Cerebrovascular Diseases Flashcards
What regions of the brain are supplied by:
- PCA
- MCA
- ACA
Circle of Willis
What is hypoxia?
Deprivation of O2 in the brain
What are the 3 mechanisms of hypoxia?
What are some examples?
-
Low level of O2 in blood
- Respiratory arrest, near drowning, severe anemia, CO poisoning
-
Low blood flow to tissue (ischemia)
- Cardiac arrest, vessel obstruction, increased intracranial pressure
-
O2 utilization by tissue is impaired
- Cyanide poisoning
Which statement is true?
- Ischemia causes more damage than hypoxia.
- Hypoxia causes more damage than ischemia.
Ischemia causes more damage than hypoxia.
What is global ischemia?
- Systolic pressure <50 mmHg
- Generalized reduction in cerebral perfusion, usually due to cardiac arrest, shock or severe hypotension
- Clinical outcome dependent upon severity & duration of ischemia
With global ischemia, where is the damage most severe? What can this cause?
- Brain damage is most severe in watershed/borderzone territories
- If ischemia is severe, widespread neuronal death may result in:
- Persistent vegetative state
- Brain death
Borderline infarcts occur in watershed areas between……
Anterior cerebral & middle cerebral arteries
Middle & posterior cerebral arteries
Focal Ischemia
Definition
Causes
- Infarction from obstruction of local blood supply (stroke)
- Results from arterial stenosis and/or thrombosis, atheroemboli or thromboemboli
What is selective vulnerability?
Certain brain cells & regions are more susceptible to hypoxia/ischemia than others
What are the 3 most vulnerable cells of the brain?
(in decreasing order)
- Neurons
- Oligodendrocytes
- Astrocytes
What are the 3 most vulnerable regions of the brain?
(in decreasing order)
- Hippocampus (CA1 sector – Sommer sector)
- Lamina 3 & 5 of cerebral cortex (laminar necrosis)
- Purkinje cells in cerebellum
What determines selective vulnerability?
- Variable O2/energy requirements of different neurons & neuronal populations
-
Glutamate receptor densities
- Glutamate is neurotoxic when present in excess, as occurs in hypoxic/ischemic brain damage
What do acutely hypoxic/ischemic neurons look like microscopically?
- “Red is dead”
- Pyknotic cell w/ shrunken & dark nucleus, no nucleolus visible
- Red cytoplasm (no Nissl substance visible)
What is severe global ischemia?
- Severe ischemia –> widespread neuronal death irrespective of regional vulnerability
- Corresponds to brain death
- Non-perfused brain
What are the clinical signs & symptoms of severe global ischemia?
-
Persistent vegetative state
- Unconscious, but w/ retention of sleep-wake cycles, primitive orienting responses, brainstem & diencephalon reflexes
-
Brain death
- Diffuse irreversible cortical injury w/ brainstem injury (absent reflexes & respiratory drive)
What does severe global ischemia look like….
Grossly?
Microscopically?
-
Gross
- Swollen brain
- Slit-like ventricles
- Often herniation
-
Microscopic
- Pallor
- Vacuolation of parenchyma
- Sparse eosinophilic neurons
What are the 3 most common causes of focal ischemia?
- Thrombosis
- Emboli
- Lacunar infarcts/slit hemorrhages
How does thrombosis cause focal ischemia?
- Atherosclerosis
- Most common sites
- Carotid bifurcation
- Origin of middle cerebral artery
- Origin or end of basilar artery
How do emboli cause focal ischemia?
Cardiac vs. non-cardiac sources?
- Infarcts are most likely hemorrhagic
-
Cardiac source
- Mural thrombus
- L atrium or L ventricle
- Predisposing factors: MI, valve disease, atrial fibrillation, paradoxical embolism
- Endocarditis
- Bacterial or marantic
- Mural thrombus
-
Non-cardiac source
- Atheroma (plaques in carotid arteries)
- Fat, neoplasm, air
______ is the most frequent vessel affected by emboli.
MCA
How do lacunar infarcts/slit hemorrhages cause focal ischemia?
- Hyaline arteriolosclerosis (HTN & DM)
-
Lacunes
- Small strokes (<1-1.5cm) in subcortical brain structures
- Basal ganglia, internal capsule, thalamus, white matter, pons
- May be hemorrhagic
What are some less common causes of infarction? (6)
-
Vasculitis
- Non-infectious causes
- Infectious causes
- Arterial dissection of carotid arteries
- Coagulation disorders
- Microvasculopathy
- Arteriosclerotic Leukoencephalopathy
- CADASIL
- Amyloid angiopathy
- Drug abuse
What is primary angiitis (vasculitis) of the CNS?
What is it characterized by?
Histology?
