Hello, everyone. My name is Shraddha Mainali. I'm an Associate Professor of Neurology and the Director of Clinical Research for the Division of Stroke and Neurocritical Care at the Virginia Commonwealth University. I have no relevant disclosures related to this presentation. At the end of this presentation, viewers will be able to learn about the neurovascular anatomy, learn about the pathophysiology of ischemic stroke, learn about etiology-based classification of ischemic stroke, and learn about the management of malignant cerebral edema. So let us get started with the cerebrovascular anatomy. But before we get there, let's look at this case here. This is a case of a 65-year-old female who presented to the emergency department with right facial droop, right arm and leg weakness. She was aphasic and had left gaze preference. She had a stat CT head in the emergency department, which looks like this on the right-hand side. What you can see here is this very bright and prominent hyperdensity within their left middle cerebral artery, indicating acute thrombus within the artery. So this patient had a left middle cerebral artery occlusion. Now, let us take a look at the anterior circulation to the brain. So here you have your aorta that gives rise to brachycephalic trunk, which divides into right common carotid and right subclavian. Then comes your left common carotid and then your left subclavian. And this is one of the most common types of anatomy that you can find in people. And the right common carotid or both common carotid arteries divide into the internal carotid artery and the external carotid artery. Now, how do you differentiate internal from the external? The external carotid artery has discernible branches like these within the neck, whereas internal carotid artery does not have any discernible branch in the neck and the first branch is inside the head, which is the ophthalmic artery. Now, let's take a look at the course of the internal carotid artery. So your internal carotid artery can be divided into seven segments, the cervical segment or the C1, then you have your petrous segment or the C2, the lacerum segment that courses across the form and lacerum or C3, then you have the cavernous segment or C4, then comes the clinoid segment. And from here on, it becomes intradural, that's the ophthalmic segment and the first discernible branch would be the ophthalmic artery. And then it finally terminates into the terminal or the communicating branch, which further groups rise to your posterior communicating, your anterior coroidal, ACA and the MCA branches. Let us now look into the posterior circulation. So the subclavian artery, the proximal portion of that artery gives rise to the vertebral artery here. And as you can see, the vertebral artery has four components, B1, which is the preforminal component, where the vertebral artery arises from the subclavian, then around C6, the foramen of the transverse process of C6, it enters the foramen of the transverse process, courses vertically up towards the transverse process of C2, and it exits that and up till that is the V2 segment. Then you still have the extradural segment, which is the V3, which has a vertical component, which kind of loops around the transverse process off the C1. And then there's a horizontal component, which goes posterior immediately. And then it goes in, crosses the atlantoaxial membrane into the, to become the intradural segment or the V4 segment right here. So where both vertebral arteries join to form the basilar artery, as you can see here, the right side and the left side from the basilar artery. So what are the branches of the vertebral artery? Of course, there's some muscular branches in the neck, but before it joins to form the basilar artery, you can see the posterior inferior cerebral artery coming off here. It can also give rise to the anterior spinal artery. There's other some branches to the medulla as well as meninges from the vertebral artery. Then comes the basilar artery. The anterior inferior cerebellar artery comes off of the basilar artery. There are multiple branches or the perforating branches of the pons here. And then you see the superior cerebellar artery on either side. Then comes the posterior cerebral artery, which is a terminal branch of the basilar artery. And you can see the posterior cerebral artery on either side is connected to the anterior circulation by the posterior communicating artery, which is a branch of this internal carotid artery. This is the internal carotid artery. This is the middle cerebral artery here, anterior cerebral artery. And you see how all these arteries together form the circle called the circle of Willis. Here we just have a slice of the coronal section of the brain, but this basically gives a picture of the arterial supply of the brain. So the medial frontal region is supplied by the anterior cerebellar artery. The lateral frontal parietal and the superior temporal region is primarily supplied by the middle cerebellar arteries. The inferior temporal region is supplied by the posterior cerebellar artery in addition to the occipital region, which you don't see here. The deep branches of the