Podcasts about iv tpa

Stroke Alert June 2021 On Episode 5 of the Stroke Alert Podcast, host Dr. Negar Asdaghi highlights two articles from the June 2021 issue of Stroke: "Preexisting Mild Cognitive Impairment, Dementia, and Receipt of Treatments for Acute Ischemic Stroke” and “Body Mass Index in 1.9 Million Adolescents and Stroke in Young Adulthood.” She also interviews Dr. Shyam Prabhakaran, from the University of Chicago, about his article "Predictors of Early Infarct Recurrence in Patients With Symptomatic Intracranial Atherosclerotic Disease." Dr. Negar Asdaghi: 1) Do people with mild cognitive impairment receive the same quality of stroke care as their cognitively normal counterparts? 2) Is there a causative relationship between the alarming rise in adolescent obesity and the rise in the incidence of stroke under the age of 50? 3) What are the independent predictors of radiographic recurrence in patients with symptomatic intracranial atherosclerotic disease? These are the topics that we will cover in today's podcast. You're listening to the Stroke Alert Podcast. Stay with us. Dr. Negar Asdaghi:                        From the Editorial Board of Stroke, welcome to 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. For the June 2021 issue of Stroke, we have a range of publications that cover a variety of topics from activation of neuroinflammatory pathways and intracerebral hemorrhage to predictors of outcome in patients with mild and rapidly improving ischemic stroke, which I encourage you to review, in addition to our podcast. Later in today's podcast, I have the privilege of interviewing Dr. Shyam Prabhakaran from University of Chicago on his work with various radiographic biomarkers as predictors of outcome in patients with symptomatic intercranial atherosclerotic disease. But first, with these two papers. Dr. Negar Asdaghi:                        In the United States, one in five adults over the age of 65 have mild cognitive impairment, and one in seven have a formal diagnosis of dementia. With our aging population, these numbers are estimated to triple by year 2050. Prior studies suggest that patients with dementia are less likely to receive evidence-based stroke care as compared to those with normal cognition. Less is known about the quality of stroke care amongst patients with mild cognitive impairment. In their paper titled "Preexisting Mild Cognitive Impairment, Dementia, and Receipt of Treatments for Acute Ischemic Stroke," Dr. Deborah Levine from Departments of Neurology and Internal Medicine at the University of Michigan and colleagues studied the quality of care in acute ischemic stroke patients with mild cognitive impairment, or MCI, and preexisting dementia as compared to patients with normal cognition. Dr. Negar Asdaghi:                        This was a cross-sectional analysis of prospectively obtained data on adults with acute ischemic stroke included in the Brain Attack Surveillance in the Corpus Christi project from 2008 to 2013. Primary outcome of the study is a composite quality measure of defect-free care calculated by dividing the number of treatments that a patient received by the number of treatments they were eligible to receive. Defect-free care was defined as receipt of seven stroke performance measures when eligible, and included administration of IV tPA, use of antithrombotic therapy by end of hospital day two, administration of DVT prophylaxis, assessment for rehabilitation, discharge on antithrombotic therapy, discharge on lipid-lowering therapy, and discharge on anticoagulation therapy for atrial fibrillation. Dr. Negar Asdaghi:                        Amongst 836 adults included in this study with a median age of 65, 58%, that's over half of the patients in this study, had some degree of cognitive impairment prior to their presenting stroke. 44% of patients with preexisting dementia received defect-free care as compared to 55% with either normal cognition or mild cognitive impairment. The difference, they did not reach statistical significance after adjusting for the sex, vascular comorbidities, and BMI in multivariate analysis. However, preexisting MCI remain an independent factor to be negatively associated with receipt of IV tPA echocardiogram and assessment for rehabilitation. Similarly, after adjusting for all confounders, preexisting dementia remained negatively associated with receipt of antithrombotic therapy by day two, lipid-lowering therapy at discharge, and receiving an echocardiogram. The authors highlighted their findings as a call to action to improve the overall delivery of stroke care and measures to all stroke patients, and caution that disparities noted in their study might contribute to differences in post-stroke outcomes, such as functional disability and recurrent stroke in the growing population of patients with mild cognitive impairment and dementia. Dr. Negar Asdaghi:                        Having a stroke at a young age has profound personal, societal, and economic implications. For the young stroke survivors, a long life expectancy after stroke, and the cost of long-term care pose huge challenges to healthcare systems, which are different than that encountered in the elderly stroke population. Over the past two decades, the incidence of ischemic stroke has substantially increased in the young, with adults under the age of 50 now comprising 10% of all ischemic stroke cases. This comes in parallel with the continuous rise in the prevalence of adolescent obesity in many Western countries, but the association between the two remains unclear. In the current issue of the journal, Dr. Aya Bardugo from the Department of Military Medicine, Hebrew University, in Jerusalem, and colleagues studied the association of adolescent body mass index, or BMI, with first stroke event in young adults as part of a nationwide population-based study of 1.9 million adolescents, followed for a cumulative 9.48 million person-years. BMI values were categorized in five groups of underweight, low-normal, high-normal, overweight, and obese. Dr. Negar Asdaghi:                        So, what they found was that the incident rate of any stroke and ischemic stroke increased gradually across the five BMI categories. Importantly, the hazard ratio for ischemic stroke became significant, even in the high-normal BMI group at 1.4, and increased to 2 for the overweight and 3.5 in the obese category. Though a similar increase in the rate of hemorrhagic stroke was noted, there was no significant association between BMI and hemorrhagic stroke in the study. Not surprisingly, many vascular risk factors, including high blood pressure and diabetes, were also elevated in the higher category BMI adolescents. However, alarmingly, these trends remain significant even after adjustment for age, sex, sociodemographic factors, and when the data was limited to otherwise healthy adolescents, those without diabetes and those without high blood pressure. Overall, the authors found that overweight and obese adolescents had approximately two- to threefold increased hazard for ischemic stroke that could present prior to the age of 30 irrespective of sex, race, ethnicity, and socioeconomic status. Dr. Negar Asdaghi:                        The authors detailed various mechanisms in which increased adolescent BMI may lead to stroke in the young, including progressive risk of large vessel intra and extracranial atherosclerotic disease, increased cardiovascular disease, and a shift to young onset heart failure and atrial fibrillation, as well as a strong association with being high BMI in children and adolescents, and that of obesity in adults. These findings are important observations as we face a growing epidemic of childhood and youth obesity worldwide with the potential to increase the future burden of stroke in young adults. Dr. Negar Asdaghi:                        Intracranial atherosclerotic disease, or ICAD, is an important cause of ischemic stroke worldwide. In addition to neurological deficits caused by index event, patients with ICAD remain at high risk for development of recurrent ischemic events. The risk of clinical recurrence is estimated to be between 12% to 20% at one year based on prior studies, despite best medical management. But recent studies have shown that up to 25% of patients with symptomatic ICAD have evidence of radiographic recurrence on follow-up MRI imaging. Dr. Negar Asdaghi:                        Who will remain stable and who will have more events with symptomatic ICAD is a common question that practicing clinicians