which is small atherosclerosis plaques thrombi can also be caused by Sickle Cell red blood cells clumping together and thrombi may also generate emboli which are the second mechanism for ischemic stroke the emboli are entities that travel in the blood and can be part of a thrombus that has been broken off they can be fat they can be air or even cancer or clumps of bacteria most commonly the source of the embolus is the heart due to atrial fibrillation atrial or ventricular thrombi rheumatic heart disease recent myocardial infarction or even recent coronary artery bypass grafting emboli may also travel from sources..." Learn more about your ad choices. Visit megaphone.fm/adchoices

"...the World Health Organization definition of stroke is rapidly developing clinical signs of focal or Global disturbance of cerebral function with symptoms lasting 24 hours or longer or leading to death with no apparent cause other than a vascular origin this means that patients with similar symptoms caused by other causes such as tumors subdural hematomas poisoning or trauma and not considered Strokes so the difference between a stroke and a TI a or a transient ischemic attack is that a TI a is a brief episode of neurological dysfunction typically less than one hour but up to 24 hours with a vascular cause and with no evidence of infarction meaning cell death on Imaging they were previously distinguished by the duration of the neurological symptoms but now a distinguished based on the absence of in fact evidence on it Jing and resolution of symptoms the two main types of stroke ischemic stroke or hemorrhagic stroke with around 80% being ischemic an ischemic stroke is caused by the blockage of blood flow while a hemorrhagic stroke is caused by a rupture and extravasation of blood in the brain or surrounding tissue also note that Strokes with ischemic areas have a risk for breeding there for ischemic stroke can undergo what is known as a hammer dragic transformation there are four main mechanisms for an ischemic stroke the first is thrombosis which is divided into large and small vessel disease large vessel disease involves the common and internal carotid 's the vertebral arteries and The Circle of Willis the main causes of thrombi here include atherosclerosis vasoconstriction dissection and vasculitis small vessel disease involves smaller she's of The Circle of Willis and arteries in the distal vertebral and battler arteries causes here include lightbulb highly gnosis which is a build-up of fatty hyelin matter secondary to hypertension and aging as well as micro after ohms which is small atherosclerosis plaques thrombi can also be caused by Sickle Cell red blood cells clumping together and thrombi may also generate emboli which are the second mechanism for ischemic stroke the emboli are entities that travel in the blood and can be part of a thrombus that has been broken off they can be fat they can be air or even cancer or clumps of bacteria most commonly the source of the embolus is the heart due to atrial fibrillation atrial or ventricular thrombi rheumatic heart disease recent myocardial infarction or even recent coronary artery bypass grafting emboli may also travel from sources..." Learn more about your ad choices. Visit megaphone.fm/adchoices

References: Miles MVP, Beasley JR, Reed HE, Miles DT, Haiflich A, Beckett AR, Lee YL, Bowden SE, Panacek EA, Ding L, Brevard SB, Simmons JD, Butts CC. Overutilization of Helicopter Emergency Medical Services in Central Gulf Coast Region Results in Unnecessary Expenditure. J Surg Res. 2022 May;273:211-217. doi: 10.1016/j.jss.2021.12.038. Epub 2022 Jan 29. PMID: 35093837. Roman J, Shank W, Demirjian J, Tang A, Vercruysse GA. Overutilization of Helicopter Transport in the Minimally Burned-A Healthcare System Problem That Should Be Corrected. J Burn Care Res. 2020 Jan 30;41(1):15-22. doi: 10.1093/jbcr/irz143. PMID: 31504602. Adcock AK, Minardi J, Findley S, Daniels D, Large M, Power M. Value Utilization of Emergency Medical Services Air Transport in Acute Ischemic Stroke. J Emerg Med. 2020 Nov;59(5):687-692. doi: 10.1016/j.jemermed.2020.08.005. Epub 2020 Oct 1. PMID: 33011044; PMCID: PMC8006070. Chen X, Gestring ML, Rosengart MR, Peitzman AB, Billiar TR, Sperry JL, Brown JB. Logistics of air medical transport: When and where does helicopter transport reduce prehospital time for trauma? J Trauma Acute Care Surg. 2018 Jul;85(1):174-181. doi: 10.1097/TA.0000000000001935. PMID: 29787553. Chen X, Gestring ML, Rosengart MR, Billiar TR, Peitzman AB, Sperry JL, Brown JB. Speed is not everything: Identifying patients who may benefit from helicopter transport despite faster ground transport. J Trauma Acute Care Surg. 2018 Apr;84(4):549-557. doi: 10.1097/TA.0000000000001769. PMID: 29251708.

