Creutzfeldt-Jakob Disease

Question 1

Three types

Answer 1

-Sporadic
Familial
Variant

Question 2

Pathological features

Answer 2

• no pathological features due to the short course of the disease
• people living for over 6 months may have a degree of generalised cerebral atrophy

Question 3

Microscopic features

Answer 3

• shows spongiform encephalopathy secondary to nueropil vacuolisation
• many round to oval vacuoles are seen in the neuropil of cortical grey matter
• vacuoles may be single or multiloculated
• vacuoles may coalesce to microcysts
• most cases of CJD demonstrate neuronal loss and gliosis

Question 4

Prion protein (PrPc)

Answer 4

• normal neuronal cell surface protein encoded by gene on chromosome 20
• in CJD this is converted via a conformational change to an abnormal form designated as PrPsc
• the abnormal form is protease-resistant and can accumulate in the CNS of affected persons
• this accumulation triggers further conversion of normal PrPc to Pr Psc and accounts for the degenerative changes in the cerebral cortex

Question 5

Identifying PrP

Answer 5

-use immunoperoxidase staining

Question 6

Transmission

Answer 6

-these abnormal PrPsc can be transmitted from one person with spongiform encephalopathy to another person via pituitary extracts, corneal transplants, dual grafts and contaminated electrodes from neurosurgical procedures

Question 7

Variant CJD

Answer 7

• related to bovine spongiform encephalopathy

- there is marked accumulation of the prion protein and the plaques are florid

Question 8

Familial CJD

Answer 8

• the typical EEG changes are often lacking
• the 14-3-3 proteins are absent in the CSF in more than 50% cases
• polymorphisms at codon 129 of PrP may have an influence on the suceptibility for the disease

Question 9

MRI

Answer 9

• most supportive diagnostic test in variant CJD
• abnormality seen in the posterior thalamic region (pulvinar sign)
• this is highly sensitive
• found in more than 90% if pathologically proven vCJD cases
• FLAIR sequences of MRI are most likely to show the abnormality

Question 10

Classic CJD

Answer 10

• seen in 7th or 8th decade of life
• short course of 5 months
• early neurological signs and dementia
• triphasic sharp waves often seen
• Pulvinar sign is not seen
• only a few plaques noted
• prion protein cannot be isolated from lymphoid tissue

Question 11

Variant CJD

Answer 11

• seen in 3rd or 4th decade of life
• course is more prolonged to 1 year
• early psychiatric/behavioural signs with delayed neurological features
• triphasic waves are rare and changes are often non-specific
• Pulvinar sign is present
• large number of plaques seen
• tonsillar tissue carries prion agent