Stroke Alert podcast

Stroke Alert October 2021

21/10/2021
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On Episode 9 of the Stroke Alert Podcast, host Dr. Negar Asdaghi highlights two articles from the October 2021 issue of Stroke: “Endovascular Therapy of Anterior Circulation Tandem Occlusions” and “Automated Perfusion-Diffusion Magnetic Resonance Imaging in Childhood Arterial Ischemic Stroke.” She also interviews Dr. Sepideh Amin-Hanjani about her article “Outcome Following Hemorrhage From Cranial Dural Arteriovenous Fistulae.”

Dr. Negar Asdaghi:

1) Should perfusion imaging be incorporated into routine neuroimaging for stroke-like presentation in the pediatric population?

2) Is performing emergent cervical carotid stenting beneficial in patients undergoing endovascular thrombectomy for a tandem occlusion?

3) What are the outcomes of patients with intracranial hemorrhage secondary to dural AV fistula?

These are the questions that we will answer in our podcast today. Stay with us.

Dr. Negar Asdaghi:                        Welcome back to 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 October 2021 issue of Stroke, we have a comprehensive list of publications, from studying the role of C-reactive protein in outcome prediction after subarachnoid hemorrhage to studying the association of over 81 classes of routinely prescribed drugs with the risk of ischemic stroke, which I encourage you to review in addition to our podcast today. Later in the podcast, I have the pleasure of interviewing Dr. Sepideh Amin-Hanjani on her work with outcome prediction in patients with dural AV fistula–related intracranial hemorrhage. But first, with these two articles.

Dr. Negar Asdaghi:                        Between 10-20% of patients with an anterior circulation large vessel occlusion have tandem occlusions. That means that they have a concurrent cervical carotid occlusion or significant stenosis in addition to their target intracranial occlusion. Performing endovascular therapy for a tandem occlusion is often difficult, providing technical and access challenges for the operator.

Dr. Negar Asdaghi:                        In practicality, we have two options for carotid treatment in the acute setting. One option is doing nothing, or do carotid angioplasty predominantly to gain access to that target intercranial occlusion. But the second option is to do an emergent carotid stenting. Currently, we have two ongoing clinical trials to assess the very question of whether emergent cervical carotid stenting is an option in tandem occlusions. One is the ongoing TITAN trial out of France, and the second one is a Canadian trial, Endovascular Acute Stroke Intervention - Tandem OCclusion Trial, or EASI-TOC.

Dr. Negar Asdaghi:                        And while we await the completion of these trials, the treatment option for cervical carotid remains a contentious subject. Though performing emergent cervical ICA stenting is feasible, the opponents of the procedure highlight that emergent stenting is associated with higher rates of intracranial hemorrhage, a high risk of in-stent thrombosis, iatrogenic artery-to-artery embolization, and hemodynamic instability during stent deployment. Not to mention that it will increase time to reperfusion if stenting is done prior to the intracranial recanalization. In contrast, the proponents of emergent cervical ICA stenting argue that leaving the carotid alone can lead to an increased risk of infarct recurrence and infarct progression. Of course, it goes without saying that the current practice pattern is widely variable. So, in the current issue of the journal, Dr. Mohammad Anadani, from the Department of Neurology at Washington University School of Medicine, and a group of international collaborators from the TITAN and ETIS registries compared the outcomes of endovascularly treated patients with tandem occlusions in the anterior circulation who received concurrent carotid stenting to those who did not receive stenting of the carotid.

Dr. Negar Asdaghi:                        It is important to note that the no-stent group included those with either no cervical carotid intervention or angioplasty alone.

So, the authors identified 760 patients with a tandem occlusion that were included in the pooled analysis of TITAN and ETIS registries. TITAN stands for Thrombectomy in Tandem Lesions and endovascular treatment in ischemic stroke. That included EVT-treated patients; these are endovascularly treated patients with tandem occlusions from 18 comprehensive stroke centers across Europe and United States.

And ETIS is an ongoing prospective multicenter registry that enrolls all patients treated with endovascular thrombectomy at six large comprehensive stroke centers in France. In both cohorts, treatment of cervical ICA was left at the discretion of the treating physician. Overall, cervical ICA stenting was performed in 56% of total patients with tandem occlusion. In the adjusted model, they found that the odds of favorable outcome and successful reperfusion were higher in the stent group. In contrast, the risk of any hemorrhage was higher in the stent group, but the rate of symptomatic hemorrhage was not different within the two groups.

