Prion diseases

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By Raymond P Roos MD

Prion disease is also known as or subsumes Subacute spongiform encephalopathy (SSE) and Thalamic dementia. -ed.

In this clinical article, Dr. Raymond Roos, Marjorie and Robert E Straus Professor in Neurological Science at the University of Chicago Medical Center, reviews the group of diseases known as prion diseases, also referred to as the subacute spongiform encephalopathies. These diseases have a subacute to chronic clinical syndrome with a similar neuropathology. All the diseases are transmissible and induced by an abnormal form of the prion protein that is extremely resistant to physical and chemical inactivation. The unusual nature of the transmissible agent and the emergence of variant Creutzfeldt-Jakob disease (as a result of ingestion of contaminated beef) have had a significant impact on public health in addition to science and medicine. New diagnostic tests and new ideas about treatment of the subacute spongiform encephalopathies are noted.

Key Points

  • The transmissible subacute spongiform encephalopathies, or prion diseases, have a similar noninflammatory spongiform pathology and are caused by a similar transmissible agent -- an abnormal (“scrapie-like”) protease-resistant conformation of the prion protein (PrP), which is designated PrPSc.
  • Sporadic human prion diseases include Creutzfeldt-Jakob disease, kuru (a subacute cerebellar disease found in the Highlands of New Guinea that was spread by ritual endocannibalism), and sporadic fatal insomnia new variant Creutzfeldt-Jakob disease. Familial human prion diseases, which are usually 10% of the overall cases, include familial Creutzfeldt-Jakob disease, Gerstmann-Straussler-Scheinker syndrome, and familial fatal insomnia.
  • Creutzfeldt-Jakob disease is a subacute fatal disease with a clinical triad of dementia, myoclonus, and EEG abnormalities that is usually also associated with other neurologic abnormalities, along with neuropathological evidence of neuronal loss, spongiform changes, and astrocytosis.
  • Prion diseases are transmissible after a prolonged incubation period by inoculating the infected CNS into nonhuman primates and some other species via multiple routes of inoculation; however, transmission is most efficient with an intracerebral inoculation into a species identical to the source of the infected CNS tissue.
  • Some investigators consider Alzheimer disease, Parkinson disease, and amyotrophic lateral sclerosis to be prion-like diseases in which a particular misfolded protein converts a normal form of the protein to the misfolded one that aggregates and propagates throughout the CNS.