- Involves multiple small/medium sized meningeal & parenchymal vessels
-
Characterized by
- Chronic inflammation
- Fibrinoid necrosis
- Multinucleated giant cells
- Wall destruction
- Histology: fibrinoid necrosis of vessel wall w/ inflammation
**Gross Morphology of Infarct **
- Acute
- Subacute
- Chronic
-
Acute
- Up to 48 hrs
- Soft, swollen
- Gray-white distinction blurred
-
Subacute
- Up to 2-3 wks
- Liquefactive necrosis
-
Chronic
- Several months
- Cavitated, all dead tissue removed
Microscopic Morphology of Infarct
- Acute
- Subacute
- Chronic
-
Acute
- 8-12 hrs: red neurons, pallor
- Up to 48 hrs: neutrophils (not always)
-
Subacute
- 48 hrs to 3 wks
- MΦ, necrotic tissue, reactive astrocytes, vascular proliferation
-
Chronic
- Several months: cavity w/ glial scar
What does an acute infarct look like microscopically?
- Pallor, neutrophils
- Preservation of small area around vessel
- Red neurons
Subacute infarct
Histology
Imaging
- Days to wks
-
Histology
- Liquefactive necrosis
- Many MΦ, reactive astrocytes, vascular proliferation, necrotic tissue
-
Imaging
- Maximum swelling
- Shifting of midline structures
- Compression of uninfarcted areas
Chronic Infarct
Gross/Histology
Imaging
- Gross/Histology: cavity w/ fibrillary astrocytic scar
- Imaging: large cavity, scar tissue
Vascular Dementia
Definition
Patterns of damage
- Clinical S/S: stepwise progression
- Patterns of damage
- Small areas of infarction – multiple lacunar infarcts
- Diffuse white matter disease – Binzwanger disease & CADASIL
-
Strategic infarcts – areas important for cognition/memory
- Hippocampus, dorsomedial thalamus, frontal cortex, cingulate cortex
- Many individuals will have multiple strokes & some changes of Alzheimer’s disease (mixed dementia)
Cerebral Venous Thrombosis
Definition
Causes
- Hemorrhagic infarcts
-
Superior sagittal sinus or lateral sinuses
- Parasagittal hemorrhagic infarcts
- Causes
- Infection, injury, neoplasm, surgery
- Pregnancy, oral contraceptives, hematologic abnormalities, dehydration, malignancy
What are the 3 major causes of Intracerebral Hemorrhage?
- HTN
- Vascular Malformations
- Amyloid angiopathy
How does HTN cause intracerebral hemorrhage?
- Most common cause of primary ICH
- Peak occurrence in 60s
- Abrupt onset of severe neurologic dysfunction when hematoma is large
- Putamen, thalamus, pons, cerebellum
- Hyaline arteriolosclerosis
What does hypertensive intracerebral hemorrhage look like….
Grossly?
Histologically?
- Gross
- Extravasation of blood, compression of adjacent brain
- Histology
- Hyaline arteriolosclerosis
- Weakens arteriole & predisposes rupture
- Charcot-Bouchard microaneurysm
What are the 2 types of vascular malformations that cause intracerebral hemorrhage?
- Arteriovenous malformations
- Cavernous angioma
Arteriovenous Malformation
Definition
Epidemiology
Clinical Presentation
- Most common
- M > F
- 10-30 YO
- MCA distribution
- Can present w/ bleeding
- Often presents as:
- Seizures
- Headaches
- Focal deficits
Arteriovenous Malformation
Gross
Histology
- Gross
- Tangled network of vessels w/ arteriovenous shunt
- Histology
- Greatly enlarged blood vessels separated by gliotic tissue (evidence of prior hemorrhage)
What is a cavernous angioma?
- Cerebellum, pons, white matter
- No intervening brain tissue
- _Evidence of prior bleeding _
What is amyloid angiopathy?
- Deposition of β-amyloid into the vessel wall
- Elderly, Alzheimer’s disease
- Histology: Congo red stain, β-amyloid immunostain
What are 5 common causes of lobar hemorrhage?
- Neoplasms
- Drug abuse
- Vasculitis
- Hemorrhagic diathesis
- Amyloid angiopathy
What are the 2 common causes of subarachnoid hemorrhage?
- Trauma
- Aneurysms
What types of aneurysms can cause a subarachnoid hemorrhage? (3)
- Saccular (berry)
- Mycotic (fungus)
- Fusiform, atherosclerotic
Saccular “Berry” Aneurysm
Definition
Clinical Presentation
Histology
- “The worse headache I’ve ever had!”
- Increased risk w/ HTN, smoking, AVM, etc.
- Increasing risk of rupture as size increases
- Not present at birth, but defect in media is congenital & aneurysm develops over time
- Occurs at branch points, 90% in anterior circulation
- Histology
- Fibrous wall
- Defect in elastic & media (elastic stain)
