What is Creutzfeldt-Jakob Disease?
Creutzfeldt-Jakob disease (CJD) is a rare, degenerative,
invariably fatal brain disorder. It affects about one person in every one million people
worldwide and about 200 people in the United States. CJD usually appears in later life and
runs a rapid course. Typically, onset of symptoms occurs about age 60, and about 90
percent of patients die within 1 year. In the early stages of disease, patients may have
failing memory, behavioral changes, lack of coordination and visual disturbances. As the
illness progresses, mental deterioration becomes pronounced and involuntary movements,
blindness, weakness of extremities, and coma may occur.
There are three major categories of CJD:
- In sporadic CJD, the disease appears even
though the person has no known risk factors for the disease. This is by far the most
common type of CJD and accounts for at least 85 percent of cases.
- In hereditary CJD, the person has a family history
of the disease and/or tests positive for a genetic mutation associated with CJD. About 5
to 10 percent of cases of CJD in the United States are hereditary.
- In acquired CJD, the disease is transmitted by
exposure to brain or nervous system tissue, usually through certain medical procedures.
There is no evidence that CJD is contagious through casual contact with a CJD patient.
Since CJD was first described in 1920, fewer than 1 percent of cases have been acquired
CJD belongs to a family of human and animal diseases known
as the transmissible spongiform encephalopathies (TSEs). Spongiform refers
to the characteristic appearance of infected brains, which become filled with holes until
they resemble sponges under a microscope. CJD is the most common of the known human
TSEs. Other human TSEs include kuru, fatal familial insomnia (FFI), and
Gerstmann-Straussler-Scheinker disease (GSS). Kuru was identified in people of an isolated
tribe in Papua New Guinea and has now almost disappeared. Fatal familial insomnia and GSS
are extremely rare hereditary diseases, found in just a few families around the world.
Other TSEs are found in specific kinds of animals. These include bovine spongiform
encephalopathy (BSE), which is found in cows and often referred to as "mad cow"
disease; scrapie, which affects sheep; and mink encephalopathy. Similar diseases have
occurred in elk, deer, and exotic zoo animals.
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What are the Symptoms of the Disease?
The first symptoms of Creutzfeldt-Jakob disease typically
include dementia personality changes together with impaired memory,
judgment, and thinking and problems with muscular coordination. People with the
disease also may experience insomnia, depression, or unusual sensations. CJD does not
cause a fever or other flu-like symptoms. As the illness progresses, the patients
mental impairment becomes severe. They often develop involuntary muscle jerks called myoclonus,
and they may go blind or lose bladder control. They eventually lose the ability to move
and speak and enter a coma. Pneumonia and other infections often occur in these patients
and can lead to death.
There are several known variants of CJD. These variants
differ somewhat in the symptoms and course of the disease. For example, a variant form of
the disease (nv-CJD or v-CJD), described in Great Britain and some other parts of Europe,
begins primarily with psychiatric symptoms, affects younger patients than other types of
CJD, and has a longer than usual duration from onset of symptoms to death. Another
variant, called the panencephalopathic form, occurs primarily in Japan and has a
relatively long course, with symptoms often progressing for several years. Scientists are
trying to learn what causes these variations in symptoms.
Some symptoms of CJD can be similar to symptoms of other
progressive neurological disorders, such as Alzheimers or Huntingtons disease.
However, CJD causes unique changes in brain tissue which can be seen at autopsy. It also
tends to cause more rapid deterioration of a persons abilities than Alzheimers
disease or most other types of dementia.
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How is the Disease Diagnosed?
There is currently no single diagnostic test for CJD. When
a doctor suspects CJD, the first concern is to rule out treatable forms of dementia such
as encephalitis (inflammation of the brain) or chronic meningitis. A neurological
examination will be performed or the doctor may seek consultation with other physicians.
