Creutzfeldt-Jakob disease (CJD) is a form of transmissible spongiform encephalopathy (TSE) also known as spastic pseudosclerosis of Jakob and corticostriatospinal degeneration of the spinal cord. TSEs that affect humans include 2 very rare hereditary disorders, Gerstmann-Straüssler-Scheinker syndrome and fatal familial insomnia, as well as variant CJD and kuru. Kuru is unique to the Fore tribe of Papua New Guinea, as it is transmitted by exposure from cannibalism to human infected brain tissue. The ban on this practice in 1950 has led to the progressive disappearance of the disease. Human TSEs are related to animal TSEs such as sheep scrapie, bovine spongiform encephalopathy, and deer and elk chronic wasting disease.
CJD and other TSEs are caused by a class of infectious agents called prions (from the contraction of the words proteinaceous and infectious) that are remarkable because they are endogenous and devoid of nucleic acids. The PRNP gene located on the short arm of chromosome 20 codes for a cellular protein called PrPC whose function is unknown. The misfolding of PrPC into an isoform called PrPsc that forms amyloid filaments and plaques characterizes prion diseases. PrPC and PrPsc share the same amino acid sequence (primary structure) but differ in their secondary and tertiary structures. PrPsc facilitates the conversion of PrPC into PrPsc. Therefore, another unique characteristic of prion diseases is that not only can they result from mutations in the PrP gene and other spontaneous events, but also from infection by an exogenous PrPsc protein.
Three forms of classic CJD are recognized:
Sporadic (random) – This form is the most common, accounting for 85% of cases. It affects middle-aged and older adults, with a mean age of onset of 60 years. It has an incidence of 1 in a million (200 annual cases in the United States), split equally between men and women. Subtypes are based on molecular classification and include classic, ataxic, thalamic, cortical, Heidenhain (visual) variant, and Oppenheimer-Brownell (cerebellar) variant.
Familial – Represents 5%-15% of cases in the United States and occurs in younger patients. Patients with this form are identified by having a family history or by testing positive for a PRNP gene mutation. The inherited TSEs are caused by about two dozen mutations and corresponding altered PrP proteins. Some mutations are associated with CJD, while others are linked to Gerstmann-Straüssler-Scheinker syndrome or fatal familial insomnia.
Acquired (iatrogenic) – This is the least common form of CJD and is transmitted through exposure to infected tissues during medical procedures, such as dura mater grafts, corneal transplants, skin transplants, or contaminated stereotactic electrodes or surgical instruments. CJD has been also acquired from the administration of growth hormone extract prepared from pooled pituitary glands.
CJD has a variable duration ranging from 1 to 64 months before leading to death. However, it is usually rapidly progressive and fatal in less than a year for 90% of patients.
A new form of CJD called variant CJD (vCJD) was first described in the United Kingdom in 1996 and was found to be related to the epidemic of bovine spongiform encephalopathy ("mad cow disease") that was then occurring. vCJD differs in several ways from classic CJD. The age of onset is younger, ranging from the second to the seventh decade of life (median age 29 years). The progression is also slower, with an average of 14 months. Behavioral symptoms typically predominate, along with sensory complaints, myoclonus, and ataxia. The neuropathology shows abundant plaques and little spongiosis, with prominent involvement of the cerebellum in addition to the cerebrum.
A cluster of patients have been identified in New Brunswick, Canada, with a neurologic disease resembling CJD, termed the "New Brunswick cluster of neurological syndrome of unknown cause." As of March 2021, the cause is not identified, and tests for prion disease have been negative.
Pediatric Patient Considerations: A synthetic growth hormone has been available since 1985. It carries no risk of transmission of CJD.