Good afternoon, thank you so much for attending today. So I'm going to talk about the clinical research in neurosciences over the past year in 2022. I have no disclosures. There's been a lot of great research in the neurosciences over the past year in 2022, but I'm going to focus this review on randomized control trials that are clinically relevant to our treatment and care in the neuro ICU, neurocritical care. Most of that research has been done this past year on acute ischemic stroke, including the use of tenecteplase, the bridging with IV thrombolytics prior to endovascular therapy, and expanding indications for endovascular therapy in patients who would otherwise not have been candidates for treatment. There's some research on subarachnoid hemorrhage, as well as comatose survivors and cardiac arrest. So I'm going to show you one paper on tenecteplase for acute ischemic stroke. Dr. Lynn, who will be talking after me, will give you more detail on the pharmacology aspect of using tenecteplase, but this was a trial that was published this year from 22 centers in Canada looking at IV tenecteplase versus IV alteplase in acute ischemic stroke. They had over 1,500 patients that were analyzed in this study, and what they found was there was no difference in outcome in the patients who received IV tenecteplase over IV alteplase, and therefore they showed that there was no benefit to changing or using alteplase over tenecteplase. So since 2015, when the release of Mr. Clean showed that patients with large vessel occlusions benefited from endovascular therapy, providers have been wanting to know whether or not thrombolytics are indicated prior to the endovascular treatment. So there were three studies that were produced over the last year. This one was actually published in 2021, but it was November of 2021, that had attempted to answer this question. This was the Mr. Clean no IV. Patients were randomized to either endovascular treatment alone or IV thrombolytics prior to endovascular treatment. The study used IV alteplase. This one looked at the superiority of endovascular therapy alone and also the non-inferiority of endovascular treatment alone. They had over 500 patients, which is 533, and they looked at the outcome, which you can see here, and this outcome failed to meet the superiority or non-inferiority criteria, so therefore did not recommend a change. They did see similar mortality and a similar symptomatic ICH. This was a SWIFT direct trial. This also looked at randomizing thrombectomy alone versus bridging with IV alteplase. They looked at the primary outcome of functional outcome. It was also non-inferiority trial. You can see the outcomes here. They were similar with slight trends for the bridging therapy. This trial also did not meet non-inferiority outcomes. They also found with this, though, that when the patient was in endovascular treatment, they found that there was decreased perfusion, reperfusion, if the patient did not receive IV thrombolytics. This was another trial published this year. It was direct-safe. They also randomized thrombectomy alone versus thrombectomy with bridging with IV alteplase or IV tenecteplase. This was also a non-inferiority trial. You can see the outcomes on the right, and you can see trends toward the benefit of bridging therapy. The outcomes did not meet non-inferiority. And so therefore, when you look at all these three trials alone, there was not a recommendation to skip the IV thrombolytics prior to the endovascular therapy. So looking at other indications for endovascular treatment, one is the isolated M2 occlusions. This was a pooled analysis from randomized controlled trials published this year. They looked at patients who had isolated M2 occlusions and found that in the patients that they analyzed, 517, those patients who had a mismatch, a perfusion mismatch, they did benefit from endovascular treatment if they had the mismatch, but medical treatment alone was beneficial if there was no mismatch. This was a trial that was published looking at endovascular treatment in large strokes with large ischemic regions. These patients are typically excluded from the trials and treatment. These patients were included if they presented within six hours of symptom onset. They had a large vessel occlusion, and their ASPECT score was 3 to 5, basically showing there was a significant amount of ischemic changes on the initial imaging. They did allow treatment up to 24 hours if there was a flare DWI mismatch on the MRI. Some patients were candidates for alteplase. This was a study in Japan, and they received low-dose alteplase if they were candidates for it, and they also looked at primary input of functional outcome. What you can see here with the 203 patients that were analyzed, the median NIH score was very high. It was 22, and the median ASPECT score was low, which is 3. They did see that there were more intracerebral hemorrhages in patients who received endovascular therapy. As you can see here, 58% versus 31. But the symptomatic ICH was non-statistically higher, basically 9% versus 4.9%. With that, though, you can see the outcome data here. There was a better functional outcome in those patients who received endovascular therapy. You can see the forest plot here, which shows that endovascular therapy is better over medical therapy. So recently, we have gotten publications looking at basilar artery occlusions. These two trials were just published in, I think it was November of 2022, looking at basilar artery occlusions. These are typically excluded in all of the endovascular trials, because we're typically looking at the anterior circulation. So these are two trials, ATTENTION and BOUCH. The ATTENTION trial enrolled patients who they presented within 12 hours of symptom onset to endovascular therapy versus standard medical treatment. The BOUCH study enrolled in 6 to 24 hours to the same groups. Thrombolytics were used if the patient was eligible to receive them. The ATTENTION trial looked at 340 patients, and the BOUCH trial was 217 included in the analysis. Here's the ATTENTION trial data. What you can see here is there was improved outcome in patients who had a thrombectomy over those who had standard medical care. And you can see the forest plot on the right that favors thrombectomy treatment in patients with basilar artery occlusions who present within 12 hours. This is the BOUCH trial that also showed that thrombectomy was better over control. This trial was actually stopped early due to the benefit of thrombectomy. And you can see the forest plot on the right. I will say that with both of these studies, there was an increase in hemorrhages in these. But despite that, there was an improved or reduced mortality and still a functional benefit with the endovascular therapy. They also, of course, had more procedural complications because of the endovascular treatment. So after the endovascular treatment, we still don't really know the optimal blood pressure target. There was a trial back in 2021 that looked at the intensive goal, which was less than 130 versus a standard, which is 130 to 185. And they found that there was no difference in radiographic hemorrhages if they used the more intensive goal, which is less than 130. These groups were