A form of neurodegenerative human prion (acronym for
“proteinaceous infectious particles”) disorder, which belongs to a group
of diseases known as transmissible spongiform encephalopathies.
Worldwide, the incidence of Creutzfeldt-Jakob disease
(CJD) in the general population is approximately 1:1,000,000 per year. A
variant of CJD (vCJD) has been associated with bovine spongiform
encephalopathy (BSE) and has the highest occurrence in the United Kingdom.
As of November 2005, the total number of definite or probable vCJD cases
(dead and alive) in the United Kingdom was 158 (in 108 cases with
neuropathologic confirmation). A causal association between vCJD and BSE is
supported by epidemiologic and laboratory evidence in areas with high
prevalence of BSE and the lack thereof in basically BSE-free regions.
The occurrence of CJD, like other forms of
prion diseases, is familial (5-10% of cases, with autosomal dominant
inheritance caused by mutations in the PRNP [prion protein] gene, which has
been mapped to 20pter-p12), sporadic (approximately 90% of patients with
noninherited mutation of the prion protein), or infectious (iatrogenic with
the first reported case of vCJD in 1974). The infectious agent in prion
disease consists almost entirely of a host-encoded protease-resistant,
neuronal cell surface sialoglycoprotein termed prion protein.
The cause is not fully understood but is believed
to be related to misfolding of the normal endogenous cellular prion protein
PrPC into a new pathogenic conformation PrPSc encoded by PRNP.
Prion protein is necessary for normal synaptic function. Iatrogenic and
infectious transmission has occurred via tissue transplants (e.g., corneal
transplants and no longer used dura mater grafts), cadaveric pituitary gland
extracts (e.g., for human growth hormone [hGH] and gonadotropin production, now
replaced by synthetic hormones), and contamination by neurosurgical
instruments and stereotactic electroencephalography electrodes. Currently,
blood is considered to pose a theoretical risk only, and no cases related to
blood transmission have been reported. Accumulation of PrPSc in the
central nervous system of affected individuals is responsible for the
typical degenerative changes, such as loss of neurons, vacuolization, and
There is no definitive clinical diagnostic test apart
from the neuropathologic investigation. Patients have variable clinical and
pathologic pictures. Pathology findings include diffuse nerve cell
degeneration, status spongiosus, and glial proliferation. The
electroencephalogram may show characteristic periodic complex changes.
The vast majority of patients are between 50 and
70 years old at the onset of the disease, although significantly younger
affected patients have been reported. The onset of familial cases is
significantly earlier than in other forms. The course of the illness may
last from a few weeks to several years, although in general it is rapidly
progressive. It is uniformly fatal, with the average length of survival from
onset of the disease being approximately 6 months. Affected patients present with
signs of dementia that often are accompanied by behavioral changes and
psychiatric anomalies. Characteristic electroencephalographic changes can be
detected (a slow background rhythm with superimposed periodic biphasic or