middle cerebellar artery supplies the caudate, the putamen, posterior limb of the internal capsule, primarily basal ganglia region. The anterior coronary artery supplies the hippocampus, perihippocampus area here, as well as part of the posterior limb of the internal capsule, and further goes on to supply the choroid plexus. The thalamus is primarily supplied by the deep branches of the posterior cerebral artery. Let us quickly review the infertentorial supply. This is your cerebellum here. As you can see, the branches from the vertebral artery, the pica, supplies the inferior cerebellar region here, posterior inferior cerebellar region. The ica, or anterior inferior cerebellar artery, supplies the anterior and part of the inferior cerebellar region. The superior cerebellar region supplies primarily the vermis and the superior cerebellar region. Here we have this table to go over the deep territories of the cerebral arteries. The lenticulostride artery branches off of the proximal portions of the ACA, which is the medial lenticulostride artery, and the MCA, which is the lateral lenticulostride artery. They basically supply the putamen, the globus pallidus, internal capsule, head of the caudate, the anterior choroidal artery. As we saw before, it supplies posterior limb of internal capsule, posterior paraventricular coronary adiata, supplies the choroid plexus, supplies hippocampus, parahippocampus, and also supplies a portion of the optic tract. There are the thalamal perforators, which the anterior thalamal perforator comes off the posterior communicating artery, and the posterior thalamal perforator comes off the proximal portion of the posterior cerebral artery. They supply the posterior part of the internal capsule, posterior thalamus, hypothalamus, subthalamus, the substantia nigra, the red nucleus, oculomotor nerve. It supplies the trochlear nucleus, reticular formation, the pretectum, and the rhomboid fossa. The artery of percheron, it's an anatomic variation where there's a common branch, one branch arising from the proximal portion of one of the PCAs, which then divides into two branches and supply bilateral medial thalami. So when you have a clot in that one artery, both medial thalami and often the rostral midbrain is affected. It's a very typical appearance of acute bilateral thalamic with some involvement of the rostral midbrain stroke, and you want to suspect an artery of percheron infarction in that case. The thalamogenic late arteries are other deep branches from the posterior circulation, which arises from the second portion of the posterior cerebral artery, or the P2 segment, and it basically supplies the geniculate nuclei, the medial and the lateral, as well as the pulmonary nuclei of the thalamus. The medial and lateral posterior choroidal artery also comes off the second segment of the posterior cerebral artery, and basically is responsible for supplying the quadrigeminal plate, the pineal glands, the portions of the thalamus, hippocampus, perihippocampus, etc. We've talked about the vascular supply of the brain, the anterior circulation, posterior circulation, the subcortical regions, as well as the infertentorial or the cerebellar vascular supply. Now let's look into the watershed infarctions. The watershed infarctions are also known as the border zone infarct, where the infarction happens in the area or the border between the two vascular territories. For example, right here is the border zone between the anterior cerebral artery and the middle cerebral artery. Here, this is the border zone between posterior cerebral artery and the middle cerebral artery. And the external infarction, the cortical infarction, are usually a wedge-shaped infarction in between these major vascular territories. There can also be a white matter, paramedian white matter infarction, and these are the border zone areas between anterior cerebral arteries and the middle cerebral arteries. The internal or the subcortical infarcts are basically between the perforating branches, such as the lenticular striate, with one of the cortical branches, such as the middle cerebral arteries, or the lenticular striate and anterior cerebral arteries, or the hubnar artery and anterior cerebral artery, or the anterior corridor artery or branch of the internal carotid artery and the middle cerebral arteries, or the anterior corridor and posterior cerebral arteries. Now that we've talked about the vascular supply of various areas of the brain, we can localize lesions. We can understand what vascular supply or what area of the brain or what vessel might be affected based on this understanding. However, there are certain limiting factors, such as anatomic variations between individuals, the neurocircuitry involved in stroke. The same function can be affected in various anatomical locations as the neurons in the white matter tract pass from the cortex to the basal ganglia, brainstem to spinal cord. Further, some people may present with symptoms that are greater than their actual core infarct than their actual core infarct because of the effect of the penumbra, which may eventually become normal in patients with good collateral, or those who receive