Abstract
Creutzfeldt-Jakob disease (CJD) is a rare neurodegenerative human prion disease with a worldwide incidence of 1-per-million. CJD typically is rapidly progressive and invariably fatal, usually within a year of diagnosis in 90% of cases. It is suggested that some cases may go under-reported due to atypical subtypes, negative supplementary testing and the low rates of brain autopsy in this population.
A 53-year-old female presented with a 3-year history of progressive dementia, and physical decline which had progressed to near complete functional incapacity. Clinical examination at this late stage revealed advanced dementia, akinetic mutism, generalized myoclonus, dystonia, rigidity and pyramidal dysfunction. Magnetic Resonance Imaging (MRI) of her brain demonstrated global parenchymal atrophy without typical T2-weighted hyperintense signal changes or diffusion restriction changes. Electroencephalography (EEG) demonstrated mild intermittent slowing without periodic sharp wave complexes. Her Cerebrospinal Fluid (CSF) demonstrated normal protein, glucose, microscopy and total Tau-protein with negative 14–3-3 protein and real-time quaking-induced conversion (RT-QuIC) assay. She underwent genetic testing with a phenotype driven exome analysis, which did not identify a disease-causing variant and specifically did not reveal a prion protein gene (PRNP) mutation. Post-mortem neuropathological examination demonstrated extensive spongiform changes with moderate degree of prion protein plaque-like aggregates diagnostic of CJD.
This case highlights the importance of the post-mortem neuropathological examination when clinical suspicion for CJD exists, but there is an atypical timeline and supplementary testing is not supportive.
