CPAT_3202_Neuro 1_Stroke_2024.pdf

CPAT 3202 – Neuro 1 COMMONWEALTH OF AUSTRALIA Copyright Regulations 1969 WARNING This material has been reproduced and communicated to you by or on behalf of the University of Sydney pursuant to Part VB of the Copy...

CPAT 3202 – Neuro 1 COMMONWEALTH OF AUSTRALIA Copyright Regulations 1969 WARNING This material has been reproduced and communicated to you by or on behalf of the University of Sydney pursuant to Part VB of the Copyright Act 1968 (the Act). The material in this communication may be subject to copyright under the Act. Any further reproduction or communication of this material by you may be the subject of copyright protection under the Act. Do not remove this notice. The University of Sydney Page 1  CPAT 3202 2024 Neuro 1 Stroke Presented by A/Prof Greg Sutherland Neuroscience, SoMS [email protected] The University of Sydney Page 2  Learning Objectives 1. Describe the pathogenesis of cerebral ischaemia 2. Understand the relationship between infarction and the resulting pattern of brain pathology 3. Describe the key morphological features of large vessel and small vessel infarction 4. Identify the common locations for haemorrhagic stroke 5. Describe the pathogenesis of haemorrhagic stroke – Pre-reading – Robbins Basic Pathology 10th Edition: Chapter 4 (p. Edema to Infarction incl.) – Robbins Basic Pathology 10th Edition: Chapter 23 (to Other Vascular Diseases incl.) The University of Sydney Page 3  Importance of stroke 1. Stroke is Australia’s third most common cause of death 2. Leading cause of disability. 3. 60,000 new and recurrent strokes in 2011 4. 1 in 5 people with first-ever stroke die within one month; 1 in 3 die within a year 5. Stroke kills more women than breast cancer and more men than prostate cancer 6. ~ 88 per cent of stroke survivors have a disability 7. Strokes cost Australia ~ $6 billion a year – $6.2 billion dollars in direct financial costs + $26 billion in premature mortality and lost wellbeing (short and long-term disability). The University of Sydney Page 4  Leading causes of death in Australia The University of Sydney Page 5  Stroke = Ischaemia Ischaemia 1. Decrease in blood supply a) Always pathogenic No delivery of nutrients No removal of metabolites Hypoxia 1. Decreased oxygen supply or utilisation a) Not always pathogenic Increase in CBF Removal of metabolites The University of Sydney Delivery of nutrients Page 6  Types of stroke 1. Ischaemic (88%) a) Large artery athero-thrombosis (most common) b) Embolism 2. Haemorrhagic (12%) 3. Unknown Boehringer The University of Sydney Page 7  Consequences of stroke 1. Depends on: a) Type of stroke (thrombotic, embolic, haemorrhagic) b) Size of vessel involved c) Anatomical location of vessel d) Time since stroke occurred (acute, subacute, remote/chronic) e) Treatment (thrombolysis within 4 hours) The University of Sydney Page 8  Risk factors for ischaemic stroke 1. age 2. hypertension 3. obesity and diabetes 4. hyperlipidemia 5. Family history of stroke (genetics) 6. heart disease, particularly atrial fibrillation 7. cigarette smoking 8. previous stroke 9. Ethnicity The University of Sydney Page 9 9  Stroke Subtypes 1. Ischaemic – Large artery athero-thrombosis – Small (penetrating) artery occlusion – Embolism 2. Haemorrhagic The University of Sydney Page 10  The pathogenesis of an athero-thrombus 1. Hyperlipidaemia and endothelial damage 2. Fatty streaks 3. Atherosclerotic plaques (atheroma) 4. Vessel occlusion – slow process 5. Unstable plaque; thin fibrous cap 6. Rupture, release of prothombic necrotic core and thrombus (clot) formation The University of Sydney Page 11 1  Clotting mechanisms Fig 4.10 The University of Sydney Page 12  The pathogenesis of an athero-thrombus The University of Sydney Page 13  Athero-thrombus_micro http://neuropathology-web.org The University of Sydney Page 14  Sites of large artery athero-thrombi 1. Extracranial vessels: AC commonest site for atherosclerosis, especially MC internal carotid artery near common carotid bifurcation B 2. Intracranial vessels: PC IC especially at origin of middle cerebral artery and ends of basilar artery V