reperfusion therapies. But regardless, large vessel occlusions typically produce more severe symptoms, and small vessel occlusions or lacunar strokes usually have smaller or minor symptoms with lower NIH stroke scales. Now that we have talked about the cerebrovascular anatomy, let's look into the pathophysiology of stroke. But before we begin, let's look at this case of a 70-year-old male with history of atrial fibrillation, hypertension, congestive heart failure, or CKD, represented with right-sided weakness, numbness, aphasia, and left eye deviation. This on the left of the screen is your CT head. You can see this large area of hypodensity in the left MCA territory. This is the MRI brain with corresponding infarction and the diffusion-weighted images. So why does this patient have infarction? What happens at the pathophysiological level? So as you know, brain is about 2% of the body weight, but it consumes about 20% of the total oxygen consumption. And about 70% of the metabolic demands of the brain is basically utilized to drive the sodium-potassium ATPase pump, which is important to maintain our neuronal membrane potential. As soon as the ischemia begins, within two minutes, there's decreased ATP production, which ultimately leads to ATP depletion. And that leads to membrane depolarization, influx of calcium and sodium, as well as efflux of potassium, which is followed by lipolysis. There's proteolysis, the microtubules disintegrate, in which ultimately culminates into cell death. And that perpetuates the cycle of excitotoxicity with increased glutamate release and failure to reuptake the glutamate, which further leads to an increased calcium influx. There's also, with increased extracellular potassium, there's also cortical spreading depression that leads the neurons in a sustained state of depolarization, which perpetuates excitotoxicity. There's increased oxidative stress, leading to apoptosis necrosis. In contrast, in the ischemic penumbra, the flow is decreased, but the cellular function is still preserved, and the cellular metabolism is still preserved. And that is why that penumbra is the region of focus for stroke therapy, where we want to save that penumbra. It's still in the reversible state, and if the blood supply is restored, that region can be saved. So that's really the goal of acute stroke intervention, is to save that penumbra. Let us now move on to reviewing some stroke syndromes. So this slide presents some of the major cerebral artery syndromes. You can see here the anterior cerebral artery supplies the medial frontal region. This is the branch of the ACA, the recurrent artery of Hübner, which supplies the head of the caudate. So the ACA territory primarily leads to lesion in the medial frontal region, and usually gives rise to contralateral hemianesthesia and weakness. Usually leg is involved more severely than the arm. The middle cerebral artery, as you know, supplies the lateral frontal parietal region, as well as the superior temporal region, obviously gives rise to contralateral hemianesthesia, hemiparesis. Usually the frontal eye field is involved, which leads to the eye deviation towards the lesion because the contralateral hemispheric frontal eye fields are activated and the patient looks towards the lesion side. If it's in the dominant hemisphere, patient can be aphasic. If it's in the non-dominant hemisphere, there could be apressodia and hemineglect. Patients often have expressive aphasia or mixed aphasia. In terms of they may also affect, given their effect in the optic tracts and optic radiations, they may also have contralateral hemianopsia. The other syndrome is the Jertzman syndrome, which is basically infarction of the dominant hemisphere of the angular gyrus, also part of the middle cerebral artery infarction syndrome, which is characterized by agraphia, acalculia, and right-left confusion, finger-nose agnosia, and there's ideomotor apraxia. The other one is the distal posterior cerebral artery infarction, usually involves the inferior temporal lobe, the PCA territory, as well as the occipital region of the brain, usually gives rise to hemianopsia. Then we also have alexia without agraphia, usually lesion of the dominant occipital lobe, and it also involves the splenium of the corpus callosum. And basically, patients have alexia, but they can write. They do not have agraphia. Anton syndrome is a syndrome when there is involvement of bilateral occipital lobes, and patients have cortical blindness, but they confabulate and deny that they're blind. The other one is the Balent syndrome, where they have bilateral parietal occipital infarctions. And these patients have oculomotor apraxia, optic ataxia, and simultanoxia. There's also infarction of the right grand artery of Fuebner, which involves the head of the caudate and the anterior limb of the internal capsule. And that leads to the contralateral face arm weakness and motor aphasia. The anterior corital artery, if you remember, supplies the hippocampus, parahippocampus, the posterior limb of the internal capsule, also supplies the posterior coronary radiata. And infarction related to that artery can give rise to contralateral