Dr. Negar Asdaghi:                        Some very important findings from their subgroup analysis include a stronger benefit from emergent carotid stenting, unfavorable outcome in patients with lower NIH Stroke Scale, and in patients in whom the etiology of carotid stenosis or occlusion was deemed to be related to atherosclerosis rather than dissection.

Dr. Negar Asdaghi:                        So, what are the top three things we learned from this paper? Number one, we learned that emergent carotid stenting overall increased the odds of favorable outcome in patients with tandem occlusion. Number two, emergent cervical ICA stenting came with a cost of increased hemorrhage, perhaps related to the necessity of administering antiplatelet therapies in the angiosuite. Number three, benefit from emergent carotid ICA stenting in the setting of endovascular therapy was confined to patients with carotid occlusion or significant stenosis in whom the etiology was deemed to be related to athero and not dissection. And of course, people seem to benefit from emergent cervical ICA stenting in whom the presenting NIH Stroke Scale was mild. So, many things to keep in mind, and most important of all, that these results are from registry-based data, and we still have to wait for the results of the two ongoing trials to confirm these findings.

Dr. Negar Asdaghi:                        Diagnosis of stroke in children is often delayed beyond the conventional thrombolytic and endovascular time windows. In 2018, randomized trials in adults showed that patients with an ischemic mismatch, that is the presence of a large ischemic penumbra in a setting of a small ischemic core, can significantly benefit from endovascular therapy. Whether these results can be directly applied to the pediatric population from simply the adult population is, of course, unknown. In this issue of Stroke, Dr. Mark Mackay and Melissa Visser, from the Department of Neurology, Royal Children's Hospital of Melbourne, and colleagues present the results of a retrospective, observational cohort study of 29 children who underwent MRI diffusion and dynamic susceptibility contrast perfusion imaging within 72 hours of stroke onset. Perfusion-diffusion mismatch was estimated using the RAPID software with the same criteria used in adults, which was defining ischemic penumbra as regions with a Tmax delay of more than six seconds and core as defined by diffusion positive lesions with corresponding low signal on the apparent diffusion coefficient, or ADC, map with values less than 620.

Dr. Negar Asdaghi:                        Favorable mismatch profile was defined the same way that they are defined in the adult population, that is, core volumes less than 70 mL and mismatch volumes of over 15 mL with a mismatch ratio of over 1.8. Now, the primary goal of this paper was to demonstrate feasibility of assessing automated perfusion-diffusion mismatch in childhood stroke. So, among 187 children with confirmed stroke on MR imaging, 58 underwent perfusion imaging in the study and only 29 fulfilled the inclusion criteria. Most cases had cryptogenic stroke followed by local cerebral arteriopathy as part of their etiology of stroke. Vessel occlusion was confirmed in 12 cases, two of which involve the posterior circulation. So, RAPID detected an ischemic core in 66% of patients only, remembering that the remaining diffusion positive cases were excluded from this finding simply because either the ADC values were not below the 620 value or they had a smaller infarct core, at which point determining the ADC values becomes very difficult.

Dr. Negar Asdaghi:                        Overall, three patients only had favorable mismatch profile as we defined earlier and we use to guide us for thrombectomy in the adult population. Of the three children who met the target mismatch criteria, only one received IV alteplase and none underwent thrombectomy, which makes this difficult to validate the penumbral thresholds that are used in the adults for the pediatric population.

Dr. Negar Asdaghi:                        So, what are the top two points from the study? Number one, in this large cohort of children with confirmed ischemic stroke, only a third had perfusion imaging, and most cases received their neuroimaging more than 72 hours after their symptom onset. Number two, the ischemic mismatch as defined by the adult criteria was present in children even as late as 23 hours from symptom onset. So, in summary, this study and others confirm the feasibility of performing perfusion imaging in the pediatric population, but there remains a necessary reluctance in adoption of perfusion imaging as part of the stroke protocols in pediatric centers.

Dr. Negar Asdaghi:                        There are a number of concerns that we should keep in mind, including contrast-induced nephrogenic systemic fibrosis and gadolinium deposition in the brain, which are major concerns in the pediatric population, especially in those kids with impaired renal function or those requiring multiple scans over time. You have to also consider unfamiliarity with stroke imaging protocols, given that the majority of stroke-like presentations in children are non-ischemic in origin, in which case, perfusion imaging performance is of little or no value. And there should also be technical considerations, including uncertainty regarding the optimal bolus injection dose, rate, and scan duration of kids. Lots to learn, but still, studies like this represent the first step forward to further our understanding of the role of perfusion imaging in pediatric stroke.

