Good day, everyone. I am Hannah Noblesa, the medical director of the Neurocritical Care Service in Baptist Memorial Hospital. I'm here to discuss with you the second part of acute ischemic stroke. I have no disclosures. My objectives for today are to apply the current concepts in the assessment and therapy of acute stroke as it applies to emergent neurocritical care, to describe the concepts of multisystem care for the critically ill stroke patient, and to discuss how neuroimaging can play a role in acute stroke therapy. This slide gives you an overview of the general principles of acute stroke care from the initial stabilization to prepare the patient for potential salvage therapy with thrombolytic and or endovascular therapy, then subsequent supportive care by managing other medical issues and preventing another stroke and continuing etiology search, and then eventual recovery and return to community. Cold stroke or cold brain in some centers is the general alarm used to facilitate processes to enable the fastest way to achieve stroke therapy to restore blood flow, to save the salvageable tissue of the brain. These are the general time points as targets for any stroke that comes in the ER. So for example, the acceptable door to CT scan interpretation is less than 45 minutes. It can be sooner, but for the purpose of your boards, they may ask what is ideal door to groin time or door to needle time, and these are the time points specified here. Let's briefly go through a case. We have a 52-year-old African-American male with a history of hypertension, diabetes, not on any medications, complaining of slurred speech with left facial weakness, and his last known well was two hours ago. So cold stroke was called. His neurologic exam is as follows. The NIH stroke scale score is 17, and as you can see, we have a patient with a right MCA syndrome, so he was awake. He was following commands, but he has dysarthria. He had some sort of left-sided neglect. He had a right gaze preference. He had left homonymous hemianopsia, left facial droop, left-sided weakness, and decreased sensation on the left. In any acute stroke patient, the general management approach is as follows. First, you call for help. Do not try to manage a cold stroke alone. Next is to make sure that you assess and secure airway, breathing, circulation. And then next is to quickly go over the last known well, and then go through your considerations for acute stroke therapy and other information so you quickly get the history, especially the last known well or the symptom onset. And then sometimes you will have patients that would have awakened at night. You might want to clarify, did the patient wake up with symptoms, was the patient doing something normally, and then was witness to have a stroke syndrome, or it was an unwitnessed event and the patient is able to tell you that I was able to walk, I was feeling normal, I went to the bathroom, and when I went back to bed, that's when the symptoms start. So you have to still clarify the timing. And then you do a physical exam using the NIH stroke scale, and then get a point of care glucose, subsequent neuroimaging, mainly a CAT scan of the head. And some centers automatically would get a CT angiogram along with a CAT scan. But take note here that a CT scan, a non-contrast CAT scan is enough to decide on thrombolytic therapy. So you do not, if you're having IV access for contrast, if you're having contrast issues, like you're still sorting out what the allergy to contrast is, don't delay giving IV thrombolytic just because of the delay for the CT angiogram. So you decide with regards to your acute stroke therapy, whether you're going to use IV TPA, with or without considering endovascular therapy, and as appropriate, colon or neurosurgery or endovascular colleagues. The disposition, typically, if they undergo any stroke intervention, is the neuro ICU. So this slide is the components. This slide shows the components of the NIH stroke scale. This scoring system describes the severity of the stroke. Studies have also used this as an outcome measure, but see here that the higher the score is, the worse it is for the patient. This is the modified Rankin scale, and this gives you an idea of the functional outcome of the patient, and studies have used this to indicate that. And the higher it is, the worse the functional outcome is for the patient. Very important main consideration before proceeding with stroke therapy is the blood pressure. So the goal is, before giving IV thrombolytic, it should be less than 185 mmHg for the systolic blood pressure goal, and the diastolic blood pressure goal before giving IV thrombolytic is less than 110 mmHg. And there's no specific recommendation as far as the medication that you're going to use for blood pressure control before IV tPA. The AHA guideline mentions these options and the doses. So this patient's last onset of symptoms is less than four and a half hours, and it is shown here that the patient is a candidate for thrombolysis and mechanical thrombectomy. Note also what the imaging is required for this time period. These were prior contraindications for IV tPA, which are no longer considered absolute contraindications. So take note of these just in case this come out in your exam as a problem. Patients greater than 80, you can still consider them for alteplase and thrombectomy. Mild improving symptoms can still be considered, depending on the disability. After administration of thrombolysis, one has to be prepared for possible complications such as post-alteplase