hemiparesis, hemianesthesia, and hemianopsia. So what about Lacuna syndrome? So Lacuna syndromes or Lacuna strokes usually happen because of infarction of the end vessels or distal vessels, such as the lenticulostriate arteries. Over here, these are coming off the MCA or thalamoperforators or pontine perforators in the brainstem, et cetera. So some of the syndromes include the pure motor syndrome, when there is involvement of the internal capsule, posterior limb of the internal capsule is involved, which leads to contralateral hemiparesis. Sensory motor syndrome would include posterior limb of the internal capsule along with thalamus. So there's sensory hemianesthesia in addition to hemiparesis. There's also pure sensory Lacuna stroke with involvement of the thalamus, primarily usually branches of the PCAs. Also, there's a stroke syndrome called de Jureen-Russo syndrome with infarction of the thalamus, which leads to contralateral hemisensory loss with hemibody pain. Patient can also have hemibolismus because of stroke in the subthalamic nuclei, usually involving giving rise to contralateral hemibolismus. There's an ataxic hemiparesis syndrome when patients have involvement of the coronary radiata, internal capsule, basal ganglia, or pontine Lacuna lesions. Basically, they have contralateral hemiparesis with prominent ataxia. They are a little clumsy on finger-to-nose. Dysarthria, clumsy hand, as we can see that in patients with coronary radiata, infarction, internal capsule, basal ganglia, or pontine, again. And they have dysarthria, contralateral hemiparesis, and some upper limb ataxia. Moving on, let's take a look at this case of a 48-year-old male who presented to the ED after being found down. He was intubated at the scene, brought to the ED. This right here is the first CT scan that he had on the right. The only thing that stands out in the CT scan is this hyperdensity in the vascular artery. He was admitted. He was taken for thrombectomy and admitted into the neuro-ICU where he was found to be quadriplegic. Nurse didn't think he was following any commands. He wasn't tracking the examiner. But the nurse noted that he was moving his eyes vertically. So where could his stroke be? Keep in mind, he has this hyperdensity. This is the region of the vascular artery right here. And the symptom he has and the signs he has is quadriplegia, lack of horizontal eye movements. Only preserved movement is vertical eye movement. So this person most likely has what we call the locked-in syndrome. This is a quick overview of the postural circulation syndromes. There is a pica syndrome because of stroke related to postural inferior cerebellar artery, also known as lateral medullary or the Wallenberg syndrome. Primarily, they have dysphagia, nausea, vomiting. They may have ipsilateral facial numbness and contralateral pain and temperature loss. May have ipsilateral horners, ataxia, and dysphagia on the ipsilateral side. The superior cerebellar artery syndrome or the SCA syndrome basically has limb ataxia or vertigo. They may have nystagmus or dysarthric. Usually involves the dorsal upper brainstem, cerebellum, and the superior cerebellar ventricular area. The anterior inferior cerebellar artery or the ICA. That leads to lateral pontine syndrome that involves ipsilateral labyrinth and the lateral pontine tegmentum and can give rise to ipsilateral ataxia, hearing loss. It could be ipsilateral horners and contralateral pain temperature deficit. Tip of the basilar syndrome. Usually, the stroke is at the tip of the basilar artery and may involve midbrain thalamus, medial temporal lobes, and occipital lobes. Patients are usually somnolent. They may have convergence nystagmus. They may have skewed deviation of thigh and vertical gaze palsy. In addition, they may often present in coma. The midbasilar system is the lateral pontine and medial pontine perforators right here that's affected. The lateral pontine perforators, if they're affected, gives rise to ipsilateral numbness and ataxia. The medial pontine, one gives rise to ipsilateral ataxia, contralateral weakness. And they have trouble moving the eye. Because of the involvement horizontally because of the involvement of the peripontine reticular formation. The proximal basilar syndrome affects the bilateral lower pons, gives rise to locked-in syndrome. So the lower half of the pons does not directly involve the ascending arousal system. So their consciousness is preserved. However, it significantly affects the ascending and descending fibers. So basically, they're quadriplegic. They have complete paralysis of the horizontal gaze. They often have bifacial paralysis. However, their vertical eye movement is often preserved. And they communicate through moving their eye up and down. The vertebral artery infarction can sometimes lead to medullary infarction because it gives rise to medullary branches. And because of the anterior spinal artery branches, you can have cervical cord infarction. So it can lead to medial medullary or the Dijourin-Rousseau syndrome. They can have contralateral weakness and ipsilateral tongue paralysis. And the medial medullary syndrome. Now, let's move on to the classification