Prion disease

Question 1

Tonsillar biopsy diagnostic

Answer 1

Variant CJD

Question 2

Periodic triphasic complexes on EEG
Unknown cause of abnormal Prion protein
80% of Prion disease
Old people
Rapid dementia, jerky irregular tremor, cortical blindness, akinetic mutism, LMN signs
MRI - Increased signal in basal ganglia + cortex on DWI
14-3-3 S100 protein in CSF

Answer 2

Sporadic CJD

Question 3

3 types of prion disease

Answer 3

Sporadic CJD (80%)
Acquired - Kuru, variant CJD, iatrogenic CJD (<5%)
Familial - GSS syndrome, Familial Fatal Insomnia (15%)

Question 4

Most common Prion disease

Answer 4

Sporadic CJD

Question 5

Bovine source of abnormal protein entered food chain
Young people
Psychiatric (anxiety, hallucinations, paranoia) THEN neurological signs (myoclonus, ataxia, tremor, dementia)
MM at codon 129
MRI - Pulvinar sign (high signal posterior thalamus)
Tonsillar biopsy diagnostic

Answer 5

Variant CJD

Question 6

Abnormal protein transmitted by surgical instruments, blood, GH
Progressive ataxia then dementia + myoclonus in later stages
Faster progression if direct CNS inoculation

Answer 6

Iatrogenic CJD

Question 7

AD inherited mutation in prion protein gene

Neurogenetics crucial to diagnosis

Answer 7

Familial prion disease

Question 8

Histological change in Prion disease

Answer 8

Spongiform vacuolation

Prion protein stuffed amyloid plaques

Question 9

Abnormal Prion protein

Answer 9

PrP^Sc

Beta-pleated sheet rather than Alpha-helical

Question 10

Polymorphism predisposing to Prion disease

Answer 10

MM at codon 129

Codon 129 of PrP (prion protein gene)
3 main types - MM, VV, MV
MM most common

(N.B. This is different from inherited mutations of protein that cause familial CJD - these just predispose by unknown mechanism!)

Question 11

Why is tonsillar biopsy so useful in variant CJD?

Answer 11

100% sensitive + specific for variant CJD
Abnormal protein goes into lymphoid tissue as well as neural tissue
Tonsillar biopsy is less invasive than brain biopsy!

Question 12

2 types of familial CJD

Answer 12

Gerstmann-Straussler-Scheinker

Fatal Familial Insomnia

Question 13

Inheritance of familial CJD

Answer 13

AD mutation of prion protein gene

Question 14

Human cannabilism
Rapid cerebellar degeneration
Dementia late or absent

Answer 14

Kuru