Contributor: Travis Barlock MD Educational Pearls:  Large Vessel Occlusion (LVO) is a condition where a clot blocks one of the major blood vessels in the brain, leading to a stroke. What are the vessels that can experience an LVO? Middle Cerebral artery (MCA) Internal Carotid Artery (ICA) Anterior Cerebral Artery (ACA) Posterior Cerebral Arteries (PCA) Basilar Artery (BA) Vertebral Arteries (VA) What are the locations at which a mechanical thrombectomy can be performed as a treatment for an LVO? Distal ICA, M1 or M2 segments of the MCA, A1 or A2 segments of the ACA, and some evidence for the BA. What are the symptoms of LVO? Use the mnemonic FANG-D to remember a few key symptoms: Field Cut (A person loses vision in a portion of their visual field) Aphasia (Difficulty speaking) Neglect (A person may have difficulty paying attention to or acknowledging stimuli on the affected side of their body or in their environment. For example, a person with neglect may deny that their left hand belongs to them) Gaze Deviation (One or both eyes are turned away from the direction of gaze) Dense Hemiparesis (Paralysis affecting one side of the body) What are the treatment windows for treating an LVO? 24 hours for mechanical thrombectomy 0-4.5 hours for tPA/TNK References 1. Brain embolism, Caplan LR, Manning W (Eds), Informa Healthcare, New York 2006. 2. Berkhemer OA, et al. A randomized trial of intraarterial treatment for acute ischemic stroke. N Engl J Med. 2015 Jan 1;372(1):11-20. doi: 10.1056/NEJMoa1411587. Epub 2014 Dec 17. Erratum in: N Engl J Med. 2015 Jan 22;372(4):394. PMID: 25517348. 3. Herpich, Franziska MD1,2; Rincon, Fred MD, MSc, MB.Ethics, FACP, FCCP, FCCM1,2. Management of Acute Ischemic Stroke. Critical Care Medicine 48(11):p 1654-1663, November 2020. 4. Warner JJ, Harrington RA, Sacco RL, Elkind MSV. Guidelines for the Early Management of Patients With Acute Ischemic Stroke: 2019 Update to the 2018 Guidelines for the Early Management of Acute Ischemic Stroke. Stroke. 2019 Dec;50(12):3331-3332. doi: 10.1161/STROKEAHA.119.027708. Epub 2019 Oct 30. PMID: 31662117. 5. Hoglund J, Strong D, Rhoten J, Chang B, Karamchandani R, Dunn C, Yang H, Asimos AW. Test characteristics of a 5-element cortical screen for identifying anterior circulation large vessel occlusion ischemic strokes. J Am Coll Emerg Physicians Open. 2020 Jul 24;1(5):908-917. doi: 10.1002/emp2.12188. PMID: 33145539; PMCID: PMC7593424. Summarized by Jeffrey Olson | Edited by Meg Joyce & Jorge Chalit, OMS1  

Tenecteplase in Acute Ischemic Stroke  Special Guest: Salia Farrokh, PharmD, BCCCP, FNCS 07:45 – Alteplase history and comparison 14:20 – Thrombolysis guidelines in AIS 19:15 – Tips for reading stroke literature 21:00 – Tenecteplase literature review  39:45 – Tenecteplase research-in-progress 42:30 – Thrombolytic-induced ICH management 46:25 – Arguments for and against Tenecteplase 51:30 – Advice when switching thrombolytics 58:20 – Ultimate take-aways Reference List: https://pharmacytodose.files.wordpress.com/2023/04/tenecteplase-in-acute-ischemic-stroke-references.pdf PharmacyToDose.Com  @PharmacyToDose  PharmacyToDose@Gmail.com Learn more about your ad choices. Visit megaphone.fm/adchoices

In Part 3 of a 3-part series, Sunil A. Sheth, MD, discusses his article, "Mechanical Thrombectomy for Acute Ischemic Stroke" from the April Continuum Cerebrovascular Disease issue. This article and accompanying Continuum Audio interview are available to subscribers at continpub.com/MechThromb. This podcast is sponsored by argenx. Visit www.vyvgarthcp.com for more information.

In Part 2 of a 3-part series, Sunil A. Sheth, MD, discusses his article, "Mechanical Thrombectomy for Acute Ischemic Stroke" from the April Continuum Cerebrovascular Disease issue. This article and accompanying Continuum Audio interview are available to subscribers at continpub.com/MechThromb. This podcast is sponsored by argenx. Visit www.vyvgarthcp.com for more information.

