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The Neurotransmitters: Clinical Neurology Education
IM Board Prep #3: Stroke
Hello and welcome to our mini series designed to help prepare internal medicine residents get ready for the neurology section of their board exams!
While it is aimed at IM residents, it is a good review for anyone feeling a little rusty on the classification and management of stroke.
In this episode, we'll be talking about ischemic versus hemorrhagic strokes, the initial evaluation and differences based on etiology, as well as the acute interventions.
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Hello and welcome back to the Neurotransmitters. I am so glad you're joining us today. This is your podcast about everything related to clinical neurology, with the goal of reducing your neurophobia. I'm your host, Dr. Michael Kentris. Today we are continuing our Internal Medicine Neurology Board Review series and our topic today is stroke. Just a brief outline to get us started.
Dr. Michael Kentris :We'll be talking about ischemic versus hemorrhagic strokes, as well as what are the common workup steps at the beginning and how do these things differ based on etiology and how do we figure out what the etiology is for each one of these things going forward, first of all, what do we even mean when we say stroke? So we're typically talking about negative neurologic symptoms, that is to say, the absence or loss of some sort of normal neurologic function, the loss of vision, the loss of strength, the loss of sensation. This needs to be contrasted with positive symptoms, such as someone who might be getting a visual aura with flashing lights during a migraine, or someone with a seizure who is having shaking in one of their limbs. So these are negative versus positive symptoms. So negative symptoms are typically going to be associated with stroke. Not every transient neurologic symptom that occurs that comes into the emergency department is a TIA or a stroke. Now, the word stroke is often used to refer to ischemic strokes which are due to an arterial occlusion in, usually the brain, but could also mean the spinal cord or the retina. Clinically, when we're thinking about stroke in our differential diagnosis we're usually looking for symptoms with a very hyper acute onset. Symptoms coming on over a course of seconds to minutes.
Dr. Michael Kentris :Very much related to ischemic stroke are the phenomenon of TIA or a transient ischemic attack. One thing that is important to remember is that the T stands for transient. So if the person you're evaluating is still having symptoms and it has been more than several hours, it is not transient. These symptoms are ongoing. So, kind of from a practical perspective, we can't really call it a TIA except in retrospect, because if the person is still having the symptoms actively as you are evaluating them, then it is still there. It has not been. Quote unquote transient.
Dr. Michael Kentris :Previous definitions described to TIA as neurologic symptoms lasting for less than 24 hours. Now, however, even if the person's symptoms have resolved, if the MRI of the brain still shows evidence of ischemic injury, we would still call this a stroke. Now, the majority of strokes are ischemic strokes. However, we also use that term for hemorrhagic strokes specifically for two sub types, and that is an intracerebral hemorrhage, or also known as an intraparenchymal hemorrhage, as well as a subarachnoid hemorrhage. So the initial work up for both of these two entities both ischemic and hemorrhagic stroke, look very similar to one another, both present with a patient who has an acute onset of a new neurologic deficit. For ischemic stroke, this is going to be a focal neurologic deficit and for a hemorrhagic stroke, very often we will get some derangement in consciousness, some depressed level of alertness and or a focal neurologic deficit. With hemorrhagic stroke, there may also be a report of a preceding headache, in particular subarachnoid hemorrhage. You may get a report of a quote thunder clap headache, which is a severe and rapid onset headache. Like for all emergencies, abcs are always addressed first if those options show up in a question vignette on a test. After we get to that point, we are also looking at blood work as well as a non contrast CT head, and this will very often be our main divergence point in going down the ischemic versus the hemorrhagic stroke pathway. So we're going to start with ischemic stroke.
Dr. Michael Kentris :As we are getting our imaging, we are also performing an examination right. We are doing an NIH Stroke Scale Score. Now, it is important to remember that an NIH Stroke Scale Score is not a replacement for a neurologic examination. It is a tool to help guide us in terms of what treatments we should be considering for an acute neurologic event that we believe is secondary to an ischemic stroke. Let's go briefly through the NIH Stroke Scale Score and talk about the different components that are involved in it. The NIH SS goes from 0 to 42, with the higher the number meaning, the worse the neurologic examination.
