MI: Prion Disease Pt.1

Question 1

What is the rapid plasma reagent test?

Answer 1

Screening test for active syphilis

Question 2

Name a CSF marker that supports the diagnosis of sCJD

Answer 2

14-3-3

Question 3

What is a characteristic finding of CJD on a diffusion-weight MRI?

Answer 3

High signal in the caudate/putamen or at least in cortical regions (temporal, parietal, occipital)

Question 4

What does ‘prion’ stand for?

Answer 4

Protein-only infectious agent

Question 5

What are prion diseases and what do they cause?

Answer 5

• Rare transmissible spongiform encephalopathies caused by prions
• They lead to spongiform vacuolisation of the brain and rapid neurodegeneration

Question 6

What is the prion protein gene and on which chromosome is it found?

Answer 6

PRNP gene, chromosome 20

Question 7

What is a possible physiological role of the normal prion protein?

Answer 7

It may have some role in copper metabolism

Question 8

Describe the structure of the normal prion protein.

Answer 8

Alpha-helix

Question 9

Describe the structure of an abnormal prion protein.

Answer 9

Beta-pleated sheet

Question 10

Why is the abnormal prion protein difficult to get rid of?

Answer 10

Resistant to proteases and radiation

Question 11

How does prion replication take place?

Answer 11

Seeding of an abnormal prion protein (PrPsc) seems to act as a template which promotes the conversion of PrPc to the insoluble PrPsc

Question 12

List some types of prion disease. Which type is most common?

Answer 12

Sporadic CJD (80%)

Acquired (<5%)

• Kuru
• Variant CJD (results from BSE epidemic)
• Iatrogenic CJD

Genetic (15%)

• PRNP mutations e.g. fatal familial insomnia, Gerstmann-Straussler-Sheinker syndrome

Question 13

Give some examples of inherited prion diseases. What are they caused by?

Answer 13

• Fatal familial insomnia
• Gerstmann-Straussler-Sheinker syndrome

Caused by PRNP gene mutations

Question 14

Describe the clinical features of sporadic CJD.

Answer 14

Rapid dementia with:

• Myoclonus
• Cerebellar dysfunction
• Cortical blindness
• Akinetic mutism
• LMN signs

NOTE: usually in older people (>65)

Question 15

What is the epidemiology and prognosis of sporadic CJD?

Answer 15

• Mean age of onset 65 years (range 45-75 years)
• Prognosis - death with 6 months

Question 16

What are some possible causes of sporadic CJD?

Answer 16

No known cause

• Somatic PRNP mutation
• Spontaneous conversion of PrPc into PrPsc
• Environmental exposure to prions

Question 17

How might sCJD be diagnosed?

Answer 17

• EEG - abnormal in 2/3
• MRI
• CSF
• Neurogenetics
• Brain biopsy
• Autopsy - must be done by experience pathologist

Question 18

Describe the EEG appearance in sporadic CJD.

Answer 18

Triphasic complexes

Question 19

Describe the MRI appearance of sporadic CJD.

Answer 19

Increased intensity on DWI MRI of the basal ganglia and cortex

Question 20

Which markers will be raised in the CSF of a patient with CJD?

Answer 20

14-3-3

S100

Question 21

What is the only way of confirming a diagnosis of CJD?

Answer 21

Brain biopsy (usually at autopsy)