Clinical meaning
Creutzfeldt-Jakob disease (CJD) is a rapidly progressive and universally fatal transmissible spongiform encephalopathy caused by prions -- misfolded isoforms (PrPSc) of normal cellular prion protein (PrPC). PrPSc acts as a template, converting normal PrPC into the pathological conformation through a self-propagating cascade. The misfolded proteins are resistant to proteases, heat, radiation, and standard sterilization. Accumulation of PrPSc causes neuronal vacuolation (spongiform change), astrogliosis, and neuronal death without inflammatory infiltrate. Forms include sporadic CJD (85%, mean age 65, unknown trigger), familial/genetic CJD (10-15%, PRNP gene mutations), iatrogenic CJD (contaminated surgical instruments, dura mater grafts, cadaveric pituitary hormones), and variant CJD (vCJD, bovine spongiform encephalopathy/mad cow disease, younger patients, psychiatric symptoms, 'florid plaques').
Diagnosis & workup
Diagnostics & workup: - Brain MRI (DWI/FLAIR): cortical ribboning (high signal in cortical gyri) and basal ganglia hyperintensity (caudate and putamen) -- most sensitive early test for sporadic CJD - EEG: periodic sharp wave complexes (PSWCs) at 1-2 Hz -- present in 60-70% of sporadic CJD (not seen in vCJD) - CSF biomarkers: RT-QuIC assay (real-time quaking-induced conversion) -- 97% sensitivity and ~100% specificity for prion disease; CSF 14-3-3 protein (marker of rapid neuronal destruction, less specific); total tau elevated - Definitive diagnosis: brain biopsy or autopsy showing spongiform change, PrPSc immunohistochemistry, protease-resistant prion protein - PRNP gene analysis: identifies familial CJD mutations and codon 129 polymorphism (M/M homozygosity = higher susceptibility) - Variant CJD differences: MRI shows 'pulvinar sign' (bilateral pulvinar thalamic hyperintensity); no PSWCs on EEG; tonsil biopsy positive for PrPSc