Dr. Negar Asdaghi:                        Dural arteriovenous fistulas, or dural AVFs, are intracranial vascular malformations defined by abnormal communications within the dural leaf that's between meningeal arteries and dural venous sinuses and/or cortical veins. Dural AV fistulas represent approximately 10-15% of all intracranial vascular malformations and can remain asymptomatic or have a variety of neurological presentations, the most feared of which is intracranial hemorrhage. It is important to remember that much of the research on the topic is focused on high-risk features of dural AV fistulas associated with the risk of either initial or recurrent hemorrhage, things such as the pattern of venous drainage or location of the fistulas. But less is known about the clinical outcomes of these patients after they present with a bleed.

Dr. Negar Asdaghi:                        The CONsortium for Dural arteriovenous fistula Outcomes Research, or CONDOR, Registry is an international multi-institutional database to study the outcomes of dural AV fistulas. In the current issue of the journal, in the study titled “Outcome Following Hemorrhage After Cranial Dural Arteriovenous Fistulae: Analysis of Multicenter CONDOR Registry,” Dr. Matthew Koch, from the Department of Neurosurgery at the University of Illinois in Chicago, and colleagues used this registry to determine the morbidity and mortality of dural AV fistula–related intracranial hemorrhage. I'm joined today by the senior author of the study, Dr. Sepideh Amin-Hanjani, to discuss this paper.

Dr. Negar Asdaghi:                        Dr. Amin-Hanjani needs no introduction to the Stroke readership. She's a Professor of Neurosurgery and Co-Director of Neurovascular Surgery at the University of Illinois. She's the past Chair of the American Association of Neurological Surgeons and the Congress of Neurological Surgeons Cerebrovascular Section. She serves on multiple national and international cerebrovascular committees, including serving as the Chair of the Neurovascular Intervention Committee for the American Heart Association Stroke Council. Good morning to you, Sepi, and thank you for joining us on the podcast.

Dr. Sepideh Amin-Hanjani:          Good morning, Negar. I really appreciate the opportunity to have time to discuss this paper a little bit with you and the folks listening in today.

Dr. Negar Asdaghi:                        Great, Sepi, let's start off with discussing the prevalence of dural AV fistulas. In the current era of increased availability and accessibility of vascular imaging, how often are these malformations found? And importantly, what are the known predictors of so-called bad neurological behavior or intracranial hemorrhage in these fistulas?

Dr. Sepideh Amin-Hanjani:          So, I would say these are rare lesions, which is, I think, what makes it particularly useful sometimes to pay a little bit more attention to them because they're less frequently encountered, and so there's not as much thought about looking for these lesions when a patient presents with neurological symptoms or hemorrhage. And so I think highlighting it here is important. They are rare. They're probably, as you mentioned, only about 10-15% of all vascular malformations. The crude incidence is probably somewhere around 0.5 per 100,000. So, again, infrequently encountered.

Dr. Sepideh Amin-Hanjani:          Because of the nature of the lesion, they're not as easily, I would say, identified incidentally. Unlike AVMs that will show up on routine MRI or aneurysms that'll show up on routine MRA, fistulas may or may not be apparent because of their nature. They're fed by dural arterial feeders; the fistula itself is within the dural leaflets. They can have venous drainage or ectasia associated with them. So, the secondary phenomenon of the venous congestion may show up on MR, but the actual fistula may be hard to identify. And I think, in some ways, that's why we tend to see them a little bit less incidentally, at least in my own practice, in my own experience, than we do when they present with symptoms, either non-hemorrhagic or hemorrhagic symptoms.

Dr. Sepideh Amin-Hanjani:          There are some features of these fistulas that tend to predict if they're going to be bad actors, so to speak, if they're going to have those more aggressive symptoms of neurological dysfunction from venous congestion. Things like seizures, headaches, even dementia as a prolonged effect of venous congestion, or the most dreaded complications, in some ways, hemorrhage, which relates to if there is evidence of significant cortical venous reflux from the fistula itself.

Dr. Negar Asdaghi:                        Perfect. So this is a great start to get us now to the topic of the registry. What was the overall purpose of the CONDOR Registry? Please tell us a little bit about the patient population, specifically the population of your interest that you included in your study.

