INDS212_LEC_VASCULAR_ANAT_STROKE_PPT_EN (1).pptx

Stroke Monday October 2nd 2023 Dr. Fraser Moore Olajide Williams graduated from medical school in Lagos, Nigeria. He is a Neurologist and Stroke specialist at Columbia University. His research interests include stroke disparities between He is also the populations. founder of Hip Hop Public Health....

Stroke Monday October 2nd 2023 Dr. Fraser Moore Olajide Williams graduated from medical school in Lagos, Nigeria. He is a Neurologist and Stroke specialist at Columbia University. His research interests include stroke disparities between He is also the populations. founder of Hip Hop Public Health. Check out their web site (which includes educational material like the one at left) Objectives 1. Review the blood supply of the brain and the vascular territories supplied by the major cerebral vessels. 2. Understand the principles of acute stroke treatment and the idea that “time is brain”. 3. Develop an approach to the investigation of patients presenting with stroke (etiology vs risk factors). 4. Understand the components of primary and secondary stroke prevention (and the importance of treating hypertension). 5. Understand that transient ischemic attacks are just as serious as a stroke. 6. Understand the anatomical and clinical differences between the 4 basic types of hemorrhagic stroke. 7. Understand the concepts of blood brain barrier and the 3 types of cerebral edema What is a stroke? “Damage to the central nervous system caused by an abnormality of the vascular supply” • Ischemic • Hemorrhagic • Venous Outline Part One – Ischemic Stroke “Mr. Francisco” Part Two – Hemorrhagic and venous stroke Case Mr. Francisco is a 55 year old man who comes to see his GP for an annual check-up. His blood pressure is 155/90. He is advised to reduce his salt intake, eat a well-balanced diet, engage in regular physical activity, and monitor his BP. 3 months later his BP remains elevated (confirmed by readings at home). His GP recommends medical treatment. Mr. Francisco asks why. Primary Prevention • Block C • Hypertension most important for stroke • Evidence from secondary prevention • Pathophysiology makes sense • Atherosclerosis Kandel and Schwartz Primary prevention = treat risk factors before any event (stroke, heart attack, etc…) has occurred prevention = after an event has • “increased turbulence and shear Secondary stress at bifurcations” occurred The brain is supplied with blood by the two internal carotid and two vertebral arteries. Kandel and Schwartz An MR-angiogram Posterior Circulation 2 posterior cerebral arteries (via the vertebral arteries) 3 pairs of cerebellar (and brainstem) arteries: Superior cerebellar 1 basilar artery Anterior inferior cerebellar (AICA) 2 vertebral arteries Posterior inferior cerebellar (PICA) Anterior Circulation (via the internal carotid arteries) 2 Anterior Cerebral Arteries 1 Anterior Communicating Artery 2 Middle cerebral arteries 2 Internal Carotid Arteries The Circle of Willis 2 Posterior Communicating arteries link the anterior and posterior circulations, forming the circle. This can allow for collateral blood flow. For example, if the proximal anterior cerebral artery (ACA) is occluded then blood could flow from the opposite ACA, through the anterior communicating artery, and into the more distal ACA. Ventral (under) surface of the brain The Circle of Willis 3 1 8 6 5 4 anatomytool.org The vertebral arteries (4) form the single basilar artery (5), which then forms the posterior cerebral arteries (6); the “posterior circulation”. 2 7 4 The internal carotid arteries (1) form the anterior (2) and middle (3) cerebral arteries; the “anterior circulation”. The anterior communicating artery (7) and the posterior communicating arteries (8) connect the other vessels to form the circle of Willis. This allows for the development of collateral blood flow. The anatomy varies between patients (for example, one posterior communicating artery might be absent). Ventral (under) surface of the brain The Circle of Willis A few things to notice: The internal carotid artery (1) divides to form the anterior (2) and middle (3) cerebral arteries (like a “Y”). 3 2 7 1 8 6 The middle cerebral artery is in the sylvian fissure; to see it well you need to move or remove the temporal lobe. 5 4 The single anterior communicating artery (7) is very short; a small stub between the two anterior cerebral arteries. 4 The basilar artery (5) terminates by dividing into the two posterior cerebral arteries (6). There are two posterior communicating arteries (8). anatomytool.org The Circle of Willis Don’t forget the: Posterior inferior cerebellar artery (9) Anterior inferior cerebellar artery (10) 11 10 9 anatomytool.org Superior cerebellar artery (11) (All are bilateral) Notice how close the superior cerebellar artery is to the posterior cerebral artery. The Circle of Willis For practice! anatomytool.org The figure at left shows the actual arteries. Note again that the tip of the right temporal lobe (arrow) has been cut away so you can see the MCA and its branches. Also, the arteries have been injected and appear nice and red. That is not always the case… In the lab… …start by orienting yourself. The arteries will be on the ventral surface of the brain. Where is anterior/posterior? Identify the temporal lobes (1) and the pons (2). The basilar artery sits on top of the pons (3). You can work out the vessels coming off the basilar by their caudal to rostral order (AICA-SCA-PCA). The vertebral arteries are more caudal and form the basilar*. The PICA’s come off the vertebrals. For the anterior circulation, do not expect to see big internal carotid arteries. At most you will see a small stub. 1 From there, the MCA moves laterally while the ACA moves anteriorly. 