Complexities in Acute Stroke Treatment and Making the Best, Timely Decision for Patients

Podcast Transcript

Alex Rae-Grant: Neuro Pathways, a Cleveland Clinic podcast for medical professionals, exploring the latest research discoveries and clinical advances in the fields of neurology and neurosurgery. Welcome to another episode of 'Neuro Pathways.' I'm your host, Alex Rae-Grant, neurologist in Cleveland Clinic's Neurological Institute. In an effort to explore the latest advances in neurological practice, today we're going to talk about the complexities of acute stroke treatment, and making the best timely decision for patients. I'm very pleased to have Dr. Shazam Hussain here with us. Dr. Hussain is an interventional neurologist and director of the Cerebrovascular Center in Cleveland Clinic's Neurological Institute. Shazam, welcome to 'Neuro Pathways.'

Shazam Hussain: Great, thank you for having me.

Alex Rae-Grant: I'd like for our listeners to get a better idea about you. Tell us just a little bit about yourself. Where are you from? Where did you train? When did you begin your career at the Cleveland Clinic?

Shazam Hussain:  Yeah, well actually I grew up in Canada. Was born in Saskatoon, Saskatchewan, and grew up there. I actually did my medical school there at the University of Saskatchewan, as well. From there, transitioned over to the University of Alberta, where I did my neurology and stroke training. From there then, actually came down to Cleveland Clinic. Let's see, coming down here to do the fellowship in interventional neuro-radiology; supposed to be a two year stay, and then head back to Canada, but they've treated me very, very well at Cleveland Clinic. I've been here ever since. That was, I came here in 2008.

Alex Rae-Grant: Well, we're very lucky to have you.

Shazam Hussain: Thank you, it's good to be here.

Alex Rae-Grant: So Shazam, let's start off with this. For those of us who don't do a lot of stroke work, can you just talk generally about how common and important stroke is to the general population?

Shazam Hussain:  Yeah, it's important to talk about this as well. It's a really underappreciated condition. Overall, it's actually the fifth leading cause of death. Perhaps more importantly, it's the leading cause of medical disability in the United States, with estimated cost per year of around 70 billion dollars. It has a huge impact to the population. Unfortunately, we're actually seeing younger and younger patients having strokes as well, which is really hitting them in the prime of their lives. As you know, at one time, it was really considered a disease of the elderly, but that's really not the case anymore. Almost about 40% of the patients we're seeing at the Cleveland Clinic, for example, are under the age of 65.

Alex Rae-Grant: Wow.

Shazam Hussain:  A pretty big number.

Alex Rae-Grant: Really important. So stroke treatment can be really pretty complex. Tell us about the current options available to assess someone with a new stroke. How do we check them out?

Shazam Hussain:  Yeah, it's a great time in stroke, actually, because as opposed to before when it was really thought to be an untreatable disease, we have really good treatments now that are available for stroke. Our focus when a person first arrives to the hospital is to try to determine, is this the type of stroke that we can potentially offer some kind of treatment for? Very, very broadly, one of the biggest differentiations we have to make early on is whether it's a ischemic type of stroke where a blood clot blocks a blood vessel, and blocks it from blood flow; or is it a hemorrhagic type of stroke, or a bleeding type of blood stroke.

Even the best clinicians in the world, you cannot tell if it’s an ischemic stroke or a hemorrhagic stroke unless they have that CAT scan being performed.  A lot of the focus in from a process standpoint early on is how can we get that CT scan done very, very quickly to allow us to see whether there's a bleeding type stroke or the ischemic type stroke. Once we've made that determination, then in the meantime, we're also working on trying to determine when the last seen well time of the patient was. Are there any other co-morbidities or other factors in their case that would prevent some of these acute treatments to be offered. Then, making sure we're activating the system to be able to either deliver the types of treatments. Overall, there's two major types of treatments. One is the thrombolytic therapy, TPA, which we can deliver through the intravenous, and also then thrombectomy treatment, where we can move the clot out of the blood vessel.

Alex Rae-Grant: Stroke treatment can obviously be very complex. What are the current options available to assess someone with a new stroke?