Dr. Sepideh Amin-Hanjani:          So, given the rarity of the condition, you find that in the literature, there's lots of kind of relatively smaller case series, and it's hard to make broader assessments of outcomes and treatments, etc., when you're looking at small retrospective series.

So, the idea behind CONDOR, which was really launched by one of my colleagues, neurosurgeon Greg Zipfel at Wash. U. in St. Louis, was the idea of getting together a consortium of centers who have either previously published or have a particular interest in dural AV fistulas to collate our series and get a larger cohort of patients together that could be analyzed for just the kinds of interventions and outcomes that would be of interest in looking at a larger sample size.

Dr. Sepideh Amin-Hanjani:          So, the consortium now is up to, I think, 16 or 17 centers. The data that was collected and analyzed for the purposes of this particular manuscript came from 12 centers and was over a thousand patients. So, really a large cohort that allowed us to do a deeper dive analysis on a number of topics, including looking at folks who had presented with hemorrhage. There's a number of other studies that have come out of this registry, and the collaboration to form the registry has also been published as well. And it's retrospective data, but the hope is that CONDOR will eventually transform into a prospective database that will allow us to get even higher level data for this condition.

Dr. Negar Asdaghi:                        So, perfect. Sepi, I was going to ask this question of whether the registry's ongoing, so thank you for clarifying that, but coming back to your paper. So, you included those patients who have bled. This was data up until 2017. And it's important to look at this number, 25% of patients with dural AV fistulas in the CONDOR Registry up until the time that you looked at the data. That's 1 in 4 patients presented with an intracranial hemorrhage. Is this an overall good estimate of the risk of hemorrhage for this malformation, especially when we're counseling patients on this? Or do you think this number is higher than routine practice and that it's just basically biased because it's a hospital-based registry?

Dr. Sepideh Amin-Hanjani:          I think both things are true in some ways, meaning that because this is a consortium of tertiary care centers, obviously there's a referral bias. Patients who are symptomatic or who have hemorrhage are more likely to be cared for in that setting. So, we are going to tend to see a higher proportion of the patients that are presenting with aggressive symptoms or with hemorrhage within this kind of cohort.

Dr. Sepideh Amin-Hanjani:          But along with that, similarly, if you look at the features of these fistulae, they're the ones that have the cortical venous reflux, the high-risk features. So, in as much as to say, "do 25% of all fistulas hemorrhage?" No, because presumably there's a lot of more benign fistulas, ones that aren't discovered or aren't worked up that are low risk for hemorrhage that don't show up. But within the paradigm of, again, the construct of a consortium where you're looking at centers who are really taking care of patients presumably presenting more actively with neurological symptoms, I think this proportion is fairly representative. And it, again, speaks to the fact that depending on the type of fistula and the features of the fistula, it's going to be more or less likely to present in an aggressive manner, hemorrhage being one of those presentations.

Dr. Negar Asdaghi:                        Perfect. So now let's talk about treatment modalities. A majority of patients in your study had undergone surgical intervention of the fistula. What was the most common intervention in this registry? And can you briefly tell us about the current treatment modalities, whether endovascular or surgical, that are available for dural fistulas?

Dr. Sepideh Amin-Hanjani:          So, I think what we found with this registry, and these were centers both within the U.S. and internationally, that the most common treatment paradigm is endovascular, so embolization of AV fistulas. And I think that very much reflects current practice because of the relative, I think, being not an endovascular person, I probably shouldn't comment on the ease or lack thereof, but the ability to access these fistulae endovascularly and use a number of agents, including glue or other embolization materials to obliterate them. So, we certainly found that in the series, embolization, either alone or in combination with other modalities, was the most prevalent.

Dr. Sepideh Amin-Hanjani:          Having said that, surgical intervention still has a significant role. Sometimes these fistulas can be difficult to access, depending on their supply or drainage endovascularly, and then the surgical option for obliterating them becomes important as well. And then, more rarely, lesions that are not amenable to either of those modalities can be treated with radiosurgery, although the concern there always with a hemorrhagic lesion is that the effect is not immediate, as opposed to embolization or surgery, where your goal is to obliterate the fistula and remove the source of hemorrhage, which is really the cortical venous reflux, immediately to make sure that there's not a risk for recurrence.

Dr. Negar Asdaghi:                        Thank you. This is a great review of AV fistulas. So, coming back to the paper now to recap, you had a highly selected group of AV fistulas that presented with an intercranial hemorrhage, the majority of which underwent embolization in this cohort. So, what were the outcomes? And let's start with just a brief overview of what outcomes are actually collected in your study, and what did you find?