struggle with in routine practice. The Mechanisms of Early Recurrence in Intracranial Atherosclerotic Disease, or the MYRIAD study, aimed to get us closer to that answer. Joining me now is Dr. Shyam Prabhakaran, Professor of Neurology and Chair of the Department of Neurology at the University of Chicago, who was one of the principal investigators of the MYRIAD study and the first author of the paper in the current issue of the journal titled "Predictors of Early Infarct Recurrence in Patients With Symptomatic Intracranial Atherosclerotic Disease." Good afternoon, Shyam. Thank you for joining us. Dr. Shyam Prabhakaran:              Thank you, and good afternoon to you. Dr. Negar Asdaghi:                        Thank you. Shyam, can you please start by telling us how MYRIAD's design was different from prior studies of symptomatic ICAD? And what were the main objectives of the study? Dr. Shyam Prabhakaran:              Sure, so MYRIAD was conceived as a study to really unravel and study the mechanisms of recurrent stroke after symptomatic ICAD presentation. Prior studies, I think, have really helped in many ways, obviously to understand the natural history of the disease, including through clinical trials, where we learned about the different interventions that could be applied, medical and endovascular, through WASID and then SAMMPRIS. However, both of those studies, which provided probably the bulk of information about the disease in multi-center study, did not really focus on mechanisms, per se, understanding it through biomarkers, understanding whether certain subsets of patients have higher or lower risk of recurrence. So, MYRIAD was conceived to try to tackle that particular aspect of research that we felt was understudied. Dr. Negar Asdaghi:                        Yes, thank you. Traditionally, as you mentioned, the location and the degree of stenosis have been considered as important radiographic factors to predict outcomes in symptomatic ICAD. MYRIAD looked at many more imaging biomarkers than just degree of stenosis and the location. Can you please elaborate on those radiographic biomarkers that were included in MYRIAD? Dr. Shyam Prabhakaran:              Yeah. So, again, MYRIAD wanted to explore these imaging biomarkers, and we split them into three categories. One was biomarker of antegrade flow. What would help us understand the amount or volume of flow through a particular diseased artery? And we used quantitative MRA for that, which is a technique that's been around a long time, a phase contrast MR approach, to get vessel-specific flow measurements. And aim two thought of the distal flow beyond the stenosis and aimed to look at two types of imaging biomarkers that might answer the question of flow in the distal territory, one through perfusion imaging. So looking at CT or MR perfusion, but MR was the one that we selected, where we would measure the tissue flow through Tmax measurements, and then the other using TCD, transcranial Doppler, and vasomotor reactivity testing of the distal arterials. So that was aim two. Can we look at those biomarkers potentially as predictors of recurrence? And then the third was emboli detection, so the plaque vulnerability or instability biomarker. So, could we look at distal emboli in the territory and assess its role in predicting recurrence? So, those were really the main biomarkers tied to the objectives of the grant. Dr. Negar Asdaghi:                        Perfect. So, obviously, great, and a comprehensive various biomarkers looking at different imaging predictors of early recurrence. We're excited to hear about your primary results. So, what did your study find? Dr. Shyam Prabhakaran:              So, in MYRIAD, we enrolled 105 subjects who had symptomatic intercranial stenosis at 10 centers across the US. And we were able to track them for both the primary outcome, which was stroke in the territory of the stenosis, clinical stroke at one year, and the secondary outcome, which was radiographic occurrence of new infarcts on six- to eight-week MRI. So that was a prespecified outcome. In the primary analysis of the clinical outcome, we did find a fairly high rate of recurrent events. Roughly 10% of patients in the cohort had a recurrent clinical event at one year, consistent with findings from, say, SAMMPRIS, which with maximum medical or aggressive medical management found a roughly 12% recurrence. So, we were able to confirm that there is a high rate of clinical recurrence. However, none of the biomarkers that we were looking at, quantitative MRA, profusion imaging, transcranial Doppler for BMR or emboli detection were predictors of the clinical outcome at one year. So, that was our main results. Dr. Shyam Prabhakaran:              Our secondary outcome was recurrent infarcts on study-specific research MRIs performed at the sites, and looked for recurrences compared to baseline MRIs that were performed at the time of their index stroke or TIA. So, in this paper, we were really interested in looking at whether there were any specific predictors of recurrent radiographic infarct, and that really was an interest of ours because we did find such a high rate of radiographic recurrence. Roughly 24% of our cohort had a recurrent infarct on brain imaging at six to eight weeks. So, we recognized right away that this is potentially an unrecognized phenomenon, that there's potentially an excess of radiographic events to clinical events. And there could be, obviously, a potential consequence of this radiographic accumulation of disease. Particularly, it might be important to prevent those radiographic occurrences in the future if they are affecting an individual's performance on cognition or even physical function as a result of accumulating lesions. So, we were really interested in seeing whether there were some early predictors of this six- to eight-week recurrence that we saw at a high rate. So, the paper looked at clinical factors, as well as imaging factors, that were available in the MYRIAD cohort, really trying to delve into a model that we could use to identify a subset that is at the highest risk of these early recurrent infarcts. Dr. Negar Asdaghi:                        Right, so very, very important findings. So, just to reiterate for our listeners, one in four patients in your study had evidence of radiographic recurrence despite clinically seemingly having no clinical events. So, this clinical radiographic dissociation would have absolutely gone unnoticed had it not been for these early MR images that were performed in the study. So, I want to clarify this from a pathophysiological standpoint. Is it hypoperfusion, plaque rupture, or both? Based on your results, what is the driving factor in development of new ischemia in symptomatic ICAD? Dr. Shyam Prabhakaran:              So, one of our main findings here, which is reported in this paper, is that those with multiple infarcts at their index stroke, so a pattern on diffusion-weighted imaging that was more than a singular infarct lesion, was a strong, independent predictor of having a recurrent event, recurrent infarct at six to eight weeks. And the part that isn't really highlighted in the paper, but is true, is the other factor that was co-mingled with multi-lesion, multi-infarct and index was borderzone pattern. They were co-linear, and they were essentially the same patients who were borderzone also had multiple lesions. So, one way we've interpreted this, and I can speak to a little bit about the different biomarkers that were studied in addition to the infarct pattern, but one way we've interpreted this is that multi-lesions can probably fall under two subsets. Dr. Shyam Prabhakaran:                           It could either be in this borderzone pattern, where you have multiple lesions due to hypoperfusion mechanisms, typically within either cortical or internal borderzones. And that may be then telling us about a mechanism of low flow. On the other hand, some of these patients could also have scattered lesions that are embolic in etiology and suggest a plaque that was unstable and potentially showered at their index event, resulting in that pattern that we saw. So, both of them probably are mixed in. We're favoring the borderzone because they were so co-linear that that probably was the more likely mechanism. And we're probably concerned that that could also be a factor that leads to early recurrence because flow failure typically is associated with critical hypoperfusion and imminent recurrence. Dr. Shyam Prabhakaran:              