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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. Prominent types include

A new prion disease, preliminarily called prion disease associated with diarrhea and autonomic neuropathy, has recently been identified.

Prion diseases result from misfolding of a normal cell-surface brain protein called prion protein (PrP C ), whose exact function is unknown. Misfolded prion proteins are called prions or scrapie PrP (PrP Sc —from the name of the prototypic prion disease of sheep).

Prions (PrP Sc ) are pathogenic and often infectious. They produce prion disease by

  • Replicating: PrP Sc induces conformational transformation of PrP C , creating duplicate PrP Sc , which, in chain reaction, induces further transformation of PrP C into PrP Sc . This transformation process spreads to various regions of the brain.

  • Causing CNS degeneration

A large percentage of PrP Sc is markedly resistant to degradation (similar toβ-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 the initial exposure to PrP Sc .

Prion diseases originate

  • Sporadically (apparently starting spontaneously, without a known cause)

  • Via genetic inheritance

  • Via infectious transmission

Sporadic prion diseases are the most common, with a worldwide annual incidence of about 1/1 million people.

Familial prion diseases are caused by defects in the PrP gene, which is contained in the short arm of chromosome 20. The genetic mutations causing prion diseases are autosomal dominant; ie, they cause disease when they are inherited from only one parent. Also, penetrance is variable; ie, depending on the type of mutation, a variable percentage of carriers of the mutation have clinical signs of the disease. 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 that are the building blocks of genes) may determine the predominant symptoms and rate of disease progression.

Infectiously transmitted prion diseases are rare. They can be transmitted

  • From person to person: Iatrogenically, via organ and tissue transplants, use of contaminated surgical instruments, or, rarely, blood transfusion (as in vCJD); or via cannibalism (as in kuru)

  • From animal to person: Via ingestion of contaminated meat (as in vCJD)

Prion diseases are not known to be contagious through casual person-to-person contact.

Prion diseases occur in many mammals (eg, mink, elk, deer, domestic sheep and cattle) and can be transmitted between species via the food chain. However, transmission from animals to humans has been observed only in vCJD, after people consumed beef from cattle with bovine spongiform encephalopathy (BSE, or mad cow disease). 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 of Prion Diseases

  • Supportive care

There is no treatment for prion diseases. Treatment is supportive.

Patients should be encouraged to prepare advance directives (eg, preferred end-of-life care) soon after the disorder is diagnosed.

Genetic counseling may be recommended for family members of patients with a familial prion disease.

Prevention of Prion Diseases

Prions resist standard disinfection techniques and may be a risk to other patients and to surgeons, pathologists, or technicians who handle contaminated tissues or instruments.

Transmission can be prevented by taking precautions when handling infected tissues and by using appropriate techniques to clean contaminated instruments. Using one of the following procedures is recommended:

  • Steam autoclaving materials at 132° C for 1 h

  • Immersing them in Na hydroxide 1 N (normal) or 10% Na hypochlorite solution for 1 h

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