BSE, CJD and Prions Flashcards
BSE
Bovine Spongifory Encephalopathy
CJD
Creutzfeld Jakob Disease
TSE
Transmissable Spongiform Encephalopthay
What are TSEs?
rare forms of progressive neurodegenerative disorders that affect both humans and animals
What are TSEs caused by?
Prions
What changes occur in the brain?
spongiform - severe atrophy
What is the incubation period?
2-8 years from infection
What is the deterioration period in cows?
2 weeks to 6 months
What is the first phase of BSE?
low infectivity rate and cow is not a threat to humans
What is the second phase of BSE?
cow is very infective but symptoms not apparent
prion is abundant in brain and spinal cord
What is the third phase of BSE?
clinical symptoms followed by death
What changes may be seen in an affected cow?
changes in temprament, nervousness or aggression, abnormal posture, inco-ordination or difficulty rising, decreased milk production or weight loss
How is BSE diagnosed?
via pathology post mortem
microscopic look at brain tissue or detection of abnormal prion protein
What histological findings exist in BSE?
- vacuolation of neurons and neuronal ground substance in cerebella and cortex
- perivascular fibrils of amyloid in PrPsc - immunostaining
- astrocyte infiltrations
When was BSE first identified in Britain?
1985
What was considered the cause of BSE in the UK?
use of meal and bone mill feed (contained infected brain and spinal cords of sheep with scrapies)
How did BSE spread to humans?
large companies used dairy cattle and fatted up their burgers for taste using spinal cord and brain of infected cattle
what is vCJD?
BSE in humans, mostly young patients, 1996 onwards - about right time period
what are the symptoms of CJD?
loss of expressiveness
muscular tremble
spasm
loss of memory & dementia (rare in vCJD)
What are the features of CJD caused by eating the cattle products?
increased risk of CJD - most cases in 2001
predominantly in 20-30 years
What are the clinical features of CJD?
67years, 4 months to live, dementia common, rarely psychiatric issues
what are the clinical features of vCJD?
29years, 13 months to live, dementia is rare, psychiatric illness common
What is the most important variation in prion proteins?
at 129 where it can be a valine or methionine (worse if homozygous)
What are the features of Kuru?
found in papa new guinea
due to cannabilism of the dead
causes fatal cerebellar ataxia
with kuru plaques which are amyloid-like
What are the forms of CJD?
classic and variant
What is a feature of classic CJD?
can be transmitted to other species but they cannot carry it
How is CJD sub-classified?
sporadic >85% cases or iatrogenic (caused by healthcare)
what mutation do the majority of iatrogenic cases have?
90% homo 129 Methionine
How are familial forms of CJD influenced?
by polymorphisms in the 129 Val/Meth
What are the forms of familial CJD?
Familial fatal insomnia
GSS
What occurs in FFI?
4-6th decade autosomal dominant 129 Met leads to FFI Val -> CJD insomnia, ataxia and dementia
What occurs in GSS?
autosomal dominant
PrP mutation Proline 102-Leucine
further influenced by polymorphism
What is the pathology surrounding SEs?
spongiform degeneration
neuronal loss
astrocytic proliferation
anatomical distribution varies between forms of TSE
What are prions?
shortened forms of proteinacious infections particles 250aa
abnormal variants of a protein with normally occurs in a cell PrPc
What do abnormal prions do?
convert normal forms that they come into contact with PrPc->PrPsc
What is the result of the continual conversion of PrPc?
- clusters of tangled, non-functional proteins in plaques
- neuronal apoptosis
What causes the spongiform degeneration?
when the immune system removes the neurons and PrPsc aggregates
What makes prion diseases so difficult to target?
resistant to digestion can't be targeted with antibiotics or anti-virals heat resistant no immune response difficult to decompose biologically
What are the neuropathological criteria for vCJD?
- multiple florid plaques with eosin staining
- severe spongiform changes in caudate nucleus and putamen
- marked astrocytosis and neuronal loss in posterior thalamic nuclei
- PrPsc accumulation in lymphoid tissue around the body
What has been found in the 129 polymorphism in vCJD?
100% have MM at polymorphism
How many sporadic cases of CJD have MM?
65%