2 3 The acomm connects the two ACAs. The pcomm connects the PCAthis to the *In specimen the vertebral arteries have QUESTIONS Imaging We can image a patient’s vessels with: • A “conventional” Angiogram* • A CT-Angiogram (or CTA) • A magnetic resonance angiogram (or MRA) An MR-angiogram *Visualization of injected radio-opaque dye A sagittal view of the medial surface of one cerebral hemisphere, emphasizing the anterior cerebral artery (initially moving anteriorly, then A coronal view of the brain emphasizing how the middle cerebral arteries move laterally, supplying deep brain structures before entering the Sylvian fissure and supplying the lateral side of the brain. The lenticulostriate arteries are a common site of hypertensive damage (small arteries Are there other risk factors for stroke? • Modifiable risk factors include: • Smoking • Diabetes • Lipids • Atrial fibrillation is a very important risk factor (Block C) • The CHADS2 score quantifies the risk CHADS2 score CHF 1 point HTN 1 point Age > 75 1 point Diabetes 1 point S2 Prior* 2 points Anticoagulate if ≥ 1 *Stroke or thromboembolism Case Mr. Francisco has understood the importance of good BP control and is compliant with his new medication. He has done some reading and would like to know more about when he should be concerned that he might be having a stroke. Stroke Symptoms Sudden and focal Loss of function Rarely • Loss of consciousness • Headache, Pain • Abnormal movement “Never” 1. Weakness 2. Numbness (loss of sensation) 3. Aphasia or dysarthria 4. Visual loss • Loss of memory • Decreased concentration • Confusion Strokes can also be asymptomatic. This can be because they are small or because they involve areas of the brain whose function is less obvious Case Six months later Mr. Francisco was talking with his wife after dinner when he suddenly began to have slurred, “garbled” speech. He understood but when he spoke his wife could only understand a few words. As he tried to get up, he realized that he could barely move his left arm and leg. His wife called 911 and they arrived at the ER 90 minutes after the onset of his symptoms. Case On examination Mr. Francisco has weakness of the left side of the face (sparing the forehead*). His speech is slurred and difficult to understand. He appears to be talking in full sentences. He has weakness of the left arm with a pronator drift and clumsy finger movements. There is some proximal left leg weakness. Reflexes are slightly increased on the left with a positive Babinski sign. 1. Did he have a stroke? 2. Where was the stroke? *Do you recall why this is important? We localize strokes based on our knowledge of “vascular territories” • Each part of the brain is supplied with blood by a specific artery. • If the artery is occluded, that part of the brain receives no blood supply (so no oxygen and no glucose). • The person will lose the functions normally controlled by that part of the brain. Vascular Territories Lateral  The MCA moves laterally and supplies the “outer” convexity of the hemisphe Medial The ACA moves anteriorly then posteriorl y and supplies the medial side of Homunculus Axial CT Coronal View Vascular Territory determines symptoms ACA medial surface MCA lateral surface PCA posterior leg weakness face, arm, proximal leg visual cortex The symptoms tell us which artery might be affected and where to look on imaging QUESTIONS Axial view Cortical vs. Subcortical Stroke Sagittal view Coronal view) The small penetrating arteries circled (above right) are prone to hypertensive injury. Damage to one of these arteries causes a smaller infarct deeper in the brain. The volume of infarction is smaller compared to occlusion of a major vessel like the MCA. Symptoms depend on location. The blue infarct could damage the internal capsule and still cause Axial view Cortical vs. Subcortical Stroke The blue infarct still results in weakness of face, arm, and leg because descending motor fibres from wide areas of cortex converge in the internal capsule (blue circle). The orange infarct is in the deep white matter of the frontal lobe. This is important for functions like judgment and personality that involve wider areas of the brain, so a small infarct may be asymptomatic (or the symptoms are less obvious). “Sub-cortical” infarcts like these usually spare language, spatial, and visual (“cortical”) functions. They are also referred to as “lacunar” infarcts because of their small volume. QUESTIONS? A stroke involving only the brainstem can produce quite varied symptoms. Cranial nerves III to XII, connections to the cerebellum, descending motor tracts, and ascending sensory tracts can all be involved. Visual function is spared unless the stroke also involves the posterior cerebral arteries and damages the occipital cortex. We will talk more about the brainstem vascular supply after Brainstem Blood Supply Brainstem lacunar infarcts Basilar artery Pons These are two examples of pontine infarcts probably caused by occlusion of small “perforating” branches from the basilar artery. These would also be considered “lacunar” infarcts and the pathophysiology is similar to those involving the lenticulostriate arteries (slides 19 and 29). Case – Mr. Francisco What should we do now? • • • • • CBC* Why? PT, PTT SMA-7** CT head CT angiogram Slurred, garbled speech. Barely moving his left arm and leg. In the ER 90 minutes after onset. Weakness left face (sparing forehead). Speech slurred. Talking in full sentences. Weakness of left arm, pronator drift, clumsy finger movements. Some proximal left leg weakness. Reflexes slightly increased on the left with a positive Babinski sign. *Complete blood count **A panel of blood tests including Na, Cl, K, bicarb, creatinine, urea, and Imaging in acute stroke – CT head Wechsler NEJM 20 On the left is a normal axial CT scan. Notice the hypodense (darker) internal capsule between more hyperdense caudate/thalamus and putamen/globus pallidus. The axial CT on the right shows an acute left middle cerebral artery territory ischemic stroke; note the blurring of the Imaging in acute stroke Ischemic stroke becomes more visible on CT once there is infarction