Dr. Michael Kentris :So first off, we have the level of consciousness, that is to say, how arousable is the patient? This is assessed in three parts. The first is just observing how arousable they are, if they are alert, if it takes stimulation to wake them up, etc. You will also ask them two orientation questions their age and the month, as well as ask them to perform two different commands, often times opening and closing their eyes, and or making a fist or closing their hand. Next up, you are checking horizontal gaze, looking to see if there is any restricted gaze or gaze deviation. Now you are looking for visual fields, seeing if there is any visual field loss, whether that is a partial or complete hemianopia. Looking at facial palsy, what is the degree of weakness? And now you are looking at all four limbs, looking at the strength, to see if there is any drift. Ideally, you should be checking each limb independently.
Dr. Michael Kentris :One component that I find often trips up people who are a little less familiar with performing the NIHSS is limb ataxia. So you are doing finger to nose and heel to shin testing and you are looking for coordination issues that are out of proportion to the amount of weakness that you noticed on the previous part of the examination. Now you're looking at sensations, seeing if there's any impairment left versus right. This is followed by a language assessment, although you've ideally been assessing the patient's language the entire time you've been doing this examination with them, but you have them go through some sentences on the NIHSS stroke cards and then you're also assessing some dysarthria after this as well. This is followed, lastly, by checking for any evidence of extinction or inattention. So, as I mentioned before, the NIHSS is not a replacement for a neurologic assessment, and certain kinds of strokes can be missed or scored lower than expected, given the amount of disability they may lead to.
Dr. Michael Kentris :There is a test to get NIH Stroke Scale certified. This used to be free. You can still do it through the AHA for about $10. A lot of institutions that you may work at will usually cover the cost, and I do think it is valuable to at least get the certification done at least once, although the licensing is good for two years afterwards. So, depending on your institution, you may need to do it, and I do recommend that, if you take care of stroke patients especially acutely, that you do go through that certification process. I think it's very educational.
Dr. Michael Kentris :Now, moving back just a little bit, we talked about getting our non-contrast CTs of the head to help us decide if we're talking about ischemic versus hemorrhagic stroke. But one thing we really need to know is the last known normal. When we're talking about ischemic stroke, a lot of our acute interventions are related to last known normal. That is not when was the patient found to have symptoms, but when were they last seen by anyone or able to tell you that they did not have symptoms, and this is a subtle but important difference. Now, if someone is presenting within the time period for an acute intervention and there are two main interventions that we're talking about for ischemic stroke are thrombolytic therapies with either alteplase, tpa or tenectaplase in many places TNK, and that is typically three to four and a half hours from last known normal. Our other main treatment is endovascular therapy for mechanical thrombectomy and that can potentially be up to 24 hours from the last known normal. Very often the non-contrast CT head for an acute stroke will be normal and that's fine. We're really looking to rule out other causes and intracranial hemorrhage for the symptoms.
Dr. Michael Kentris :In some cases there may already be an area of hypodensity on the CT scan, in which case you do question the timeline a little bit. But there is one scoring system called the ASPEC score or the Alberta Stroke Program Early CT score. This is a 10-point score and it essentially assigns one point to different areas of the middle cerebral artery or MCA vascular territory. So a normal score is 10, and the lower the score gets, the more area of tissue in the middle cerebral artery territory is suspected to already be infarcted. In many institutions, when someone comes in as a stroke alert or a code stroke or whatever the terminology may be at your particular institution we will often be getting CT angiograms of the head and neck as well. In particular we're getting these on people who have an NIH Stroke Scale over four, sometimes six. Again, it depends a little bit. One thing that I do want to emphasize is that I'm recording this in February of 2024, and some of the things that are being tested on internal medicine in service exams and things like that are already out of date. So some of the things we're discussing may not be 100% applicable to actual clinical practice. So do keep that in mind as we talk and I try to include those caveats as they come up. But anyway, back to CTAs. So we're usually getting these on folks who have at least an NIH of four to six. We're looking for large vessel occlusions or LVOs. These are the patients who will be a candidate for mechanical thrombectomy or endovascular therapy, and we'll talk a little bit more about what LVO means for the test and also, hopefully, in real life.
