Pathology of Cerebrovascular Disease Flashcards
What is the most important predisposing factor to cerebrovascular disease and is it worse in intracranial or extracranial vessels?
Atherosclerosis
- could be worse in either, not necessarily occurring together
- intracranial vessels i.e. circle of willis
- extracranial vessels i.e. vertebral artery, internal carotid artery
Other than atherosclerosis, what are some other vascular disorders which can cause damage to the brain?
Arteriolosclerosis - i.e. hyaline, due to chronic HTN or diabetes
Aneurysms - saccular, mycotic
Cerebral amyloid angiopathy - Abeta amyloid
Vasculitidies
Clotting disorders
Nonthrombotic emboli
What gives rise to the anterior and posterior circulation of the brain?
Anterior - internal carotid arteries. Includes anterior and middle cerebral arteries
Posterior - vertebral arteries. Combine to form basilar and splits to form posterior cerebral arteries.
Give the arteries travelled around one trip of the circle of Willis, starting at basilar artery
Top of basilar artery -> P1 segment of PCA -> PCA junction -> posterior communicating artery -> MCA/ICA junction -> A1 segment of ACA -> anterior communicating artery -> A1 segment of ACA -> MCA/ICA junction -> posterior communicating artery -> PCA junction -> P1 segment of PCA -> top of basilar artery.
What are the main arteries supplying the basal ganglia and thalamus?
Basal ganglia - lenticulostriate arteries - arise from M1 segment of MCA
Thalamus - branches of the posterior cerebral artery
What artery supplies the medial convexity of the brain? The lateral surface?
Medial convexity - primarily the ACA, back to the occipital lobe, then it’s he PCA
Lateral surface - supplied by MCA
What makes cutting off blood supply to the brain so problematic and which zones are most susceptible?
There is no collateral circulation. Watershed zones (border zones) are susceptible to decreased flow and oxygen delivery
What is the definition of stroke? TIA?
Acute neurologic dysfunction developing over minutes / hours which rapidly progresses, due to parenchymal damage due to a vascular process. Continues for more than 24 hours
TIA will have symptoms resolve in less than 24 hours (no lasting damage)
What is diffuse hypoxic ischemic injury?
Injury reflecting global brain insult such as systemic hypotension or hypoxia
What is the pathology of a brain infarct known as?
Encephalomalacia - brain softening
What is the timeline of histological changes which occur in ischemic stroke?
12 hours: Red dead neurons - eosinophilic cytoplasm with pyknosis
24-72 hours: Necrosis + neutrophilic acute inflammation
3-5 days: Microglial infiltration + liquefaction, inflammatory edema peaks
1-2 weeks: Gliosis with increased astrocytes / progressive liquefaction and removal of necrotic debris
Weeks later: Fluild-filled cystic cavitation surrounded by gliosis
What neurons in the brain are most susceptible to ischemic infarct during diffuse ischemic injury?
- Pyramidal neurons of cortex in layers 3, 5, and 6
- Pyramidal neurons of hippocampus in Sommer’s sector (CA1)
- Cerebellar Purkinje cells
- Watershed zones
What is the most likely cause of death in a patient with stroke?
Increased ICP due to inflammatory edema which occurs a few days after stroke (influx of neutrophils and microglial cells with brain swelling due to vasogenic / cytotoxic edema)
When is development of a secondary hemorrhagic infarct common?
Embolic (rather than thrombotic, superimposed on vessel) stroke, where the embolus is broken up by the body so the organ is reperfused.
What is a lacunar stroke and why do they generally occur?
A small infarct (<1cm) which occurs due to small vessel occlusion.
Commonly due to hyaline arteriolosclerosis secondary to chronic hypertension
-> occurs in lenticulostriate arteries most commonly
What secondary changes occur in the brain following infarct?
Wallerian degeneration of affected fiber pathway
Atrophy of involved adjacent structures (orthograde or retrograde degeneration)
Hydrocephalus ex vacuo may occur
What are the causes of diffuse hypoxic / ischemic injury in the brain (global stroke)?
- Global ischemia -> failure of systemic circulation (i.e. cardiogenic shock, atherosclerosis)
- Systemic hypoxia -> anemia, CO poisoning, or respiratory issue
- Hypoglycemia -> systemic, i.e. due to insulinoma (brain needs glucose)
What are the mediators of neural injury in ischemia?
- O2 deprivation
- Metabolic disruption: calcium influx, lactate buildup, free radical damage due to reperfusion
- Release of excitotoxins during injury (glutamate, aspartate) -> more calcium influx
How long does it take for ischemic injury to set in for neurons?
