Dr. MJ Bazos MD,
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% 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% 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% of cases of CJD in the United States are
•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% of cases have been acquired CJD.
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.
What Are the Symptoms of the
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.
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 Alzheimer's or
Huntington's 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
person's abilities than Alzheimer's disease or most other types of dementia.
How Is CJD 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 brain's 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 patient's 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. A fact sheet with guidance on these procedures is
available from the NINDS.
working to develop laboratory tests for CJD. One such test, developed at NINDS,
is performed on a person's 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%. 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.
Is the Disease 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.
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 person's 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.
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 body's 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 person's normal
prions spontaneously change into the infectious form of the protein and then
alter the prions in other cells in a chain reaction.
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 affect symptoms.
About 5% to 10% 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 body's
normal prions. If the prion gene is altered in a person's sperm or egg cells,
the mutation can be transmitted to the person's 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.
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 these
In a few very rare cases, CJD
has spread to other people from grafts of dura mater (a tissue that covers the
brain), transplanted corneas, implantation of inadequately sterilized electrodes
in the brain, and injections of contaminated pituitary growth hormone derived
from human pituitary glands taken from cadavers. Doctors call these cases that
are linked to medical procedures iatrogenic 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 extremely small.
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.
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 smoking.
cuts and abrasions with waterproof dressings.
•Wear surgical gloves when handling
a patient's tissues and fluids or dressing the patient's wounds.
•Avoid cutting or sticking
themselves with instruments contaminated by the patient's blood or other
•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.
•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 Centigrade.
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
How Can I Help Research?
Scientists are conducting biochemical
analyses of brain tissue, blood, spinal fluid, urine, and serum in hope of
determining the nature of the transmissible agent or agents causing