Creutzfeldt-Jakob disease

Raymond P Roos MD (Dr. Roos of the University of Chicago owns stock in Amgen, Best Doctors, Express Scripts, Isis, and Merck.)
John E Greenlee MD, editor. (Dr. Greenlee of the University of Utah School of Medicine received an honorarium from Merck for authorship.)
Originally released October 27, 1993; last updated April 12, 2016; expires April 12, 2019

This article includes discussion of Creutzfeldt-Jakob disease, Heidenhain syndrome, Jakob-Creutzfeldt disease, and spastic pseudosclerosis. The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations.

Overview

The author reviews Creutzfeldt-Jakob disease, a member of the group of diseases known as prion diseases or the subacute spongiform encephalopathies. Creutzfeldt-Jakob disease has a subacute clinical course and distinctive gray matter pathology. This disease is transmissible and is 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 information suggests there will not be an epidemic of variant Creutzfeldt-Jakob disease. New diagnostic tests, protein misfolding cyclic amplification and real time quaking-induced conversion, and new ideas about treatment of Creutzfeldt-Jakob disease are discussed.

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.
  • Creutzfeldt-Jakob disease is a subacute fatal disease with a clinical triad of dementia, myoclonus, and EEG abnormalities that is usually associated with other neurologic abnormalities, along with neuropathological evidence of neuronal loss, spongiform changes, and astrocytosis.
  • Iatrogenic cases of Creutzfeldt-Jakob disease have been described related to corneal transplantation, implantation of intracerebral electrodes (inadequately sterilized with formaldehyde), growth hormone injection (from pooled pituitary glands), and dura mater implantation (from pooled dura maters).
  • A variant form of Creutzfeldt-Jakob disease caused by bovine spongiform encephalopathy (mad cow disease) is distinctive because of the relatively young age of the patients, frequent behavioral abnormalities early in the disease, few EEG abnormalities, an MRI finding of increased signal in the pulvinar, and abundant “florid” plaques in the brain (similar to those seen with kuru).
  • 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.

Historical note and terminology 

Jakob deserves credit for being 1 of the first to draw attention to a clinical and pathologic syndrome that we now refer to as Creutzfeldt-Jakob disease. Although Jakob believed that a previously published case by Creutzfeldt reported on the same condition, this patient is now thought to have probably suffered from another disease process. In 1959 Klatzo and colleagues remarked on the similarity between the neuropathology of Creutzfeldt-Jakob disease and that seen in kuru, a noninflammatory ataxic spongiform encephalopathy found among the Fore tribesmen of the Eastern Highlands of Papua, New Guinea (Klatzo et al 1959). In 1966 kuru was transmitted to subhuman primates following intracerebral inoculation of CNS tissue (Gajdusek 1966); this prompted the inoculation of subhuman primates with Creutzfeldt-Jakob disease-infected brain and its successful transmission (Gibbs et al 1968).

Creutzfeldt-Jakob disease, kuru, Gerstmann-Straussler-Scheinker syndrome, fatal familial insomnia, sporadic fatal insomnia, and a number of animal diseases (including scrapie, bovine spongiform encephalopathy, and chronic wasting disease of deer and elk) are grouped as prion diseases, or transmissible subacute spongiform encephalopathies, because of their similar clinical and pathologic features and their transmissibility (Gajdusek 1966). The transmission is of special interest because of the noninflammatory nature of the clinicopathologic syndrome, the long incubation period (ie, a slow virus infection), and the unusual nature of the transmissible agent, the prion (Prusiner 1997; Prusiner et al 1998). The importance of these diseases was demonstrated by Gajdusek’s and Prusiner’s receipt of the Nobel Prize in 1976 and 1997, respectively. The prion diseases have become more visible in recent years because of an epidemic of bovine spongiform encephalopathy (“mad cow” disease), found primarily in the United Kingdom, and the subsequent emergence of a new variant of Creutzfeldt-Jakob disease, which is thought to result from oral transmission of the bovine spongiform encephalopathy agent to humans. In addition, the recognition of chronic wasting disease as a prion disease of deer and elk in the United States has focused attention on the prion diseases.

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