But, interestingly, in the paper, we talk about this, none of the specific prespecified biomarkers that were looking at flow, perfusion imaging, vasomotor reactivity were significant by themselves as predictors of recurrent infarct. So, it's a little hard for us to know why. It could be that the technology that we use, perfusion imaging, is still not quite picking up the kind of flow failure that we need to. Maybe it's more subtle than even we found because we looked at different cut points of Tmax and other parameters on perfusion imaging, and yet, we're not able to find a cutoff that was predictive, likewise with vasomotor reactivity. So, it could be that those are not quite good enough surrogates of hypoperfusion. And yet, borderzone or multi-infarct patterns may have been a surrogate of hypoperfusion. So, I think the short answer here is that it could be both mechanisms, plaque instability and hypoperfusion, although we're maybe favoring hypoperfusion because there was a strong co-linearity with borderzone pattern. Dr. Negar Asdaghi:                        Understood. Now Shyam, recurrent events on maximum medical therapy, this is not what we like to hear. Where do you see the future of symptomatic ICAD therapy? Now in your view, is there a role for interventional treatment or other therapies in a select group of ICAD patients? Dr. Shyam Prabhakaran:              I think that's really where we still face real challenges. I think the work done by many of the investigators before us on maximum medical therapy and interventional therapies have found, obviously, that there are some benefits to the medical approaches that we now consider standard of care. The dual antiplatelet therapy, the lipid-lowering therapy, the lifestyle management that SAMMPRIS also implemented and successfully showed some benefits of physical activity. So, those things clearly matter. And yet, the clinical event rate is still very high, and the radiographic event rate is even higher. So, you have this real challenge facing clinicians and patients of a disease that has a very high rate of recurrence, much higher than the other subtypes of ischemic stroke, and certainly higher than, say, AFib patients even, where we sometimes obviously are concerned and adopt strategies to lower risk. So, we are in a position, I think, today where we have to go back to the well and think about novel strategies. Dr. Shyam Prabhakaran:              Now, flow is a component of this, and I do think that SAMMPRIS, albeit now almost a decade ago, tested an interventional approach. It may be worth revisiting interventional strategies. Of course, we know from endovascular therapy for ischemic stroke, try once and fail, and try again, and you might find a different result because technologies get better, practitioners, proceduralists get better. So, that's one angle that I think people are very interested in, is whether or not an interventional approach for flow failure patients is a path forward. And that, I think, will get a lot of attention in the years to come with new studies that are being designed. Dr. Shyam Prabhakaran:              I think the other important point here is that aggressive medical management in the current day and age may still have room for improvement. Maybe the drugs that we're using, especially with DAPT and lipid-lowering therapies, they're not as quick or necessarily universally responsive for every patient. So, we know that about clopidogrel, that there's a certain rate of non-responders. We could probably do better than that with other choices, antiplatelet choices or even anticoagulant choices, which are being considered. And we know that lipid-lowering therapy with statins works well, but perhaps PCSK9 drugs could be considered in this population to lower cholesterol levels even more rapidly and more aggressively. So, all of these, I think, should be on the table as we move forward. Dr. Negar Asdaghi:                        Dr. Shyam Prabhakaran, thank you for joining us on the podcast today. We look forward to having you back here and covering more of your work in the future. Dr. Shyam Prabhakaran:              Thank you for having me. Dr. Negar Asdaghi:                        Thank you. And this concludes our podcast for the June 2021 issue of Stroke. Please be sure to check out the June table of contents for the full list of publications, including an important update from the American Stroke Association and the Stroke Council on how cerebrovascular disease is expected to temporarily fall from the fifth to the sixth leading cause of death in the United States in 2020. Sadly, this is not because of advances in stroke prevention and therapies, but rather because mortality from COVID-19 will displace stroke as a leading cause of death, a grim reminder of the year we put behind us and the many lives lost to this global pandemic. And yet we look ahead with hope, and with the promise that science has the power to resolve and the ability to push the human race forward. Every small step, every question will get us closer to learning more, answering more and knowing more. So, as we end this podcast today, we look forward to asking more at our next, and our promise to stay alert with Stroke Alert. This program is copyright of the American Heart Association, 2021. 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.

The NINDS trial was the seminal study of IV-tPA in the treatment of acute stroke. Yet controversy still exists around the trial methodology and the interpretation of the data. Was anything missing from NINDS? Does it still resonate nearly 25 years later?

Host: Interim President Michael Bernstein About Dr. Fiorella: Dr. David J. Fiorella, Director of the Stony Brook Cerebrovascular Center, Co-Director of the Stony Brook Cerebrovascular and Comprehensive Stroke Center, and Professor of Neurosurgery and Radiology joined the Department of Neurosurgery in 2009. Dr. Fiorella is considered a pioneer in the field of neuro-interventional therapies, advancing new devices and techniques for the treatment of Cerebrovascular disease. Dr. Fiorella spearheaded the acquisition of 2 Mobile Stroke units for Stony Brook University Hospital, the first program in Suffolk County. He is the Principle Investigator or Co-PI on numerous national trials evaluating new devices and techniques for the treatment of aneurysms, acute stroke and intracerebral hemorrhage. He is a senior member of the Society for Neuro-interventional Surgery (SNIS) and senior associate editor of the Journal of Neurointerventional Surgery. Dr. Fiorella has been named amongst the best interventional radiologists/endovascular surgeons in Castle Connolly's Top Doctors for several years in a row. About the Episode: Stony Brook Medicine Mobile Stroke Unit founder, Dr. David Fiorella, is considered a pioneer in the field of neuro-interventional therapies -- advancing new devices and techniques for the treatment of Cerebrovascular disease. He took that pioneering inspiration one step further in 2019 when he and a team of Stony Brook clinicians and colleagues launched the first two Mobile Stroke Units on Long Island. These Mobile Stroke Units enable stroke patients to be triaged and treated in the field, wherever the patient is located. Clinicians can administer IV TPa, a medication that minimizes brain injury, at any remote location and then immediately transport the patient to the closest appropriate care facility, where physicians can initiate further care. In this episode of “Beyond the Expected,” Michael Bernstein talks to Dr. Fiorella about his trajectory as a vascular brain surgeon and what inspired him to pursue the complex initiative of starting a Mobile Stroke Unit program. You'll also hear heartwarming stories of patient survival, and learn what this groundbreaking program has meant for Long Island stroke care since it launched in April 2019. Credits: Thanks to Dr. David Fiorella Guest Host: Michael Bernstein Executive Producer: Nicholas Scibetta Producer: Lauren Sheprow Art Director: Karen Leibowitz Assistant Producer: Emily Cappiello Assistant Producer: Joan Behan-Duncan Social Media: Meryl Altuch, Casey Borchick Podcast photography and YouTube Technician: Dennis Murray Podcast Director: Jan Diskin-Zimmerman Engineer/Technical Director: Phil Altiere Production Manager: Tony Fabrizio Camera/Lighting Director: Jim Oderwald Camera: Brian DiLeo Camera: Greg Klose Original score: “Mutti Bug” provided by Professor Tom Manuel Special thanks to the Stony Brook University School of Journalism for use of its podcast studio.