About 5 minutes. Cessation of function occurs in just 10 seconds though.
How does glucose affect cellular damage in stroke? How does temperature?
Hyperglycemia - promotes damage dude to overproduction of lactate, slight hypoglycemia may be protective
Temperature - hypothermia (under 30 degrees C) permits longer period of ischemic cell survival
What happens in mild, moderate, and severe diffuse hypoxic/ischemic injury? What condition does this cause varying degrees of?
These are varying degrees of diffuse encephalopathy:
Mild - Transient post-ischemic confusion with recovery
Moderate - damage to most susceptible areas -> permanent deficits in memory / learning, ataxia, etc
Severe - diffuse necrosis = persistent vegetative state -> if some autonomic / brainstem functions are spared
What is it called when you have necrosis of cerebral cortex layers 3, 5, and 6?
Laminar necrosis -> affecting only certain laminae
How do brain death and respirator brain occur?
Ultra-severe diffuse encephalopathy
-> prolonged ischemic affects even brainstem
Braindeath: cessation of electrical activity and cerebral blood flow
Respirator brain: autolytic change from failure of perfusion following diffuse brain swelling
What are the most common types of nontraumatic and traumatic intracranial hemorrhages?
Nontraumatic - intraparenchymal hemorrhage and subarachnoid hemorrhage
Traumatic - epidural and subdural hematoma (but can be any compartment)
What are the two types of intraparenchymal hemorrhage? Where do they each occur?
- Ganglionic - “deep” - occurs in basal ganglia (lenticulostriate arteries), thalamus, pons, or deep cerebral hemisphere
- Lobar - superficial in cerebral lobes, not as severe
What are the causes of each type of intraparenchymal hemorrhage?
Ganglionic - typically secondary to chronic hypertension -> arteriosclerosis of small vessels with formation of Charcot-Bouchard aneurysms -> massive rupture / bleed
Lobar - May also be secondary to hypertension, but often due to cerebral amyloid angiopathy, vascular malformations, coagulopathies, or vasculitis
What is the clinical presentation of intraparenchymal hemorrhage?
Massive headache, nausea, vomiting, and rapid loss of consciousness due to increased ICP
Ganglionic - more severe, usually causes massive hemorrhage which is lethal
Lobar - variable clinic outcome depending on severity
If one is to ultimately survive intraparenchymal hemorrhage, what does the pathology look like?
Hematoma is resorbed from periphery, and cavity is ultimately formed with gliotic hemosiderin-stained brain surrounding it
Where in the brain does subarachnoid hemorrhage usually occur and what are two important causes?
Usually occurs at the base of the brain where the Circle of Willis lies
- Saccular “berry” aneurysm
- Congenital arteriovenous malformation
What conditions predispose to berry aneurysms and where do they often occur? How do they predispose?
- Autosomal dominant polycystic kidney disease
- Marfan syndrome
Often occur at branch points in the circle of willis:
- Anterior communicating/ACA junction
- Posterior communicating / MCA junction
- MCA/lenticulostriate junction
How do the associated syndromes of berry aneurysm predispose to forming them and what is the #1 factor for their progression?
Congenital loss of the tunica media at the branch points
-> #1 factor for progression is hypertension
What is the clinical presentation of subarachnoid hemorrhage? What will lumbar puncture show?
Acute onset of “most severe headache of my life” due to stretching of blood vessels
-> rapid deterioration of neurologic function and increasing ICP
Lumbar puncture shows xanthochromia (yellow) or blood depending on how soon after the event it’s taken
What are the acute and chronic complications of subarachnoid hemorrhage and what drug can be used to reduce this?
Acute - arterial vasospasm leading to ischemia / infarction of structures supplied by vessels (secondary ischemic stroke)
-> prevented by nimodipine
Chronic - Breakdown of hematoma with scarring which may cause a communicating hydrocephalus (damage to granulations)
What is the most common location for lacunar infarcts secondary to hypertension?
Basal ganglia and internal capsule (deep cerebral white matter)
Other that Charcot-Bouchard aneurysms and lacunar infarcts, what is one important brain pathology finding that chronic hypertension can cause?
Etat crible - loss of tissue density around small arteries without any infarction
“perivascular vacuolization”
- frequently occurs in basal ganglia or white matter
What brain syndrome does chronic hypertension cause?
Chronic hypertensive encephalopathy - progressive vascular dementia, gait abnormlaities, loss of reflex inhibition (pseudobulbar signs), and focal deficits
What does malignant hypertension cause in the brain and clinically?
Acute hypertensive encephalopathy
Increased ICP, confusion, headache, brain edema, petechial hemorrhages, and fibrinoid necrosis of arterioles