and the affected tissue becomes less dense. This takes time to develop. The CT on the preceding slide showed the kind of subtle changes seen within the first hours after stroke. The above axial CT scans show the later evolution of ischemic infarcts involving partial left MCA territory (left image) or the complete left MCA territory Imaging in Acute Stroke This is an axial “diffusionweighted” MRI, which is useful for detecting small areas of ischemia or infarction that might not be seen with CT. Ischemic brain tissue swells because of failure of energydependent ion pumps. This results in locally decreased diffusion of water molecules (and a change in MRI signal). (In Canada MRI is usually not used for acute strokes in the Imaging in Acute Stroke Wechsler NEJM 2011 A perfusion CT scan is a specialized CT scan that allows us to image blood flow (perfusion) in the brain. The perfusion CT at right corresponds to the conventional CT at left and shows reduced blood flow (blue) in the left MCA territory (note again Imaging in Acute Stroke Internal carotid artery dividing into anterior and middle cerebral arteries Basilar artery dividing into posterior cerebral arteries A CT angiogram uses an intravenous radio-opaque contrast agent to directly visualize the cerebral vessels. On the left is an axial image and on the right is a reformatted coronal image. In practice we would scroll through a series of images and follow the course of the vessels, looking for Imaging in Acute Stroke A few points to remember: 1. CT changes in stroke (hypodensity) take time to appear 2. We look for subtle blurring of normal anatomy* 3. CTA is being routinely used in acute stroke 4. Diffusion-weighted MRI can help *Rarely we can see the thrombus itself appearing as a hyperdensity (brighter) within the vessel QUESTIONS Can we do anything to help Mr. Francisco? Acute stroke treatment options include: • ASA and/or clopidogrel* • iv tPa (tissue plasminogen activator) • Thrombectomy In each case these would be offered only after confirming the absence of a hemorrhage with a CT scan *Giving an ASA and/or clopidogrel acutely has a benefit but it is small, so in practice we don’t emphasize this. The only situation where this would apply would be if the person could not receive Thrombolysis for Acute Stroke • What does it do? • Block C • tPa catalyses formation of plasmin from plasminogen, with lysis of thrombi • “Ischemic stroke (in first 3 hours only – questionable)”… Not Questionable! tPa given within 4.5 hours for ischemic stroke results in better functional outcomes at 3 months. The graphs to the left show data from the original NINDS tPA trial (top) and a later meta-analysis (bottom, colour). NINDS NEJM 1995 They show the percentage of patients with scores on different functional scales used to assess stroke outcome. Being towards the left for each scale is better. For example, in the bottom graph there are more tPa patients than placebo patients with scores of 0-1. Hacke NEJM 2008 What does tPa really do? These are the same images shown previously, before this patient received tPa… Wechsler NEJM 2011 The entire dark blue area has reduced blood flow…it is at risk of infarction (= cell death) What does tPa really do? …and now post-tPa. There is an area of infarction (arrows) but it is much smaller than the “perfusion defect” on the preceding slide. Lyse (remove) clot? Improve collateral circulation? Rescue penumbra (the area of ischemia surrounding the core infarct)? Wechsler NEJM The “ischemic penumbra” Imagine that the orange artery in the centre of the image becomes occluded (the blue represents brain tissue). The “ischemic penumbra” Infarcti on Ischemi a Normal Imagine that the orange artery in the centre of the image becomes occluded. The area of brain supplied by that artery (inner circle) will receive no blood flow and will infarct (the cells will die). The outer circle of brain receives blood from adjacent arteries and is not harmed. In between there is an area that normally receives blood from the centre artery and the surrounding arteries. Occlusion of the centre artery results in reduced but not absent blood flow to that area, so the tissue is ischemic. The cells do not function and this contributes to the person’s symptoms. The cells may or may not survive. This is the penumbra. The “ischemic penumbra” Infarcti on Ischemi a Normal Whether the cells in the penumbra survive depends on: 1. How well the other vessels (termed “collateral vessels”) maintain blood flow to the area and/or 2. If blood flow in the centre artery can be restored Thrombolysis might do both Thrombolysis for acute stroke • What do you need to know? • Time is brain! • Given by neurologists within 4.5 hours of symptom onset • Referred by nonneurologists This data shows that clinical outcome is better the earlier tPa is given (experimental evidence shows the same thing e.g. less cell death) Time is brain! Saver Lancet Neurol 2010 QUESTIONS? Thrombectomy Patients with evidence on CTA of a proximal vessel occlusion (e.g. MCA) benefit from (physical) clot removal up to 12 hours or more after onset. CT-head (below) and CTA images (coronal above, axial below) with occlusion of an MCA branch Arrow in top image shows lack of distal vessels in that area. Early “Code stroke” calls are ischemic Arrow in received from the changes are lower seen in the ambulance. image MCA shows Stat CT and CTA upon territory abrupt arrival. cut-off of the MCA. iv tPa within 4.5 hours if *There are some contraindications to tPA use such as active anticoagulation, very recent surgery, or history of intracranial eligible*bleeding. Patients could receive tPa, thrombectomy, both, or neither depending on timing, stroke type, Why “up to 12 hours or more” after onset? • Treatment protocols continue to evolve based on new evidence • Evidence for thrombectomy benefit up to 24 hours in patients with a “mismatch” between clinical deficit and imaging • Occlusion of a proximal vessel • Tissue ischemia causing symptoms • Collateral blood vessels maintain enough flow so that some or all of the ischemic tissue has not yet undergone infarction (cell The patient has symptoms because of ischemia in the large green area. However, only the smaller purple area has undergone infarction (is “dead”). This is the “mismatch” If we can identify this “mismatch” we might be able to treat up to 24 hours. (and save a volume of tissue of 105 mL) NEJM 2018; 378: 708 Acute Stroke Treatment 1. Symptomatic patient arrives in ER 2. CT head shows if there is hemorrhage or early ischemic changes 3. CTA shows if there is a proximal large vessel occlusion 4. If eligible (within 4.5 hours & no hemorrhage) they receive iv tPa 5. If eligible (within 24 hours & a large vessel occlusion) Use ofthey the “time windows” continues for to evolve as we better understand (and can better visualize are referred a mechanical thrombectomy with imaging) that two patients with identical symptoms may have different volumes of ischemia vs. infarction (if there is predominantly ischemia we maywith considerASA treatment even outside “traditional 6. If neither they are treated and/or time windows”) QUESTIONS? Make sure that you understand acute stroke treatment! Case After receiving iv tPa, Mr. Francisco has some slight improvement in strength of his left arm. What now? Mr. Francisco is admitted to hospital. There are two parallel objectives: 1. Identify and treat the cause to prevent recurrence 2. Aid adaptation and recovery Treat the cause and risk factors Etiology is inferred from results of investigations. For example, if we find atrial fibrillation, we infer that was the cause. • Cardiac embolus (afib or other) • Identified on EKG, Holter, echocardiogram • Large artery embolus (carotid/vertebral) • Indentified with Dopplers, CT/MRI angiography *The only common indication for anticoagulation (with warfarin or a newer oral anticoagulant) is atrial fibrillation. All other etiologies are treated with antiplatelet agents. Anticoagulation* Antiplatelet/ Surgery • Intracerebral thrombus • Identified with CT/MRI angiography In all of the above Antiplatelet Identify and Rx risk factors (2o prevention) Aid adaptation & recovery “The Stroke Team” Nurse (prevent complications)* Physiotherapy (mobility) Occupational therapy (ADL’s) Speech therapy (speech/language/swallowing) • Social worker (home/living/financial situation) • Dietician (swallowing/diet) • • • • • Evaluation and treatment in hospital • Decision re: discharge – – – – In-patient rehab Out-patient rehab Home Adaptive housing, increased supervision and services *Aspiration pneumonia, other infections, deep venous thrombosis Multidisciplinary Rounds Members of the stroke team typically meet every morning, Monday to Friday, to each patient’s progress and plan. Case Mr. Francisco’s wife asks what his prognosis is. What do you think? • The earlier there is recovery the better • Recovery can continue for at least 3-6 months • Adaptation to permanent deficit(s) can continue for much longer… What does a stroke feel like? “not painful…something wasn’t connected...all these simple things you do, they weren’t working*....couldn’t make any sound...it was (*eg.Kindle - she liked to scary...really strange experience” read) “It’s unbelievable…it’s like being hit by a train” (going from no weakness to suddenly dysarthria and 81592 very limited left arm movements 1677087 Mr. Francisco results Left EKG: unremarkable Holter: unremarkable Echocardiogram: unremarkable Dopplers: 80-99% R ICA stenosis 40% ICA Patients with a Lsymptomatic* stenosis ICA Right ICA The left internal carotid artery is relatively normal. The right internal carotid artery shows narrowing of the vessel lumen (top) and higher peak flow velocity at the area of stenosis (bottom). ICA stenosis of 70%-99% benefit from a carotid endarterectomy, a surgical “Dopplers” are properly called doppler ultrasound; they image the procedure to remove the vessel with ultrasound and also atherosclerotic plaque and record the flow velocity with doppler technology. widen the artery lumen** *Symptomatic means stroke symptoms in “the territory of the artery.” (Do you understand what rationale this means?) **The for doing this is to prevent distal embolization of part of the plaque, not simply to Findlay CJNS 2004 1 Common carotid 2 External carotid 3 Internal carotid Carotid Endarterectomy Retraction of vessel wall plaque Removal of Science photo library Intra-op pictures showing the artery being exposed (A at left), the artery opened (B at left– curved arrows indicate atherosclerotic plaque), plaque removed (above), and the artery closed (C). teachmesurgery Carotid Endarterectomy Findlay CJNS 2004 **The rationale for doing this is to prevent distal embolization of part of the plaque, not simply to widen the lumen On the right are pre and post angiograms, with the arrow showing the pre-op stenosis (narrowing of lumen). Surgery (right carotid endarterectomy) is successfully performed without complications. Mr. Francisco remains in hospital for two weeks and is then discharged to in-patient rehab. He is now taking ASA, a statin, and blood pressure medication. A rehabilitation hospital is not simply somewhere to send the patient. The goals are to maximize experience-dependent neural plasticity* and develop *Neural plasticity is a general term that refers to the brain’s ability to adapt and change. In thisstrategies context it means intact brain regions taking compensatory to improve This is one example of a strategy that can be used to promote plasticity. QUESTIONS? After two months in rehab there has been sufficient improvement that Mr. Francisco is able to return home. He returns for follow-up 1 month later. What do you want to talk to him about? Medications for blood pressure etc… • Medication compliance • Blood pressure monitoring are preventive medications. They do not make the person feel better. In fact, people usually