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 |
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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 |
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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) |
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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 |