Microbiology 5: Prion Diseases

Question 1

What are prion diseases?

Answer 1

• protein-only infectious agent
• They do contain DNA inside, but they are only made of protein
• When they enter the brain, they can trigger a cascade where existing prion proteins become rapidly affected and develop the abnormal isoform of the prion protein
• leads to the development of spongiform vacuolisation of the brain
• results in rapid neurodegeneration
• UNTREATABLE

Question 2

What polymorphism can predispose to prion disease, and what codon is this on?

Answer 2

• MM: methionine-methionine
• Codon 129

Question 3

Which test detects active syphilis ?

Answer 3

RPR (Rapid plasma reagin)

(can also send VDRL)

Question 4

Which protein is a marker of rapid neurodegeneration in Creutzfeld Jacob Disease?

Answer 4

14-3-3

Question 5

What is the difference between PrP and PrP^sc ?

Answer 5

• PrP is the normal prion protein found in the body. It forms alpha helical configurations and is soluble
• PrP^sc is the pathological prion protein seen in prion diseases. It forms beta pleated sheets which are insoluble and deposit in the brain. PrP^sc acts as a template causing rapid conversion of normal PrP to PrP^sc - CAN’T GET RID OF THESE - results in rapid neurodegeneration

Question 6

Name a sporadic prion disease (MOST COMMON - 80% of prion diseases?

Answer 6

Creutzfeldt-Jakob disease (CJD)

Question 7

Name an acquired Prion disease ? (3)

Answer 7

Kuru
Variant Creutzfeldt-Jakob Disease
Iatrogenic Creutzfeldt-Jakob Disease

Question 8

Name a genetically acquired prion disease ?

What mutation causes it?

Answer 8

Gerstmann-straussler-sheinker syndrome (GSSS)

Mutation: PRNP

Question 9

List 4 signs of Creutzfeldt-Jakob Disease?

Answer 9

• In elderly
• Dementia
• Myoclonus
• Cortical blindness
• Akinetic mutism (loses ability to speak and mobilise)

Question 10

Which EEG finding which may suggest sporadic CJD ?

Answer 10

Periodic, triphasic complexes - These are periodic bursts of abnormal activity widespread throughout the brain

Question 11

What is the characteristic histological finding in CJD ?

Answer 11

Spongiform vacuolisation

Question 12

Which symptoms are seen in variant CJD that are not seen in sporadic CJD ?

Answer 12

• Psychiatric signs: hallucinations, dysphoria, anxiety
• Peripheral sensory changes
• Typically affects younger p(- 30 yrs)

Question 13

What is the characteristic MRI sign for variant CJD ?

Answer 13

Pulvinar sign (high signal in the putamen)

Question 14

What is the diagnostic test for variant CJD ?

Answer 14

Tonsillar biopsy

Question 15

List features of Sporadic CJD ?

Answer 15

4LAMB

• 4 months to live after onset of rapidly deteriorating dementia
• Lower motor neurone signs
• Akinetic mutism
• Myoclonus
• Cortical blindness

Question 16

what does an increased signal in the cortex of the R parietal lobe on diffusion-weighted MRI suggest

Answer 16

CJD

Question 17

MRI finding of variant CJD

Are 14-3-3 or S100 useful markers?

What test is 100% sensitive?

Answer 17

MRI - pulvinar sign (high intensity in the putamen)

Nope, but are in sporadic CJD

TONSIL BIOPSY - 100% sensitive and specific

Question 18

features of familial prion disease

Answer 18

• AD mutations
• non specific EEG
• neurogenetics is crucial (has to be +ve)

Question 19

what is Gerstmann-Straussler-Sheinker Syndrome

Answer 19

• presents as slowly progressing ataxia
• diminished reflexes
• dementia
• PRNP P102L mutation most common

Question 20

what can e used for treatment of CJD

Answer 20

• symptomatic - clonazepam, valproate
• delaying prion conversion - quincarine, pentosan, tetracycline
• anti-prion antibody - blocks progression to disease

Question 21

Prion protein gene is on what chromosome?

Answer 21

20

Question 22

What is the commonest form of prion disease?

Answer 22

Sporadic Creutzfeldt-Jakob Disease

Question 23

Median survival time for prion diseases

Answer 23

<6 months