Dr. Sepideh Amin-Hanjani:          Yeah, so we were interested to see, in kind of the current paradigm of management of these fistulae, when they present with hemorrhage. As you said, the great majority were treated. So, this is not a natural history study in the sense that it's not looking at untreated malformations after hemorrhage. It's looking at patients in the real world who pragmatically are going to present into tertiary centers with hemorrhage. What is their overall outcome with the current state of interventions that are available and with whatever primary injury is caused by the hemorrhage itself?

Dr. Sepideh Amin-Hanjani:          That's really what the study is looking at, is what is morbidity and mortality after hemorrhage from a lesion like this, and current management paradigm for these fistulas. And in that context, we were looking to see if there were predictors of worse or better outcome in that situation following the hemorrhage itself, and defining morbidity as Modified Rankin score of 3 or greater, with the idea of looking at independent versus dependent outcome, and also looking at mortality.

Dr. Sepideh Amin-Hanjani:          In other words, how severe are these patients in terms of their neurological outcomes if they do suffer hemorrhage event? We were able to define and look at a variety of potential predictors of outcome. The hemorrhage from dural AV fistulas can be either intraparenchymal intracranial hemorrhage or it can be subarachnoid, or it can be a combination thereof. There can be intraventricular hemorrhage, all depending on the venous congestion pattern related to the fistula. And the idea was, do any of those hemorrhage subtypes matter? Do the comorbidities of the patient matter? Do the specific angio-architecture or location of the fistula matter as relates to the outcome from the hemorrhage?

Dr. Negar Asdaghi:                        Perfect. So, at 13% morbidity and 3.6% mortality associated with AV fistula hemorrhages in your study, tell us please about some of the independent factors associated with this primary outcome.

Dr. Sepideh Amin-Hanjani:          Yeah. So, after we analyzed the features that were available within the database, really age emerged as a predictor of poor outcome. And I think that's not surprising. That's very true for the full range of cerebrovascular conditions. If we thresholded at age 65, folks older than 65 had a twofold risk of a worse outcome.

Dr. Sepideh Amin-Hanjani:          The other things that we found, really a lot of the other features fell out on multivariate analysis, but the couple that remained strongly associated with poor outcome were folks who were on anticoagulants at the time of the hemorrhage. It was a small number within the cohort, but nonetheless, a very robust effect in that those folks did worse following their hemorrhage and certainly recurrent hemorrhage.

Dr. Sepideh Amin-Hanjani:          Now, a lot of these fistulae were treated, but in the instance where recurrent hemorrhage did occur prior to treatment, or if the patient had not undergone treatment, recurrent hemorrhage certainly had a really significant effect on worsening outcome as well. That age effect, as I said, has been seen in other vascular conditions. Anticoagulant use as a predictor of poor outcome at the time of hemorrhage has also been seen as a predictor of worse outcomes and other conditions like aneurysmal hemorrhage, things of that nature, and, similarly recurrent hemorrhage. So we're finding similar features as have been described for other cerebrovascular conditions as relates to hemorrhagic lesions as being important predictors of poor outcome.

Dr. Negar Asdaghi:                        Perfect. Very important features to keep in mind when we are dealing with patients with intracranial hemorrhage that are found to have these fistulas. So, things that you mentioned that I want to repeat just for our listeners were: age; recurrent hemorrhage that occurs if a patient is not treated and presented with a hemorrhage initially and added a recurrent one prior to receiving the appropriate therapy; and obviously, and not surprisingly as you mentioned, being on anticoagulants at the time of presentation with their hemorrhage. So, 1 in 6 patients, in summary, with dural AV fistula–associated hemorrhage in your study is dead or dependent follow-up. How does this morbidity and mortality, Sepi, compare to the outcomes from other vascular malformations, say, for instance, that of AVMs?

Dr. Sepideh Amin-Hanjani:          Yeah, I think that's one of the things we're particularly interested to kind of compare and contrast. Now, one end of the spectrum, you have aneurysmal subarachnoid hemorrhage. I think out of all hemorrhagic vascular lesions, that has the worst outcome. We know morbidity and mortality of that far exceeds 50%. For AVMs, it's been pretty well described even from prospective series that you can have 10-15% mortality and about 30% morbidity related to an AVM hemorrhage.

