CJD

Types

•   Types of CJD

o   Sporadic CJD (sCJD) – 85%

o   Variant CJD (vCJD) – transmission from animals - rare

o   Familial CJD (fCJD) – 5-15%

o   Iatrogenic CJD (iCJD) - rare

•   Other prion disease

o   Kuru

o   Gerstmann-Strausseler-Scheinker Syndrome (GSS

o   Fatal Familial Insomnia (FFI)

 

Epidemiology

•   Sporadic

o   1/million/year

o   Onset mean age 57-62

 

•   Variant – much younger onset (~30)

Pathogenesis

•   PrPc misfolds to create PrPSc

•   This involves transformation os alpha helix to beta sheets

•   These structrures polymerize to cause pathology

•   Familial forms have mutation in PRNP gene – which encodes PrPc

Pathology

•   Spongiform change

o   Relatively specific change in cortex and often in deep grey matter

o   Small vacuoles in the neurophil (Intracytoplasmic).

o   No inflammatory change

•   Overall little atrophy as disease progresses so fast

•   Astrocytic gliosis – non-specific change

•   Amyloid plaques – 10%

•   Variant CJD

o   Extracellular plaques commonly observed

o   Eosinophilic centre, pale periphery and surrounding spongiform changes giving a flower like pattern (Florid)

Clinical manifestations

•   Cardinal features

o   Rapidly progressive mental deterioration

o   Myoclonus

•   Wide spectrum of mental changes

•   Dementia, mood and pshychiatric changes

•   Myoclonus is present in 90%

o   Provoked by startle

•   EPS signs – hypokinesia and cerebellar signs occur in 2/3

•   Corticospinal signs in a significant proportion

Variant CJD

•   Younger age of onset – mean 29

•   Prominent sensory disturbances and psychiatric symptoms on presentation

•   Ataxia often first clear neurological sign

Diagnosis - sCJD

 

MRI

•   Hyperintensity of basal ganglia on FLAIR/T2

•   Cortical ribboning (hyperintensity)

•   Reasonably specific, not sensitive (40-50%)

•   Also picked up on DWI – more sensitive (~90%)

EEG

•   Periodic synchronous bi- or tri- phasic sharp wave complexes (PSWC)

•   Generalized or lateralised

•   Occur in ~60%

•   Specificity ~86%

14-3-3 protein in CSF

•   Presence of ‘stress’ protein 14-3-3 frequently present

•   Variable reports of sensitivity and specificity

Sn 89%

Sp 66%

CJD probability

PPV%

NPV%

Probable

99

26

Possible

96

66

Unlikely

45

100

Tau protein in CSF

•   Sn 85%

•   Sp 82%

•   Low tau correlated with longer survival (15.6 months vs 4.5month)

 

RT-QuIC assay on CSF

•   Sn >80%

•   Sp ~100%

 

Brain biopsy

•   Can demonstrate presence of PrPSc

•   Patchy distribution of abnormal protein limits sensitivity. 

Diagnosis - vCJD

•   CSF

o   14-3-3 less common

o   RT-QuIC less useful

•    

•   MRI

o   Hyperintensity of pulvinars nucleus of thalamus

o   Hyperintensity of dorsomedial thalamus (hockey stick sign)

•   EEG – PSWCs generally not seen

•   Biopsy – analysis of tonsillar tissue (western blot for PrPSc) has good sensitivity

Treatment

Prognosis

•   sCJD

o   4-5 month duration – always fatal

•   vCJD

o   Longer disease duration – 14months

o   Still universally fatal