feel no different regardless of whether they do or do not take the medication. Cost can also be an issue. • Risk factor modification (smoking, exercise, diet) ***Quality of life/function (how do you feel?) “Doctor, what else can I do?” Many patients will specifically ask this. In addition to diet and exercise, consider talking about climate change. See also: Louis et al. Impacts of Climate Change and Air Pollution on Neurologic Health, Disease, and Practice Neurology 2023; 100: Case You have continued to follow Mr. Francisco. He mentions that he had an episode of decreased vision one week ago. He suddenly lost vision in the left eye. He covered each eye in turn and the vision on the right was normal. On the left he saw only black. The symptoms lasted 20 minutes and resolved completely. Did Mr. Francisco have another stroke? (Atherosclerosis can lead to partial thrombosis and stenosis of an internal carotid artery. An embolus from that area of stenosis can travel distally to cause a TIA or stroke. If it goes to the brain it will usually cause contralateral symptoms. The embolus can also go to the ophthalmic artery, the last branch of the carotid artery before it divides into the anterior and middle cerebral arteries. If Transient Ischemic Attack • Old textbook definition: “A transient neurological deficit caused by ischemia with full resolution within 24 hours” • Reality: • Most TIA’s last 5 minutes to 1 hour • Longer events are probably small strokes What is more concerning, a TIA or a stroke? ABCD2 score (for having a stroke after a TIA) 90 day stroke risk • Age > 60 1 point • SBP >140 or DBP > 90 1 point • Clinical: – Weakness 2 points – Language 1 point • Duration: – >60 minutes 2 points – 10-59 minutes 1 point • Diabetes1 point Score > 2 21%* ≤2 4% “TIA = Stroke” Treating risk factors and identifying etiology is just as urgent and important for TIA *A 21% risk of a stroke in the next 90 days is significant! Even though a patient with a TIA has fully recovered their function, it is just as important to see and treat them as a patient with a stroke and a functional deficit. Ischemic Stroke Conclusions 1. Primary Prevention • Hypertension • Atrial fibrillation 2. Blood Supply & Vascular Territories • Understand the concept & major territories 3. Stroke Symptoms • “not everything is a stroke!” 4. Imaging Acute Stroke • What are the options? • What do you expect to see (based on patient symptoms and imaging modality)? 5. Acute Stroke Treatment • iv tPa and thrombectomy are effective treatments • “Time is brain”: within 4.5 hours for tPa, within 24 hours for thrombectomy • If in doubt speak to the neurologist on call (at your hospital or another hospital) Ischemic Stroke Conclusions 6. Hospitalization • Identify and treat etiology and risk factors • Aid adaptation and recovery (stroke team) 7. Etiology • Atrial fibrillation (major indication for anticoagulation) • Symptomatic carotid artery stenosis 8. Rehabilitation • Active process; enhance plasticity and adaptation 9. TIA • Stroke = TIA; high risk patients QUESTIONS? Four Types of Hemorrhagic Stroke • Epidural = bleeding between skull and dura • potential space • dura attached to skull at multiple points • Subdural = bleeding between dura and • potential space • no strong attachment “Potential space” means that it does not arachnoid normally take up any significant volume, but it can expand to do so. • Sub-arachnoid = bleeding between arachnoid and pia • real space (cerebral arteries, circle of Willis) • pia adheres tightly to brain • Intra-parenchymal = bleeding within the brain itself (=intracerebral) Each of these is considered a type of intracranial (within the Hemorrhagic Stroke Epidural Skull Subdural Dura Arachnoid Skull Sub-arachnoid Intraparenchymal (=intracerebral) Close-up coronal sections through the brain, meninges, and skull Pia Parenchy ma Hemorrhagic Stroke SKULL Epidural Hemorrhage DURA Subdural Hemorrhage ARACHNOID Sub-arachnoid Hemorrhage PIA Intra-parenchymal Hemorrhage What does the anatomy tell us? • Epidural = restricted spacebiconvex (lens) appearance • Subdural = spreads along convexity (crescent appearance) • Sub-arachnoid = follows contours of brain • Intra-parenchymal = within the brain (round or oval) A picture is worth a thousand words… This axial CT scan of the brain shows all 4 kinds of hemorrhage in one trauma patient. There are subdural and intra-parenchymal hemorrhages on the right side of the brain (remember which side is which!) There is an epidural hemorrhage on the left. NEJM There is a subtle subarachnoid hemorrhage identified by the longer black arrow at the top of the image Very serious for two reasons… 1. Dura attached to skull • Large volume in a restricted space means increased local pressure 2. Arterial blood (higher pressure) • Usually from middle meningeal artery • Accumulates rapidly A life-threatening surgical emergency • Remove blood Epidural Less serious for two reasons… Subdural 1. Blood can spread 2. Venous blood (lower pressure) • Injury to “Bridging veins”* • Accumulates more slowly common in elderly More (atrophy, falls, antiplatelets, anticoagulation). A subdural can have different appearances on a CT scan depending on the age of the blood. Acute blood is hyperdense, subacute blood is isodense, and chronic blood is hypodense. The CT on the left shows an acute left subdural, while the CT on the right shows a chronic left *Drain blood from the brain into cerebral venous sinuses (must cross or “bridge” the subarachnoid subdural. and subdural spaces). Atrophy of the brain with aging increases this distance Change in appearance over time Ischemic stroke becomes MORE visible over time, once infarction has occurred. Ischemic Stroke Time Hemorrhagic Stroke Hemorrhagic stroke (all 4 types) becomes LESS visible over time, as the blood cells get broken down and the blood becomes less dense. QUESTIONS? Does that make sense? Subdural • A subdural can cause focal symptoms due to