Dr. Michael Kentris :The other primary reason to get a CTA of the head and neck is if you do see evidence of subarachnoid blood on that initial non-contrast CT head, you're going to want to look for an aneurysm as a potential source. Let's take a hypothetical patient. Let's say we've got a person who comes in. They have aphasia, they have right-sided weakness, they have an NIH that is high enough and you are talking about thrombolytic therapy with either the patient or the patient's representative and you find out they are within an hour of onset of symptoms. They have no contraindications, or so you think. But let's run through. What do we need to make sure is not happening so we can safely administer thrombolytic therapy to this person? After making sure that they are definitely within the last known normal time limit of four and a half hours, we get our non-contrast CT of the head and we make sure there is no intracranial hemorrhage, there is no bleeding. We also make sure there is no active bleeding anywhere else and they have no bleeding diathesis.
Dr. Michael Kentris :Other possible contraindications that we want to think about. I think a good way to categorize these isn't the four different camps. We have one historical contraindications, two clinical contraindications, three imaging contraindications and four laboratory contraindications. In the history, things that might be possible contraindications to giving TPA or TNK is if the person has a history of intracranial hemorrhage and the etiology the situation, how recent. All of these things do matter in that consideration. Have they had a stroke or serious head or spinal trauma in the last three months? A prior large stroke in the last few months is something that can definitely increase the risk of bleeding. Have they had major surgery? This includes cardiac, thoracic, abdominal or orthopedic surgery in the last two weeks? Have they had a recent arterial puncture at a non-compressible site in the last week? So you do want to ask about all of these things, if you're able to get that information, to reduce your risk of having complications.
Dr. Michael Kentris :If you administer thrombolytics, potential clinical contraindications If the patient comes in with symptoms suggested of a subarachnoid hemorrhage. In rare cases patient may have a thunderclap headache but there may not be any blood noted on the initial CT head, in which case we're often talking about doing a lumbar puncture to check for xanthochromia in the spinal fluid, in which case, if you're doing an LP, you definitely shouldn't be giving any thrombolytic therapy. Another possible contraindication could be that you suspect the symptoms are due to another etiology, a non-stroke etiology such as seizure with post-dictal paralysis, a post-dictal tons paralysis, or perhaps there's a significant metabolic arrangement, like severe hyper or hypoglycemia. That might be an explanation for the symptoms. Similarly, hypertension that is refractory to aggressive treatment, such that we can't get the blood pressure below 185 over 110. Significantly elevated blood pressure can also cause neurologic symptoms. Lastly, is the patient currently taking a direct non-vitamin K oral anticoagulant Think of a pixaban, river, rocksaban, debigatran, etc. Although, again, as we said earlier, these guidelines are changing and there are some papers that are coming out at this point in time that suggest that might be changing in the future to a relative contraindication as well. Again, not set in stone, but things to keep an eye out for in the literature.
Dr. Michael Kentris :Our next category imaging. I mentioned this briefly with the aspect score earlier. But if the CAT scan is already showing early signs of extensive stroke, then again you do have to wonder first, is your timeline that you received from the patient or the patient's family or whomever, actually accurate? And two, is the risk of symptomatic intracranial hemorrhage after giving thrombolytics higher than it would be? The short answer is yes, it probably is, and you do have to talk about that as a possible risk.
Dr. Michael Kentris :Our fourth category laboratory values. We always want to check in INR and in APTT. If the INR is over 1.7, that is a contraindication. If the platelets are less than 100, also a contraindication. If the patient is significantly hyper or hypoglycemic, also a contraindication.