Shazam Hussain:  It's a good question. I think to take it one step before we get into the different options, I think we ... Let's talk a little bit about the different treatments that are available, because really, the workup is tailored towards determining which of the treatments you might be able to deliver. We're talking about the ischemic type of strokes where the blood clot has blocked the blood vessel. Essentially, there's two main therapies that we can offer. One is intravenous thrombolytic therapy using an agent called TPA; which we can offer within the first four and a half hours after their appearance from symptom onset. The other is for a sub-type of the ischemic strokes called emergent large vessel occlusions, or ELVO type strokes. This is where we can use mechanical thrombectomy treatment where we can actually take a catheter up through the blood vessels to where the clot is located, and remove it out of the blood vessel.

Really that early time period what we're trying to focus in on is trying to determine if a patient's eligible for those therapies or not, and then activating the system in order to get them those therapies delivered. In terms of the types of things that we can do for patients is usually when a patient first arrives to the hospital, we're going to do a very, very quick evaluation of the patient to determine, very important, historical factors, also about co-morbidities, or other conditions that might influence the type of therapies. For example, the last seen well time, which is where the time clock really starts for us. At the same time, we're really activating our imaging. Usually most of it is done by CT, where we can get a CT scan done, a CT angiogram to check the status of the blood vessels, and potentially using things like CT profusion, or MRI to help select out the patients that might have more severe type strokes, to determine how much brain can be saved.

Alex Rae-Grant: When you have a patient with acute ischemic stroke, and you've done the initial evaluation, how do you determine the course of treatment after that? When do you decide they should go an endovascular approach? How does that happen?

Shazam Hussain:  Yeah, it's all really happening sometime ... We like to talk about this parallel processing when we talk about acute stroke evaluation; that yeah, we don't do things kind of ... checking off the box to say, 'is this a thrombolytic candidate,' and then, the endovascular candidate. We're going to try to do it all simultaneously. But really, given how quickly this has to occur, you have to have good processes in place to try to make sure you're doing it as efficiently as possible.

For the thrombolytic therapy side of things, what we really need there is to see, is the patient within a time window for thrombolytic therapy, which is first four and a half hours after their symptom onset. Then in determining that, are they eligible for the therapy, meaning is the CT scan showing is there any bleeding on the scan or not? Do we have other contraindications to the thrombolytic therapy? For example, have they had recent surgery? Have they had bleeding, like a GI bleed, or something in the last ... in the short period before the patient is being considered for these treatments; or other contra-indications that might be present.

Then of course, making assessment of the risk and benefit of the medication. The medication thrombolytic therapy, TPA, through the NINDS TPA trial, does show substantial benefit within the first three hours of being administered. We know from ECST-2 that within three to four and a half hours, it also has a substantial benefit in improving outcomes at the three month mark. But the flip side of it is it does carry a risk of bleeding with it as well. Overall, we generally quote about a 6% risk of bleeding, which the most catastrophic being if it occurred as some kind of intracranial bleeding. A lot of the contraindications are kind of tailored towards assessing that bleeding risk that the patient has. At the same time, we see what the stroke deficit is. If it makes sense, if it looks like it's a disabling stroke deficit, and we don't have a lot of those contraindications, or that those contraindications that would seem to be at higher risk, then we can give the intravenous thrombolytic therapy.

Often times, the system's so primed now, it's very, very nice that the patients are going very, very quickly to CT scan. We can often deliver the thrombolytic therapy right there in the CAT scan, actually, to get that going as quickly as possible. On the mechanical thrombectomy side of things, what we're doing there is that we need to get first the identification that there is some kind of large vessel occlusion. You can do that somewhat from the clinical examination if we're seeing that the patient has a very, very high stroke scale. We use the National Institutes of Health stroke scale, NIHSS stroke score. If that's very, very high, that can give you some clues that it could be very likely; but really you want some kind of vessel imaging, which in practical purposes, tends to be the CT angiogram. Once we have a CT angiogram that identifies a clot that's sitting in either the internal carotid artery, M1, or M2 segments of the middle cerebral artery, or in the vertebral or basilar artery, then that patient potentially can be a candidate for the mechanical thrombectomy.

