Foundations · Year 1 · from Foundations
Case 2: Creutzfeldt-Jakob Disease (Prion Disease)
Clinical Image
Source: Radiopaedia - Creutzfeldt-Jakob disease - CC BY-NC-SA 3.0
Case Presentation
A 62-year-old woman is brought by her family for evaluation of rapidly progressive cognitive decline over the past 3 months. She was previously healthy and independent but now requires assistance with basic activities. Her family notes personality changes, visual hallucinations, and jerking movements of her limbs. Neurological examination reveals myoclonus, cerebellar ataxia, and global cognitive impairment. MRI brain shows characteristic "cortical ribboning" with diffusion restriction in the cortex and basal ganglia. EEG demonstrates periodic sharp wave complexes. CSF analysis is positive for 14-3-3 protein and RT-QuIC assay is positive for prion seeding activity. The diagnosis is sporadic Creutzfeldt-Jakob disease (sCJD). The family is counseled that this is a rapidly fatal neurodegenerative disease with no treatment, typically progressing to death within 4-6 months. The pathogenesis involves conversion of normal cellular prion protein (PrP^C) to a misfolded, aggregation-prone form (PrP^Sc) that templates further conversion in a self-propagating cascade.
Key Learning Points
- Prion diseases demonstrate that protein misfolding alone can be infectious - the misfolded PrP^Sc protein templates conversion of normal PrP^C
- The conformational change from predominantly alpha-helical PrP^C to beta-sheet-rich PrP^Sc creates an aggregation-prone, protease-resistant form
- MRI findings of cortical ribboning and basal ganglia hyperintensity on DWI are highly sensitive and specific for CJD diagnosis