pressure on the underlying brain • Treatment is surgical removal or conservative depending on degree of mass effect (clinical, radiological), age, comorbidity, anticoagulation. • A subdural could also cause increased intracranial pressure (ICP)… What kind of symptoms might the person with this subdural hematoma present with? Increased intracranial pressure (ICP) • Monroe-Kelley Hypothesis • ICP due to either  normal components within the intracranial space (CSF, brain, blood) or addition of new components (tumor, pus, extravascular blood) • Increased ICP is harmful for 3 reasons: 1. Direct damage to neural tissue 2. Decreased cerebral perfusion pressure (CPP = BP – ICP) 3. Displacement of brain (herniation) What happens if ICP > BP ? Types of Herniation 1. Sub-falcine 2. Central 3. Uncal (transtentorial) 4. Tonsillar (cerebellar) Blumenfeld The four kinds of herniation usually occur in order as the ICP increases (the exception would be a cerebellar hemorrhage that could lead directly to tonsillar herniation). In this figure a subdural hemorrhage is increasing the ICP. Causes ipsilateral III nerve injury (“blown pupil”) and ipsilateral hemiparesis. Why? The left uncus (arrow) is swollen and herniating down (toward you, out of the screen). This directly compresses the ipsilateral 3rd nerve as it exits the midbrain. If the process continues it pushes the midbrain to the other side. The contralateral cerebral peduncle (star) can be compressed against the edge of the tentorium cerebelli (part of the dura). This edge is called Kernohan’s notch. The contralateral cerebral peduncle contains axons from the motor cortex that descend, cross over lower down in the medulla, and innervate lower motor neurons controlling the ipsilateral side of the body. Uncal Herniation Symptoms & Signs of Increased ICP 1. Headache 2. Nausea 3. “false localizing sign”* 4. Papilledema 5. Cerebral dysfunction 6. Decreased level of consciousness Symptoms 1-4 could be caused “directly” by the increased ICP (without a focal lesion, without herniation…elevated ICP alone could result in these symptoms)** Caused by focal mass effect (e.g. a subdural) Caused by subfalcine herniation (and now dysfunction of both cerebral hemispheres) *A sixth nerve palsy. Normally this would make us think that the lesion was directly touching/damaging the 6th nerve or nucleus. However, the 6th nerve is very long and thin and can be indirectly damaged by the increasing ICP caused by a lesion elsewhere in the brain. **You do not always need a focal lesion to increase ICP. For example, a venous sinus thrombosis can decrease venous outflow and increase the volume of blood in the cranial cavity (like a blocked drain) If it continues… 1. Sub-falcine 2. Central 3. Uncal (transtentorial) 4. Tonsillar Blumenfeld The four kinds of herniation usually occur in order as the ICP increases (The exception would be a cerebellar hemorrhage that could lead directly to tonsillar herniation). QUESTIONS? Herniation can be a difficult (visual) concept so we will cover it again later in the Block Case 2 A 48 year old woman presents with a sudden-onset, severe headache. She was standing washing the dishes when it began. She only rarely gets headaches. She describes this as the worst headache she has ever experienced. On exam she is in considerable discomfort and has some neck stiffness. A CT scan of the head is performed There is bright, “hyperdense” blood in the subarachnoid space at the base of the brain Normally the subarachnoid space contains hypodense CSF Suarez NEJM Subarachnoid Hemorrhage • Aneurysmal • “Berry aneurysm” • Traumatic • Idiopathic • Peri-mesencephalic hemorrhage • Aneurysms are developmental (not congenital) and are usually asymptomatic until they bleed/rupture • Less commonly aneurysms cause symptoms by exerting pressure • For example, a posterior communicating artery aneurysm can push on and injure the 3rd nerve (a ”3rd This figure shows the appearance and common locations of cerebral aneurysms (The top two labels are cut off – they indicate aneurysms arising from the anterior communicating artery and the anterior cerebral artery). Notice how close the posterior communicating (pcomm) aneurysm is to the 3rd nerve. Brisman NEJM Two common clinical presentations of a ruptured aneurysm (causing SAH) • “Sentinel bleed” with headache • Sudden onset • Maximal at onset (peak intensity within 1 minute) • “Worst headache of my life” • Constant for many hours In both situations blood has leaked out of the aneurysm into the subarachnoid space. A “sentinel bleed” has milder symptoms; only a severe headache. “Full” rupture is more severe • “Full” Rupture • Loss of consciousness • Seizure • Why? Not ischemia or pressure Why is rupture bad? Initially it is not because of either ischemia or raised ICP, although both occur later. Rather, it is the direct toxic Diagnosis • Clinical suspicion (worst headache…) or severity (coma) lead to CT brain; very sensitive for detecting SAH if performed within 6 hours of symptom onset • If the CT is negative then a lumbar puncture is done. This may initially show blood in the CSF or, after approximately 12 hours, xanthochromia (a yellowish discoloration of the normally clear CSF caused by breakdown of blood cells) • Angiography can be done (CT vs. MRA vs. “conventional”) but will only reveal the presence or absence of an aneurysm. It will not tell you whether the patient did or did not have a SAH. Brisman NEJM 2006 Treatment of Aneurysms Angiogra ms preand post- Either surgical clipping (top left) or endovascular coiling. Coiling is preferred because it is less invasive; passing via the arteries, without displacing the brain, to access the aneurysm. Long-Term Outcome • Severity of SAH can be graded (based largely on volume of blood) • Comatose patients with large volume of hemorrhage do poorly • Patients who recover LOC do physically well • “Subtle” cognitive deficits can be disabling for the patient but may be difficult to