really 128 and 138 were the blood pressures that they ended up achieving. This year, they did publish a subgroup analysis in those. And they looked at contrast enhancement. It's always a question that we have. If you see contrast enhancement, is there an increased risk of hemorrhage? And they did see that if there was contrast enhancement, they did have more hemorrhages. So this year was the ENCHANTED-2 trial. This one looked at the more intensive blood pressure management, which was a systolic pressure of less than 120 versus a more standard treatment or less intensive of 140 to 180. This was done in 44 centers in China, and they looked at functional outcome. What they found was actually that the trial was stopped early due to safety concerns. They analyzed 810 patients after it was halted and found that the more intensive group, the less than 120, had a worse functional outcome, more likely to have early neurological deterioration, and more likely to have major disability at 90 days. And so therefore, the less than 120 seems to be harmful in these patients after the endovascular therapy. We do have ongoing trials right now that's looking at less than 140. And so hopefully this time next year, we'll have a little bit more data on that. Changing the course a little bit, this is the SET.2 trial that was published this year. This is looking at early tracheostomy versus a standard approach to tracheostomy or timing on patients with severe stroke. They used a SET point score, which you can see here. I don't know if you can read those words or not, but basically it's a 15-point score that they had externally validated to say that if there's a score and it's greater than 10, then those patients were more likely to require a tracheostomy. So they randomized those patients with those higher scores and said, okay, they have a severe stroke. We're going to randomize them to early tracheostomy within five days, or the standard approach would be around day 10. The median was day 4 for the tracheostomy for the early group and 11 in the standard approach. They looked at the primary endpoint of functional outcome, which was actually a modified ranking of 0-4. Remember these were severe strokes. And so the outcome is a little bit worse for those. What they found was there was no difference in the outcome of those patients who received early versus standard tracheostomy. They also looked at some secondary outcomes as well that you can see here, including more likely to have the cessation of sedation, the start of the weans, the mechanical ventilation days, discharge from the ICU, or discharge destination, or cause of death. They found no difference in those either in those patients who received early versus standard approach to tracheostomy. We've also had some questions on what is the ideal way to wean an EVD. It's not standardized anywhere, and we really don't have a lot of answers on the best way. So this was a trial that was looking at the EVD weaning in subarachnoid hemorrhage patients. They had six centers, and some centers did a rapid wean, and some did a standard wean. So two, basically whenever the patient was decided that the EVD was going to be weaned, they clamped it immediately. Another center, they did whatever they wanted for the wean for 48 hours, and then they clamped it. Two centers did a standard gradual wean, and one center did rapid and graduals. Multiple weans were allowed, and the shunt when it was placed was at the discretion of the provider. There were no protocols based on that. So what they found was that the patients who had a more rapid EVD wean, they actually had less VP shunt days, and that's not just in the hospital days. Those are the patients who sometimes we see return for a shunt later because they've decompensated outside of the ICU or after they've been discharged. They also found with the rapid weans and those who had fewer weans and earlier weans, they also had the reduction in EVD duration, or number of days, and decrease in ICU length of stay as well. Remote ischemic preconditioning is something that's done in other literature. This is actually a blood pressure cuff that is inflated above systolic pressure in one of the extremities. So there is an ischemic region to this extremity, and it's held for a certain period of time, and then that is released. And this is felt to help the body systemically fight inflammation, apoptosis, and is believed to be a protectant against ischemia. So now they're starting to do some possibility of neuroprotectants. So these are a couple of just kind of early pilot studies to look at the feasibility of doing this RIPC, and it's able to be done. And the one on the bottom is just another pilot study that looked at the RIPC in subarachnoid hemorrhage patients, and they looked at cerebral oxygen desaturations during the peak vasospasm period, day 7 to 10. And in this small pilot study, they found that if they did this RIPC, they actually had decreased numbers of cerebral desaturations. So this year, there was a study looking at RIPC in patients with moderate ischemic stroke. This was done in 55 hospitals in China, and their RIPC was five cycles, and they would do five minutes each of inflated and then deflated for five minutes. They did that for 10 to 14 days versus just a standard treatment without it. They looked at the outcome of the patients after having this RIPC, and this study showed that there was an improved outcome in the patients who had the RIPC, as you can see here on the right. There were just a few studies in comatose survivors after cardiac arrest. The top two are the box trials. This was an attempt to find the ideal oxygen targets and blood pressure targets in these patients and looked at outcome. And you can see the goals here with the PA02, 68-75, or 98-105. They found no difference in the outcomes of death, severe disability, or coma. In blood pressure targets, they looked at a map of 77 versus 63. They also found no difference in outcomes. The bottom study you see there is looking at the EEG patterns in these comatose patients after cardiac arrest. And we always have these rhythmic changes or periodic changes on the EEG, and we always have a question whether or not we should treat them. So they randomized patients to actually having those treated for 48 hours using anti-epileptic drugs versus just standard care. And when they looked at the outcome in those patients, they also found no difference in outcome if those periodic changes were treated. So basically, we've had a lot of good data over just one year, in 2022, that's starting to answer a lot of questions and actually starting to allow us to ask more questions. So we have the use of tenecteplase versus alteplase that Ken will talk more on that. We've looked at some other indications and getting some data, some positive data to show that we can expand some patient populations for endovascular treatment. We're starting to kind of focus on some blood pressure targets after endovascular treatment. We still have more room to go on that, but I think we're getting close. And the new data that's starting up on the remote ischemic preconditioning. Thank you.

neurosciences

randomized control trials

acute ischemic stroke

endovascular therapy

neurocritical patients