Contributor: Dylan Luyten, MD Educational Pearls: After you diagnose a pulmonary embolism (PE) via CT or VQ scan, we need to categorize the PE as massive, sub-massive, or just PE to dictate treatment.   Massive PE: shock with hypotension due to an embolism, and the treatment of choice is thrombolysis with IV tPA with anticoagulation after lysis. Catheter thrombolysis is not used in the hemodynamically unstable patient but can be done after they are stable. Sub-massive: signs of right heart strain/failure but hemodynamically stable. This can be EKG changes, positive biomarkers, or imaging findings. These patients can be treated with IV heparin as there may benefit from catheter directed thrombolysis which has been shown to lead to better functional outcomes.   Everything else can be stratified to determine whether inpatient even outpatient treatment is necessary  Pulmonary Embolism Severity Index (PESI) or Hestia criteria and can help determine if the patient is better suited for in or outpatient management. Non massive or sub-massive PEs are treated with heparin/Lovenox bridged to Warfarin, a factor Xa inhibitor (ex. Xarelto), or direct oral anticoagulants (DOAC). Editor’s note: intravenous heparin is preferable to other anticoagulants when considering interventional radiology as it can be shut off and/or reversed if necessary prior to procedure References 1. Sista, A. et al. Stratification, Imaging, and Management of Acute Massive and Submassive Pulmonary Embolism. 2017 Jul;284(1):5-24 2. Aujesky D, Obrosky DS, Stone RA, Auble TE, Perrier A, Cornuz J, Roy PM, Fine MJ. Derivation and validation of a prognostic model for pulmonary embolism. Am J Respir Crit Care Med. 2005 Oct 15;172(8):1041-6 3. Jimenez, D. et al. Risk stratification of patients with acute symptomatic pulmonary embolism. Intern Emerg Med. 2016 Feb;11(1):11-8. Summarized by Jackson Roos, MS3 | Edited by Erik Verzemnieks, MD

Lost time = lost brain function when it comes to patients who have had a stroke. Dr. Rocco Armonda discusses mechanical thrombectomy, a minimally invasive procedure that can provide lifesaving treatment for strokes caused by large blood clots.   TRANSCRIPT Introduction: MedStar Washington Hospital Center presents Medical Intel, where our healthcare team shares health and wellness insights and gives you the inside story on advances in medicine. Today, we’re talking about mechanical thrombectomy with Dr. Rocco Armonda, Director of Neuroendovascular Surgery and Surgical Co-Director of the Neuro Intensive Care Unit, MedStar Washington Hospital Center. Mechanical thrombectomy is a breakthrough procedure to quickly and effectively remove blood clots from the brains of stroke patients using a stent retriever device. The procedure often is used when the patient is suffering a large-vessel occlusion. Host: Dr. Armonda, what is a large-vessel occlusion? Dr. Armonda: Right, so what this refers to is basically the major conductance vessels of the brain, the major vessels that basically bring blood into the brain, so we’re talking about mainly the carotid artery, the middle cerebral artery and the posterior circulation—it’s primarily the vertebral artery and the basilar artery. These are the major conducting vessels that we’re looking at, and what studies have shown of recent is that mechanical intervention with the use of catheters, a combination of mechanical devices called stent retrievers and aspiration techniques, have actually dramatically changed outcomes to the point where we basically are seeing a success rate of on the order of 70 to 90 percent if we can get to patients early enough. And, we’re talking about huge life savings in terms of preventing paralysis, preventing them from death, preventing them from being bedridden, maintaining their independence, their ability to speak, communicate, relate to their families. An individual who is typically in the prime of their life or just post-retirement, and they go from being paralyzed on one side of their body and unable to speak, to basically speaking and moving and walking and back to their normal baseline, and that’s pretty dramatic. But it takes a well-organized system to do this. And, it really took a number of studies that basically showed at the highest level of evidence dramatic changes in terms of outcome. With those vessels who have large-vessel occlusion, you can get to them in a very rapid fashion, and in fact, the core of the infarct was smaller than the tissue at risk. Host: One of the better-known stroke treatments is tPA, which is a medication given through an IV to help dissolve blood clots. Is mechanical thrombectomy a replacement for tPA? Dr. Armonda: You know, when IV tPA first came out, the clot-busting medication was given through the IV. That was the only FDA-approved intervention. And now, you know, the paradigm has shifted, so it’s not that mechanical thrombectomy replaces IV tPA; we actually do both in a lot of cases. There’s three different scenarios. There is one scenario in a patient where we’ll start the IV tPA and you might shift them to a place that does mechanical thrombectomy. There’s another scenario where you start the IV tPA while you’re ongoing doing the mechanical thrombectomy. And, then there’s a third scenario which is a patient who can’t qualify for IV tPA. Let’s say they have had recent surgery. Let’s say because of other time-window reasons you can’t exactly place the onset of the stroke. So, it’s beyond perhaps the 4.5-hour period, so those patients will go straight to mechanical thrombectomy. So, the idea is that mechanical thrombectomy is not competitive with IV tPA; it is complemented. You know, there’s some cases where, honestly, we started the IV tPA, we do the mechanical thrombectomy, and given the fact that they started the IV tPA, the clot suctions up much quicker, and/or we’ll do an angiogram and the clot’s now gone, in rare cases. But, you know there’s situations where you don’t want to stop and wait and see if the patient gets better because you’re already putting into that situation of 20 percent-plus decline in their outcome. IV tPA is usually given earlier, typically under three hours, but up to 4.5 hours, but if you have a patient who is beyond that 4.5-hour period, but whose imaging shows evidence of a large-vessel occlusion, but still preservation of a large portion of brain, and that the core of the infarct doesn’t exceed a certain volume, those patients may not be able to get tPA, but we can do a thrombectomy. And, then you have another group of patients who may have just woken up from a stroke. Those wake-up strokes beyond the typical 6 hours may also benefit from mechanical thrombectomy. Host: Is six hours the typical window for a patient to receive mechanical thrombectomy? Dr. Armonda: The sooner, the better. The way it works, basically, is that the best outcomes are those patients treated under three hours. Time is brain here. Each 30-minute period of time lost is 10 percent loss of good outcome. So, if you compare outcomes in patients who are treated within a three-hour period versus patients within a five-hour period, the difference could be as much as 70 percent good outcome versus 50/50 percent good outcome, and maybe even lower. So that means that you start at 50 percent and then it decreases from there at the five-hour mark. Beyond five hours, it may actually get lower and lower, so five hours is usually, you know, the optimal time period that we really shoot for. But, the idea here is that you want to be able to get to patients as quickly as possible. And, you know, there’s a couple areas of delay. You know, one of the areas of delay is in patients and families just recognizing signs of a stroke. Does the patient have problems with their speech? Does the patient have a problem with a paralysis? Does the patient have asymmetry in terms of their face? Is it arm