Ep. 175: Acute Ischemic Stroke: Evolving Guidelines and Clinical Decisions

00:00:00: Welcome to EA Uncast, your weekly source for education, research and updates from the European Academy of Neurology.

00:00:14: Hi everyone, my name is Theodoros Mavridis, I'm a consultant neurologist in Dublin, Ireland and I welcome you to another and cast.

00:00:24: This week we're happy to have Professor Anna Katarina von Zenka, who is a professor in neurology in Lisbon, Portugal, with the main interest in cryptogenic stroke, heart, brain interactions, and precision medicine.

00:00:40: Professor von Zenka has published many, many papers and studies regarding the treatment and precision medicine stroke specifically in young patients.

00:00:51: And we're glad to have her to speak about this week's EA in-cast, which is about the new guidelines and what the future holds in terms of stroke treatment.

00:01:08: Before I start diving into the matter more, I will ask you, Katarina, to give me a brief overview about the current European guidelines for acute ischemic stroke treatment.

00:01:21: Yeah, so whenever I think about ischemic stroke treatment, I think you are referring mainly to reperfusion treatment, because the treatment itself is composed of different parts of a chain, right?

00:01:33: But here I will mainly concentrate on reperfusion treatment.

00:01:36: and namely, intravenous thrombolysis and thrombectomy.

00:01:39: So currently, the intravenous thrombolysis guidelines state that you should use auto plus or techno plus within four to five hours of symptoms onset.

00:01:51: We know now that sooner the treatment is done, better is the prognosis of the patient.

00:01:56: And you have to take into account if the patient has some contraindications also.

00:02:02: So usually you have to do a very fast evaluation of the patient, usually in the NHS score.

00:02:09: And then you go and do a CT scan to try to exclude if the patient has an intraconial hemorrhage or a stroke mimic that may preclude the use of intravenous thrombolysis.

00:02:20: So if the patient comes normally within the four to five hours time window, and if he has a deficit that is higher than four in the NHS score, then you should absolutely consider do thrombolysis.

00:02:31: You have to think about some contraindications that still exist, namely the blood pressure of the patient.

00:02:38: If it's higher than eight, one hundred and fifty five, one hundred and ten, you should have to think about lowering blood pressure before using a thrombolytic agent.

00:02:47: Also, you have to ask either the patient or relative about some details about his personal history.

00:02:54: Now, for example, if he has an active tumor that may bleed during thrombolysis and also.

00:03:00: if he has some kind of bleeding disease or diathesis that may increase the odds of a complication.

00:03:07: And also think about things like recent at trauma, recent procedure within the last fourteen days that may have happened in a place that's not compressible, and that may bleed in meanwhile.

00:03:22: Also, if the patient has an intracranial hemorrhage that hasn't been completely treated, there's also another contraindication.

00:03:30: And think about also is raking score at the moment is pretty raking score.

00:03:36: if it's higher than three you should consider to benefits versus the risks of doing the procedure in these patients.

00:03:44: so In general, if the patient comes in for four point five hours, you can just use the data from the CT scan and just be aware of the contraindications when deciding to do or not thrombolysis.

00:03:56: So, to initial guidelines, mainly stated and worry about trivenous use of altoplas, but now we have more data, more clinical trials have been done, and technoplas can also be used.

00:04:09: It's mainly advised whenever a patient has a large vessel occlusion, but there are some more clinical trials nowadays that indicate that they can also be used in other situations where the pulse is also used.

00:04:21: It's got some advantages because usually it's administered in just one pulse and it's got a longer half-life and so it's easier to use in the clinical setting.

00:04:32: You don't have to wait for one hour of a perfusion of a drug like Altoplas.

00:04:39: This is what you usually do.

00:04:41: in your normal circumstances, right?

00:04:43: If the patient has a large vessel occlusion that you can see on any due to the CTI, then the patient has education to also do thrombectomy.