Alex Rae-Grant: I guess there's a couple of different endovascular techniques that can be done. Again, how do you guys decide which way to go, and which patients to do what procedure with? Take us a little further down that road.

Shazam Hussain: Sure. From selecting for mechanical thrombectomy, really the first step is decide whether they're a candidate or not for a mechanical thrombectomy. There, what you're really trying to determine is, is there brain that we can save by removing that clot out of the blood vessel? Usually when we're going through it, we're assessing three major factors. Is there a large vessel occlusion or not, as we've talked about. Which you can get very, very quickly from your vessel imaging. You need to know where's the brain lacking blood flow, which you can get from either the clinical examination, determining which parts of the brain are not functioning; because by definition, brain tissue that's at risk from lack of blood flow is going to be electrically silent. It has to produce symptoms.

The other really key piece of information is trying to determine what the core of the infarction is. What is the brain that's already damaged and irreversibly damaged that you're not going to be able to reverse? That is really a very imaging-based decision. You can do it off CT scans using things like the aspect score, but potentially also using your other imaging modalities, diffusion weighted imaging on MRI, or using your CT profusion. You can get an estimation of that core infarction.  What you're really looking for is the patient that has a small bit of core infarction, small bit of irreversibly damaged tissue; but there's a large area that's lacking blood flow. That's really the ideal patient to go for these mechanical thrombectomies, because if you get that blood flow restored, you're going to be able to save all that brain that's lacking blood flow, and prevent it from becoming that irreversibly damaged core tissue in the future.

Alex Rae-Grant: So Shazam, I understand there are different techniques you can use when you're doing mechanical thrombectomy. Can you talk a bit more about the different techniques, and how you might think about using them?

Shazam Hussain:  Sure. Right now, there's probably two main techniques that are utilized when we're in the setting of a mechanical thrombectomy. That is the either using direct aspiration, which basically you take a large flexible catheter, up to where the clot is located, and essentially apply a vacuum to it to try to get it to engage with the catheter. Sometimes even ingesting the whole thing, and just sucking it right out, or other times, trapping it at the end of the catheter, and then being able to pull it out the system. The second technique is what we call a stent retriever technique, where essentially it's like a stent on a stick. You have a stent that's on a wire. We open it up into the clot, give it about five minutes or so to let the clot engage with the stent retriever, and then with the stent still open, pull down the whole system all together as one. Usually with some aspiration in association with that as well. Then, the idea there is you're essentially going to drag that clot out with that stent being open.  Most of the clinical trials that were done, were done with the stent retriever technique. That's probably been of the two modern techniques, as we like to call them, probably the one that has a little more evidence behind it.

Although more recently now, the direct aspiration technique has been really compared in a randomized fashion along with the stent retriever technique, and largely found to be equivalent. Most people in the field, I think feel that the two techniques are very similar in terms of their effectiveness in removing clots out of the blood vessels, as well as safety. Now from a cost perspective, this is where it gets a little bit interesting then. If you're talking about doing a direct aspiration, you can just use that using the large port catheter. You really don't need additional devices or things to be utilized. So potentially, people are arguing that the cost of the procedure might be a lot less in using, and using less devices. So whether or not that will completely sway practice towards use of the direct aspiration, hard to say at the moment; especially as there's new and newer device technology that's coming around.

Alex Rae-Grant: So how far out, ... Let's say I have an acute ischemic stroke. How many hours out potentially could you be able to do an endovascular treatment?

Shazam Hussain:  Yeah, it's a good question. Really, the thinking has changed a lot on this as well, over time. Initially, we were very, very time based and had time windows. We used to say well, only within the first six hours after the stroke symptom onset, we'd be able to then go and offer the thrombectomy. That was largely people had a nervousness or a fear about potentially causing hemorrhagic transformation once you open up that blood vessel, restoring blood flow to that part of the brain, and you could have bleeding into the brain as a result. As time has gone on, we've found that using imaging modalities, we are actually able then to pick out those patients who have a small core infarction, but a lot of brain to save, really irrespective of where they are in the time window. You can still safely open up those blood vessels, and their risk of having a hemorrhagic transformation seems to be still quite low.

