Arun Amar, MD, a neurological surgeon at Keck Medicine of USC, provides a conceptual approach to the workup and management of patients with acute ischemic stroke. He also reviews the interpretation of CT perfusion parameters as the basis for selecting appropriate recanalization strategies, such as intravenous thrombolysis and mechanical thrombectomy.
Yeah, this is a roux Neymar, and I'll be discussing the evaluation and treatment of patients with acute ischemic stroke. This image comes courtesy of one of my mentors, doctors Lakovic, who injected latex into the arteries of the brain and then dissolved the substance of the brain to reveal this cast. Of all the blood vessels that are left behind, the brain weighs only 2% of the body that receives 20% of blood flow, and the total length of the capital Aries, if some mated together, is more than 400 miles. It's therefore easy to understand. With such a robust vasculature and the need for blood flow. That stroke is the second leading cause of death worldwide. The number one cause of disability in the United States, with over 900,000 new strokes per year, or one every 40 seconds. Stroke effects four out of five households with a direct cost of more than $300 billion. And that does not factor in the additional costs due to lost productivity. Stroke can be broadly classified into two groups. The more common of them is a scheme IQ stroke due to a blockage of blood flow, which accounts for about 80 to 85%. And of those, the various causes include atherosclerosis of a large artery that causes insight to clotting or thrombosis. Another potential mechanism is a clot that forms in the heart and then travels distantly to the brain. What we call embolization. There can also be intrinsic damage and disease of the small blood vessels of the brain leading toe, particular types of strokes that we call le Kunar and they tend to occur in characteristic regions of the brain, like the basil ganglia and the cerebellum. And in about one quarter of strokes, we can't identify the underlying cause. The remainder of strokes are hemorrhagic. This consists of bleeding in the brain either into the substance of the brain, which we call interest re Brel, or into the space surrounding the brain, which is subarachnoid hemorrhage, typically from a ruptured brain aneurysm. Our conceptual approach to a patient with acute ischemic stroke is always the same. We want to know three things. First is the vessel status. Which artery is included, and to what extent is it included? Next is the status of the tissue, and we'll distinguish ischemic tissue which has insufficient blood flow but still is potentially salvageable and functional versus infarction, which is permanently damaged tissue. Lastly, we want to know the profusion status by quantifying and measuring various parameters of blood flow. The premise of a scheme IQ stroke treatment is that there is a central core region of permanently damaged tissue depicted here in red. This is the area of infarction where there has been a critical reduction of blood flow, or ology mia, that leads to complete bio energetic failure and death of the tissue. This region is surrounded by a larger area of ischemic tissue depicted here in green. In this region, the degree of decreased blood flow is enough to cause dysfunction of the brain. But the tissue is still salvageable, and if the flow can be restored, the tissue could be saved and those impairments or deficits can be reversed. The difference between these two areas is what we call the ischemic penumbra. We know that with time, if the vessel remains occluded, the area of the infarct expands and grows, whereas the area of salvageable penumbra decreases. But this esque emmick progression is highly variable from patient to patient. Some patients can have salvageable penumbra even beyond six hours since the onset of their stroke symptoms. And the neurologic exam cannot reliably distinguish between the tissues that that's already permanently damaged or the infarct versus the ischemic territory that's at risk of converting Thio infarct later on. However, advanced missed getting tools such as the ones I'll discuss later can help identify this mismatch and inappropriate patients re profusion therapy to open up the vessel can help restore lost neurological function if such mismatch is present, this principle is illustrated in the next two slides. So all of these lines on this chart represent different patients who had the same type of occlusion, ah, thrombosis or blockage in the proximal segment of the Middle Cerebral Artery. And these patients were then imaged at various time intervals and the degree of permanent infarct depicted as the regions of pink on the accompanying Marie scan is measured quantitatively. So, for instance, this patient here, depicted with the Blue line has a relatively small volume of stroke even more than 10 hours since the onset of symptoms. Conversely, this patient here, depicted by the Red line, has a very large volume of stroke after just three hours since the onset of symptoms, we know that re profusion matters. And in a large meta analysis of thousands of patients across more than 50 studies, the odds ratio of a good outcome after three months was 4.43 for those who achieved re canonization versus those that had persistent occlusion of the vessel, we also know that the benefit is directly related to the speed of re cannibalization. For every 30 minute delay between the onset of symptoms and the time that the tissue is repre fused, there's a 10% decrease in the probability of a good functional outcome measured by the modified rank and score or Maher S. So our mantra is time is brain. And to just put that into numbers in a typical acute ischemic stroke. Every minute the brain loses nearly two million neurons, 14 billion synapses, or the connections between neurons and more than 7.5 miles of violin ated fibers. There are, principally to methods of recounted ization. One is to administer an intravenous drug that breaks up the clot. Um, in the United States, we typically use tissue plasminogen activator, or T P A and the window for giving that medicine is up to 4.4. Excuse me, 4.5 hours after the onset of the stroke. But there's another drug that's another thrum politic agent that's gaining more and more popularity called Connect to Place. Alternatively, or sometimes, in conjunction with an intravenous agent, we can perform mechanical thrown back. To me, this is a surgical procedure that involves navigating a tube called a catheter from an artery in the leg or the wrist and using it to extract the clot that's blocking a blood vessel in the brain. The window of opportunity for performing this procedure