Dr. Michael Kentris :Another phrase that you might run into amongst the contraindications is minor or non-disabling or rapidly improving symptoms. So what do we mean by disabling versus non-disabling stroke symptoms? These have a definition, but they are somewhat malleable in practice, I would say so. Disabling symptoms are considered to be a complete hemianopia, visual or sensory extinction, weakness against gravity in any limb, that is to say, a score of 2 through 4 on any of the limbs, or a total NIH stroke scale of over 5. Again, another caveat here as the NIH SS is weighted towards anterior circulation territory strokes, if you have a high suspicion for a stroke and the patient is otherwise a candidate, consider walking them. If they are unable to walk, that is also considered disabling. I would also consider aphasia to be a disabling deficit.
Dr. Michael Kentris :Now, we just went through a lot of hoops to talk about who should and should not receive acute thrombolytic therapy for stroke. Now, the reason for that is that we want to very clearly define who are the people who are most likely to benefit from it, and we're really talking about it in terms of a risk-benefit balance. So there are some studies out there, for instance, comparing loading with dual antiplatelet therapy like aspirin and clopidogrel versus things like alteplase. The most recent one is the Aramis A-R-A-M-I-S and patients with minor, non-disabling acute ischemic stroke presenting within 4.5 hours of symptom onset. The dual antiplatelet therapy was non-inferior to IV-TPA with regard to, quote, excellent functional outcome at 90 days, end quote. So if we're going to give a medication we should probably know the risks.
Dr. Michael Kentris :The main risk that everyone always thinks about with thrombolytic therapy is intracranial hemorrhage. So there is an approximately 6% risk of symptomatic intracranial hemorrhage. Those who are at higher risk are those who have a large stroke, that is, a high NIH SS or a low aspect score at presentation, older age, hyperglycemia and uncontrolled hypertension. There is also, in addition to the risk for symptomatic ICH, a risk for angioedema about 1.3% and anaphylaxis about 0.5%. Thank you, if someone does receive thrombolytic therapy, we want to maintain their blood pressure less than 180 over 105. We are going to avoid anti-platelets and anti-covalculation for the first 24 hours. We are going to get repeat head imaging, either a CT of the head without contrast or an MRI of the brain around that 24 hour mark before starting any anti-platelets or anti-covalculation. And they will be admitted to an ICU and there they'll be getting frequent repeat NIHs and very often hospital protocols may differ slightly but an NIH Stroke Scale Score increase of 4 points or more typically leads to repeat stat head imaging. Similarly, if they have other symptoms worrisome for an acute intracranial hemorrhage, like Nuonset headache or other new neurologic deficits. That also tends to prompt repeat head imaging at that point in time.
Dr. Michael Kentris :For patients who underwent CTA of the head and neck and there is evidence of a large vessel occlusion, they are potential candidates for endovascular therapy slash mechanical thrombectomy. So what is a large vessel? So typically we consider it to be the internal carotid artery, the M1 segment of the middle cerebral artery, or MCA. In real life, most of the neuro-interventionalists that I know will pursue other vessels. So these are kind of old data, but this is what shows up on the test in some cases for the IM in-service exam slash boards. So we do want to think about the M2 segment. That's the next smallest. And then there are papers supporting the use of mechanical thrombectomy in posterior circulation strokes, most notably in basilar occlusions. In reality it is often a question of the patient's anatomy how disabling the symptoms are, which vessels are blocked. Is that going to eloquent cortex, non-eliquent cortex? So it is not as algorithmic as we tend to think of stroke being, and there are a lot of considerations that need to go into deciding who is a good candidate For those who are not a candidate for acute therapy with thrombolytics or endovascular therapy.
Dr. Michael Kentris :What can we do to medically manage and optimize these patients for future recovery and stroke prevention. For those with TIA or minor slash non-disabling stroke, typically we will load with dual anti-pallet therapy and this is often continued for 21 days, potentially up to 90 days if the stroke etiology is found to be secondary to symptomatic intracranial stenosis. For the first 24 hours after onset of symptoms we will also allow permissive hypertension. This is often up to 220 over 120, unless there is evidence of other end-organ injury things like kidney injury or other abnormalities on blood work or examination.
