4 minute read

Creutzfeldt-Jakob Disease

Clinical Features

Creutzfeldt-Jakob disease occurs worldwide, with an incidence rate of one per million, most commonly between the ages of fifty and seventy. There are familial forms of the disease, due to mutations in the prion protein gene, best studied in populations in Slovakia and among Libyan Jews. The disease can be iatrogenic, caused by exposure to infectious tissue, such as corneal transplants, dura mater grafts, contaminated surgical instruments, and medications made from human brain tissue, most notably human growth hormone. The time between exposure and onset of the disease can be many years. Most cases, however, are sporadic, or random. There has never been a known case of person-to-person infection. Although it can theoretically be transmitted by blood transfusion, no such case has been identified. There was much interest in the 1970s and 1980s in dietary risk factors, particularly ingestion of animal brains, but this has not been supported by more recent studies. Preliminary data reported in September of 2000 suggest Table 1 Transmissible Spongiform Encephalopathies SOURCE: Author that variant Creutzfeldt-Jakob disease can be passed on through blood transfusions and from a mother to her fetus.

The diagnostic criteria for Creutzfeldt-Jakob disease are presented in Table 2, and are self-explanatory. Often patients with Creutzfeldt-Jakob disease, particularly those with myoclonus, have a typical pattern of sharp waves on their electroencephalograph. Elevated levels of the 14-3-3 protein, a neuronal protein of unknown function, have been found in the cerebrospinal fluid of patients with Creutzfeldt-Jakob disease, and occasionally other cerebral diseases. If Creutzfeldt-Jakob disease is suspected, testing for this protein can help confirm the diagnosis.

Creutzfeldt-Jakob disease progresses rapidly, with a median duration from onset to death of four and a half months. There is no effective treatment for any of the Transmissible Spongiform Encephalopathies. Treatment is limited to comfort care and, if appropriate, genetic counseling. The search for possible therapies involves agents that may stimulate the body to break down the abnormal prion protein, that may disrupt the conformational chain reaction, or that may prevent spread of the prion to the nervous system in an exposed individual.

The epidemic of Bovine Spongiform Encephalopathy in the United Kingdom in the Table 2 World Health Organization diagnostic criteria for Creutzfeldt-Jakob disease SOURCE: Author 1980s produced fears that this disease might enter the food chain, and affect humans and other species. This fear has proven true, although the eventual magnitude is as yet unknown. New diseases with prions identical to that causing bovine spongiform encephalopathy have been found in humans, cats, and zoo animals, most likely from prion-contaminated food. This new human disease, variant Creutzfeldt-Jakob disease, differs in that it typically affects people in their twenties and thirties; psychiatric symptoms are prominent; and the pathological appearance is different, with many prion protein-containing plaques found throughout the cortex. Only people with a prion protein gene coding for the amino acid methionine at codon 129 on both gene copies (homozygous for methionine) are susceptible to the disease. People homozygous for valine, or heterozygous for both valine and methionine, are not known to be susceptible to the new variant. Cases have occurred only in Great Britain and France. It is difficult to know if an epidemic will occur, but the incidence increased by 33 percent between 1994 and 2000. Some of this increase may reflect new diagnostic methods.

Not all scientists support the prion hypothesis. They hypothesize that a cofactor, probably a virus, is also present. The works by Manuelidis and Balter cited in the bibliography present these alternative views.


See also DEMENTIA.


BALTER, M. "Prions: A Lone Killer or a Vital Accomplice." Science 286 (22 October 1999): 660–662.

CAUGHEY, B. "Transmissible Spongiform Encephalopathies, Amyloidoses and Yeast Proteins: Common Threads?" Nature Medicine 6 (2000): 751–754.

COLLINGE, J. "Variant Creutzfeldt-Jakob Disease." Lancet 354 (24 July 1999): 317–323.

MACKNIGHT, C. "Clinical Implications of Bovine Spongiform Encephalopathy." Clinical Infectious Diseases 32 (2001): 1726–1731.

MANUELIDIS, L. "Dementias, Neurodegeneration, and Viral Mechanisms of Disease from the Perspective of Human Transmissible Encephalopathies." Annals of the New York Academy of Sciences 724 (1994): 259–281.

PRUSINER, S. B., ed. Prion Biology and Diseases. Cold Spring Harbor Monograph Series, no. 38. Cold Spring Harbor, N.Y.: Cold Spring Harbor Laboratory, 1999.

SOTO, C.; KASCSAK, R. J.; SABORIO, G. P.; AUCOU TURIER, P.; WISNIEWSKI, T.; PRELLI, F.; KASCSAK, R.; MENDEZ, E.; HARRIS, D. A.; IRONSIDE, J.; TAGLIAVINI, F.; CARP, R. I.; and FRANGIONE, B. "Reversion of Prion Protein Conformational Changes by Synthetic B-sheet Breaker Peptides." Lancet 355 (January 15, 2000): 192–197.

SUPATTAPONE, S.; NGUYEN, H.-O. B.; COHEN, F. E.; PRUSINER, S. B.; and SCOTT, M. R. "Elimination of Prions by Branched Polyamines and Implications for Therapeutics." Proceedings of the National Academy of Sciences 96 (1999): 14529–14534.

WILSON, K.; CODE, C.; and RICKETTSM. N. "Risk of Acquiring Creutzfeldt-Jakob Disease from Blood Transfusions: Systematic Review of Case-Control Studies." British Medical Journal 321 (1 July 2000): 17–19.

World Health Organization. "Transmissible Spongiform Encephalopathies." World Wide Web document. www.who.int

Additional topics

Medicine EncyclopediaAging Healthy - Part 1Creutzfeldt-Jakob Disease - Prions, Clinical Features