MI: Prion Disease Flashcards
What is the rapid plasma reagent test?
Test for active syphilis
Name a marker of rapid neurodegeneration.
14-3-3
What is a characteristic finding of CJD on a diffusion-weight MRI?
Increased signal in the cortex of the right parietal lobe
What does ‘prion’ stand for?
Protein-only infectious agent
What are prion diseases?
- Rare transmissble spongiform encephalopathies caused by prions
- They lead to spongiform vacuolisation of the brain and rapid neurodegeneration
On which chromosome is the normal prion gene found?
20
What is a possible physiological role of the normal prion protein?
It may have some role in copper metabolism
On which codon are the three polymorphisms of prion proteins found?
What are the three polymorphisms?
- Codon 129
- MM (predisposes to prion diseases)
- MV
- VV
NOTE: M = methionine, V = valine
Describe the structure of the normal prion protein.
Alpha-helix
Describe the structure of an abnormal prion protein.
Beta-pleated sheet
Why is the abnormal prion protein difficult to get rid of?
Resistant to proteases and radiation
How does prion replication take place?
Seeding of an abnormal prion protein (PrPsc) seems to act as a template which promotes the conversion of PrP to the insoluble PrPsc
List some sporadic and acquired types of prion disease.
Sporadic - CJD (mainly in older people)
Acquired:
- Kuru
- Variant CJD (results from BSE epidemic)
- Iatrogenic CJD
Which gene mutation is associated with prion disease?
PRNP
Give some examples of inherited prion diseases.
- Fatal familial insomnia
- Gerstmann-Straussler-Sheinker syndrome
Describe the clinical features of sporadic CJD.
- Rapid dementia
- Myoclonus
- Cortical blindness
- Akinetic mutism
- LMN signs
- NOTE: usually in older people (>65)
What are some possible causes of sporadic CJD?
- Somatic PRNP mutation
- Spontaneous conversion of PrP into PrPsc
- Environmental exposure to prions
Describe the EEG appearance in sporadic CJD.
Period, triphasic complexes
Describe the MRI appearance of sporadic CJD.
- Increased signal in the basal ganglia
- Increased intensity on DWI MRI of the cortex and basal ganglia
Which markers will be raised in the CSF of a patient with CJD?
14-3-3
S100
What is the only way of confirming a diagnosis of CJD?
Brain biopsy (usually at autopsy)
Describe the histological appearance of CJD.
Spongiform vacuolisation
NOTE: there are amyloid plaques but these are different from the plaques seen in Alzheimer’s disease
List the differential diagnosis for CJD.
- Alzheimer’s disease
- Vascular dementia
- CNS neoplasms
- Cerebral vasculitis
- Paraneoplastic syndromes
What is variant CJD?
CJD in younger people that has resulted from the BSE epidemic
Describe the clinical features of vCJD
- Younger age of onset (20s)
- Psychiatric onset (dysphoria, anxiety, delusions, hallucinations)
- Followed by neurological symptoms (peripherap sensory symptoms, ataxia, myoclonus, chorea, dementia)
What is a characteristic MRI feature of vCJD?
Pulvinar sign - high intensity in the putamen
How is the use of CSF markers different in vCJD?
14-3-3 and S100 are NOT useful in vCJD
Which investigation is most useful for vCJD?
- Tonsillar biopsy - prions localise in lymphoid tissue
NOTE: this is not useful in CJD
Describe the role of neurogenetics in vCJD.
Almost 100% of patients are MM at codon 129
List some causes of iatrogenic CJD.
- Human cadaveric growth hormone
- Corneal transplants
- Neurosurgical procedures
- Blood transfusions
Outline the clinical features of iatrogenic CJD.
- Starts with progressive ataxia
- Dementia and myoclonus occur at a later stage
What is the inheritance pattern of inherited prion disease?
Autosomal dominant
What are some alternative diagnoses for someone presenting with features suggestive of prion disease?
- Spinocerebellar ataxia
- Huntington’s disease
Describe the clinical features of Gerstmann-Straussler-Sheinker syndrome.
- Slowly progressive ataxia
- Diminished reflexes
- Dementia
NOTE: PRNP P102L mutation is most common
Describe the clinical features of fatal familial insomnia.
- Untreatable insomnia
- Dysautonomia (blood pressure and heart rate dysregulation)
- Ataxia
- Thalamic degeneration
NOTE: PRNP D178N mutation is most common
Outline the principles of treament of CJD.
- Symptomatic - clonazepam for clonus
- Delaying prion conversion - quinacrine, pentosan, tetracycline
- Anti-prion antibody - blocks progression in mice but cannot access CNS
- Depletion of neuronal cellular prion protein - blocks neuronal cell loss and reverses early spongiosis in mic
Where should possible cases be reported to?
- National prion clinic (Queen Square, UCL)
- NCJDSU in Edinburgh