In Part 1 of a 3-part series, Sunil A. Sheth, MD, discusses his article, "Mechanical Thrombectomy for Acute Ischemic Stroke" from the April Continuum Cerebrovascular Disease issue. This article and accompanying Continuum Audio interview are available to subscribers at continpub.com/MechThromb. This podcast is sponsored by argenx. Visit www.vyvgarthcp.com for more information.

Editor's Summary by Kirsten Bibbins-Domingo, PhD, MD, MAS, Editor in Chief of JAMA, the Journal of the American Medical Association, for the February 28, 2023, issue. Related Content: Audio Highlights

Bradyarrhythmia during AF screening, thrombolysis in stroke, NP vs MD care, and the most biased paper this year — on LAAO — are the topics John Mandrola, MD, discusses in this week's podcast. This podcast is intended for healthcare professionals only. To read a partial transcript or to comment, visit: https://www.medscape.com/twic I. Screening with ILR - Ade Adamson Tweet https://twitter.com/AdeAdamson/status/1625878856820482048?s=20 - The Rapid Rise in Cutaneous Melanoma Diagnoses https://www.nejm.org/doi/full/10.1056/NEJMsb2019760 - Loop Trial https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)01698-6/fulltext - Prevalence and Prognostic Significance of Bradyarrhythmias in Patients Screened for Atrial Fibrillation vs Usual Care https://jamanetwork.com/journals/jamacardiology/fullarticle/2801362 II. Thrombolysis in Mild Stroke Thrombolysis Not Necessary in Mild Nondisabling Stroke: ARAMIS https://www.medscape.com/viewarticle/988381 - PRISMS Trial https://jamanetwork.com/journals/jama/fullarticle/2687354 - Risk of selection bias assessment in the NINDS rt-PA stroke study https://pubmed.ncbi.nlm.nih.gov/35705913/ - Tissue Plasminogen Activator for Acute Ischemic Stroke https://www.nejm.org/doi/full/10.1056/NEJM199512143332401 - Effects of alteplase for acute stroke; Hacke et al meta-analysis https://journals.sagepub.com/doi/10.1177/1747493017744464 - Methodological survey of missing outcome data in an alteplase for ischemic stroke meta-analysis https://onlinelibrary.wiley.com/doi/full/10.1111/ane.13656 - ECASS; Thrombolysis with Alteplase 3 to 4.5 Hours after Acute Ischemic Stroke https://www.nejm.org/doi/full/10.1056/nejmoa0804656 - Thrombolysis with alteplase 3-4.5 hours after acute ischaemic stroke: trial reanalysis adjusted for baseline imbalances https://pubmed.ncbi.nlm.nih.gov/32430395/ III. NP vs MD Care This Doc Still Supports NP/PA Led Care ... With Caveats https://www.medscape.com/viewarticle/967073 - The Productivity of Professions: Evidence from the Emergency Department https://www.nber.org/papers/w30608 - Independent Nurse Practitioners and Physician Assistants: A Doc's View https://www.medscape.com/viewarticle/924047 IV. LAAO vs OAC - Comparative Effectiveness of Left Atrial Appendage Occlusio Versus Oral Anticoagulation by Sex https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.122.062765 You may also like: Medscape editor-in-chief Eric Topol, MD, and master storyteller and clinician Abraham Verghese, MD, on Medicine and the Machine https://www.medscape.com/features/public/machine The Bob Harrington Show with Stanford University Chair of Medicine, Robert A. Harrington, MD. https://www.medscape.com/author/bob-harrington Questions or feedback, please contact news@medscape.net

In this week's episode, we'll discuss involvement of IL-13 and IL-4 signaling in fibrotic progression of myelofibrosis; next, we review results on a novel agent using vWF-dependent mechanisms to lyse pathological thrombi in acute ischemic stroke. Finally, we'll shed new light on findings that implicate the GARP-TGF-beta-1 pathway in the loss of natural killer cell cytotoxicity in relapsed AML.

In this podcast, JNIS Editor-in-Chief, Dr. Felipe C. Albuquerque, speaks with Dr. Krishna C. Joshi(1) and Dr. Michael Chen(2) about their paper "Endovascular thrombectomy for acute ischemic stroke in patients with cancer: a propensity-matched analysis" - https://jnis.bmj.com/content/14/12/1161. Please subscribe to the JNIS Podcast via all podcast platforms, including Apple Podcasts, Google Podcasts, Stitcher and Spotify, to get the latest episodes. Also, please consider leaving us a review or a comment on the JNIS Podcast iTunes page: https://podcasts.apple.com/gb/podcast/jnis-podcast/id942473767 Thank you for listening! This episode was edited by Brian O'Toole. (1) Neurological Surgery, Rush University Medical Center, Chicago (2) Neurological Surgery, Rush University Medical Center, Chicago

