L4 Prion Disease Flashcards

1
Q

what types of disease come under transmissble spongiform encephalopathies and what species are they related to

A
scrapie = sheep and goats
mink encephalopathy
chronic wasting disease = mule deer elk
 bovine S E = cattle
feline SE = domestic cats
kuru = humans
creutzfeldt-Jakob disease = humans 
Gerstmann-Straussler-Scheinker disease = humans
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2
Q

what is the neuropatholgy involved in prion

A

spongiosis
astrocytosis
neuronal loss
amyloid deposits

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3
Q

what macroscopic changes are seen in sporadic CJD

A
spongiform
perineural PrP
kuru-like plaques
gliosis and spongiform change
synaptic PrP
perivacuolar staining
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4
Q

what % of human prion diseases are inherited, sporadic, acquired

A

15% - inherited
85% - sporadic
acquired - rare

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5
Q

what are the clinical presentations in sporadic CJD

A

cortico-basal syndrome = dominated by extrapyramidal symptoms, dsypraxia, asymmetry

stroke-like = asymmetrical rapid-onset motor presentation

sleep/thalamic = disordered sleep peripheral pain or sensory disturbance

visual variant = cortical blindess, hallucinations

psychiatric = depression, withdrawn, hallucinations, delusions

ataxic variant = myoclonus

cognitive = executive dysfunction, expressive dysphasia, parietal lobe signs, apraxia

classical = global cognitive decline, cerebellar ataxia, myoclonus, motor signs

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6
Q

what can mimic sporadic CJD

A
steroid responsive, NMDA, VGKC
primary/secondary vasculitis
viral encephalitis
hepatic encephalopathy
neoplastic syndromes
vitamin deficiences
drug toxicities
AD
DLB
FTD-MND
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7
Q

what can a CSF test /EEG/MRIshow in sporadic CJD

A

CSF - not particularly specific
EEG - pseudoperiodic sharp wave activity in around 40-50%
MRI - becoming most valuable test - 90% sensitive (DWI, FLAIR sequences best)

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8
Q

properties of sporadic CJD

A
  • fast
  • little peripheral prion infection
  • caudate, putamen, cortex, thalamus
  • monoglycosylated on Western blot
  • transmission to lab animals
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9
Q

properties of acquired (variant) CJD

A
modestly fast
marked peripheral infection
striatum, pulvinar nucleus
not modified by oral or IV exposure
diglycosylated on Western
transmission to lab animals
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10
Q

what is brighter in a FLAIR scan for sporadic vs variant

striatum or thalamus

A

sporadic: striatum brighter
variant: thalamus brighter

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11
Q

How are amplification assays tests done? How specific are they

A

90% specific
1.prion seed in the biofluid csf
put it in the reaction mixture that contains recond prp (without any glycosilation)
2. incubate at 40 degrees and shake - creates strucuturl impact on aggregates where you form bubbles at the water surface
replicate prion dieases
3. or do sonication
4. monitor with dyes
on traces first have lag time then get burst of exponential growth then levels off

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12
Q

what is RT-QuIC

A

real time quaking induced conversion assay (RT-QuIC) method, which measures the activity of PrP aggregates or amyloid formation triggered by PrP seeds in the presence of recombinant PrP.

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13
Q

what are features of vCJD variant

A
psychiatric abnormalities:
depression
delusion
hallucinations
dysaesthesiae and pain:
usually lower limbs, persistent and unrelated to anxiety level, no sensory signs
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14
Q

what are later clinical features of vCJD

A

dementia (5-6months after onset)
ataxia (6-7 m)
myoclonus, chorea, athetosis (9m)
akinetic mutism (12-14m)

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15
Q

name 2 structures bright on MRI in vCJD

A

pulvinar

thalamus

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16
Q

what do the 3 bands mean in the western blot for biochemical profiles

A

different glycosylation states

17
Q

type 1,2,3 is observed in what types of prion

A

sporadic CJD
iatrogenic CJD
kuru
PrP^Sc type with codon 129 genotype

18
Q

type 4 of PrP^Sc is observed in…

A

100% of all vCJD cases tested

19
Q

what are the ways of secondary transmission in prion

A
blood
blood products
surgery
dentistry
organ donation
20
Q

what is the gene like in inherited prion disease

A

gene has different structures

21
Q

what mutation is it you have you may be resistant to koru

A

g127v

22
Q

what are the names of some inherited prion disease and what are their features

A

GSS = progressive chronic ataxia with pyramidal features with a late onset dementia
FFI = progressive insomnia, dysautonomia, dementia
Familial CJD = dementias, myoclonus, ataxia, chorea seizures, amyotrophic features