Table 2

 Diagnosis of prion disease

*Clinical duration typically 6 months or less but high variability: type 1 PrPSc associated with short duration (∼8 weeks); ∼10% have duration >2 years.
Sporadic (classical) CJD
    Rapidly progressive* dementia with two or more of myoclonus, cortical blindness, pyramidal signs, cerebellar signs, extrapyramidal signs, akinetic mutism
    Most cases aged 45–75
    Serial EEG shows pseudoperiodic complexes in most cases
    CSF 14-3-3 protein usually positive
    CT and MRI normal, or atrophy, or abnormal signal basal ganglia
    PRNP analysis: no pathogenic mutations, most are 129 MM (VV and MV may be of longer duration, clinically atypical, and with EEG less often positive)
    Brain biopsy in highly selected cases (to exclude treatable alternative diagnoses): PrP immunocytochemistry or western blot for PrPSc types 1–3
Iatrogenic CJD
    Progressive cerebellar syndrome and behavioural disturbance or classical CJD-like syndrome with history of iatrogenic exposure to human prions (pituitary
    derived hormones, tissue grafting or neurosurgery)
    May be young
    EEG, CSF, and MRI generally less helpful than in sporadic cases
    PRNP analysis: no pathogenic mutations, most are 129 homozygotes
    Brain biopsy in highly selected cases (to exclude treatable alternative diagnoses): PrP immunocytochemistry or western blot for PrPSc types 1–3
vCJD (Human BSE)
    Early features: depression, anxiety, social withdrawal, peripheral sensory symptoms
    Cerebellar ataxia, chorea, or athetosis often precedes dementia, advanced disease as sporadic CJD
    Most in young adults; however, age at onset 12–74 years seen
    EEG non-specific slow waves, CSF 14-3-3 may be elevated or normal
    MRI: most show high T2 weighted signal in posterior thalamus bilaterally
    PRNP analysis: no mutations, all 129 MM to date
    Tonsil biopsy: characteristic PrP immunostaining and PrPSc on western blot (type 4t)
Inherited prion disease
    Varied clinical syndromes between and within kindreds: should consider in all pre-senile dementias and ataxias irrespective of family history
    PRNP analysis: diagnostic, codon 129 genotype may predict age at onset in pre-symptomatic testing