detect on examination (processing speed, judgment, etc…). • Neuropsychological testing can help identify these deficits. A general physician can play a key role here* *These kind of symptoms are often only noticed after the patient has left the hospital and tried to Incidental (asymptomatic) aneurysm - Should this be treated ? • Risk of rupture is less than a symptomatic* aneurysm, and depends on: • Size • Location • Expected lifespan of the patient • Risk of intervention • Patient factors • Aneurysm anatomy *One that has already Larger aneurysms (more than 1 cm) and anterior circulation aneurysms have higher rupture rates. Aneurysms with a narrow neck are easier to treat (either surgical clipping or endovascular coiling). Case 3 “What if instead…” A 48 year old woman presents with a sudden-onset, severe headache. Her CT scan of the brain done 4 hours later is normal. A lumbar puncture is attempted by the ER physician but results in a “bloody tap”*. You are asked if an angiogram should be ordered to “rule-out” a sub-arachnoid hemorrhage. *The CSF that is collected is thought to be contaminated by How do you respond? • Sudden onset and severe  SAH is possible Case 3 • Normal CT head makes SAH very unlikely* but can’t completely exclude it • The LP is unhelpful because it was traumatic (the CSF is contaminated by peripheral blood) • An angiogram will detect the presence of an aneurysm, but not tell you whether a SAH occurred. Why does this matter? • Risk of rupture of a symptomatic aneurysm is much greater than an asymptomatic aneurysm (and the risk of rupture can be important when deciding on the risks vs. benefits of treatment) *If performed within 6 hou Case 3 The (common) dilemma in this case is that if you do the angiogram and find an aneurysm, you still don’t know if the patient had a SAH (and therefore you don’t know if the aneurysm is symptomatic or not). What do you do? 1. Take a very good history. Do you think, clinically, it was a SAH? 2. Explain the situation toto the discuss it with (You do not always need have apatient test result and in order to them. decide what to do) QUESTIONS? Intraparenchymal Hemorrhage • Clinical features similar to ischemic stroke • More sudden, severe at onset • More likely to have headache, increased ICP, and altered level of consciousness • Common causes • Chronic Hypertension • Cerebral Amyloid Angiopathy • Other causes • Anticoagulation • Arterio-venous malformation (AVM) • Drug use (e.g. cocaine) • Bleeding disorder • Trauma (remember what a vascular • Symptoms/signs do notterritory is?) Location, location, location Hypertensive hemorrhages occur deep in the brain (basal ganglia, Amyloid hemorrhages occur superficially in the cerebral Why does a hypertensive hemorrhage occur? Hypertension hemorrhages occur from damage to small thin-walled arteries that branch at right angles from larger vessels; the small arteries cannot withstand the long-term effects of the higher pressure. Common locations are branches from the MCA (circle at right) and basilar artery. (If this sounds familiar…chronic hypertension puts these vessels at risk of both atherosclerosis AND vessel rupture, leading to lacunar strokes OR hypertensive hemorrhages) Blumenfel d Amyloid is a protein that is folded in a way that makes it insoluble and resistant to degredation. Why do amyloid hemorrhages occur? Sacco NEJM 2000 Blumenfel d Greenberg NEJM 2010 Amyloid is deposited in the walls of small terminal arteries in the cerebral cortex. The figures show this in H&E staining, polarized light, and immunohistochemical staining. The amyloid deposition makes the vessels brittle and prone to rupture. (Amyloid plaques are also part of the pathology of Alzheimer’s disease but, in that case, they occur within the brain, vs. cerebral amyloid angiopathy which occurs in these small cortical arteries. The pathology is similar but Does it matter? (HTN vs amyloid) • The treatment for both is usually supportive (the patient improves as the blood is resorbed)* • A hypertensive hemorrhage implies that the patient needs better blood pressure control long-term** • The risk of recurrence of an amyloid hemorrhage is higher • If there is something atypical (younger patient, location, not hypertensive) *In a young patientunusual with a high risk of herniation we may rarely recommend surgical removal of the hematoma (but recent clinical trials may make surgical we would look for other causes such as an treatment more common) QUESTIONS? Hemorrha ge vs. Tumor An acute hemorrhage on CT has a very hyperdense (bright) and homogeneous appearance. A tumor on CT will not be as hyperdense (not as bright), and will often be surrounded by a hypodense area of edema. (I have not shown MRI images for two reasons. In Canada, a CT would nearly always be the first imaging modality used and it shows blood very well, so very rarely would a patient with an acute hemorrhage undergo an MRI. The second reason is that the appearance of blood and tumors on MRI Contrast Enhancement The presence of contrast enhancement can also help to identify a tumor. On the left is a plain CT scan of the head showing a small round hyperdense metastatic tumor surrounded by hypodense edema. On the right is a CT scan obtained after administration of iv contrast. Normally this can’t enter the brain, but it can in the area of the tumor because of a breakdown of the blood brain barrier (BBB). This results in the tumor showing up more brightly. Blood Brain Barrier (BBB) With a few exceptions, the bbb severely restricts movement between the circulation (blood in brain capillaries) and the brain parenchyma. Why? Initially it was thought to be due to foot processes of astrocytes (in grey) that surround brain capillaries. Now we know that it is actually the result of unique properties of endothelial cells in the brain. • Endothelial cells in the brain have tight junctions (in black) and lack endocytosis • Present from early in development • Although