Standard diagnostic tests will include a spinal tap to rule out more common causes of
dementia and an electroencephalogram (EEG) to record the brains electrical pattern,
which can be particularly valuable because it shows a specific type of abnormality in CJD.
Computerized tomography of the brain can help rule out the possibility that the symptoms
result from other problems such as stroke or a brain tumor. Magnetic resonance imaging
(MRI) brain scans also can reveal characteristic patterns of brain degeneration that can
help diagnose CJD.
The only way to confirm a diagnosis of CJD is by brain
biopsy or autopsy. In a brain biopsy, a neurosurgeon removes a small
piece of tissue from the patients brain so that it can be examined by a
neuropathologist. This procedure may be dangerous for the patient, and the operation does
not always obtain tissue from the affected part of the brain. Because a correct diagnosis
of CJD does not help the patient, a brain biopsy is discouraged unless it is needed to
rule out a treatable disorder. In an autopsy, the whole brain is examined after
death. Both brain biopsy and autopsy pose a small, but definite, risk that the surgeon or
others who handle the brain tissue may become accidentally infected. Special surgical and
disinfection procedures can minimize this risk.
Scientists are working to develop laboratory tests for
CJD. One such test, is performed on a persons cerebrospinal
fluid and detects a protein marker that indicates neuronal degeneration. This can help
diagnose CJD in people who already show the clinical symptoms of the disease. This test is
much easier and safer than a brain biopsy. The false positive rate is about 5 to 10
percent. Scientists are working to develop this test for use in commercial laboratories.
There have been reports of other ways of diagnosing the disease, including tonsil
biopsies, which may lead to other tests.
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How Is CJD Treated?
There is no treatment that can cure or control
Creutzfeldt-Jakob disease. Researchers have tested many drugs, including amantidine,
steroids, interferon, acyclovir, antiviral agents, and antibiotics. However, none of these
treatments has shown any consistent benefit.
Current treatment for CJD is aimed at alleviating symptoms
and making the patient as comfortable as possible. Opiate drugs can help relieve pain if
it occurs, and the drugs clonazepam and sodium valproate may help relieve myoclonus.
During later stages of the disease, changing the persons position frequently can
keep him or her comfortable and helps prevent bedsores. A catheter can be used to drain
urine if the patient cannot control bladder function, and intravenous fluids and
artificial feeding also may be used.
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What Causes Creutzfeldt-Jakob Disease?
Some researchers believe an unusual "slow virus"
or another organism causes CJD. However, they have never been able to isolate a virus or
other organism in people with the disease. Furthermore, the agent that causes CJD has
several characteristics that are unusual for known organisms such as viruses and bacteria.
It is difficult to kill, it does not appear to contain any genetic information in the form
of nucleic acids (DNA or RNA), and it usually has a long incubation period before symptoms
appear. In some cases, the incubation period may be as long as 40 years. The leading
scientific theory at this time maintains that CJD and the other TSEs are caused not by an
organism but by a type of protein called a prion.
Prions occur in both a normal form, which is a harmless
protein found in the bodys cells; and in an infectious form, which causes disease.
The harmless and infectious forms of the prion protein are nearly identical, but the
infectious form takes a different folded shape than the normal protein. Sporadic CJD may
develop because some of a persons normal prions spontaneously change into the
infectious form of the protein and then alter the prions in other cells in a chain
Once they appear, abnormal prion proteins stick together
and form fibers and/or clumps called plaques that can be seen with powerful microscopes.
Fibers and plaques may start to accumulate years before symptoms of CJD begin to appear.
It is still unclear what role these abnormalities play in the disease or how they might
About 5 to 10 percent of all CJD cases are inherited.
