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Overview of Prion Diseases

(Transmissible Spongiform Encephalopathies)

by Pierluigi Gambetti, MD

Prion diseases are progressive, fatal, and untreatable degenerative brain disorders. They include

  • Creutzfeldt-Jakob disease (CJD), the prototypic example

  • Variably protease-sensitive prionopathy (VPSPr)

  • Gerstmann-Sträussler-Scheinker disease (GSS)

  • Fatal insomnia (FI)

  • Kuru

Prion diseases usually occur sporadically, with a worldwide annual incidence of about 1/1 million.

All prion diseases result from misfolding of a normal cell-surface brain protein called prion protein (PrP), whose exact function is unknown. Misfolded prion proteins (called prions) induce normal PrP to misfold into a pathogenic and often infectious PrP isoform commonly called scrapie PrP (PrP Sc —from the name of the prototypic prion disease of sheep). A large percentage of PrP Sc is markedly resistant to degradation (similar to β-amyloid, which it resembles), resulting in slow but inexorable cellular accumulation and neuronal cell death. Accompanying pathologic changes include gliosis and characteristic histologic vacuolar (spongiform) changes, resulting in dementia and other neurologic deficits. Symptoms and signs develop months to years after exposure.

Prion diseases can be hereditary (familial); they can be caused by defects in the PrP gene, contained in the short arm of chromosome 20. Some defects cause familial CJD, some cause GSS, and others cause fatal familial insomnia (FFI), the familial form of fatal insomnia. Small abnormalities in specific codons (nucleotide sequences in genes) may determine the predominant symptoms and rate of disease progression.

Prion diseases can also be acquired, transmitted from person to person (eg, as in kuru) or from animals to humans (eg, as in variant Creutzfeldt-Jakob disease). Ritualistic cannibalism caused the spread of kuru in New Guinea. Prion transmission may occur iatrogenically via organ and tissue transplants, use of contaminated surgical instruments, or, rarely, blood transfusion. Prion diseases, which occur in many mammals (eg, mink, elk, deer, domestic sheep and cattle) can be transmitted between species via the food chain (eg, in variant CJD). In several western US states and Canada, there is concern that chronic wasting disease (CWD), the prion disease of elk and deer, may be transmissible to people who hunt, butcher, or eat the affected animals; however, transmission of CWD from animals to humans is unlikely unless CWD has been transmitted from animal to animal several times (as may happen in the wild), weakening the barrier between species.

Prion diseases should be considered in all patients with dementia, especially if it progresses rapidly.

Treatment is symptomatic. Prions resist standard disinfection techniques and pose risks to surgeons, pathologists, and technicians who handle contaminated tissues and instruments. Steam autoclaving of materials at 132° C for 1 h or immersion in 4% Na hydroxide or 10% Na hypochlorite solution for 1 h is recommended.

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