Microbiology 9 - Prion disease Flashcards
(34 cards)
What does ‘prion’ stand for?
PRotein-only InfectiOus ageNt.
What is the general pathophysiology of prion diseases?
enter brain → trigger cascade where existing prion proteins become rapidly affected → develop abnormal isoform → spongiform vacuolisation of brain → rapid neurodegeneration
Seed of PrPSc→ template to promote conversion of PrP into insoluble PrPSc → rapid neurodegeneration
Upon which chromosome is prion encoded?
C20
Describe the structure and function of healthy prion
Alpha helical structure - involved in copper binding
What is the structure of pathological prion?
Beta pleated sheet
RESISTANT to proteases and radiation
Difficult to get rid of e.g. surgical instruments contaminated with diseased prions are impossible to clean
What is the name given to sporadic prion disease?
Creutzfeld Jacob Disease
tends to be in older pop
What are the 2 types of acquired prion disease currently known about?
Kuru
Variant CJD - earlier BSE (bovine spongiform encephalopathy) epidemic (younger ppl)
Iatrogenic CJD
- Growth hormone (from cadavers)
- Blood
- Surgery
Recall 3 genetic causes of prion disease
- PRNP mutations
- Gertsmann-Strausser-Sheinker syndrome
- Familial fatal insomnia
Describe some possible symptoms of prion disease
Ataxia
UMN weaknesses
Nystagmus
Limb spasticity
Hyperreflexia
Paraesthesia
Tremor
(all neuro symptoms!)
How does sporadic CJD present?
RAPID DEMENTIA with:
- myoclonus
- cortical blindness
- akinetic mutism
- LMN signs
What would EEG show in sporadic CJD?
an EEG that looks like an ECG
Periodic, triphasic complexes (non-specific)
What is the only test to confirm CJD?
Brain biopsy (only way of confirming CJD - autopsy)
What do spondiform vacuolation and PrP amyloid plaques indicate?
sporadic CJD
What marker of Creutzfeld Jacob Disease may be identified in CSF?
↑ 14-3-3 protein and S100 (rapid neurodegeneration)
What is the recognised abnormailty on MRI that is indicative of CJD?
Increased signal in basal ganglia
Increased intensity on DWI MRI of the cortex and basal ganglia
What is the mean age of onset of CJD?
65
How quickly does CJD cause death?
Within 6/12
What is the mean age of presentation of variant CJD/ BSE?
26 younger
What is the mean survival time in variant CJD?
14 months
Recall the typical presentation of variant CJD/ BSE
Dysphonia
Hallucinations
Anxiety
Paranoia
(Psychological symptoms mostly)
Also some neuro -
Peripheral sensory symptoms
Ataxia
Dementia
Myoclonus
Chorea
What would an MRI show in variant CJD/ BSE?
shows pulvinar sign (high intensity in the putamen NOT BG)
What would EEG show in vCJD?
non-specific slow waves
not v useful
What test is 100% sensitive and specific for variant CJD/ BSE, but useless in sporadic CJD?
Tonsilar biopsy
What would neurogenetics show in vCJD?
Almost 100% MM at codon 129