00:04:52: If your center is not a thrombotic capable center, you can transfer the patient.

00:04:57: That should be something that's already organized.

00:05:00: So if the patient has a large vessel occlusion, it starts to do the intravenous thrombolysis and it should be dispatched to a center that's able also to do thrombectomy.

00:05:10: Here to do thrombectomy, we know that patients that benefit the most are the ones that have aspect score higher than six and that come into the hospital within the first six hours.

00:05:21: However, we now can use also advanced imaging methods both to extend to time window in patients that can undergo intravenous thrombolysis and also to extend time window to undergo thrombectomy.

00:05:32: So there are some things that we can use nowadays to extend time windows and also to increase number of patients that can be treated.

00:05:40: Yeah.

00:05:42: Thank you, thank you very much for this nice overview of the guidelines.

00:05:46: So we know that the mainstay of our practice is and will remain thrombolysis.

00:05:52: Can you tell me, we'll start first, what are the major changes or updates regarding the eligibility criteria for thrombolysis from the previous guidelines?

00:06:02: We know that previously there was a relative contraeducation regarding AIDS that now it's not, so you can use thrombolysis also safely in the elderly as well and of course in patients with severe hyperglycemia.

00:06:19: But what are other major your update or changes on those recent guidelines compared to the previous ones?

00:06:27: Yeah, so initially when intravenous thrombolitis started to be used, it was based on the criteria that were used in the clinical trials.

00:06:35: And they were very cautious because they really wanted to tilt the advantage of using this treatment.

00:06:40: So they tried to minimize or not to include as many patients that could probably have some complications.

00:06:47: So they really wanted to show the benefit.

00:06:49: So they were very cautious regarding patients that they included or excluded in the clinical trial.

00:06:53: But nowadays, and people initially were also very afraid of inducing or causing draconial hemorrhage in patients.

00:07:01: But now they are more used to using the drug.

00:07:03: So they started also to use it in patients that weren't part of the initial indication.

00:07:09: So we had a lot of data, namely in and observational studies about some patients that were initially excluded from the clinical trials.

00:07:17: Like you said, in patients older than eight years old, now we know that it's safe and these patients also benefit, although age is still a marker of poor prognosis.

00:07:27: Patients with frailty, they should also receive thrombolysis that can benefit it as well.

00:07:33: You see, a severe hyperglycemia is true that it can include patients with levels of glucose superior to four hundred.

00:07:41: But we should be cautious because we don't have really very good data regarding this topic because we know that at the same time it can increase the risk of intraconial hemorrhage.

00:07:51: So if the patient has a severe deficit, very high NHS score.

00:07:56: You should still do intravenous trouble as in patients with severe hyperglycemia, but be cautious.

00:08:02: I won't do it probably if the patient is just mild deficit because the data supporting its use is... very, very few actually.

00:08:09: But there are some patients also on which we now have more data, namely patients with the previous stroke.

00:08:14: Initially, patients that had a stroke within the last three months were excluded.

00:08:19: We went through the data and actually there's no good reason to exclude all patients that have had a stroke in the last three months.

00:08:26: We think that risk is actually higher in patients that had a stroke in the last month.

00:08:32: So these ones are probably the ones that we have to be more careful about.

00:08:35: And also another thing that you have to take into account is the severity of the deficit and also the area of deletion or the volume of deletion of the previous stroke.

00:08:44: So if they have a small stroke, if they're recovered completely, if the stroke happened like two months or three months ago, it's probably a safe to do thrombolysis.

00:08:54: Other patients that were excluded initially, your patients are through cervical dissections.

00:08:59: for example by sections of the carotid arteries or vertebral arteries.

00:09:03: In this page, this observation data shows that it seems to be safe to also do thrombolysis.

00:09:09: We don't have data regarding tercoinal dissections, so here we have to be more cautious.

00:09:14: Other patients that we know that it seems to be safe to do also thrombolysis were patients that have had subarcoin hemorrhage in which an aneurysm was identified and treated.