is up to eight or more hours after the onset of stroke symptoms. This is a animation of how that procedure is performed. In this case, the patient has a thrombosis or a blood clot that's including a large artery in the brain and through access, either in the femoral artery of the groin or sometimes in the wrist. We can steer a catheter through the body now all the arteries in the body or connected under X ray guidance. Once we've entered into one of them, we can steer this tube or catheter into the brain and use it to deliver a system that will extract the thrombosis. In this case, it's a catheter that's used to connect to a suction device to engulf the clot and aspirated out of the brain. In the process, it restores blood flow to the brain and, if performed in a timely fashion, can completely resolve the patient's symptoms. After removing the clot, the catheter was removed from the body. There's an alternative device called a stent retriever, which is an expandable metal cylindrical cage that can engage with the clot and use it Thio, pull out the clot, and that technique is depicted in the following video. In this case, very similar toe what was depicted in the prior animation. The catheter is advanced up to the ACC lucid clot, and then the stent retriever device is placed within the center of it. When it's delivered, it's compressed into the micro catheter. But as it's released from that micro catheter, its intrinsic, self expanding radio force causes it to engage with the clot. This produces an instantaneous channel of flow, and then subsequently the whole clot with stent retriever can be removed from the body This is an example of the type of cloth that can be retrieved with such a device. So I mentioned the three data elements that we want to assess in every patient with acute ischemic stroke, and I'll focus now, particularly on profusion. Profusion measures blood flow to the brain, and although it correlates with the vessel status, it also depends on collateral blood flow from other sources. It depends on blood pressure, the time that's elapsed and many other factors. So there are four different profusion imaging parameters, including cerebral blood flow, or CBF. This is the volume of blood flow through a given volume of tissue per unit time, and it's typically about 50 to 60 milliliters per 100 g of tissue per minute. Electro cannon, called dysfunction, occurs when that is reduced to about 20 to 30 mL, and cell death occurs when it's below 12 mL per 100 g per minute. Cerebral blood volume is the total volume of blood in a given volume of tissue, and it's been shown to be reduced in tissue that's permanently damaged or infarct it. The mean transit time is the average transit time of blood passing through a given brain region measured in seconds, and the time to peak is the time to which the maximum contrast signal arrives in a given brain region after it's injected intravenously. Also measured in seconds at U. S. C. We were relatively early adopters of a software platform called Rapid. This provides a fully automated operator, independent way to post process data from SETI and Marie scans. It generates two maps, one is in pink and one is in green. The pink map represents an area of core infarction, which has been proven to correlate with regions of the brain, where the cerebral blood flow is less than 30% of that. On the opposite side, the green map represents an area of critical hypo profusion where there is a delay of the arrival of blood, measured with the contrast of more than six seconds. And this software can quantitatively calculate the relative volumes and the degree of mismatch between them or, in other words, help figure out what is the ischemic penumbra. The processing time for this is less than two minutes, and it can facilitate clinical decision making such as I'll illustrate in the next few slides. So these parameters are not just arbitrary. Uh, there have been studies that validate them using receiver operating characteristic curves. To establish those thresholds that I mentioned. It was shown that the tissue depicted in the pink map, where there's less than 30% of flow of the opposite side, or more than a 70% reduction in cerebral blood flow, accurately predicts the volume of infarct, as shown by a subsequent Marie scan on a particular Siri's called D W I or diffusion weighted imaging for patients who do achieved timely re profusion. Conversely, that tissue at risk depicted in the pink map where there's a T max of six seconds or more accurately predicts what's gonna happen and the degree of final stroke volume. Um, if the vessel does not get opened and there is no re profusion. So here's an example of a patient who is an ideal candidate for re cannibalization. On the left side of the screen is the map of core infarction, which in this case is 0 mL of tissue, whereas on the right side of the screen is the volume of tissue that's vulnerable or at risk depicted in green. The ratio between these is infinite because the denominator is zero. Here's an example of a patient with some core infarction but still a significant mismatch and would be a good candidate for re cannibalization. On the left is the pink map, demonstrating about 42 mL of infarction. But there's 98 millimeters of tissue at risk for a ratio. Excuse me, there's 140 millimeters of tissue at risk within this MASH ratio of 3.3. This is an example of a patient who would not be a good candidate for re canonization because the area of decreased blood flow and green and the decreased infarction in pink is nearly identical. Okay, so we can use this rapid software to extend the treatment window for patients who have salvageable tissue. And it's particularly useful when the onset is greater than six hours. Um, since the time of their presentation in some studies, there has been a benefit When patients selected using this type of imaging software can be treated even up to 24 hours since the onset of their symptoms, it can also be used to avoid administrating futile or harmful re profusion therapies in patients who already have established large infarction, and it could be used to facilitate transfer and triage decisions. For instance, hospital in the community that may not have availability of those endovascular procedures that I described using the catheters to remove the clot can make decisions about whether it's worth transferring such a patient to a center like USC, where those surgeries can be performed. Lastly, for the medical students and residents in the audience, I just want to remind them that stroke is a neurosurgical disease and I encourage their interest in the research and treatment of this condition, Thank you very much.