angioedema. If angioedema develops, you will still need to reassess ABCs again, your airway, breathing, and circulation, and administer the appropriate medications as per recommendation. Also we will give methylpred, nisalone, lefenhydramine, we stop the alteplase infusion, we hold any ACE inhibitors, and proceed with supportive care. One of the possible devastating effects of thrombolytics that we closely watch for is symptomatic intracranial hemorrhage. So here if there is any acute change in the patient's examination, if there's an acute deterioration, typically we will stop the alteplase infusion and rule out bleed. And if you see that there's a bleed and the deterioration of the patient can be attributed to that bleed, so that's a symptomatic intracerebral hemorrhage. And you will not need to wait for a fibrinogen level, you can already infuse cryoprecipitate 10 units, and then depending on your fibrinogen level result, you can re-dose it. Depending on your center's protocols, you can add tranexamic acid, and then the subsequent consultations for the intracerebral hemorrhage. You will continue supportive care including blood pressure management, and as applicable if there is a component of intraventricular hemorrhage, you will need to consult neurosurgery for possible EVD placement. Since our patient is still at the window for endovascular therapy, we will consult the endovascular neurology. Here we can see where the occlusion is in the other corresponding blood vessels, just to review your anatomy, you can see here this is the ACA, this is the occlusion, in the right MCA territory, this is the left MCA, this is the basilar artery, the PCA, or the posterior cerebral artery, and these are the vertebral arteries. So let's say for this patient that the symptoms now started with a last known well of 5 hours ago, same patient, but the last known well was 5 hours ago. So the patient still qualifies for acute stroke therapy, but now your only option is endovascular therapy. So now for the same patient, we will move the last known well to 6.5 hours ago. So at 6.5 hours from last known well, take note that you will need perfusion imaging in addition to your vascular imaging to move forward and decide on acute stroke therapy. I just wanted to show here some of the landmark stroke trials that led to the guidelines that we have today. So I just wanted to go over some of the terminologies that you might encounter in your case vignettes for the board. So namely the Alberta Stroke Program Early CT Score, or ASPEX, Penumbra, Core Infarct, Perfusion Imaging, and Concept of Mismatch. So ASPEX is just a topographical scoring system based on a score of originally TAN, and for every area that is hypodense, here in pre-specified areas of the CAT scan, you will subtract one point from TAN. So the lower the ASPEX is, the higher area of stroke that's present. So it divides, as you can see, it divides the area of the MCA into 10 regions of interest and it correlates inversely with the NIH Stroke Scale. So this patient has an ASPEX of 10, meaning that there are no obvious areas of hypodensity or stroke, which may make this patient qualify for acute stroke therapy. So the typical threshold for endovascular therapy, for example, the ASPEX score should be more than 6. Now briefly on perfusion, when there's an occlusion of the artery, we would expect that there is a decrease in blood supply, which leads to tissue hypoperfusion of the area supplied by the occluded blood vessel. So that's the stroke. This decrease in cerebral blood flow is typically less than 10 cc's per 100 grams per minute of brain tissue, and that's a severely hypoperfused tissue, and that will become the core infarct. Imaging software, I'll show you later, define their threshold at less than 30 cc's most commonly. So this area is non-salvageable. So this area would die, would infarct regardless of reperfusion. So this is the core infarct. And then surrounding this brain tissue is what we call penumbra or tissue at risk. That is getting cerebral blood flow of about 20 cc's per 100 grams per minute, which is a critical hypoperfusion threshold. This penumbra is the potentially reversible area that has not infarcted yet. But with time, that's the area that will be at risk for becoming a core infarct. So if reperfusion does not happen, this penumbra area can become a core infarct. Surrounding the penumbra is the area undergoing benign oligemia. So no infarct risk, but there is some decrease in blood flow. So here, the infarct core is the tissue that's no longer salvageable. Typically, the threshold that's used now for studies in most centers is a decrease in cerebral blood flow of less than 30%, so the volume of tissue that has this decrease in blood flow. So that's the infarct core. And this typically corresponds to the area of restricted diffusion on MRI. The penumbra is a salvageable tissue. And you subtract the infarct core from the total hypoperfused area, which is typically shown as an area with a Tmax of greater than six seconds. The mean transit time is the time in seconds for blood to move from arteries to capillaries to veins. And it indicates a vasodilatory response to a decrease in cerebral blood flow. So Tmax represents a delay of arrival of contrast bolus, so that area where there's a delay in contrast bolus. And we talked about the cerebral blood flow. And then the cerebral blood volume actually indicates the percentage of blood vessels in a specific volume of brain tissue. And there's blood vessel size changes that is reflected by this because of water