Now as opposed to having just the first six hours in which to offer therapy, we have clinical trials now that have gone up to 16 and 24 hours that have established that it's a safe paradigm, and actually highly effective in improving patients' outcomes to go even out to up to 24 hours.  There even are patients even after 24 hours that we've come across where again, we have that small core infarction. Large area of lack of profusion, indicating a lot of penumbral tissue or brain to be saved. We've been able to open up those patients also successfully.  The other interesting thing about the time windows when we come to the posterior circulation, when you have these basilar artery occlusions. There, it seems that there's actually ... You can even go up to 72 hours or more after the last seen well time. Although there are, really I think that what structure clock ticking in that situation is probably when they develop either coma or quadriparesis, probably there's not as much time, if those symptoms start to develop. Often times with the stuttering types of strokes, they can be very, very far outside their window, and you can still effectively and safely offer therapy.

Alex Rae-Grant: What makes you excited about stroke treatment for the future? Where do you envision things going in the next five, 10, 15 years beyond where we've already gotten to?

Shazam Hussain:  Yeah, acute stroke therapy, and it's been exciting even just in the last five years ago, to see all the leaps and bounds that treatment has developed. I think coming forward in the future, I think the most immediate challenge that we have is now that we have this very, very highly effective therapy of mechanical thrombectomy, trying to get the patients to the right hospital the first time. So organizing stroke systems with care has been a real focus and will continue to be a focus, I think over the next few years.  We've had a tendency when we talk about interactions with EMS professionals to try to bring patients to the hospital. The tendency is just to try to get that patient as quickly as possible to the closest hospital, mainly because of the intravenous thrombolytic therapy, trying to deliver that as fast as possible.

It's becoming very apparent that for these large vessel or severe types of strokes, it's probably better to get them, even if you have to bypass the smaller center, and it would take you an extra, say 10, 15 minutes to get to a larger center that can offer the thrombectomy, ... It's probably better to actually bypass that closer hospital and get to the larger center because we know getting to the first hospital is usually very quick, but getting from hospital A to hospital B can sometimes takes up to three hours of time. When you're talking about losing two million brain cells a minute in the situation of acute stroke, three hours can be really devastating to a patient.

 So similar to what was done in trauma, where we've designed trauma centers, level one, level two, level three, I think we're going to have to do something similar within stroke where patients are going to be able to be identified in the field as perhaps being a more severe type of stroke, and bringing those patients to your level one or comprehensive stroke center. In that way, we have all of the potential treatments available to that patient as quickly as possible.  Looking past that, looking forward to even more down the line, I think there's a lot of really great development that's going on in the field. When we talk about either acute stroke therapy, I think there's new device technology that's going to be coming around. I think we're just seeing the beginnings of nanotechnology, and how its impact might be on acute stroke treatment.

Of course, on the ... we've just really been focused on acute stroke therapy. When we talk about the recovery side of things, also very, very interesting work that's being done with different devices, deep brain stimulation as well as stem cells, and other treatments that could potentially ... those patients who unfortunately do suffer a stroke, how can we get them to recover better from the event that's occurred?

Alex Rae-Grant: Thanks, Shazam. It sounds like a very exciting time in stroke, and we're looking forward to more in the future.  This concludes this episode of our Neuro Pathways podcast. You can find additional podcast episodes on our website, ClevelandClinic.org/NeuroPodcast. Subscribe to the Neuro Pathways podcast on iTunes, Google Play, Spotify, SoundCloud, or wherever you get your podcasts. Don't forget, you can access real time updates from experts in Cleveland Clinic's Neurological Institute on our consult QD website, ConsultQD.ClevelandClinic.org/Neuro, or follow us on Twitter @CleClinicMD, all one word. That's at, C-L-E-Clinic M-D on twitter. Thank you for listening. Please join us again soon.