Creutzfeldt-Jakob Disease
Creutzfeldt-Jakob disease (CJD) is rare, affecting less than one person
in a million per year. Though it has been reported to occur at a variety
of ages, the median age of onset is in the seventh decade, with most
sporadic cases occurring between the ages of 55 and 65, but familial or
infectious cases can occur in younger adults. The course of the illness
can be from a few weeks to eight years. However, the average length
of survival from onset of the disease is less than a year. CJD is a
uniformly fatal rapidly progressive dementia. (Markus et al, 2005)
The clinical features of CJD include dementia, often with psychiatric or
behavioral disturbances, in 100% of cases. About 80% of cases are
marked by the appearance of myoclonus. By electroencephalography
(EEG), there are periodic biphasic or triphasic synchronous sharpwave complexes that are superimposed upon a slow background
rhythm. Both myoclonus and characteristic EEG changes may subside
late in the course of disease. Other neurologic findings may include
cerebellar signs, pyramidal tract signs, extrapyramidal signs, corticla
visual defects, abnormal extraocular movements, lower motor neuron
signs, vestibular dysfunction, seizures, sensory deficits, and autonomic
abnormalities. (Johnson, 2005)
Routine laboratory findings are not helpful. There is no dysfunction of
major organ systems besides the central nervous system.
Cerebrospinal fluid (CSF) will not show an increase in cells or
immunoglobulins, and occasionally a mildly elevated protein. An
abnormal protein called 14-3-3 can be found in the CSF by
immunoassay, but this protein may be found in association with viral
encephalitis and stroke. A Western blot assay or immunohistochemical
staining of cells can be performed to try and identify PrPres in biopsied
lymphoid tissue (tonsil), but this may not always be helpful. (Johnson,
2005)
There are no characteristic gross pathologic features of CJD. In fact,
because of the typical short course of the disease, no gross changes
are seen at all. Persons living beyond 6 months to a year may have
some degree of generalized cerebral atrophy. The spongiform
encephalopathy of CJD is seen microscopically to exhibit many round
to oval vacuoles varying in size from one to 50 microns in size in the
neuropil of cortical gray matter. These vacuoles may be single or
multiloculated. The vacuoles may coalesce to microcysts. Most cases
of CJD also demonstrate neuronal loss and gliosis. In general, the
longer the course of the disease, the more pronounced the microscopic
changes will be. The PrPres can be identified in tissues with
immunohistochemical staining. (Prusiner, 1998)
The agent associated with CJD appears to be a prion protein (PrP), a
neuronal cell surface sialoglycoprotein that is encoded by just 3 exons
of the PRNP gene on chromosome 20. It is thought that the normal
cellular prion protein, designated PrPc, is converted via a
conformational change to an abnormal form of PrP, designated PrPSc,
that is protease-resistant and can accumulate in the central nervous
system of affected persons. This accumulation of abnormal protein,
thus designated PrPres accounts for the degenerative changes in the
cerebral cortex by inducing conformational change in the normal PrP,
designated PrPC. The accumulation of PrPres leads to loss of neuronal
cell function, vacuolization, and death. (Prusiner, 1998) (Markus et al,
2005)
These abnormal PrP's can be transmitted from a person with
spongiform encephalopathy to another person, at least by the evidence
from transmission via pituitary extracts, corneal transplants, dural
grafts, and contaminated electrodes. Transmission via close personal
contact, in the workplace, or via transfusion of blood products does not
appear to occur. How transmission occurs naturally is not clear, though
an acquired mutation of the gene encoding for PrP may account for the
appearance of sporadic cases. The abnormal PrP can catalyze the
conversion of normal to abnormal PrP. (Prusiner, 1998)
The presence of particular polymorphisms at codon 129 of PrP may
have an influence on susceptibility to disease. The amino acids
methionine (M) or valine (V) may be present. In healthy persons, both
inherited PrP genes code for methionine. Many persons with sporadic
CJD have abnormal phenotypes. However, subgroups of sporadic CJD
can be found with all polymorphisms, but differing characteristics.
(Mead, 2006)
CJD is one form of spongiform encephalopathy; others include Kuru
and fatal familial insomnia. There are other forms of which can affect
mammalian species besides humans. The spongiform encephalopathy
known as scrapie that is seen in sheep is poorly transmissible to other
species. However, bovine spongiform encephalopathy (BSE), also
called "mad cow disease", can be transmitted more readily to animals
other than cattle. The relationship of human spongiform
encephalopathy with animal forms of this disease is not entirely clear.
An outbreak of BSE among cattle in England in the 1980's was
followed by the appearance of rare cases of a CJD-like illness in the
1990's that were characterized by younger age of onset, lack of
characteristic EEG findings, longer course of disease, and more
extensive spongiform change with plaques in the brains of affected
persons. These cases are known as variant Creutzfeldt-Jakob disease
(vCJD). This suggests the possibility of a relationship, but the rarity of
vCJD cases, similar to the rarity of standard CJD cases, precludes
compelling epidemiologic evidence. Cases of vCJD continue to appear
in regions were BSE was prevalent. (Johnson, 2005)