weakness? Is it leg weakness? Is this something new compared to before? Sometimes, it could be a level of consciousness problem, and if they have problems speaking, they may not necessarily be able to communicate this, especially for elderly patients who may live alone. The other problem is that we’re also seeing an increase in stroke in the young. There’s been some reports on this just recently. And, the problem with stroke in the young is that, two things. One is that the individual is young and he may actually deny or she may deny that they are actually having a stroke. They may attribute it to, you know, a muscle spasm or problem with overexertion. The other problem is that because they are in the younger ages, when they present to the emergency room, they may not get as rapidly triaged because an ER physician may not be thinking of a stroke in a young person. But again, sudden-onset symptoms involving a paralysis, you know, the evidence of eye preference where they may be looking to one side, paralysis of their arm, leg, and/or face asymmetry should make, you know, ER physicians, family members, EMS think of a large-vessel occlusion. And it’s different. You know, there’s not many hospitals in this area that have the ability to do emergency thrombectomy. You know, emergency thrombectomy is a very specialized procedure that is best done by practicing neurointerventionalists, people who are using the tools, the devices in that circulation, day in and day out. It’s not appropriate for a peripheral interventionalist or cardiologist, or someone who dabbles in peripheral vascular to now be trying to attempt mechanical thrombectomy in the delicate vessels of the brain. They’re at much more risk for causing damage.  So, it demands a lot from a hospital system.  Host: How do the specialist teams work together to treat people who need mechanical thrombectomy? Dr. Armonda: So, it’s a—it’s a critical balance of multiple different team members. We’re a comprehensive stroke center, the first one in DC. We’ve had this ability to sort of bring the expertise and scientists from NIH Stroke Team together with the neurointerventionalists and with our capacity to do this emergency work, and it transfers from emergency work from trauma to emergency work to stroke care, and it goes hand-in-hand. It means that the hospital system has to be very well streamlined in terms of the efficiency of receiving patients, rapidly imaging patients and being able to have a whole team of individuals to treat this individual. So, it’s not just the neurointerventionalist. It’s also, you know, the stroke team, neurologists who are screening these patients. It’s the imaging team in terms of CT or MR personnel from radiology who are screening them. It’s the anesthesia team who is supporting the anesthetic during that patient’s neurointerventional procedure. And, then the follow-on care in terms of management in the ICU is absolutely critical. You know, you can win the battle in the angio suite and open up the vessel, but if you can’t control the blood pressure, you know, you’re at risk for that patient converting this dry stroke into a hemorrhagic stroke, and that could be fatal. You know, a lot of patients don’t know the difference between a primary stroke center and a comprehensive stroke center. And, they see a sign that says “stroke center,” so they bring their loved one to the closest hospital, and that might be a block away, a mile away, but they realize that that patient can’t get – their loved one can’t get an emergency thrombectomy at that hospital, and then they have to be transferred. So when they look at studies where patients had to be transferred, it was a minimum of 1 hour in the best of scenarios for that patient to then make it to another hospital, so that’s already at least a minimum of a 20 percent decline in outcome. So that’s why it’s so important in terms of, you know, getting the message out there to EMS, getting the message out there to other clinicians to ensure that, you know, rapid transfer is made and rapid evaluation is made, patients are brought to the right place. Host: So, it’s really a combination of fast action and the hospital team working together?  Dr. Armonda: The idea is, once you see the patient in terms of early warning systems throughout your network, you want to start mobilizing the neuro-rescue. You want to start mobilizing the thrombectomy team. That means, you know, a team of nurses, technologists, anesthesia and the neurointerventionalist. And the unique thing about what we have here is that we have radiologists, neurologists, neurosurgeons all working together in the same procedure. So, there might be a patient who presents with a stroke and it might be a neurosurgeon doing the thrombectomy because he’s on call that night. Or it might be a radiologist doing it, or it might be a stroke neurologist who is neurointerventional-trained because all of us, from different specialties, work together in the same arena, and we work together day in and day out, so we have a very comprehensive team approach. Every single step of the treatment care has to be the most efficient workflow. It’s like a car pulling in for a pit stop. You know, you have to work in parallel. You can’t work in series. Everybody has to have a job and they have to sort of approach at the same time. So, in trauma, we do the same thing. We have to be able to rapidly get the patient from the door to imaging, and then from imaging, if they’re a candidate, to the interventional suite. You know, and our interventional suites here are state-of-the-art. We have two biplane machines. What biplane means is that you’re imaging both from the frontal plane and the lateral plane. You know, these are basically endovascular operating rooms. And, both are set up for anesthesia, so we could literally run two thrombectomy cases at the same time. There’s very, very few institutions around the country that could do that, and we have the personnel to do that. So, it’s not just, you know, have the rooms because an x-ray machine can’t run itself. It’s having the nurses, it’s having the technologists, it’s having the anesthesiologists. And, the beauty of our anesthesiologists, they are very adept to patients with multiple comorbidities. They are very adept of emergency airway, you know, from all their experience with cardiac patients, all their experience with trauma patients. Anesthesia is one of the most solid services that we have here. And you have to have that because while you’re busy trying to get access into their arterial system and get your catheters up there, you want someone who is maintaining the patient’s blood pressure, who’s securing the patient’s airway, who’s ensuring that the patient remains immobile so that you’re not dealing with a moving target. You know, and that’s a difficult situation because these patients are not intrinsically healthy patients. These patients usually have problems with their lungs, usually cardiac problems as well, variations of all kinds of blood pressure problems, kidney problems, and so forth. So, it takes a real level of sophistication and team approach. Whenever I see a patient come back in a clinic or a patient who, and family, comes in my office and thanks me, I try to redirect those patients back up to the ICU so they could visit with the nurses who took care of them. They could thank the PAs who were part of their care, and the nurse practitioners, because we never do anything here as a single individual. Everything that we do is as part of the team. And, the best things we do are with the best teams, and I think we really have one of the best teams here.         Conclusion: Thanks for listening to Medical Intel with MedStar Washington Hospital Center. Find more podcasts from our healthcare team by visiting medstarwashington.org/podcasts, or subscribing in iTunes or iHeartRadio.