CC The University of Sydney Page 15  Athero-thrombus The University of Sydney Page 16 The University of Sydney Page 17  Infarct position and size relates to arterial territory ACA MCA MCA MCA PCA The University of Sydney Choroidal PCA Page 18  Large vessel infarct The University of Sydney Page 19  Brain infarct - Pathophysiology 1. Neuronal electrical failure develops at 30% normal cerebral blood flow 2. Membrane failure develops at 15% normal cerebral blood flow 3. Ischemic penumbra retains viability if blood flow is restored, but…. The University of Sydney Page 20  Ischaemic penumbra No flow Partial flow The University of Sydney Page 21  Acute ischemia - molecular events 1. Glutamate release a) Increased intracellular calcium b) Stimulation of reactive intermediates leading to membrane and DNA damage 2. Decreased energy production a) Failure of ionic pumps b) Mitochondrial injury produces free radicals 3. Ischaemia-reperfusion injuries a) Post-treatment (thrombolytic) Leucocyte arrival, inflammation, BBB damage, haemorrhagic infarct The University of Sydney Page 22  Brain infarct: acute ≤ 2 days 1. Softening 2. Swelling secondary to oedema 3. Infiltration of neutrophils 4. Ischemic (“red cell”) neuronal change The University of Sydney Page 23  Brain infarct: subacute days to weeks 1. Liquefaction ® Cavitation 2. Foamy macrophages (start at about 3 days) - remove debris 3. Reactive astrocytes (start at about 10 days) - form glial scar The University of Sydney Page 24  Brain infarct: remote - weeks to ……. 1. Cavitation 2. Glial scar 3. Haemosiderin-laden macrophages The University of Sydney Page 25  Remote infarct The University of Sydney Also see Fig 23.7C Page 26 The University of Sydney Page 27  Stroke Subtypes 1. Ischaemic – Large artery athero-thrombosis – Small (penetrating) artery occlusion – Embolism 2. Haemorrhagic The University of Sydney Page 28  Small penetrating artery infarct “Lacunar” infarct 1. Occlusion (arterial wall fibrous thickening or atheroma) of a small penetrating artery 2. Causes small (up to 2 cm) infarct in deep structures of brain (basal ganglia, thalamus, internal capsule) and in the brain stem 3. Associated with arterial hypertension 4. Transient ischemic attacks (TIA) 5. Often clinically silent The University of Sydney Page 29 The University of Sydney Page 30  “Lacunar” infarcts 731.363.6 The University of Sydney Page 31  Stroke Subtypes 1. Ischaemic – Large artery athero-thrombosis – Small (penetrating) artery occlusion – Embolism 2. Haemorrhagic The University of Sydney Page 32  Embolic infarcts 1. Most embolic strokes are due to cerebral arterial atherothrombosis 2. They may be multiple 3. Most are in the middle cerebral artery territory The University of Sydney Page 33  Sources of emboli Thrombo-emboli Other emboli 1. Artery (carotid artery, 1. Atheroma, cholesterol, aortic arch) calcific debris (from 2. Heart arteries or cardiac valves) a) Left atrium (mitral stenosis, atrial 2. Atrial myxoma fibrillation) 3. Systemic emboli (fat, b) Left ventricle air, amniotic fluid) (myocardial infarction) c) Valves (infective endocarditis) 3. Venous source + cardiac septal defect (rare) The University of Sydney Page 34  Left atrial thrombi & AF The University of Sydney Page 35  Stroke Subtypes 1. Ischaemic – Large artery athero-thrombosis – Small (penetrating) artery occlusion – Embolism 2. Haemorrhagic The University of Sydney Page 36  Parenchymal haemorrhage The University of Sydney Page 37  Major risk factor = hypertension Arteriolar sclerosis (collagen buildup, loss of elasticity and weakening) The University of Sydney Page 38  Small vessels and slit haemorrhages The University of Sydney Page 39  Large vessel haemorrhage 1. Ischaemia 2. Space occupying lesion 3. Secondary injury 4. CT scans – critical to detect haemorrhage – if yes, don’t thrombolyse Also See Fig 23.8 The University of Sydney Page 40  Lobar haemorrhage H&E Congo red 1. Pathogenesis = cerebral amyloid angiopathy (CAA; composed of beta amyloid; CAA seen in > 80% AD)) 2. Most common cause of normotensive stroke in the elderly The University of Sydney Page 41 The University of Sydney Page 42