BSE, CJD and Prions

Question 1

BSE

Answer 1

Bovine Spongifory Encephalopathy

Question 2

CJD

Answer 2

Creutzfeld Jakob Disease

Question 3

TSE

Answer 3

Transmissable Spongiform Encephalopthay

Question 4

What are TSEs?

Answer 4

rare forms of progressive neurodegenerative disorders that affect both humans and animals

Question 5

What are TSEs caused by?

Answer 5

Prions

Question 6

What changes occur in the brain?

Answer 6

spongiform - severe atrophy

Question 7

What is the incubation period?

Answer 7

2-8 years from infection

Question 8

What is the deterioration period in cows?

Answer 8

2 weeks to 6 months

Question 9

What is the first phase of BSE?

Answer 9

low infectivity rate and cow is not a threat to humans

Question 10

What is the second phase of BSE?

Answer 10

cow is very infective but symptoms not apparent

prion is abundant in brain and spinal cord

Question 11

What is the third phase of BSE?

Answer 11

clinical symptoms followed by death

Question 12

What changes may be seen in an affected cow?

Answer 12

changes in temprament, nervousness or aggression, abnormal posture, inco-ordination or difficulty rising, decreased milk production or weight loss

Question 13

How is BSE diagnosed?

Answer 13

via pathology post mortem

microscopic look at brain tissue or detection of abnormal prion protein

Question 14

What histological findings exist in BSE?

Answer 14

• vacuolation of neurons and neuronal ground substance in cerebella and cortex
• perivascular fibrils of amyloid in PrPsc - immunostaining
• astrocyte infiltrations

Question 15

When was BSE first identified in Britain?

Answer 15

1985

Question 16

What was considered the cause of BSE in the UK?

Answer 16

use of meal and bone mill feed (contained infected brain and spinal cords of sheep with scrapies)

Question 17

How did BSE spread to humans?

Answer 17

large companies used dairy cattle and fatted up their burgers for taste using spinal cord and brain of infected cattle

Question 18

what is vCJD?

Answer 18

BSE in humans, mostly young patients, 1996 onwards - about right time period

Question 19

what are the symptoms of CJD?

Answer 19

loss of expressiveness
muscular tremble
spasm
loss of memory & dementia (rare in vCJD)

Question 20

What are the features of CJD caused by eating the cattle products?

Answer 20

increased risk of CJD - most cases in 2001

predominantly in 20-30 years

Question 21

What are the clinical features of CJD?

Answer 21

67years, 4 months to live, dementia common, rarely psychiatric issues

Question 22

what are the clinical features of vCJD?

Answer 22

29years, 13 months to live, dementia is rare, psychiatric illness common

Question 23

What is the most important variation in prion proteins?

Answer 23

at 129 where it can be a valine or methionine (worse if homozygous)

Question 24

What are the features of Kuru?

Answer 24

found in papa new guinea
due to cannabilism of the dead
causes fatal cerebellar ataxia
with kuru plaques which are amyloid-like

Question 25

What are the forms of CJD?

Answer 25

classic and variant

Question 26

What is a feature of classic CJD?

Answer 26

can be transmitted to other species but they cannot carry it

Question 27

How is CJD sub-classified?

Answer 27

sporadic >85% cases or iatrogenic (caused by healthcare)

Question 28

what mutation do the majority of iatrogenic cases have?

Answer 28

90% homo 129 Methionine

Question 29

How are familial forms of CJD influenced?

Answer 29

by polymorphisms in the 129 Val/Meth

Question 30

What are the forms of familial CJD?

Answer 30

Familial fatal insomnia | GSS

Question 31

What occurs in FFI?

Answer 31

``` 4-6th decade autosomal dominant 129 Met leads to FFI Val -> CJD insomnia, ataxia and dementia ```

Question 32

What occurs in GSS?

Answer 32

autosomal dominant PrP mutation Proline 102-Leucine further influenced by polymorphism

Question 33

What is the pathology surrounding SEs?

Answer 33

spongiform degeneration neuronal loss astrocytic proliferation anatomical distribution varies between forms of TSE

Question 34

What are prions?

Answer 34

shortened forms of proteinacious infections particles 250aa | abnormal variants of a protein with normally occurs in a cell PrPc

Question 35

What do abnormal prions do?

Answer 35

convert normal forms that they come into contact with PrPc->PrPsc

Question 36

What is the result of the continual conversion of PrPc?

Answer 36

- clusters of tangled, non-functional proteins in plaques | - neuronal apoptosis

Question 37

What causes the spongiform degeneration?

Answer 37

when the immune system removes the neurons and PrPsc aggregates

Question 38

What makes prion diseases so difficult to target?

Answer 38

``` resistant to digestion can't be targeted with antibiotics or anti-virals heat resistant no immune response difficult to decompose biologically ```

Question 39

What are the neuropathological criteria for vCJD?

Answer 39

- 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

Question 40

What has been found in the 129 polymorphism in vCJD?

Answer 40

100% have MM at polymorphism

Question 41

How many sporadic cases of CJD have MM?

Answer 41

65%