Dr. Carolyn Lam:               Welcome to Circulation on the Run, your weekly podcast summary and backstage pass to the journal and its editors. I'm Dr. Carolyn Lam, associate editor from the National Heart Centre and Duke-National University of Singapore. Our feature discussion today centers on patients with acute stroke due to large vessel occlusion, and asks the question, "Does interhospital transfer prior to thrombectomy relate to delayed treatment and worse outcomes?" Well, stay tuned for more right after these summaries.                                                 Our first original paper this week tells us that cardio protection is alive, and mitochondrial cardiomyocyte calcium-activated potassium channels of the BK type may be a promising target. In this study from first author Dr. Frankenreiter, corresponding author Dr. Lukowski, from University of Tuebingen in Germany, the authors used a combination of transgenic, pharmacologic and electrophysiological approaches to show that mice with a cardiomyocyte-specific knockout of BK channels had larger infarct size after 30 minutes of coronary occlusion, and 120 minutes of reperfusion, and were less protected by ischemic pre- and post-conditioning maneuvers, such as guanylate cyclase stimulators or activators and phosphodiesterase-5 inhibitors.                                                 In a chronic infarct model, mice with cardiomyocyte-specific knockout of BK channels had more fibrosis and lower left ventricular function. Mechanistically, the activation of BK channels in the inner mitochondrial membrane by cyclic GMP and protein kinase G was identified by patch clamping, and resulted in reduced formation of reactive oxygen species and activation of cardioprotective signaling. In summary, deficiency of BK channels in cardiomyocyte mitochondria rendered the heart highly vulnerable to ischemic and reperfusion injury, whereas the beneficial effects of cardioprotective agents known to target the nitric oxide cyclic GMP pathway required these cardiomyocyte BK channels. This thus establishes these cardiomyocyte mitochondrial BK channels as a promising target for limiting acute cardiac damage and adverse long-term events following myocardial infarction.                                                 The next study suggests that integration of maximal myocardial blood flow and coronary flow reserve, termed coronary flow capacity, may be helpful in predicting cardiovascular mortality in patients with stable coronary artery disease. First author Dr. Gupta, corresponding author Dr. Di Carli, and colleagues from Brigham and Women's Hospital, quantify myocardial blood flow and coronary flow reserve in more than 4,000 consecutive patients referred for myocardial perfusion PET scans from 2006 to 2013.                                                 Maximal myocardial blood flow of less than 1.8 mLs per gram per minute, and coronary flow reserve of less than two, were considered impaired. Four patient groups were then identified based on the concordant or discordant impairment of maximal myocardial blood flow, or its coronary flow reserve. The authors found that in patients with known or suspected coronary artery disease, impaired coronary flow reserve with preserved maximal myocardial blood flow identifies patients at an increased risk of cardiovascular mortality, despite a lack of myocardial ischemia. Patients who may be targeted for initiation or intensification of lifestyle preventive therapies for cardiovascular risk reduction. Conversely, preserved coronary flow reserve, even in the absence of impaired myocardial blood flow, identifies patients at low risk, in whom the need for revascularization should be reevaluated.                                                 The next study provides insights into cardiac regeneration, particularly with regards to using resident cardiac progenitor cells expressing the tyrosine kinase receptor c-Kit, which is being tested in clinical trials. In this study from first authors Dr. Chen and Zhu, corresponding authors Dr. van Berlo from University of Minnesota and colleagues, the authors used single-cell sequencing and genetic lineage tracing to show that there was innate heterogeneity within these c-Kit positive cardiac cells, where some have either endothelial or mesenchymal identity. Cardiac pressure overload resulted in a modest increase in c-Kit derived cardiomyocytes, with significant increases in the number of endothelial cells and fibroblasts. On the other hand, doxorubicin-induced acute cardio toxicity did not increase c-Kit derived endothelial cell fates, but instead induced cardiomyocyte differentiation.                                                 Although the overall rate of cardiomyocyte formation from c-Kit positive cells was below clinically-relevant levels, the authors further showed an important role for p53 in the differentiation of c-Kit positive cells to cardiomyocytes. Thus, this paper shows that different pathologic stimuli induced different cell fates in c-Kit positive target cells. These are novel findings that could aid in the development of strategies to preferentially regenerate cardiomyocytes.                                                 Since December 2014, a series of pivotal trials have shown that endovascular thrombectomy was highly effective in acute stroke management, prompting calls for reorganization of stroke systems of care. But how have these trials influenced the frequency of endovascular thrombectomy in clinical practice? Well, the last original paper in this week's journal tells us how. First and corresponding author, Dr. Smith from University of Calgary in Alberta, Canada, and colleagues, used data from the Get With The Guidelines stroke program to determine how the frequency of endovascular thrombectomy has changed in U.S. practice. They analyzed prospectively-collected data from a cohort of more than two million ischemic stroke patients, admitted to more than 2,000 participating hospitals between 2003 and the third quarter of 2016.                                                 The authors found that the use of endovascular thrombectomy for acute ischemic stroke accelerated sharply after the publication of pivotal randomized control trials beginning in December 2014. The endovascular thrombectomy case volume doubled at hospitals providing therapy. In the third quarter of 2016, endovascular thrombectomy was provided to 3.3% of all ischemic stroke patients. This represented 15.1% of all patients who were potentially eligible for endovascular thrombectomy based on stroke duration and severity. In summary, endovascular thrombectomy use is increasing rapidly, however there are still opportunities to treat more patients. Reorganizing stroke systems to route patients to adequately resourced endovascular thrombectomy-capable hospitals might increase treatment of eligible patients, improve outcomes, and reduce disparities.                                                 Coming right up, we will be discussing even more about endovascular thrombectomy in acute stroke management. Just hang on, our feature discussion is coming right up.                                                 Endovascular treatment with mechanical thrombectomy is beneficial for acute stroke patients suffering a large vessel occlusion. And that is in the guidelines, however we also know that treatment efficacy is highly time-dependent. And so, will interhospital transfer to an endovascular-capable center help in cases of acute large vessel stroke? Well, today's feature paper really helps to present novel data to answer that question. And it is from the STRATIS study. I'm so delighted to have with us the first and corresponding author, Dr. Michael Froehler from Vanderbilt University Medical Center, who will tell us about his findings, as well as Dr. Graeme Hankey, associate editor from University of Western Australia, joining us today. Welcome, gentlemen. Dr. Michael Froehler:     Hello Carolyn. Dr. Graeme Hankey:       Thank you Carolyn. Dr. Carolyn Lam:               Thanks for making the time. Mike, tell us about the STRATIS study. What inspired it, what you found. Dr. Michael Froehler:     Well, the STRATIS study was actually a large registry of the use of the Solitaire device for large vessel occlusion. Those results, the primary results, were published separately. But what we did in this study is look at one key aspect of the system of care for stroke delivery, in terms of its effect on time to treatment and patient outcomes.                                                 And so in short, what we found is that patients that are transferred from one hospital to another for mechanical thrombectomy take longer to receive treatment, and do worse in terms of functional outcome, compared to the patients that present directly to that thrombectomy center. Dr. Carolyn Lam:               Wow. Could you put some numbers to that? Dr. Michael Froehler:     Well, so we looked at 984 patients, almost a thousand patients. And what we found was that the time from stroke onset to revascularization, until the time the vessel was actually opened, was 202 minutes on average, for patients that presented directly to the thrombectomy center. Compared to over 311 minutes for patients that were transferred from one hospital to another. So that's a difference, on average, of over 100 minutes. Dr. Carolyn Lam:               And I really was impressed with this other analysis you did. So I was wondering if you could share, where you did a hypothetical bypass modeling. Could you tell us about that? Because I thought that was really practical with a feasible message as well. Dr. Michael Froehler:     I'm excited about that, and I should also share with you that we're working on a more in-depth bypass analysis, to really understand the implications of going to one center directly versus another. But the model that is built in to this publication is really designed to answer one or two questions. And the first is, how much time would we save if we went directly to the thrombectomy-capable center, compared to what actually happened? Meaning the patient was taken to a regional hospital and then subsequently transferred to the thrombectomy-capable center. And this was basically an ideal scenario.                                                 