Microbiology 5: Prion Diseases

Question 1

Which test detects active syphilis ?

Answer 1

RPR (Rapid plasma reagin)

can also send VDRL

Question 2

Which protein is a marker of rapid neurodegeneration ?

Answer 2

14-3-3

Question 3

What is the difference between PrP and PrP^sc ?

Answer 3

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

Question 4

Name a sporadic prion disease ?

Answer 4

Creutzfeldt-Jakob disease (CJD)

Question 5

Name an acquired Prion disease ?

Answer 5

Kuru
Variant CJD
Iatrogenic CJD

Question 6

Name a genetically acquired prion disease ?

Answer 6

Gerstmann-straussler-sheinker syndrome (GSSS)

Familial fatal insomnia

Question 7

List 4 signs of CJD ?

Answer 7

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

Question 8

Which EEG finding which may suggest sporadic CJD ?

Answer 8

Periodic triphasic complexes

Question 9

What is the characteristic histological finding in CJD ?

Answer 9

Spongiform vacuolisation

Question 10

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

Answer 10

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

Question 11

What is the characteristic MRI sign for variant CJD ?

Answer 11

Pulvinar sign (high signal in the putamen)

Question 12

What is the diagnostic test for variant CJD ?

Answer 12

Tonsillar biopsy

Question 13

List features of Sporadic CJD ?

Answer 13

4LAMB

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

Question 14

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

Answer 14

CJD

Question 15

what are prion diseases

Answer 15

protein-only infectious diseases
transmissible spongiform encephalopathies in humans and animals
leads to development of spongiform vacuolisation of the brain
rapid neurodegeneration
untreatable

Question 16

where is prion protein encoded

Answer 16

chromosome 20 
on codon 129 there are 3 polymorphisms 
MM - predisposes to prion disease
MV 
VV

Question 17

features of sporadic CJD

Answer 17

rapid dementia + myoclonus, cortical blindness, akinetic mutism, LMN signs 
cause uncertain 
EEG - triphasic complexes (abnormal)
MRI - increased signal in basal ganglia 
CSF - raised protein 14-3-3 and S100 
histology - spongiform vacuolisation

Question 18

describe the presentation of vCJD

Answer 18

psychiatric onset

followed by neurological symptoms - peripheral sensory, ataxia, myoclonus, chorea, dementia

Question 19

diagnosis of vCJD

Answer 19

MRI - pulvinar sign (high intensity in the putamen)
EEG - non-specific slow waves
TONSIL BIOPSY - 100% sensitive and specific
histology - accumulated plaques
some areas of vacuolisation

Question 20

list causes of iatrogenic CJD

Answer 20

human cadaveric GH 
corneal transplants
neurosurgical procedures 
blood transfusions 
* no blood test for CJD

Question 21

features of familial prion disease

Answer 21

AD mutations
non specific EEG
neurogenetics is crucial

Question 22

what is GSSS

Answer 22

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

Question 23

what is familial fatal insomnia

Answer 23

untreatable insomnia
dysautomnia
ataxia
PNRP D178N

Question 24

what can e used for treatment of CJD

Answer 24

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