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My name is Corey Zacherson. I am an emergency physician at Massachusetts General Hospital in Boston, Massachusetts, uh, in the United States. So we'll move on to the 4th section, which is preventing acute mismanagement through coordinated ARIA escalation. And so coming back to our patient, Margaret, I will recall she's a 73 year old woman who's receiving anti-amyloid therapy for early Alzheimer's disease. And now, Margaret is experiencing sudden confusion, expressive dysphagia, and a right arm tremor. And she presents to an emergency department, but unfortunately, at the emergency department where she goes, it's not connected with her um treatment center, and so her anti-amyloid therapy and prior ARIA um status are not known or visible in that emergency department's record. And so as she presents to that ED, the differential uh by the treating uh team is clearly going to include ischemic stroke and intracranial hemorrhage, seizure, other emergency, stroke mimics. Also, it should include symptomatic aria. And so, how do we make sure that our systems are set up in a way that when Margaret presents, Aria is on our differential and on our treatment, um, uh, evaluation and treatment pathway. So, for our first poll, uh, in this section, the, um, we have Margaret with these uh symptoms and the stroke assessment in the emergency department has begun, and fortunately, the team has known to ask the right questions. Her anti-amyloid exposure is identified. And so now in this setting, what should they do first? A pause their stroke assessment, await a routine MRI and specialist review before continuing. B, continue the stroke assessment, give thrombolysis as soon as the CT excludes hemorrhage. C, continue the stroke assessment, verify the exposure and obtain urgent specialist review. D, diagnose RA clinically, contact the memory clinic before emergency imaging, or E, transfer to the treating center before local stabilization and initial imaging. So, in this case, the right answer is C. To continue the stroke assessment, verify the exposure, and obtain urgent specialist review. And really, this is uh uh taking a lot of our approach in emergency medicine and the emergency department. We're parallel processing. We're thinking about a patient's differential and um evaluating multiple things on that differential diagnosis, even as we're sort of considering Um, the different possibilities of our treatment path. And so we want to both, uh, preserve the time critical stroke assessment, while also making the treatment exposure for prior aria, uh, something that we're, um, knowing about, thinking about, and including in the way that we're approaching our patient. And so how do we do that? Uh, we want to run these things in parallel. So our time critical acute assessment is not going to change. We're going to stabilize our patient, define the onset and the trajectory of symptoms, also, uh, be activating our appropriate stroke pathway. On that stroke pathway, we're obtaining initial emergency imaging without delay. Typically, stroke protocols include a a first pass with a non-contrast head CT and that should still be the case here. And um as we're doing that, we're keeping stroke, intracranial hemorrhage, seizure, um, and AI in our differential. And so as we're doing that time critical acute assessment, we're simultaneously thinking about um identifying risk for AI and our evaluation there. So we're looking at when the patient um began anti-amyloid therapy, what is their treatment duration, what medication are they on, when did they have their last administration? We're looking at their AIA history. What did their baseline MRI look like? What did their most recent MRI look like? Um, and when was that last imaging, uh, completed? We're looking at their anticoagulant and antiplatelet exposure, and we're including the specialists in this, um, evaluation as well. This is just a reminder that symptoms alone do not identify a cause or etiology of the symptoms focal deficits, confusion, visual changes, seizures, headaches, aphasia. These can occur in aria. These can occur in stroke, in ICH, in seizure, in migraine, and you know, and so the differential of Of these acute changes in neurologic status for patients is much broader than just stroke, much broader than just RA. We're thinking about all of these things. Um, and our differential, um, we're going to work through as we're thinking about the exposure, we're thinking about the time course, and we're moving toward imaging for patients and engaging our experts in, um, our treatment. Medication history as uh we've seen on the previous slides, um, just to reiterate here, this is a really a time-critical diagnostic input. So knowing the patient's um medication that they're on, what is the route, uh, when was the last administration, what is their AA history, um, what is their anti-thrombotic history, and engaging the full team in our, um, evaluation and management decisions. And as we're doing this acute evaluation, we're thinking about imaging in a couple of ways. So, CT and MRI are both important, um, and they're looking at and answering different questions for us. So, our stroke protocol, um, typically starts with a CT. With a non-contrast CT we're looking for intracranial hemorrhage, um, sometimes we're picking up a large vessel occlusion or other acute findings. This is part of our local stroke pathways. Generally at baseline. Um, and we're not changing that. We're sort of continuing on that path. But at the same time, when we have a patient on anti-amyloid therapy in the emergency department with acute neurologic findings, we want to be thinking about how are we evaluating for ARIA and how are we, um, either identifying it or eliminating it from our differential so that we can move on to appropriate treatment decisions for the patient. And so to do that, we really need the MRI. Uh, what is the MRI doing? It's looking for edema and so Focal effusion, hemorrhagic findings, it's really giving us more information about this full differential that we're looking at and ideally we're using that in comparison with baseline and prior MRIs for these patients on anti-amyloid therapy so that we can evaluate sort of the trajectory. Um, and so when MRI is not available and we have a patient with Um, acute neurologic findings on anti-amyloid therapy in an emergency department. One of the things we need to be thinking about is how we're going to get that MRI. Because the reperfusion and antithrombotic decisions that we're going to be making about this patient also really need specialist input. They need um both all of the information that we can get from the imaging, and they need the specialists to be coming together and thinking about these decisions with us. Um, we want to sort of Know our exposure, know our um imaging findings, know whether there's an occlusion and be thinking about what guidance we have for these treatment decisions. In particular, you know, sort of the um the elephant of the room of thrombolysis in A is one that uh deserves some um explicit attention in um in this presentation. And so, You know, we have case reports of patients who've been on anti-amyloid therapy, who've presented with acute neurologic findings to an emergency department, and who've um had RAM misdiagnosed as an acute stroke and had uh thrombolytics administered with devastating consequences. And so, um, this has really been an important lesson and is um something that's informed uh some of the ways that we're thinking about our acute evaluation and our um Our approaches in the emergency care delivery for these patients. The FDA has issued guidance on this in the US. The American Heart Association has also put out a scientific advisory that summarizes the limited evidence and in the 2026 acute ischemic stroke guidelines put out by the American Heart Association. Anti-amyloid therapy and AIA are explicitly listed as contraindications to thrombolytic treatment. And this is all based on sort of our limited experience so far. There's very little um evidence to date, um, certainly not robust evidence to inform our understanding of how patients with anti-amyloid therapy should be considered for thrombolytic, but the thing that we do know is that when RA is identified, thrombolytics are contraindicated. Of course, thrombolytics um are not the same as anticoagulation or antiplatelet therapy. And so, um, thinking about all of those treatment decisions are really going to be, um, places where understanding the indi indication and the bleeding context and the, um, the approach, it will be taken together and should be done in coordination with the patients, um, Treatment team. OK, so for our next poll, the question is, what if Aria and stroke both remain possible? So, coming back to our case with Margaret in um our scenario, she's had her CT. It's excluded intracranial hemorrhage, but she's still aphasic in the emergency department. Aria cannot be excluded.