Microbiology - Prion Disease Flashcards
What is a Prion Disease and some features?
Protein-only infectious agent
- Rare transmissable spongiform encephalopathies in humans + animals resulting in rapid neuro-degeneration + death in months
- Currently untreatable
- Prion protein gene on Chr 20 - predominantly expressed in CNS
What is the pathophysiology of Prion Disease?
- Normal protein structure PrPc
- Abnormal PrP(SC) abnormally folds into a β sheet configuration + protease/radiation resistant
- Seed of PrP(SC) acts as template which promotes irreversible conversion of PrP to insoluble PrP(SC)
What is the genetics of Prion Disease?
- Codon 129 polymorphism
- Specific PRNP Mutations
What are some DDx for Prion Disease?
Other neuro-gentic conditions
- Huntington’s
- Spinocerebellar ataxia
What is the general treatment for CJD (Creutzfeldt-Jakob Disease)?
Symptomatic:
- Clonazepam - myoclonus (Valproate, Levetiracetam, Piracetam)
Delaying Prion “Conversion”:
- Quinacrine
- Pentosan
- Tetracycline
What are the different types of Prion Disease?
- Sporadic CJD
- Variant CJD
- Iatrogenic CLD
- Inherited Prion Disease
What are the EEG, MRI, CSF, PNRP, Genetic, Western Blot PrP(SC) + Post-mortem findings of Sporadic CJD?
EEG:
- Seial EEG shows periodic triphasic changes
MRI:
- Normal/highlighting basal ganglia
CSF Analysis:
- 14-3-3 Protein +ve
PNRP Analysis:
- No mutations
Genetics:
- Most cases
- 126 codon MM
Western Blot PrP(SC):
- Types 1-3
Post-mortem:
1. Spongiform vacuolation
2. PrP amyloid plaques
What are the EEG, MRI, CSF, PNRP, Genetic, Western Blot PrP(SC) + Post-mortem findings of Variant CJD?
EEG:
- Non-specific slow waves
MRI:
- Posterior thalamus highlighted on MRI-T2 (pulvinar sign)
CSF Analysis:
- 14-3-3 can be normal
PNRP Analysis:
- No mutations
Genetics:
- ALL cases
- 129 codon MM
Western Blot:
- Type 4t from tonsillar biopsy (100% sens + spec)
Post-mortem:
1. PrP(SC)4t detectable in CNS + lymphoreticular tissue
2. Florid plaques
What are the PNRP, Genetic + Western Blot PrP(SC) findings of Iatrogenic CJD?
PNRP Analysis:
- No mutations
Genetics:
- Most
- 129 codon homozygous (MM or VV)
Western Blot:
- Types 1-3
What are the EEG, MRI, PNRP + Genetic findings of Inherited Prion Disease?
EEG:
- Non-specific
MRI:
- Sometimes high signal in basal ganglia
PNRP Analysis:
- Mutations present + diagnostic
Genetics:
- 129 codon homozygosity may confer earlier onset
What is the prevalence of Sporadic CJD and its aetiology?
80%
- Either somatic PRNP mutation or spontaneous conversion of PrPc to PrP(SC) + subsequent seeding
What is the course of progression of Sporadic CJD?
- Rapid, progressive dementia
- Myoclonus
- Blindness
- Akinetic mutism
- LMN signs
- Mean onset = 45-75yrs
- Mean survival time = 6/12 of Sx onset
What is the overall prevalence of acquired CJD and its various types?
<5%
- vCJD (variant)
- Iatrogenic
- Kuru
What is the aetiology and course of progression of vCJD (variant) - Acquired CJD?
Aetiology:
- Exposure to bovine spongiform encephalopathy (BSE)
Course:
- Age of onset = ~30yrs
- Mean survival = 14/12
- Psychiatric Sx to start (anxiety, paranoia, hallucinations)
- Neurological Sx follow (peripheral sensory Sx, ataxia, myoclonus)
- Later Sx = chorea, ataxoa, dementia
What is the aetiology + course of progression of Iatrogenic acquired CJD?
Aetiology:
- Inoculation with human prions most commonly from surgery
Course:
- Initially: Progressive ataxia
- Later: Myoclonus + dementia
- Speed of progression depends on route of inoculation
- CNS inoculation fastest