Today let's talk a little about some considerations for the patient presenting with an acute ischemic stroke.  I've got a couple of references for you below as well!Guidelines for the Early Management of Patients With Acute Ischemic Stroke: 2019 Updatehttps://www.ahajournals.org/doi/10.1161/STR.0000000000000211The Code Stroke Handbook: Approach to the Acute Stroke Patienthttps://www.amazon.com/Code-Stroke-Handbook-Approach-Patient/dp/0128205229/ref=sr_1_6?crid=3C5STQ82E9UYW&keywords=acute+stroke+hand&qid=1668425511&sprefix=acute+stroke+hand%2Caps%2C92&sr=8-6&ufe=app_do%3Aamzn1.fos.18ed3cb5-28d5-4975-8bc7-93deae8f9840 Find me on Twitter @Drkentris (https://twitter.com/DrKentris) Email me at theneurotransmitterspodcast@gmail.com https://linktr.ee/DrKentris The views expressed do not necessarily represent those of any associated organizations. The information in this podcast is for educational and informational purposes only and does not represent specific medical/health advice. Please consult with an appropriate health care professional for any medical/health advice.

Dr. Jonathan M. Coutinho discusses his paper, "Diagnostic Yield of ECG-gated Cardiac CT in the Acute Phase of Ischemic Stroke vs Transthoracic Echocardiography". Show references: https://n.neurology.org/content/early/2022/08/01/WNL.0000000000200995 This podcast is sponsored by argenx. Visit www.vyvgarthcp.com for more information.

Date: September 20th, 2022 Reference: Menon et al. Intravenous tenecteplase compared with alteplase for acute ischaemic stroke in Canada (AcT): a pragmatic, multicentre, open-label, registry-linked, randomised, controlled, non-inferiority trial. The Lancet 2022 Guest Skeptic: Professor Daniel Fatovich is an emergency physician and clinical researcher based at Royal Perth Hospital, Western Australia. He is Head of the Centre […]

Dr. Dan Ackerman talks with Dr. Jonathan Coutinho about ECG-gated cardiac CT in the acute phase of ischemic stroke vs. thransthoracic echocardiography. Read the full article in Neurology. This podcast is sponsored by argenx. Visit www.vyvgarthcp.com for more information.

In this episode of the podcast, we discuss the management of Acute Ischemic Stroke (AIS). Our guest is Dr. Fred Rincon, a neurologist and critical care specialist with expertise in the resuscitation and management of acute brain injured patients. He is a Professor of Neurology at Cooper Medical School of Rowan University and Director of the Neuro-ICU at Cooper University Health Care in Camden, New Jersey. Additional Resources Management of Acute Ischemic Stroke. F. Herpich and F. Rincon: https://pubmed.ncbi.nlm.nih.gov/32947473/ AHA Guidelines for the Management of Acute Ischemic Stroke (2019): https://pubmed.ncbi.nlm.nih.gov/31662037/ Link to NIHSS Certification Course: https://www.nihstrokescale.org/ The intensive care management of acute ischemic stroke. D. Sharma and M. Smith: https://pubmed.ncbi.nlm.nih.gov/35034076/ Association of Neurocritical Care Services with Mortality and Functional Outcomes for Adults With Brain Injury. Meta-analysis. JAMA Neurology 2022: https://pubmed.ncbi.nlm.nih.gov/36036899/ Book Recommendations: The Servant: A Simple Story of About the True Essence of Leadership. By James C. Hunter: https://amzn.to/3U6u6SI How to Be a Leader: An Ancient Guide to Wise Leadership. By Plutarch: https://amzn.to/3eMBxhU