So if they were taken to one hospital and then transferred to another, we simply calculated what the maximum driving time from the starting position to the thrombectomy-capable center would be. And that did rest on the assumption that you actually had to drive past the first hospital. We didn't take any shortcuts in terms of the driving, and probably that small amount of driving time is actually shorter than the number that we found in our calculation.                                                 So the first question was, how much time would we save with that bypass? And the second question was, what kind of impact would that have on IV-tPA? Because, as a lot of us are thinking right now, with strong evidence in support of endovascular therapy for large vessel occlusion, if necessary how should we prioritize getting to endovascular treatment versus the standard therapy that we've known for 20 years, which is IV-tPA? And if you've got a choice, which one is more important?                                                 I don't know the answer to that question, but to try and help lead up to it, we did this hypothetical bypass analysis to look at the impact of bypass, driving directly to the thrombectomy center, the impact of that on the time to delivery of IV-tPA. And so that was really the second question that we asked with this hypothetical bypass analysis. Dr. Carolyn Lam:               Yeah. I love that analysis, because I agree with you, it's a very, very practical question, and it's the way we clinicians think, right? So, tell us, what's the bottom line? Dr. Michael Froehler:     So, the bottom line is, you're gonna save about an hour and a half if you bypass the regional hospital and go directly to the thrombectomy-capable center. On average, you're gonna get to the ultimate treatment center 91 minutes sooner, compared to the transferred group. Contrast that 91-minute time savings with a delay of IV-tPA delivery of 12 minutes. So yes, tPA will be delivered a little bit later, but endovascular therapy will be delivered much sooner.                                                 Now, that solution is probably not going to work everywhere, depending on your geography. So one of the other things we did within the hypothetical bypass analysis was limit that analysis only to patients who were transferred within a 20-mile radius. And that doesn't seem like a long distance, but actually there's a lot of patients in that group, that are still taken to the nearest hospital and then need to be transferred to another hospital that may be less than 20 miles away.                                                 So if we looked at that group of patients, then thrombectomy is still performed an hour and a half earlier, in that analysis it was 94 minutes earlier, but IV-tPA was delayed by only seven minutes. So certainly, there is a large group of patients out there that are perhaps being taken to hospitals that are not necessary, it's not a necessary stop. Dr. Carolyn Lam:               Wow, Mike, this is really amazing results, it's starting to make me think of the old days of acute myocardial infarction treatment, when we were thinking of intravenous thrombolytics, comparison to primary PCI, an analogy and comparison that was also mentioned in the accompanying editorial that you invited. Graeme, would you like to share some of your thoughts on the implication of all this? Dr. Graeme Hankey:       Just to take a step back, of course this begins with a stroke occurring out in the field. And unlike acute coronary syndromes, where chest pain is the major symptom, there are many symptoms of stroke. And the first problem is trying to identify the patient who has actually had a stroke, and in particular, one of the 15% or so who's had a large vessel occlusion, who's amenable to large vessel mechanical thrombectomy. So in the field we have an issue with clinical triage, and trying to work out who's the one in six who really need endovascular therapy, and who are the five in six who perhaps don't.                                                 And we're trying to develop clinical triage scales like the RACE scale to work out in the ambulance where someone should go. But we still haven't nailed that yet. Then you have scales that are very sensitive but not very specific, and have a high sort of false-positive rate. So then the question at the ambulance is, where does it go, to the hospital, the primary stroke center nearby, and give the patient the earliest opportunity to get tPA?                                                 And that's the potential benefit of early transfer to a primary center, but tPA is not very effective in dissolving these big clots in large arteries. And so, of course the trials have shown a substantial benefit of endovascular therapy to remove the clots via thrombectomy. But those resources, they're only really limited to comprehensive stroke units, and that's what this paper was about. So the trade-off is early transfer to the primary center so you can get some tPA, versus delaying, as Michael has shown, by 1 1/2 to two hours on average, to get to a comprehensive center that can access the expertise of endovascular thrombectomy experts.                                                 And this paper is really taking us forward in emphasizing again that time is brain, and we really don't want to delay. Perhaps there's a small trade-off in driving a little bit further, another 20 miles at the most perhaps, to get to a comprehensive center directly. And there may be some who are not shown to have a large vessel occlusion at that comprehensive stroke center, but the overall benefit is probably offset, the few who might miss out on tPA. And so this is a really important study, the largest registry of large vessel occlusion patients to observe and compare the outcomes after adjusting for all the different factors. And give us some clues, that perhaps we really need to be trying to focus on building our resources in comprehensive stroke centers, and also being able to more accurately identify those who are likely to benefit and go directly there. Dr. Michael Froehler:     I agree with everything Graeme said, and I would just amplify one thing that he said, that it does depend on distance, and those distances in turn depend on your own geography. We did an analysis of all our transferred patients and then limited it to those that were within a 20-mile radius. For Graeme in Western Australia, you know Graeme's mailbox is probably 20 miles away. And so there are huge distances in Western Australia to account for. And it may not be possible. Dr. Carolyn Lam:               Contrast that to me in Singapore. I think if I drive any bit more, and I'll be driving out of my country already. Dr. Michael Froehler:     I think that you make a great point though, Carolyn, that the solution that works for metro Singapore is not what's going to work for rural Western Australia. And we've seen this in New York City, for example. My colleagues at Mount Sinai are looking at different ways to deliver care across metro New York, which obviously is very different compared to myself in Nashville, Tennessee. So the right solution is not gonna be the same solution for everyone. Dr. Graeme Hankey:       And that's right Carolyn, because in rural places like out in Western Australia, we are learning now that another important message is to try and help upscale and reorganize our primary stroke centers, or just our medical centers out in the rural and remote areas. Because as Mike's paper shows, the delays once someone comes to a primary stroke center or a rural center, is about 30 minutes for diagnosis, about 30 minutes to arrange the transport, and about 30 minutes to actually do the transport.                                                 So we need to once trying to develop comprehensive stroke units, also build up those peripheral hub and spoke centers to be more slick with their diagnosis, arrangement of transport, and transport times. And one of the important things I think is, we need our primary centers, when a stroke does come, to not just do a plain CT to exclude hemorrhage, but to do a CT angiogram at the time. And find out those who really do have an occlusion, rather than putting them all on the plane and sending them down, and quite a few of them don't actually have an occlusion by the time that they've got here. They haven't been fully investigated, it's just an extra five minutes to do the contrast CT angiogram at the time in the primary center if they're gonna go there. Dr. Michael Froehler:     I think the one other thing I should add, and this is just to reflect back on something Graeme said a minute ago, is that one of the differences we found that really came out of that bypass analysis is the impact on tPA was smaller than we expected. Because the door-to-needle times are actually much longer at the regional hospitals that are not thrombectomy-capable, compared to the thrombectomy centers themselves, that are not only obviously delivering mechanical thrombectomy, but are actually delivering IV-tPA much sooner in terms of door-to-needle times. Dr. Carolyn Lam:               So, room for improvement even for non-endovascular-capable centers, isn't it? Dr. Michael Froehler:     Right, I think it's another area where there's room for improvement. Dr. Carolyn Lam:               Please don't forget to tune in again next week.

