Path: Chapter 22: CNS Pathology

Question 1

‘fried egg’ cells in a brain tumor

Answer 1

oligodendroglioma

Question 2

biopsy shows: “sheets of regular cells with spherical nuclei containing finely granular chromatin surrounded by a clear halo of cytoplasm”

Answer 2

oligodendroglioma

“fried egg” cells

Question 3

Genetics of oligodendroglioma?

Answer 3

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

Question 4

calcification of a CNS tumor

Answer 4

calcification is present in 90% of oligodendrogliomas

Question 5

populations of neurons most susceptible to global cerebral ischemia?

Answer 5

• pyramidal neurons of hippocampus and neocortex

- Purkinje cells of cerebellum

Question 6

Intracellular vs. extracellular lesions of Alzheimer’s?

Answer 6

intracellular - hyperphosphorylated tau forms neurofibrillary tangles

extracellular - beta amyloid plaques

Question 7

Order of brain areas in which pathologic changes are observed in Alzheimer’s?

Answer 7

first in ERC, then in hippocampal formation, finally in the neocortex

Question 8

Neuromyelitis Optica?

Answer 8

inflammatory demyelinating dz centered on optic nerves and spinal cord.

antibodies to AQ4

Question 9

Presentation of CPM?

Answer 9

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

Question 10

What is in a Lewy body?

Answer 10

alpha-synuclein, neurofilaments and ubiquitin

Question 11

Genetics of Parkinson’s?

Answer 11

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)

Question 12

Lewy bodies may be found where in Parkinson’s even before nigral involvement?

Answer 12

dorsal motor nucleus of vagas and in reticular formation

Question 13

Most common primary sites of brain mets?

Answer 13

lung, breast, skin (melanoma), kidney, GI tract

Question 14

What is the Syndrome of Rapid-Onset psychosis, cataonia, epilepsy, and coma?

Answer 14

a paraneoplastic syndrome associated w/ ovarian teratoma and antibodies against the NMDA receptor

Question 15

Genetics of glioblastoma?

Answer 15

loss-of-function in p53 or Rb

gain-of-function in PI3K

Question 16

Genetics of lower-grade astrocytomas?

Answer 16

mutations altering enzymatic activity of isocitrate dehydrogenase (IDH1, IDH2)

Question 17

Immunostaining for mutated forms of IDH1 has become an important diagnostic tool in evaluating biopsy specimens for the presence of…

Answer 17

low-grade astrocytoma

Question 18

Genetics of Tuberous Sclerosis?

Answer 18

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

Question 19

increased mTOR activity is central to…

Answer 19

tuberous sclerosis

and everything that it causes

Question 20

What are shagreen patches?

Answer 20

leathery thickenings in localized patches seen in Tuberous sclerosis

Question 21

What are ash leaf spots?

Answer 21

hypopigmented areas seen in tuberous sclerosis

Question 22

Triad of CNS toxoplasmosis?

Answer 22

hydrocephalus, chorioretinitis, intracranial calcifications

Question 23

What bug causes neurocysticerosis?

Answer 23

Tenia Solium

pork tapeworm; typically presents as a mass lesion

Question 24

Recurrent HSV-1 encephalitis may be caused by what genetic problem?

Answer 24

mutations involving TLR3

Question 25

What do you call the intranuclear inclusions of HSV-1?

Answer 25

Cowdry type A bodies

Question 26

Which type of prion disease features abundant amyloid plaques?

Answer 26

variant CJD

Question 27

Which type of prion disease can be spread by blood transfusions?

Answer 27

variant CJD

Question 28

Lesions of the _____________ seem to best correlate with the memory loss observed in Korsakoff syndrome.

Answer 28

medial dorsal nucleus of the thalamus

Question 29

What are Alzheimer type II cells?

Answer 29

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

Question 30

Timeline of healing for subdural hematoma?

Answer 30

lysis of the clot (1 week) growth of granulation tissue from dural surface into hematoma (2 weeks) fibrosis (1 - 3 months)

Question 31

Most common sites for Berry aneurysm?

Answer 31

40% - junction of AComm and ACA 34% - junction of M1 of MCA and M2 of MCA 20% - juntion of internal carotid and PComm

Question 32

Only one type of aneurysm is found more commonly in posterior circulation:

Answer 32

atherosclerotic aneurysm (in the basilar artery)

Question 33

Cytoplasmic inclusions in ALS are composed of what?

Answer 33

TDP-43 (except in those cases of ALS caused by a mutation in SOD-1 [super oxide dismutase -1]

Question 34

What does neurofibromin normally do?

Answer 34

neurofibromin is a negative regulator of the oncoprotein Ras | neurofibromin is on chromosome 17 and is mutated in the condition Neurofibromatosis 1

Question 35

Cutaneous signs of Neurofibromatosis 1?

Answer 35

cafe-au-lait spots (areas of hyperpigmentation) | and Lisch nodules (pigmented nodules of the iris)

Question 36

Which artery may be compressed by an uncal herniation?

Answer 36

PCA | and don't forget about kinking of basilar artery -> Duret hemorrhages

Question 37

There is an association b/t meningiomas and what congenital CNS-tumor disorder?

Answer 37

NF2 | mutation on chromosome 22. even 50% of sporadic meningiomas have mutations in NF2 gene

Question 38

'Midline tumor on cerebellar vermis'

Answer 38

medulloblastoma (typically kids get midline medullos, lateral tumors are seen in adults but this is rare)

Question 39

Genetics of medulloblastoma?

Answer 39

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

Question 40

Most common demyelinating disorder?

Answer 40

MS

Question 41

Polymorphisms in what cytokines may predispose to MS?

Answer 41

IL-2 and IL-7 | and don't forget about HLA-DR2

Question 42

Type of T cells involved in MS?

Answer 42

Th17 and Th1 cells

Question 43

In what form of dementia would you see microglial nodules w/ multinucleate giant cells?

Answer 43

AIDS

Question 44

Locations of ependymomas?

Answer 44

first 2 decades of life - 4th ventricle | adults - spinal cord

Question 45

Genetics of NF2?

Answer 45

loss of function mutation in merlin gene of chromosome 22 | cytoskeletal protein that facilitates E-cadherin mediated contact inhibition

Question 46

Genetics of pilocytic astrocytoma?

Answer 46

BRAF mutations | often V600E

Question 47

Neurons most affected by hypoglycemia?

Answer 47

hippocampal pyramidal neurons most affected purkinje neurons of the cerebellum relatively spared