of stroke. The Toche criteria or trial of ORG10172 in acute stroke treatment was the trial in the early 1993s. It was a placebo-controlled, randomized, blinded study using low-molecule weight heparanoid within 24 hours of stroke. And in this trial, they developed a system of classification based on etiology. So basically, it was related to large artery atherosclerosis. It was the large artery atherosclerosis etiological classification. If there was cardioembolic sores, like atrial fib, bladder, or cardiac thrombus, then it was a cardioembolic stroke. If there was small vessel occlusion or basically diabetes, hypertension, risk factors for small vessel disease with Lacuna syndrome, then there was a small vessel stroke. If there was stroke of other determined etiologies, such as patient had apicoacobility or they had genetic syndrome leading to stroke, then that would be a stroke of other determined etiology. And then finally, cryptogenic stroke or stroke of undetermined etiology could be if, after extensive workup, there was no etiology determined, or more than one cause of stroke was found, or the evaluation was not complete. So it was still a stroke of undetermined etiology. So this is a very commonly used classification for stroke. These days in our clinical environment. So now we've looked at the vascular supply of the brain, basically the pathophysiology of stroke, some of the stroke syndromes in the supratentorial, infratentorial regions. Let's look at one of the biggest worries after the stroke. So you know acute management of stroke is either IBTPA or interarterial thrombectomy, which will be reviewed in Acute Ischemic Stroke 2 lecture. But let's quickly review what to do if there is a patient admitted to your ICU and that patient develops severe malignant edema. So here's a case of a 55-year-old male who's admitted for the left MC infarction. Patient's ventilated, sedated. Neuro exam is limited. Nurse notes that around 9 AM, the pupil was 4 millimeter and sluggish but reactive on the left and 3 millimeter and brisk on the right. However, at 10 AM exam, she reported 5 millimeter dilated and fixed pupil on the left, while the right pupil was still around 3, 3 and 1 half and reactive. So what is your immediate next best step for management? So this is obviously herniating brain from malignant cerebral edema after a stroke. Patient's either failed thrombectomy or could not be a candidate and has large arterial territory involvement. This is often a possible scenario we can encounter in our ICUs. So the cerebral edema can be managed with either type of hyperosmolar therapy, whether 23.4% or mannitol. There is really no clear guidance on the benefit of continuous therapy versus bolus therapy. But largely, our practice is to do bolus therapy because continuous therapy can eventually help equilibrate because of generation of edogenic osmols intracellularly. So bolus therapy is commonly practiced, although clear benefit of one versus the other is not clearly identified. So what about the surgical management in patients with stroke? So apart from the acute intervention of IA thrombectomy, patients may need ventriculostomy if there is signs of obstructive hydrocephalus, either from the mass effect or complications of hemorrhagic transformation or stroke. Patients can undergo decompressive hemicraniectomy if there is an infertentorial infarction. The decompression depend on the infarct size, patient's neurologic condition, whether or not there is mass effect on their brainstem, and whether or not the medical therapy has been effective. And if there is significant mass effect, concern for herniation, either supertentorial, infertentorial herniation, occipital crania is indicated with dural expansion. And this is usually done in patients who either fail maximum medical therapy or there's impending risk of brainstem compression and herniation. For supertentorial infarct, the decompressive craniectomy, hemicraniectomy in patients 60 years of age or less is usually recommended for large territory MCA infarctions within 48 hours of injury. And who demonstrate neurologic deterioration, we want to do large decompressive cranial arterial expansion. There is reduction of mortality by close to 50%. About 55% of the patients who receive this lifesaving surgery have moderate disability or better with MRS of 2 to 3, and about 18% achieve independence at 12 months. However, the benefit is less for morbidity improvement in patients older than 60 years. Although it may save life, there is no significant improvement in quality of life for elderly patients over 60 years. That brings us to the conclusion. We reviewed neurovascular anatomy, pathophysiology of stroke. We reviewed various stroke syndromes, both of the anterior-posterior circulation as well as the subcortical lacuna syndromes. We also reviewed management of malignant cerebral edema, both medical and surgical. So if you have any questions, please feel free to reach out to me. My email is at the beginning of the slide. And thank you for listening.

neurovascular anatomy

ischemic stroke

etiology classification

malignant cerebral edema

stroke syndromes

TOAST criteria

management