00:09:24: So if it was treated to aneurysm, it's probably safe to do thrombolysis.

00:09:29: If it is an interrupted aneurysm of small dimensions, it's also probably safe to do thrombolysis in these patients.

00:09:36: Another indication, and also that that comes in in the last guidelines was our patients that have had an acute myocardial infarction.

00:09:46: So we know that they can be divided in two groups.

00:09:48: Patients that have increased in ST segment.

00:09:51: This usually means that they have transmugral infarct.

00:09:54: There are two ones that are at a higher risk of having, for example, myocardial rupture or cardiac temperament.

00:10:00: And there are patients that feel like no increase in the ST segment.

00:10:05: And patients with no ST segment elevation seem to also benefit as other patients in doing thrombolysis.

00:10:13: So this should not be an exception.

00:10:16: If the malcardine infection happened in the same day, then stroke is probably safe to do it at thrombolizes also.

00:10:36: So these are some indications that weren't present in the first indications, because they were schooled from clinical trials, but that were now.

00:10:45: Some exceptions are now acceptable in the case in which you are thinking about doing intravenous thromboasin in these patients.

00:10:54: Thank you very much for those insights about that.

00:10:57: It's very, very interesting.

00:10:59: You mentioned before about advanced imaging and extending the time window.

00:11:04: We know initially it was three hours, then we extended it to four point five hours, even with a higher number needed to treat, but still a benefit.

00:11:13: And we know that, of course, time is brain.

00:11:15: But can you tell us more about the vast imaging and how we can extend that window in terms of thrombolysis?

00:11:23: And what basically we use and what is used in clinical practice, both from MRI and CD perspective.

00:11:32: Initially, the number of people that were treated just by using to four point five hours was very small.

00:11:37: That's why clinical trials were used to try to expand to window.

00:11:40: Nevertheless, I just want to reinforce really that time is a brain and sooner the patient is treated best.

00:11:45: This is prognosis, right?

00:11:47: But if you want to increase the number of patients treated, you can use advanced imaging.

00:11:51: So the clinical trials use biomarkers that come from the data that you can gather using CT perfusion, and also MRI, MRI diffusion, and MRI perfusion, both of them.

00:12:04: So currently, you can extend the time window to do intravenous stabilizes till nine hours, or in case of patients that were at an OLA, you can use this imaging, too, if patients who were more than nine hours from the main point of sleep, and you can use either advanced imaging with CT, for example, points that we have to take into account is the volume of the infarct core.

00:12:29: If the patient has infarct core, that's less than seventy milliliters.

00:12:33: If they have a relationship between critical apocryphal volume infarct core superior to one point two, indeed they have a mismatch volume superior to ten.

00:12:43: That's the main criteria that's used to use CT as advanced imaging to extend to window in patients to undergo intravenous thrombolysis.

00:12:51: Regarding MRI, you have to usually do diffusion MRI and to fare.

00:12:56: So if the patient doesn't have changes yet in fare, it's safe to do intravenous thrombosis in these patients.

00:13:06: Yeah, it's very, very interesting.

00:13:07: So basically what we're trying to do is to assess the actual infracore, so the actual tissue that is already dead and the tissue that is currently dying.

00:13:18: but we can save the penumbra.

00:13:19: so if there is a as you told us a big mismatch between those two then you can safely administer intravenous thrombolysis to save the penumbra that is left.

00:13:30: it's very very interesting because as everybody knows before we just took into consideration the last time seen.

00:13:38: well so basically patients who were going into sleep and last thing well for example last evening Yesterday evening they wouldn't get anywhere near.

00:13:49: into the thrombolytic agents because they were excluded due to time only.

00:13:54: Now let's go into nowadays a hot topic which is endovascular treatment.

00:14:00: So basically thrombectomy.