Dr. Michael Kentris :One of the most important parts of the stroke evaluation is the etiology. After we've gotten through all of the acute decisions, we need to figure out why did the stroke happen in the first place. So there is a framework that talks a little bit about this. This is an older paper and these are often referred to as the toast criteria or the toast categories. And what does toast stand for, you might ask. It stands for the trial of ORG10172 in acute stroke treatment, or toast Toast is easier. So the main categories are large artery atherosclerosis, cardioembolic, small vessel occlusion, stroke of other determined etiology. This includes things like dissection or vasculitis, and then stroke of undetermined etiology. You'll see this sometimes referred to as, in particular, embolic stroke of undetermined source or ESIS. So that's a specific subtype of stroke of undetermined etiology.
Dr. Michael Kentris :The MRI of the brain can be very helpful for us in determining if this looks more like an embolic type of stroke or if this is a small vessel ischemic-related stroke and other types of things. The pattern of ischemia on the MRI brain can be very helpful in directing our search more intensively. If we don't have someone with poorly controlled diabetes, hypertension, cholesterol, stariness in the face that we say, oh well, we've got all these reasons for having a stroke. But it is when we don't have these well-described risk factors in a certain patient and we do have an unusual-looking stroke on MRI that we need to think about these less common etiologies. Looking at lacunar strokes, these are our small vessel ischemic-disease-related strokes. Classically they are often in areas that are supplied by small penetrating vessels think the thalamus internal capsule, the deep structures in the brain, the pons, the cerebellum, those types of areas. They are the areas essentially that have the classic lacunar stroke syndrome associated with them pure motor, pure sensory, sensory motor, et cetera. Poorly controlled hypertension is going to be our main risk factor here. Other conditions do also play a role, including diabetes, hyperlipidemia and a smoking history.
Dr. Michael Kentris :Another important etiology for stroke is large artery atherosclerosis, sometimes referred to as an artery-to-artary embolism. The classic example of this would be carotid stenosis. So if it is a symptomatic carotid stenosis, the risk of recurrent stroke can be up to 26% within the next two weeks after the initial event. If they have 50 to 99% stenosis of that carotid artery on the side of the stroke, then it's worth discussing risks and benefits with carotid endoderectomy versus stenting, although those who see the most benefit have over 70% stenosis. If in the course of your workup you find asymptomatic stenosis, that is to say the carotid is stenotic on the side that the stroke is not and it's over 60%, you might look at some of the high risk factors of the plaque in terms of morphology, location etc. And not just the degree of stenosis, and that becomes a bit more of a discussion. In that situation A cardiomebolex source of stroke is often suspected when you get the MRI back and you see multiple strokes in different vascular territories, whether that's left versus right hemisphere and tear versus posterior circulation etc.
Dr. Michael Kentris :Any combination thereof. So you have to think back where's the common point for this single source? So a cardiomebolec ideology. You need your echocardiogram, you want a bubble study so you make sure, if there's a patent for any amount of val, that you go check for a DVT and you do have to maintain a high clinical degree of suspicion based on the clinical presentation.
Dr. Michael Kentris :If you catch atrial fibrillation while the patient is on cardiac telemetry in the hospital, great, you have your answer. If not, then we would usually recommend outpatient long-term cardiac monitoring. Whether that is invasive, non-invasive, you do need to continue monitoring to see if you can capture that atrial fibrillation or other potential cardiac arrhythmias. If we have done a thorough workup for an embolic source and we have come up without any evidence of atrial fibrillation, we refer to this as ESIS, an embolic stroke of undetermined source. These patients are not routinely recommended to be on anticoagulation. This has been studied multiple times and it is suspected that the patient is more heterogeneous than we think and anticoagulation does not benefit these patients across the board.
