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Flashcards in Prion Disease Deck (33)
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1
Q

Define prion diseases

A

Transmissible diseases that do not involve any transfer of DNA or RNA - only the transmission of proteins

2
Q

What is the red flag for a prion disease?

A

A rapidly progressive - over weeks - movement disorder

3
Q

What is the most common prion disease?

A

Creutzfeldt-Jakob disease

4
Q

What does prion stand for?

A

Proteinaceous infectious only

5
Q

Name at least 3 prion diseases which affect humans

A

Creutzfedlt-Jakob disease, Gerstmann-Straussler-Sheinker syndrome, fatal familial insomnia, kuru

6
Q

In which country is kuru endemic?

A

Papua New Guinea

7
Q

Name at least 3 prion diseases found in non-human animals

A

Scrapie, bovine spongiform encephalopathy, feline spongiform encephalopathy, chronic wasting disease, transmissible mink encephalopathy

8
Q

Which animal prion disease developed into human variant Creutzfedlt-Jakob disease?

A

Bovine spongiform encephalopathy

9
Q

What is the UK incidence of prion diseases?

A

1-2 per million

10
Q

What percentage of UK prion diseases are familial?

A

10-15%

11
Q

How is variant Creutzfeldt-Jakob disease different to other prion diseases?

A

Younger age of onset

12
Q

Describe the macroscopic pathology of prion disease

A

Global severe brain atrophy and enlargement of ventricles

13
Q

Describe the microscopic pathology of prion disease

A

Neuronal loss, astrogliosis, accumulation of prion protein, vacuolisation of the cerebral cortex and cerebellar molecular layer

14
Q

State some symptoms of sporadic Creutzfedlt-Jakob disease

A

Rapidly progressive dementia, EEG changes, motor disturbances, death within a year

15
Q

Give the investigations used in Creutzfeldt-Jakob disease

A

CT, MRI, EEG, frontal lobe biopsy (last resort)

16
Q

Why might a frontal lobe biopsy for Creutzfeldt-Jakob disease produce a false negative?

A

The distribution of pathology in CJD is unpredictable so can be missed

17
Q

State at least four past causes of iatrogenic Creutzfeldt-Jakob disease

A

Human hormone therapy, dural transplant, neurosurgery, stereotactic EEG, corneal transplant

18
Q

What is Gerstmann-Straussler-Scheinker syndrome?

A

An autosomal dominant prion disease causing a mild dementia

19
Q

What is the prognosis with Gerstmann-Straussler-Scheinker syndrome?

A

Mean duration 4-5 years with mean age of death 50

20
Q

What is fatal familial insomnia?

A

An autosomal dominant prion disease causing early sleep disturbances, neuropsychiatric symptoms, and a late dementia

21
Q

Where is the PRNP gene located?

A

Chromosome 20

22
Q

Where is PrP^C expressed?

A

The membranes of neurons and glia

23
Q

Which codon acts as a prion disease risk factor?

A

Codon 129, with valine-valine or methionine-methionine homozygotes at greater risk than heterozygotes

24
Q

How is variant Creutzfedlt-Jakob disease associated with codon 129?

A

All affected patients have been methionine-methionine homozygotes

25
Q

How is PrP^P different to PrP^C in sporadic prion disease?

A

It undergoes alternative post-translational modification into an insoluble beta-pleated sheet form and starts a process of autocatalytic conversion

26
Q

Why is tissue ore-treated with proteinase K to allow PrP^P detection?

A

PrP^P, unlike other proteins, is resistant to proteinase K degradation

27
Q

Can PrP^C knockout mice get prion disease?

A

No

28
Q

What appears to determine strain variation in prion disease?

A

Glycosylation of the prion protein (the number of attached polysaccharide chains)

29
Q

As characterised by genotype and glycotype, what is the most common subtype of prion disease?

A

Methionine-methionine 1 (frequency 57%)

30
Q

Describe the pattern of PrP^P deposition in the MM1 subtype of prion disease

A

PrP^P is deposited synaptically, with perivacuolar deposition around areas of spongiform change

31
Q

State at least 3 functions PrP^C has been implicated in, as summarised by Wulf et al in 2017

A

Signal transduction, vesicle trafficking, anti-apoptosis, extracellular matrix interactions, heat-shock protein, chaperone protein, metal binding

32
Q

State at least 2 potential mechanisms for local spread of proteinopathies

A

1) Cell death causing protein aggregate release, which is then taken up by viable cells
2) Exocytosis of protein aggregate, which is then taken up by viable cells
3) Synaptic release of the aggregate and spread along a neuronal network

33
Q

Name the drug proposed for use as post-exposure prophylaxis against prion disease

A

Pentosan polysulphate