1) AAN guideline summary: Treatment of restless legs syndrome in adults 2) What's Trending: Interview with Dr. Steven Messé on why acute ischemic stroke patients are not receiving IV tPA3) Topic of the month: Neurology Today story about cases of acute flaccid myelitis spike: What the Center for Disease Control says you should look out forThis podcast for the Neurology Journal begins and closes with Dr. Robert Gross, Editor-in-Chief, briefly discussing highlighted articles from the print issue of Neurology. In the second segment Dr. Michelle Fullard interviews Dr. John Winkelman about the AAN guideline summary on the treatment of restless legs syndrome in adults. Dr. Andy Southerland is interviewing Dr. Steven Messé for our “What's Trending” feature of the week about his paper on why are acute ischemic stroke patients not receiving IV tPA. In the next part of the podcast Dr. Ted Burns interviews Drs. Kevin Messacar and Ken Tyler about a Neurology Today story on the topic on cases of acute flaccid myelitis spike: What the Center for Disease Control says you should look out for.DISCLOSURES: Dr. Winkelman serves as Associate Editor for Sleep; serves as an editorial board member of Sleep Medicine and CNS Drugs; received honoraria from serving on the scientific advisory board of Merck Serono, Flex Pharma, UCB, Impax Pharmaceuticals, Pfizer Inc, Lacrima, Luitpold Pharmaceuticals, GlaxoSmithKline, Boehringer Ingelheim, Xenoport, Zeo Inc., Sunovion, Insys, Takeda Pharmaceutical Company Limited, Jazz and Neurogen; receives royalties from the publication of the books: Foundations of Psychiatric Sleep Medicine and Nocturnal Leg Cramps; holds stock options in Flex Pharma; provided expert witness work for ArentFox and CantorColburn; received funding for travel from Novartis and Otsuka; currently performs neurophysiology studies as part of his practice;receives research support from Xenoport, GlaxoSmithKline, UCB, Sepracor, Pfizer Inc, Impax Pharmaceuticals, Purdue, Neurometrix and the NIH.Dr. Southerland serves as Podcast Deputy Editor for Neurology; receives research support from the American Heart Association-American Stroke Association National Clinical Research Program, American Academy of Neurology, American Board of Psychiatry and Neurology, Health Resources Services Administration and the NIH; has a provisional patent application titled: “Method, system and computer readable medium for improving treatment times for rapid evaluation of acute stroke via mobile telemedicine;” and gave legal expert review.Dr. Messé received publishing royalties from UpToDate; received compensation from GlaxoSmithKline for consulting on protocol development for a trial of a neuroprotectant in high risk surgery; received research support from GlaxoSmithKline, Bayer Schering Pharma, WL Gore and the NIH.Dr. Ted Burns serves as Podcast Editor for Neurology®; and has received research support for consulting activities with UCB, CSL Behring, Walgreens and Alexion Pharmaceuticals, Inc.Dr. Tyler serves as an Associate Editor for Journal of Neurovirology and Neurology Today; serves as an editorial board member for Annals of Neurology, Apoptosis, JAMA Neurology, Experimental Neurology, Journal of Infectious Disease, Microbial Pathogenesis, Virology, Neurology ALL Current; serves on the scientific advisory board for PML Consortium; is a consultant for Hoffman La Roche; receives royalties from the publication of the books: Handbook of Clinical Neurology and Harrison's Principles & Practices of Internal Medicine; receives research support from the NIH. All other participants report no disclosures.

With multiple RCTs demonstrating clear benefit of mechanical thrombectomy in ELVO, the question of best approach to patients eligible for simultaneous treatment with IV TPA and mechanical thrombectomy has been debated. Dr. Hirsch interviews Drs. Leslie-Mazwi and Weber after their instructive papers on this topic. Read the full papers: “Does the use of IV tPA in the current era of rapid and predictable recanalization by mechanical embolectomy represent good value?” is available here: http://jnis.bmj.com/content/8/5/443.full. “Comparison of outcome and interventional complication rate in patients with acute stroke treated with mechanical thrombectomy with and without bridging thrombolysis” is accessible here: http://jnis.bmj.com/content/early/2016/02/22/neurintsurg-2015-012236.full. “Direct to embolectomy without IV tPA: the stage is set for a randomized controlled trial” is available here: http://jnis.bmj.com/content/early/2016/04/05/neurintsurg-2016-012388.full.

Journal Club PodCast: Flipped classroom! Assignment is to read the articles, listen to the podcast, and be prepared to apply your knowledge to clinical scenarios when you come to Journal Club. Articles are: Acute stroke intervention: A systematic review JAMA April 14, 2015 Endovascular Therapy after IV TPA versus TPA alone for stroke NEJM March 7 2013 Comparative efficacy of different acute reperfusion therapies for acute ischemic stroke: a comprehensive benefit-risk analysis of clinical trials Brain and Behavior 2014 A review of decision support, risk communication and patient information tools for thrombolytic treatment in acute stroke: lessons for tools developers BMC Health Services Research 2013 Opinions are of course are own...! Music is "Heartbeats" by Cat Hamilton created exclusively for this podcast - how cool is that!