regulation. So just to reiterate the relationship of those parameters when it comes to penumbra and infarct core. So for infarct core, you will see an increase in the mean transit time in severely decreased cerebral blood flow and cerebral blood volume. Compared to in penumbra, you will see a decrease in cerebral blood flow, not as much as the infarct core. But as a compensatory response, if the patient can still auto-regulate, there is a normal or mildly increase cerebral blood volume. And you can see the Tmax and time to peak are also delayed. So this is an example of an automated post-processing software output. So just looking here at A, you can see that the core infarct, which is the volume of brain tissue that is receiving less than 30% of cerebral blood flow is 26 cc's, while the volume of brain that has a Tmax of greater than 6 seconds is 181 cc's. So the mismatched volume between Tmax and the core is 155 cc's, and this is the area of penumbra, and the mismatched ratio is 7. So this is the mismatched volume, which is the difference in volume, and mismatched volume is typically our penumbra, and this is the mismatched ratio. So, while CTP is very helpful, we have to be mindful of these various limitations for the CTP. So note that for the posterior circulation, it is less helpful due to artifact, we usually don't use that for lacunar strokes, and then variable, there are variable findings for other stroke mimics. If there are issues with CT contrast, MR perfusion is another option. So there is limited availability, more contraindications, so these are some of the disadvantages of an MR perfusion, but that is an option. So what if we have a left MCA syndrome with a last known well of greater than 6.5 hours? So this is another example of the perfusion imaging for that patient with a left MCA syndrome. This is showing approximately 30% core infarct involved in the posterior left MCA distribution, with penumbra at risk involving about 70% of the left MCA territory. So the CTP was done along with a CTA for that patient, and based on the CTP and the vascular surgery was consulted for thrombectomy. So this slide enumerates the eligibility for mechanical thrombectomy from 0 to 6 hours. Note that the laterality of the stroke is not part of the criteria. Take note of the aspects of greater than 6, NIH of greater than 6, and trials were only done for adults, so this is the reason why it's greater than 18 years old. And I just want to go over some of the other stroke therapy considerations listed here. Take note that osmotic therapy should only be reserved for patients with clinical deterioration and not for prophylaxis. Our general criteria for consideration of decompressive craniectomy are as follows. So note again that laterality is not specified. So less than 60 years old, there's a neurologic deterioration that happened. Usually it's within 48 hours that the patient can be considered. And there's a unilateral MCA infarction despite medical therapy. Cerebellar infarctions with deterioration will need a suboccipital craniectomy regardless of maximal medical therapy. And although more recently EVDs or ventriculostomies can be used as a temporizing measure for hydrocephalus, but typically this is done with a subsequent decompressive craniectomy. There is no role for induced hypertension prophylactically as well as no known benefit of hypothermia for stroke patients. And IV tenecteplase can be a thrombolytic consideration with the same precautions and indications for acute stroke. And one of the main advantages of it is the administration as a single bolus from a process standpoint. And this is our typical dose is 0.25, 0.25 milligrams per kilogram. And then for pregnancy, without absolute contraindications such as an overt massive bleeding, you should still consider IV thrombolytic. And pregnancy is not a contraindication for endovascular therapy. There's no need for seizure prophylaxis for patients with ischemic stroke. And then this slide just shows you, and I just want to remind that for every stroke, for any stroke patient that we see, we have several multisystemic clinical issues that we still have to consider that they can present with in addition to having an ischemic stroke. So our ischemic stroke patients can have an MI. Your vignettes can have a patient with atrial fibrillation as well at the time of stroke presentation. We have to be considering aspiration precautions and other risks for infection. And here, I just want to make everyone aware of certain goals or parameters that we have to consider for our stroke patients such as a glucose target of 140 to 180 milligrams per deciliter. Avoid hypoglycemia. Our blood pressure goals for patients who have received IV tPA is 180 over 105. But before giving IV tPA, it's 185 over 110. We don't give prophylactic oxygenation or supplemental oxygen unless they need it. The goal is oxygen saturation of 94%. We treat fever. Again, no rule for prophylactic hypothermia. And then involve a multidisciplinary team for management of the patient. In summary, there are available acute stroke therapy depending on the time from last known well. Imaging has a very important role to help determine the stroke therapy management that we're going to use for the patient. And for every stroke patient, we also have to be prepared to manage other potential complications as well as other multisystemic ICU issues that can come along the way. Thank you and good luck with the boards. Thank you.

acute stroke

assessment

therapy

neurocritical care

infarct core

penumbra regions