These cases arise from a mutation, or change, in the gene that controls formation of the
normal prion protein. While prions themselves do not contain genetic information and do
not require genes to reproduce themselves, infectious prions can arise if a mutation
occurs in the gene for the bodys normal prions. If the prion gene is altered in a
persons sperm or egg cells, the mutation can be transmitted to the persons
offspring. Several different mutations in the prion gene have been identified. The
particular mutation found in each family affects how frequently the disease appears and
what symptoms are most noticeable. However, not all people with mutations in the prion
gene develop CJD. This suggests that the mutations merely increase susceptibility to CJD
and that other, still-unknown factors also play a role in the disease.
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How is CJD Transmitted?
While CJD can be transmitted to other people, the risk of
this happening is extremely small. CJD cannot be transmitted through the air or through
touching or most other forms of casual contact. Spouses and other household members of
sporadic CJD patients have no higher risk of contracting the disease than the general
population. However, direct or indirect contact with brain tissue and spinal cord fluid
from infected patients should be avoided to prevent transmission of the disease through
cases. Since 1985, all human growth hormone used in the United States has been
synthesized by recombinant DNA procedures, which eliminates the risk of transmitting CJD
by this route.
The appearance of a new variant of CJD (nv-CJD or v-CJD)
in several younger than average people in Europe has led to concern that BSE can be
transmitted to humans through consumption of contaminated beef. Although laboratory tests
have shown a strong similarity between the prions causing BSE and v-CJD, there is no
direct proof to support this theory. Furthermore, BSE has never been found in the United
States, and importing of cattle and beef from countries with BSE has been banned in the
United States since 1989 to reduce the risk that it will occur in this country.
Many people are concerned that it may be possible to
transmit CJD through blood and related blood products such as plasma. Some animal studies
suggest that contaminated blood and related products may transmit the disease, although
this has never been shown in humans. If there are infectious agents in these fluids, they
are probably in very low concentrations. Scientists do not know how many abnormal prions a
person must receive before he or she develops CJD, so they do not know whether these
fluids are potentially infectious or not. They do know that, even though millions of
people receive blood transfusions each year, there are no reported cases of someone
contracting CJD from a transfusion. Even among hemophiliacs, who sometimes receive blood
plasma concentrated from thousands of people, there are no reported cases of CJD. This
suggests that, if there is a risk of transmitting CJD through blood or plasma, it is
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How Can People Avoid Spreading the
To reduce the already very low risk of CJD transmission
from one person to another, people should never donate blood, tissues, or organs if they
have suspected or confirmed CJD, or if they are at increased risk because of a family
history of the disease, a dura mater graft, or other factor.
Normal sterilization procedures such as cooking, washing,
and boiling do not destroy prions. Caregivers, health care workers, and undertakers should
take the following precautions when they are working with a person with CJD:
- Wash hands and exposed skin before eating, drinking, or
- Cover cuts and abrasions with waterproof dressings.
- Wear surgical gloves when handling a patients tissues
and fluids or dressing the patients wounds.
- Avoid cutting or sticking themselves with instruments
contaminated by the patients blood or other tissues.
- Use disposable bedclothes and other cloth for contact with
the patient. If disposable materials are not available, regular cloth should be soaked in
undiluted chlorine bleach for an hour or more, then washed in a normal fashion after each
- Use face protection if there is a risk of splashing
contaminated material such as blood or cerebrospinal fluid.
- Soak instruments that have come in contact with the patient
in undiluted chlorine bleach for an hour or more, then use an autoclave (pressure cooker)
to sterilize them in distilled water for at least one hour at 132 - 134 degrees
A fact sheet listing additional precautions for healthcare
workers and morticians is available from the NINDS.
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What Research Is Taking Place?
Many researchers are studying CJD. They are examining
whether the transmissible agent is, in fact, a prion, and trying to discover factors that
influence prion infectivity and how the disorder damages the brain. Using rodent models of
the disease and brain tissue from autopsies, they are also trying to identify factors that
influence susceptibility to the disease and that govern when in life the disease appears.
They hope to use this knowledge to develop improved tests for CJD and to learn what
changes ultimately kill the neurons so that effective treatments can be developed.
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