Pathoma Central Nervous System Pathology Flashcards
What is wrong in Dandy-Walker syndrome? How will it appear on MRI?
Agenesis of the cerebellar vermis
- > presents as 4th ventricle being too big -> enlarges into posterior fossa
- > most of the cerebellum will be absent
What is the key complication of Dandy-Walker syndrome?
Obstructive (noncommunicating) hydrocephalus due to enlargement of the 4th ventricle
How does Chiari Malformation type I present and what causes it?
Herniation of cerebellar tonsils (1 structure) -> presents as headaches + cerebellar symptoms in adulthood
-> associated with syringomyelia
How does Chiari Malformation type II present and what causes it?
Herniation of cerebellar tonsils + vermis (2 structures) -> 2x as bad, presents in infancy
- > associated with lumbosacral meningomyelocyele
- > ALSO causes aqueductal stenosis -> hydrocephalus in infancy
What is the main way we distinguish ALS from severe syringomyelia?
ALS involves only the motor system
Syringomyelia will cause pain / temperature sensation loss.
What is Werdnig-Hoffman disease similar to? What’s the difference?
Similar to poliomyelitis. Difference is that polio occurs due to infection and causes an asymmetrical LMN degeneration, while SMA I causes a symmetrical degeneration
What is the most common familial ALS mutation, and what is the most common cause overall?
Familial ALS - superoxide dismutase 1 (SOD1) -> leads to free radical injury of neurons
-> overall, usually idiopathic
What is the most common hereditary ataxia in the Western world? What causes it?
Friedreich’s ataxia
- Trinucleotide repeat “GAA”
- Frataxin gene - iron binding protein in mitochondria causing free radical damage - chromosome 9
- > damage to multiple spinal cord tracts, ataxia with hypertrophic cardiomyopathy
- > presents in childhood as kyphoscoliosis
What germ layer gives rise to the meninges? Include the two special terms for meninges.
Leptomeninges - pia / arachnoid mater - neural crest
Pachymeninges - dura mater - mesoderm
What germ layer gives rise to each type of glial cell?
Neuroectoderm -> Macroglia, including astrocytes, oligodendrocytes, and ependymal cells
Mesoderm -> microglia (macrophages are derived from mesenchyme, like blood vessels)
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)***** very high yield to know!
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
- > cortical laminar necrosis - Pyramidal neurons of hippocampus in Sommer’s sector (CA1)
- Cerebellar Purkinje cells
- Watershed zones
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)
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 benign hypertension or diabetes
-> occurs in lenticulostriate arteries most commonly
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: Fluid-filled cystic cavitation surrounded by gliosis
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?
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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
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?
- 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? What will be seen on lumbar puncture?
Congenital loss of the tunica media at the branch points
- > # 1 factor for progression is hypertension
- > hypertension of upper extremities also associated with coarctation of the aorta
Lumbar puncture shows xanthochromia (yellow) or blood depending on how soon after the event it’s taken
What are the two types of transtentorial herniations? What might cause them?
These involve displacement of brain structures through tentorium cerebelli opening (incisure)
- Central - bilateral and symmetric, leading to caudal displacement and compression of entire brainstem -> i.e. due to diffuse brain swelling
- Uncal - unilateral, with herniation of medial temporal lobe into midbrain
- > i.e. due to supratentorial hemorrhage
What are the clinical complications of the two types of transtentorial herniations?
- Central - tends to cause Duret hemorrhages which are fatal
- Uncal - generally compresses ipsilateral CNIII - down-and-out pupil, as well as ipsilateral PCA (contralateral homonymous hemanopsia + macular sparing), + contralateral Crus cerebri problem. May cause Duret hemorrhage as well
What is a tonsillar herniation and what is the usual clinical result?
Herniation of cerebellar tonsils into foramen magnum
Compression of brain stem (medulla) leads to cardiopulmonary arrest
What enzyme is deficient in Metachromatic leukodystrophy and what will accumulate? How is it inherited? Is it common?
Arylsulfatase A - galactocerebroside sulfate will accumulate in Schwann cells / oligodendrocytes (a major component of myelin membranes)
It is an autosomal recessive lysosomal storage disease
It is the MOST COMMON leukodystrophy
How is metachromatic leukodystophy diagnosed / was classically diagnosed?
“metachromasia” in urine spot test due to presence of sulfatides in urine
Also from imaging scans showing demyelination of white matter.
Nerve biopsy showing metachromatic granules
What is defective in Krabbe’s disease? Inheritance pattern?
Galactocerebrosidase -> it is the last step in the galactocerebroside sulfate breakdown pathway, so we know it’s going to be toxic to neurons (like metachromatic leukodystrophy)
it is another autosomal recessive lysosomal storage disease
What are the key symptoms of Krabbe’s disease?
Accumulation of galactocerebroside and psychosine leads to:
- Developmental delay
- Optic atrophy
- “Globoid cells” - multinucleated macrophages filled with lipid material
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