astrocytes are not the basis for the mature BBB, they may induce BBB development • Transplanting brain astrocytes to the spleen caused spleen capillary endothelial cells to develop properties similar to brain endothelial cells What can enter (cross) the BBB ? • Small lipophylic molecules It is not important to remember these examples. • Heroin yes, morphine poorly Understand the concept: some medications cross the BBB, others do not. • Specific substances via transporters • Glucose, amino acids yes • L-Dopa yes, dopamine no* • A substance in an area lacking a This is important if you need your drug to enter the CNS. For example, if you want to use an antibiotic to treat an infection of the CNS, BBB you want to choose one that does cross the BBB. • Posterior pituitary • Choroid plexus • Periventricular (area postrema near 4th ventricle**) *So we treat Parkinson’s disease by giving oral L-Dopa, a dopamine precursor, and not dopamine. The L-Dopa is transported across the bbb into the brain, and converted there to usable dopamine **Sometimes called the “vomiting centre” because thought to “sample” blood contents and induce vomiting in response to dangerous/toxic substances Edema Vasogenic edema (tumor) Cytotoxic edema (hemorrhagic stroke) In the case of a tumor the edema is caused by breakdown of the BBB and we call it “vasogenic” edema. Edema can also occur after a stroke, but in that case it is caused by the failure of energydependent ion transport due to ischemia. It is called called “cytotoxic” edema. A third kind of edema is “interstitial” edema (caused by osmosis, usually related to hyponatremia). Hydrocepha lus An intraparenchymal hemorrhage can obstruct the ventricular system and cause noncommunicating hydrocephalus (like the example shown here). A subarachnoid hemorrhage can spread over the convexity of the brain and block the arachnoid villi, causing communicating hydrocephalus. (A subdural hemorrhage also spreads over the convexity of the brain but in the subdural space, so it does not obstruct the arachnoid villi). Left at 09:40, Right at 17:05 QUESTIONS? Cerebral Venous Circulation • Arteries bring blood to the brain • They divide into smaller arteries, arterioles, and then capillaries • “Deep cerebral veins” drain blood from capillaries deep in the brain into the inferior sagittal sinus • Superficial cortical veins drain blood from more superficial capillaries into the superior sagittal sinuses • Recall that venous sinuses are formed between two layers of dura Dr. McWatt Cerebral Venous Circulation Cortical veins SSS Trigone (confluence of sinuses)transverse sinussigmoid sinusInt Jugular Cerebral Venous Circulation The left image shows more veins/sinuses than you need to know. It does show cortical veins draining into the superior sagittal sinus (circled). These would need to cross the subarachnoid and subdural spaces as ”bridging veins” (below). IntechOpen Cerebral Venous Circulation Sagittal (left) and coronal (right) magnetic resonance venogram showing the cerebral venous drainage. Cortical veins drain into the superior sagittal sinus (SSS) and deep cerebral veins drain into the inferior sagittal sinus (ISS – not shown) and straight sinus. The SSS and straight sinus meet at a point called the trigone, before the blood flows through the transverse and sigmoid sinuses to the internal jugular veins. Cortical veinsSSS Trigonetransverse sinussigmoid sinusInt Jugular Cerebral venous sinus thrombosis • Reduced venous outflow due to thrombosis leads to increased cerebral blood volume and increased intracranial pressure Virchow’s Triad 1. HypercoaguabilityB CP* 2. Vessel injurysmoking *Also consider pregnancy including up to 3 months 3. Stasis? after birth • Patients typically present with headache and papilledema • Increased venous pressure can lead to venous infarction (often bilateral, with mix of ischemia and hemorrhage) A CT with contrast shows clot in the superior sagittal sinus. The sinus is cut in cross section and should uniformly fill with contrast and appear hyper-dense. The clot is the less dense (darker) oval in Cerebral venous sinus thrombosis A more severe case of an 84 year old woman with occlusion of the superior sagittal sinus, and a mix of BILATERAL ischemic and hemorrhagic strokes. Ischemic stroke and hemorrhagic intra-penchymal hemorrhages are usually focal and unilateral. If you see them bilaterally like this, think venous sinus thrombosis. See N Engl J Med 2021;385:59-64. for a recent review article QUESTIONS? Hemorrhagic and Venous Stroke Conclusions 1. Epidural • How does it differ from subdural (and why)? • Monroe-Kelley hypothesis • Herniation 2. Subdural • Variable clinical presentation, appearance, and treatment – why? 3. Subarachnoid • Sudden, severe, maximal at onset • An angiogram detects an aneurysm, not a SAH Hemorrhagic and Venous Stroke Conclusions 4. Intraparenchymal • What is the pathophysiology ? • Don’t forget anticoagulation as a cause 5. BBB and edema • How can we use breakdown of the bbb to aid diagnosis? • What are the three kinds of edema? Which one can we treat effectively? 6. Venous Stroke • Predisposing factors (Virchow’s triad) • Unusual clinical presentation (increased ICP with normal LOC, bilateral symptoms/signs) Acute Stroke Treatment 1. Symptomatic patient arrives in ER 2. CT head shows if there is hemorrhage or early ischemic changes 3. CTA shows if there is a proximal large vessel occlusion 4. If eligible (within 4.5 hours & no hemorrhage) they receive iv tPa 5. If eligible (within 24 hours & a large vessel occlusion) Use ofthey the “time windows” continues for to evolve as we better understand (and can better visualize are referred a mechanical thrombectomy with imaging) that two patients with identical symptoms may have different volumes of ischemia vs. infarction (if there is predominantly ischemia we maywith considerASA treatment even outside “traditional 6. If neither they are treated and/or time windows”) QUESTIONS?