Prion Disease Flashcards
What is prion disease?
This is a disease where the infecting agent is a protein. It is a rare transmissible spongiform encephalopathy that can be found in all manner of species. It causes rapid neuro-degeneration and death in months.
It is currently untreatable
What is the pathophysiology of prion disease?
While not completely understood, it is due to a mutated form of the prion protein (PrP). This is coded for by chromosome 20, and it is an abnormally folded version of the protein, PrPSC. A seed of PrPSC can cause a cascade of irreversible conversion or PrP to PrPSC. PrpSC is resistant to proteases and radiation.
Genetically, codon 129 on chromosome 20 has polymorphism of MM, MV and VV; with MM being very strongly associated with prion disease. (methionine and valine).
What are the different types of prion disease?
Sporadic (80%)
- Random or spontaneous conversion of PrP to PrPSC
Acquired (<5%)
- Acquired PrPSC either in a variant form or iatrogenic form
Inherited (15%)
- Familial disease, inherited in an autosomal dominant pattern
What is prion disease called in humans?
Creutzfield Jacob Disease (CJD)
What investigations are performed in a suspected case of CJD?
- EEG
- MRI
- CSF analysis
- PNRP analysis
- Genetics
- Biopsy
- Post-mortem
Describe the aetiology of sporadic CJD, the clinical features and the findings on investigation
It is either somatic PRNP mutation or spontaneous conversion of PrP to PrPSC.
There is rapid, progressive dementia with myoclonus, cortical blindness, akinetic mutism and lower motor neuron signs.
The mean onset is at aged 65 (45-75) and the mean survival time is 6 months from symptom onset.
Investigations: EEG: periodic triphasic changes MRI: highlighted basal ganglia CSF analysis: 14-3-3 and S100 raised PNRP analysis: no mutations Genetics: 129 codon MM Post-mortem: spongiform vacuolation and PrP amyloid plaques
Describe the aetiology of variant CJD, the clinical features, and the findings on investigation
It is due to exposure of mad cow disease, or bovine spongiform encephalopathy.
This has a younger age of onset, at around 30 years, with a mean survival of 14 months.
It begins with psychiatric symptoms (anxiety, paranoia, hallucinations) , followed by the development of neurological symptoms (ataxia, myoclonus).
Investigations: EEG: non specific slow waves MRI: highlighted posterior thalamus CSF analysis: can be normal PNRP analysis: no mutations Genetics: ALL cases are 120 codon MM Tonsillar biopsy: type 4t seen (100% specific and sensitive)
Describe the aetiology of iatrogenic CJD and the clinical features.
It is due to surgical exposure to PrPSC.
There is initially ataxia, which is progressive. It then develops into dementia and myoclonus.
The speed of the progression depends on the site of inoculation.
Describe the aetiology of inherited CJD, the clinical features of its two types, and the investigation results.
Inherited CJD is inherited in an autosomal dominant pattern and can either be Gerstmann-Straussler-Scheinker (GSS) syndrome or Fatal Familial Insomnia (FFI).
GSS: this develops between the ages of 20-60, and has a mean survival of 5 years (2-10). It begins as dysarthria, developing into cerebellar ataxia and dementia.
FFI: this begins as severe insomnia, and paranoia, progressing into hallucinations and weight loss. Death occurs around 1-18 months after symptom onset.
Investigations: EEG: non-specific MRI: sometimes a highlighted basal ganglia CSF: nil PRNP: mutations present and diagnostic Genetics: 129 codon MM
What is Kuru disease? Describe the aetiology and clinical features of the disease.
This is CJD caused by cannibalism, and ingestion of prion disease brains. It is specific to the Fore tribe in Papua New Guinea. It was as a result of a tribal feast, consuming the brains of deceased elders. This epidemic was in the 50s to 60s, and the last ever tribal feast was in 1957.
There is progressive cerebellar syndrome and can follow a very long incubation period (45 years).