As we see more patients who have had Covid-19, we ask psychiatrist, Dr. Imaan Alaidroos, to speak with us about the neuropsychiatric impact of the disease. In this episode, Dr. Alaidroos outlines the treatments that are currently being studied for the neuropsychiatric symptoms of Covid-19. We also chat about the implications of these symptoms for the field of mental health. Hosts: Alan, Toshia Guest: Imaan Alaidroos, MD References: 7. Qureshi, A. I., Baskett, W. I., Huang, W., Shyu, D., Myers, D., Raju, M., Lobanova, I., Suri, M., Naqvi, S. H., French, B. R., Siddiq, F., Gomez, C. R., & Shyu, C. R. (2021). Acute Ischemic Stroke and COVID-19: An Analysis of 27 676 Patients. Stroke, 52(3), 905–912. https://doi.org/10.1161/STROKEAHA.120.031786 8. Helms J, Kremer S, MerdjiH, Clere-JehlR, Schenck M, KummerlenC, et al. Neurologic features in severe SARS-CoV-2 infection. N EnglJ Med. 2020;382:2268–2270. doi: 10.1056/NEJMc2008597. 9. FerrandoSJ, KlepaczL, Lynch S, TavakkoliM, DornbushR, BaharaniR, Smolin Y, Bartell A. COVID-19 psychosis: a potential new neuropsychiatric condition triggered by novel coronavirus infection and the inflammatory response? Psychosomatics. 2020;61:551–555. doi: 10.1016/j.psym.2020.05.012. 10. Parra A, JuanesA, LosadaCP, Álvarez-SesmeroS, Santana VD, Martí I, et al. Psychotic symptoms in COVID-19 patients. A retrospective descriptive study. Psychiatry Res. 2020;291:113254. doi: 10.1016/j.psychres.2020.113254. 11. Farooq, S., Tunmore, J., Wajid Ali, M., & Ayub, M. (2021). Suicide, self-harm and suicidal ideation during COVID-19: A systematic review. Psychiatry research, 306, 114228. https://doi.org/10.1016/j.psychres.2021.114228 12. Stefano, G. B., Büttiker, P., Weissenberger, S., Ptacek, R., Wang, F., Esch, T., Bilfinger, T. V., & Kream, R. M. (2021). Biomedical Perspectives of Acute and Chronic Neurological and Neuropsychiatric Sequelae of COVID-19. Current neuropharmacology, 10.2174/1570159X20666211223130228. Advance online publication. https://doi.org/10.2174/1570159X206662112231 13. de Erausquin, G. A., Snyder, H., Carrillo, M., Hosseini, A. A., Brugha, T. S., Seshadri, S., & CNS SARS-CoV-2 Consortium (2021). The chronic neuropsychiatric sequelae of COVID-19: The need for a prospective study of viral impact on brain functioning. Alzheimer's & dementia : the journal of the Alzheimer's Association, 17(6), 1056–1065. https://doi.org/10.1002/alz.12255 14. PashaeiY. Drug repurposing of selective serotonin reuptake inhibitors: Could these drugs help fight COVID-19 and save lives? J. Clin. Neurosci. 2021;88:163–172. doi: 10.1016/j.jocn.2021.03.010. 15. Dąbrowska, E., Galińska-Skok, B., & Waszkiewicz, N. (2021). Depressive and Neurocognitive Disorders in the Context of the Inflammatory Background of COVID-19. Life (Basel, Switzerland), 11(10), 1056. https://doi.org/10.3390/life11101056 Kępińska AP, Iyegbe CO, Vernon AC, Yolken R, Murray RM, Pollak TA. Schizophrenia and Influenza at the Centenary of the 1918-1919 Spanish Influenza Pandemic: Mechanisms of Psychosis Risk. Front Psychiatry. 2020 Feb 26;11:72. doi: 10.3389/fpsyt.2020.00072. PMID: 32174851; PMCID: PMC7054463.

Editor's Summary by Kirsten Bibbins-Domingo, PhD, MD, MAS, Editor in Chief of JAMA, the Journal of the American Medical Association, for the August 16, 2022 issue.

Dr. James Braun, Neurosciences Pharmacy Clinical Specialist at SSM Health St. Louis, and Dr. Kyle Hoelting, Senior Manager of Drug Information at Vizient, continue to share their insights on the use of TNK vs Alteplase for treating acute ischemic stroke. They also discuss the nuances of this therapeutic area and share recent work from an expert panel led by Vizient.   Guest speakers: James Braun, PharmD, BCCCP Neurosciences Pharmacy Clinical Specialist  SSM Health   Kyle Hoelting, PharmD, BCPS Senior Manager of Drug Information  Vizient   Moderator: Gretchen Brummel, PharmD, BCPS Pharmacy Executive Director Vizient Center for Pharmacy Practice Excellence   Show Notes: [00:30-3:59] Medication safety risks associated with thrombolytics [04:00-4:42] Using one drug over another [04:43-6:48] How frontline pharmacy staff can utilize this information [06:49-11:44] What Vizient can add to the discussion [11:45-11:55] When report will be released   Links | Resources: Tenecteplase vs alteplase in acute ischemic stroke: Vizient expert panel Verified Rx: Evidenced based medicine Click here Verified Rx: Show me the data! Updates on the evidence of thrombolytic use in ischemic strokes Click here Verified Rx: Information overload: tips and tricks for staying on top of the literature, part 1 Click here Verified Rx: Information overload: tips and tricks for staying on top of the literature, part 2 Click here   Subscribe Today! Apple Podcasts Amazon Podcasts Google Podcasts Spotify Stitcher Android RSS Feed

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.