Epidemiology

Etiology

CJD is caused by misfolded proteins (prions, PrP^Sc) that are either produced by affected individual themselves, or taken up from an exogenous source.

• Sporadic (∼ 85%): no identifiable source
• Familial (∼ 10–15%)
• Acquired (< 1%)
  • Iatrogenic CJD: transmission during medical procedures, such as:
    • Brain surgery (surgical equipment)
    • Organ transplantation (e.g., corneal transplant)
    • Blood transfusion
  • Variant CJD (vCJD)
    • Occurs due to ingestion of beef infected with bovine spongiform encephalopathy (BSE)
    • BSE is a transmissible prion disease occurring in cattle also known as “mad cow disease”

Pathophysiology

• Conversion of normal cellular prion proteins with alpha-helical structure (PrPc) to prions that demonstrate an increase in beta-pleated sheet structure (PrPSc) → conformational change of physiological PrPc → PrPSc accumulation and plaque formation → neuronal cell death → progression to spongiform encephalopathy
  • Conformational change is triggered via misfolded PrPSc (from scrapie, a transmissible spongiform encephalopathy of sheep)
• Since misfolded prions are insoluble, they deposit as plaques resistant to proteases and standard autoclaving, thus contributing to the formation of more PrPSc.

Clinical features

• Neurological symptoms
  • Cerebellar disturbances (e.g., gait instability) and extrapyramidal deficits
  • Myoclonus
    • A sudden involuntary twitch of a muscle or groups of muscles caused by muscular contraction or inhibition
    • Often triggered by startling (e.g., loud noises)
    • Also associated with metabolic abnormalities found in liver and renal failure
  • Ataxia
• Neuropsychiatric symptoms
  • Rapidly progressing dementia (weeks to months)
  • Personality changes
  • Akinetic mutism

Diagnostics

• CSF analysis
  • ↑ 14-3-3 protein
• Brain biopsy
  • Diagnosis can only be confirmed by biopsy/autopsy and subsequent neuropathological examination.
  • Microscopic findings include spongiform degeneration (e.g., intracytoplasmic vacuoles within the neurons of cerebral and cerebellar cortex that can be seen on H&E)

Treatment