00:14:02: And we've seen that the initial trials, the diffuse three and the dawn trial were a bit more strict in their criteria and we'll still use them.

00:14:12: But we have more data on different populations.

00:14:15: For example, low aspect score.

00:14:18: large core infarcts or even low NITSS but still with a large vessel occlusion or even extended windows on them.

00:14:29: Can you tell us more about those?

00:14:31: and then we can jump into a more interesting topic which is the middle vessel occlusions or the distal vessel occlusion.

00:14:39: So we can go step by step if you want.

00:14:42: Yeah, so regarding to all aspect scores, we knew that some people and some patients, a number of patients appear with low aspect scores, means lower than six.

00:14:54: That means also that probably at the time that they are being evaluated, their score is already quite high.

00:15:00: Nevertheless, there are some clinical trials and namely also meta-analysis that have been done that have shown that these patients nevertheless still seem to benefit from endovascular treatment.

00:15:11: And there's a possible explanation for this.

00:15:14: That's probably because the software that we are using to measure the core, they changed the way how the core is perceived.

00:15:21: So we have generally the idea that the artist is round or oval shape, that's the core, but that's probably not a physiological way to represent it.

00:15:31: Probably there are some islands of tissue that's still viable, and that can be saved.

00:15:37: That's the reason probably why patients with low aspects still benefit from endovascular thrombectomy.

00:15:44: So I think that's something that is going to be reviewed near future and probably the indications to treat these patients will still increase.

00:15:55: But we have to see how this also can be supported by current national health services.

00:16:04: going to increase significantly the number that the patients of that have indication to be treated.

00:16:10: There's no doubt, for example, if you have a patient like in this four to your fifties that definitely benefits from this, probably older patients, but probably still have to go through and see, even in patients, the whole aspect score, we are the ones that benefit the most so that we can still select the ones that will probably benefit the most and also to make it feasible in a health service to treat all of these patients.

00:16:36: Another indication, like you said, was our patients that have a low in S score, for example, less than four, in which you find out that they have a large vessel occlusion.

00:16:47: So currently initially, in these patients, there was not a clear indication to treat them.

00:16:52: Why?

00:16:52: Because we thought that the risk of doing it in the vascular procedure probably outweighed the benefit.

00:16:59: But if you think about the patient, you also have to think about what kind of deficits the patient has.

00:17:05: For example, if it is a motor deficit that is disabling, you should still think about doing endovascular treatment, even if the patient has a low energy score.

00:17:16: Of course, if he has indication to do the thrombolysis, that's what you should do first, okay?

00:17:22: always think about the patient also itself and if the deficit is or not disabling.

00:17:27: I think that's really very important, just not to think always in general, but also to try to individualize the indication.

00:17:35: There was a third one, sorry, that you were also speaking about.

00:17:39: Yes, the third one was to jump into the new trials about middle and distal vessel occlusion.

00:17:47: and what data do we have now that we are advancing from the original trials that included only large vessel occlusion and of course mostly on the anterior circulation and now we're going also into the posterior circulation with some good results and of course we are going into further more divided vessels in the anterior circulation like the middle and distal vessels as well.

00:18:15: Yeah, sure.

00:18:16: So, because results also have been very good in patients with a large vessel occlusion, the idea like, like initially when troporazul was done, people and the idea that there's procedures are safe.

00:18:29: really have led investigators and radiologists and neurologists to expand to use of the endovascular treatment.

00:18:37: And we know that with time, it started to treat also MEVOS, middle vessel occlusions, and there was also the idea of treating these two occlusions.

00:18:47: So through results from clinical trials, it seemed to show that patients with prosome M-II occlusion benefit as well as patients with M-I occlusions.

00:18:57: The distilled trial showed distilled trial include patients also with distilled occlusions.

00:19:02: For example, M-III and M-IV and five people with occlusion of P-I and P-II segments or A-I segments.

00:19:09: And what the clinical trial showed was that there was no clear benefit.