Dr. Sepideh Amin-Hanjani:          And we were interested to see if that was similar profile for fistulas. I think our results show that it's somewhat better than the AVM hemorrhage. The mortality is lower at about 3-4%, like you noted, and the morbidity is around 13% for survivors. But all in all, if you aggregate that, that is, as you say, a 1 in 6 chance of a very poor outcome. So, it's not trivial by any means and certainly much higher than the hemorrhagic consequences of something like cavernous malformations, where hemorrhages from cavernous malformations are rarely fatal. These dural AV fistula hemorrhages can be fatal and can result in long-term morbidity. I think that has implications in terms of how we think about risk-benefit profile of treatment for a malformation, an AV fistula that's discovered and has predictors that would indicate it's at high risk for hemorrhage.

Dr. Negar Asdaghi:                        Thank you very much, Sepi. I think you've already eloquently summarized all of this, but I want us to leave our listeners with your top two or three takeaway messages on the topic.

Dr. Sepideh Amin-Hanjani:          Thanks, Negar. So, I think the key takeaways that we took from looking at this analysis is that we now at least have some idea about what the morbidity and mortality related to dural AV fistula hemorrhage is. That 1 in 6 number, as you indicated, really benchmarks what morbidity and mortality for the condition is. Now, what's the relevance of that? I think, by inference, we can take this into practice in a couple of different ways.

Dr. Sepideh Amin-Hanjani:          First would be that if a patient presents with a fistula with high-risk features for hemorrhage, that knowing this morbidity and mortality related to hemorrhage certainly informs that discussion about treatment and certainly favors the idea of treating fistulas at high risk for hemorrhage based on cortical venous drainage early to prevent this morbidity and mortality from occurring.

Dr. Sepideh Amin-Hanjani:          Secondly, I think it argues towards making sure that there's a thorough workup done when a dural AV fistula is suspected, even if it's presenting with more benign symptoms like tinnitus, for example, or is discovered incidentally, and that workup really should be thorough enough to determine if there are high-risk features from this fistula. And that workup really entails catheter angiography because that's truly the way to determine if these cortical venous reflux and other features that are most associated with hemorrhage are present or not. So, I think those two key elements should be kept in mind.

Dr. Sepideh Amin-Hanjani:          And finally, given the rarity of the condition and because these are complex and heterogeneous lesions, I think it makes sense upon discovery or suspicion of a dural fistula to really refer these to tertiary centers that manage these conditions frequently enough to be able to determine those risk features and to offer the appropriate type of treatment for it, whether it be, as we discussed, mostly embolization or surgery.

Dr. Negar Asdaghi:                        Dr. Sepideh Amin-Hanjani, congratulations on this work, a huge collaboration and a great addition to the existing literature of vascular malformation–related intracranial hemorrhage. It was a pleasure having you on the podcast today.

Dr. Sepideh Amin-Hanjani:          Thank you so much, Negar, much appreciated.

Dr. Negar Asdaghi:                        And this concludes our podcast for the October 2021 issue of Stroke. Please be sure to check out this month's table of contents for the full list of publications, including two articles published online in September simultaneous with their presentation at the European Stroke Conference, which appear in the October issue of Stroke. The first article is on clinical outcome of thrombolysis with tenecteplase, and the second one discusses the effects of fluoxetine on outcomes after acute stroke, results from EFFECTS randomized controlled trial.

Dr. Negar Asdaghi:                        Now, for a second year in a row, the European Stroke Conference was entirely online, bringing a wealth of knowledge and stroke expertise from all over the world to a completely virtual audience. Now, we hope to soon return to our good old times when we traveled for conferences, but let's take a moment and think about the magnitude of this virtual accomplishment, the incredible role that technology plays in our abilities to do research and provide healthcare. And we owe this to the men and women that pioneered the development and the ever-growing fast-paced progress of computer sciences.

Dr. Negar Asdaghi:                        Ten years ago in October, the world lost one such pioneer. Steve Jobs, the father of mobile technology and digital revolution, is recognized not just for his technical creations but also for his way of life, his incredible mind that led to the seemingly utopian ideas for how things should be. In a powerful commencement speech he delivered at Stanford University a few years before his death, he talked about his life experiences, the power of mind, and the power that lies in doing every part of one's work with absolute perfection and love. So, in honor of his genius and the legacy he left behind, we end our October podcast with his parting words of wisdom to the graduating class of 2005: "Stay hungry, stay foolish." And, as always, stay alert with Stroke Alert.

Dr. Negar Asdaghi:                        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.

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