L4 Prion Disease Flashcards
what types of disease come under transmissble spongiform encephalopathies and what species are they related to
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
what is the neuropatholgy involved in prion
spongiosis
astrocytosis
neuronal loss
amyloid deposits
what macroscopic changes are seen in sporadic CJD
spongiform perineural PrP kuru-like plaques gliosis and spongiform change synaptic PrP perivacuolar staining
what % of human prion diseases are inherited, sporadic, acquired
15% - inherited
85% - sporadic
acquired - rare
what are the clinical presentations in sporadic CJD
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psychiatric = depression, withdrawn, hallucinations, delusions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
what can mimic sporadic CJD
steroid responsive, NMDA, VGKC primary/secondary vasculitis viral encephalitis hepatic encephalopathy neoplastic syndromes vitamin deficiences drug toxicities AD DLB FTD-MND
what can a CSF test /EEG/MRIshow in sporadic CJD
CSF - not particularly specific
EEG - pseudoperiodic sharp wave activity in around 40-50%
MRI - becoming most valuable test - 90% sensitive (DWI, FLAIR sequences best)
properties of sporadic CJD
- fast
- little peripheral prion infection
- caudate, putamen, cortex, thalamus
- monoglycosylated on Western blot
- transmission to lab animals
properties of acquired (variant) CJD
modestly fast marked peripheral infection striatum, pulvinar nucleus not modified by oral or IV exposure diglycosylated on Western transmission to lab animals
what is brighter in a FLAIR scan for sporadic vs variant
striatum or thalamus
sporadic: striatum brighter
variant: thalamus brighter
How are amplification assays tests done? How specific are they
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
what is RT-QuIC
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.
what are features of vCJD variant
psychiatric abnormalities: depression delusion hallucinations dysaesthesiae and pain: usually lower limbs, persistent and unrelated to anxiety level, no sensory signs
what are later clinical features of vCJD
dementia (5-6months after onset)
ataxia (6-7 m)
myoclonus, chorea, athetosis (9m)
akinetic mutism (12-14m)
name 2 structures bright on MRI in vCJD
pulvinar
thalamus