00:19:14: There may be a reason for this negative result.

00:19:18: If we think about it... the area of volume of the tissue that can be saved in a distal occlusion is smaller than in the case of a patient that has a more proximal occlusion.

00:19:28: So it may be harder to show a benefit just by using the NHS score or the mRNA score.

00:19:34: Probably in these patients, if you want to show a benefit, you need to choose a different outcome.

00:19:40: For example, quality of life or another type of functional outcome.

00:19:45: or cognitive outcomes also can be a possible outcome to choose in these clinical trials.

00:19:50: But at a time being, there's no clear indication or it doesn't seem to be a benefit of treating patients with distal occlusions, probably in the future with new devices that will change with new outcomes, but not for a time being.

00:20:05: Regarding the procedure occlusion, yes, there are clinical trials that show that in the vascular treatment, because also I want to think about the basilar to our cushions are some of the types of stroke that have the worst outcome, right?

00:20:18: So here you just have to be sure when you start the treatment that its patient is still doesn't have like a very large infarct, right?

00:20:28: That includes to benefit the treatment, right?

00:20:30: For example, if already doesn't have like cranial nerve signs, right, that probably the patient will not benefit from the treatment.

00:20:39: Otherwise, these patients benefit from the vascular treatment and there are also some clinical trials that have shown that there's a quick also benefit of undergoing and doing intravenous thrombolysis in these patients.

00:20:51: So these patients were not part of initial guidelines, but they should be treated and vascular thrombolysis and vascular thrombectomy should be considered.

00:21:02: when considering to benefit risk of the procedures?

00:21:07: Yeah, that's very interesting.

00:21:09: and of course in posterior circulation we're a bit more flexible when it comes to to time.

00:21:14: And I think that this is very, very important.

00:21:19: Also regarding the distal, the distal and mevo retloclusions, we had three trials.

00:21:26: Two of them were nutrient one was prematurely stopped due to adverse events.

00:21:31: So it was a negative trial and discount.

00:21:34: My last question, if you don't mind now looking forward, what developments in stroke care or upcoming trials are you most excited about and what are you waiting for the future?

00:21:47: What does the future hold?

00:21:49: Yeah, I just wanted to reinforce one point.

00:21:54: We are all vaccinated about these reperfusion treatments, but we have also to maintain the idea that one thing that's very important is the stroke chain of care, right?

00:22:05: Namely the treatment that's happening at stroke units, right?

00:22:09: So we have to still maintain the focus in putting these patients in it, admitting them to a stroke unit after doing these profusion treatments to be sure that we are giving them the best treatment.

00:22:23: We are going and looking out for complications.

00:22:26: We are starting secondary prevention.

00:22:28: looking for stroke etiology, so stroke unit care is still very important, okay?

00:22:34: Regarding the treatment probably, what I'm more looking for are the advances that are happening in the pre-hospital setting.

00:22:42: So we know that time is brain, and we know that the faster the treatment is started, the better outcome, even though we now have these advanced imaging methods that can increase the number of patients that are currently being treated.

00:22:54: But these new things are being tested, like biomarkers and acute setting to try to differentiate if the patient's x-chemic or hemorrhagic stroke and even devices that will use like raw radiofrequency to see if the patient has a large vessel occlusion immediately to try to decide what's the best place to send them for treatment.

00:23:13: I think that's probably the most fascinating part right now, optimizing through pre-hospital.

00:23:18: pre-hospital setting.

00:23:20: I think that there's a large benefit that may come for the patient from the pre-hospital setting.

00:23:27: So this is probably the area that I think is more fascinating right now.

00:23:31: Thank you.

00:23:32: Thank you, Professor Fonsenga, for this very nice insight and dive into the acute stroke treatment guidelines.

00:23:41: I want to thank you for this excellent talk and I hope all the listeners are grateful for that as well.

00:23:49: Thank you very much and till the next time.

00:23:52: Thank you.

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