Path: Chapter 22: CNS Pathology Flashcards
‘fried egg’ cells in a brain tumor
oligodendroglioma
biopsy shows: “sheets of regular cells with spherical nuclei containing finely granular chromatin surrounded by a clear halo of cytoplasm”
oligodendroglioma
“fried egg” cells
Genetics of oligodendroglioma?
most common genetic findings are deletions of 1p and 19q, typically occuring together.
tumors w/ these deletions are usually highly responsive to chemo and radiotherapy
calcification of a CNS tumor
calcification is present in 90% of oligodendrogliomas
populations of neurons most susceptible to global cerebral ischemia?
- pyramidal neurons of hippocampus and neocortex
- Purkinje cells of cerebellum
Intracellular vs. extracellular lesions of Alzheimer’s?
intracellular - hyperphosphorylated tau forms neurofibrillary tangles
extracellular - beta amyloid plaques
Order of brain areas in which pathologic changes are observed in Alzheimer’s?
first in ERC, then in hippocampal formation, finally in the neocortex
Neuromyelitis Optica?
inflammatory demyelinating dz centered on optic nerves and spinal cord.
antibodies to AQ4
Presentation of CPM?
central pontine myelinolysis;
because of the involvement of fibers in the pons carrying motor signals to motor neurons in spinal cord, pts often present w/ rapidly evolving quadriplegia
What is in a Lewy body?
alpha-synuclein, neurofilaments and ubiquitin
Genetics of Parkinson’s?
can be caused by mutations in alpha-synuclein, parkin (an E3 ubiquitin ligase), and UCHL-1, an enzyme involved in recycling of ubiquitin from proteins targeted to the proteasome)
Lewy bodies may be found where in Parkinson’s even before nigral involvement?
dorsal motor nucleus of vagas and in reticular formation
Most common primary sites of brain mets?
lung, breast, skin (melanoma), kidney, GI tract
What is the Syndrome of Rapid-Onset psychosis, cataonia, epilepsy, and coma?
a paraneoplastic syndrome associated w/ ovarian teratoma and antibodies against the NMDA receptor
Genetics of glioblastoma?
loss-of-function in p53 or Rb
gain-of-function in PI3K
Genetics of lower-grade astrocytomas?
mutations altering enzymatic activity of isocitrate dehydrogenase (IDH1, IDH2)
Immunostaining for mutated forms of IDH1 has become an important diagnostic tool in evaluating biopsy specimens for the presence of…
low-grade astrocytoma
Genetics of Tuberous Sclerosis?
disruption of either TSC1 (encodes hamartin)
or TSC2 (encodes tuberin)
the two TSC proteins form dimeric complex that negatively regulates mTOR, a kinase that “senses” cell’s nutrient status and regulates cellular metabolism.
increased mTOR activity disrupts nutritional signalling and increases cell growth
increased mTOR activity is central to…
tuberous sclerosis
and everything that it causes
What are shagreen patches?
leathery thickenings in localized patches seen in Tuberous sclerosis
What are ash leaf spots?
hypopigmented areas seen in tuberous sclerosis
Triad of CNS toxoplasmosis?
hydrocephalus, chorioretinitis, intracranial calcifications
What bug causes neurocysticerosis?
Tenia Solium
pork tapeworm; typically presents as a mass lesion
Recurrent HSV-1 encephalitis may be caused by what genetic problem?
mutations involving TLR3
What do you call the intranuclear inclusions of HSV-1?
Cowdry type A bodies
Which type of prion disease features abundant amyloid plaques?
variant CJD
Which type of prion disease can be spread by blood transfusions?
variant CJD
Lesions of the _____________ seem to best correlate with the memory loss observed in Korsakoff syndrome.
medial dorsal nucleus of the thalamus
What are Alzheimer type II cells?
not related to Alzheimer’s!
they are a consequence of hepatic encephalopathy and the resultant hyperammonemia. an Alzheimer type II cell is an astrocyte in the cortex and/or basal ganglia w/ swollen, pale nuclei due to lots of ammonia processing
Timeline of healing for subdural hematoma?
lysis of the clot (1 week)
growth of granulation tissue from dural surface into hematoma (2 weeks)
fibrosis (1 - 3 months)
Most common sites for Berry aneurysm?
40% - junction of AComm and ACA
34% - junction of M1 of MCA and M2 of MCA
20% - juntion of internal carotid and PComm
Only one type of aneurysm is found more commonly in posterior circulation:
atherosclerotic aneurysm (in the basilar artery)
Cytoplasmic inclusions in ALS are composed of what?
TDP-43 (except in those cases of ALS caused by a mutation in SOD-1 [super oxide dismutase -1]
What does neurofibromin normally do?
neurofibromin is a negative regulator of the oncoprotein Ras
neurofibromin is on chromosome 17 and is mutated in the condition Neurofibromatosis 1
Cutaneous signs of Neurofibromatosis 1?
cafe-au-lait spots (areas of hyperpigmentation)
and Lisch nodules (pigmented nodules of the iris)
Which artery may be compressed by an uncal herniation?
PCA
and don’t forget about kinking of basilar artery -> Duret hemorrhages
There is an association b/t meningiomas and what congenital CNS-tumor disorder?
NF2
mutation on chromosome 22. even 50% of sporadic meningiomas have mutations in NF2 gene
‘Midline tumor on cerebellar vermis’
medulloblastoma (typically kids get midline medullos, lateral tumors are seen in adults but this is rare)
Genetics of medulloblastoma?
in general, tumors associated w/ MYC mutations have poor prognosis
tumors w/ WNT mutations have a better course
mutations in sonic hedgehog also occur but no one knows what this means
Most common demyelinating disorder?
MS
Polymorphisms in what cytokines may predispose to MS?
IL-2 and IL-7
and don’t forget about HLA-DR2
Type of T cells involved in MS?
Th17 and Th1 cells
In what form of dementia would you see microglial nodules w/ multinucleate giant cells?
AIDS
Locations of ependymomas?
first 2 decades of life - 4th ventricle
adults - spinal cord
Genetics of NF2?
loss of function mutation in merlin gene of chromosome 22
cytoskeletal protein that facilitates E-cadherin mediated contact inhibition
Genetics of pilocytic astrocytoma?
BRAF mutations
often V600E
Neurons most affected by hypoglycemia?
hippocampal pyramidal neurons most affected
purkinje neurons of the cerebellum relatively spared