Dr. Michael Kentris :As we keep going, I just want to remind everyone this is not an exhaustive stroke review. These are things that are most likely to show up on the IM boards and in-service exam. That being said, let's move on to hemorrhagic stroke. So let's start with ICH or, as I like to think about IPH intraparenchymal hemorrhages. So our main goal with the initial management is to reduce expansion of the hematoma and one of the main ways we do that is by reducing systolic blood pressure. Our goal is typically less than 140.
Dr. Michael Kentris :And we do want to make sure that we have identified an etiology. Very often these patients are going to have these bleeds due to uncontrolled hypertension. If they come in with normal blood pressure, you got to go looking for a different etiology. So things to think about Metastatic disease, cerebral venous sinus thrombosis, cerebral amyloid angiopathy or hemorrhagic transformation of an ischemic stroke those are the kinds of things that you want to be thinking about and very often you will have some kind of history in the vignette that will point you in that direction. So metastatic disease they should be undergoing treatment for some other kinds of cancer Cerebral venous thrombosis very often it's going to be a young woman, maybe on birth control, maybe a smoker. Cerebral amyloid angiopathy this is going to be a more elderly person and it will be a non-traumatic bleed. Starting these patients on preventative anti-seizure medications is somewhat debated. There is some limited evidence supporting it. There is some saying it makes no long-term difference. So it really does depend on the situation.
Dr. Michael Kentris :Our last entity that we're talking about today is subarachnoid hemorrhage. So the most common cause of subarachnoid hemorrhage is trauma. Now they will try and trip you up with this sometimes, but the most common cause of non-traumatic subarachnoid hemorrhage is aneurysm rupture. Again, just like with any other neurologic emergency, we do want to make sure ABCs are addressed first, after that our goals. We want to make sure for a ruptured aneurysm with subarachnoid hemorrhage that we are keeping that blood pressure systolic under 140. After an aneurysm is identified on CTA. Or if there is a subarachnoid hemorrhage and no aneurysm is identified on CTA of the head, they will typically be going to the IR suite for an angiogram for better resolution, imaging and, if possible, securing of that aneurysm, either endovascularly with coiling or, if it is not anatomically predisposed towards it, with an open craniotomy and potential clipping.
Dr. Michael Kentris :There are numerous complications that can come along with subarachnoid hemorrhages, and they do tend to have a prolonged course in the ICU, sometimes up to two or three weeks. So these patients do require close monitoring. So first of all, there is an entity called delayed cerebral ischemia, or more colloquially known as vasospasm, and so these patients are often placed prophylactically on nemotapine to prevent this. In severe cases they may need to go back to the IR suite for potentially intra-arterial or balloon angioplasty of certain vessels to avoid stroke associated with the subarachnoid hemorrhage. Seizures are also a possibility.
Dr. Michael Kentris :All patients prior to aneurysm securing are placed on preventative anti-seizure medication and, depending on the clinical context, this may be continued further down the road as well. Re-bleeding is obviously a concern, especially if there is an unsecured aneurysm or if no aneurysm was found on even the catheter angiogram. So that is something to keep in mind and why such an emphasis is placed on blood pressure and preventative anti-seizure medications, as during a seizure, especially a tonic-clonic seizure, spikes in blood pressure could potentially worsen any intracranial bleeding. Lastly, two entities that you do have to keep an eye out for with intracranial hemorrhage, particularly subarachnoid hemorrhage, are SIADH and cerebral salt-wasting. These can look similar in some situations, but it is really beyond the scope of what we're aiming at today to dive into that particular problem.
Dr. Michael Kentris :That is all I have for you today. If you enjoyed this podcast, please make sure to leave us a five-star review on Apple, spotify or wherever you are getting your podcast, and make sure to subscribe for future episodes. You can find me on X, formerly Twitter, at Dr Kentris. That's D-R-K-E-N-T-R-I-S, and you can find the official show at Neuro_ Podcast. You can also find us at our website, theneurotransmitters. com, for the rest of our resources. Thank you again for listening and we'll see you next time.
