A 70-year-old man with rapidly progressive dementia (weeks-months) and myoclonus has a brain biopsy showing spongiform vacuolation of the neuropil without inflammatory infiltrate, gliosis, and neuronal loss. 14-3-3 protein is positive in CSF. The definitive diagnostic confirmation requires:

• A PCR detection of PRNP mutation in genomic DNA
• B Western blot demonstrating PK-resistant PrPSc (scrapie form) after proteinase K treatment ✓
• C Detection of 14-3-3 protein combined with elevated tau in CSF
• D MRI showing cortical ribboning on DWI sequences

Explanation

The definitive diagnosis of prion disease (Creutzfeldt-Jakob disease) requires demonstration of proteinase K-resistant PrPSc by Western blot (or RT-QuIC for high sensitivity). PrPSc resists proteinase K digestion due to its beta-sheet-rich conformation, while normal PrPC is fully digested. Neuropathological diagnosis requires immunohistochemistry showing PrPSc deposits, confirmed by PK-resistant Western blot. PRNP mutation detection only applies to familial CJD (genetic form). 14-3-3/tau and MRI DWI are supportive but not definitive.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.