Creutzfeldt-Jakob Disease [CJD] may have
greater public health consequences than the suspected number of confirmed
cases might indicate. CJD is not reportable in most states and is often
misdiagnosed or omitted from death certificates. CJD is thought to be
caused by prions. While the infectivity can be reduced, it is extremely
difficult to kill these infectious agents. Normal sterilization procedures
do not eliminate contamination.
WHAT IS
IT?
Creutzfeldt-Jakob disease (CJD) is a rare, degenerative, invariably fatal
brain disorder. It affects about one person in every one million people
per year worldwide; in the United States there are about 200 cases per
year. 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.
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. FFI 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 is often referred to as
“mad cow” disease; scrapie, which affects sheep and goats; mink
encephalopathy; and feline encephalopathy. Similar diseases have occurred
in elk, deer, and exotic zoo animals.
WHO GETS
IT AND HOW?
Creutzfeldt-Jakob Disease affects both men
and women worldwide usually between the ages of 50 to 75 years. The
officially stated mortality rate is one to two deaths per one million
population per year. However, this figure appears to be an understatement
as CJD is often misdiagnosed. In one study by Yale University researchers
13% of Alzheimer patients were found upon autopsy to actually have CJD. A
similar study performed at the University of Pittsburgh showed over 5% of
Alzheimer's patients were CJD victims. There are three forms of CJD:
familial (genetic, about 10-15% of cases), sporadic (cause unknown, about
80-85% of cases) and iatrogenic (through a medical procedure such as
contaminated cadaver-derived growth hormones (GH), dura mater recipients,
use of contaminated surgical instruments, and corneal transplant
recipients, about 1% of cases) While it is theoretically possible the
infectious agent may be present in blood, there are no documented cases of
transmission by blood in humans. Pooled blood products are withdrawn as a
precaution when a donor has been confirmed as a CJD victim or they are at
a higher risk of contracting CJD. Unfortunately, in most cases blood
products have already been utilized by individuals prior to the
withdrawals. The CDC is currently under Congressional mandate to monitor
blood product recipients for any evidence of increase of CJD incidence.
WHAT ARE
THE SYMPTOMS OF CJD?
CJD is characterized by
rapidly progressive dementia. Initially, patients experience problems with
muscular coordination; personality changes, including impaired memory,
judgment, and thinking; and impaired vision. 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. 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-called new variant or variant (nv-CJD, v-CJD), described in Great
Britain and France-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 the symptoms and
course of the disease.
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 and 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 by
self-inoculation. Special surgical and disinfection procedures can
minimize this risk. A fact sheet with guidance on these procedures is
available from the NINDS and the World Health Organization.
Scientists are 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 percent. Scientists are working to develop
this test for use in commercial laboratories. They are also working to
develop other tests for this disorder.
HOW IS THE DISEASE
TREATED?
There is no treatment that
can cure or control CJD. Researchers have tested many drugs, including
amantadine, steroids, interferon, acyclovir, antiviral agents, and
antibiotics. Studies of a variety of other drugs are now in progress.
However, so far none of these treatments has shown any consistent benefit
in humans.
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 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 by a type of protein called a prion.
Prion proteins 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 have the
same sequence of amino acids (the "building blocks" of proteins) but the
infectious form of the protein 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 aggregate, or clump together.
Investigators think these protein aggregates may lead to the neuron loss
and other brain damage seen in CJD. However, they do not know exactly how
this damage occurs.
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 body’s normal
prion protein. If the prion protein 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 protein gene develop CJD.
HOW IS CJD
TRANSMITTED?
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, exposure to brain tissue and spinal cord fluid from infected
patients should be avoided to prevent transmission of the disease through
these materials.
In some 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 the new variant of CJD (nv-CJD or v-CJD) in several
younger than average people in Great Britain and France has led to concern
that BSE may 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.
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 people with hemophilia, who sometimes receive blood plasma
concentrated from thousands of donors, there are no reported cases of CJD.
While there is no evidence that blood from people with sporadic CJD is
infectious, studies have found that infectious prions from BSE and vCJD
may accumulate in the lymph nodes (which produce white blood cells), the
spleen, and the tonsils. These findings suggest that blood transfusions
from people with vCJD might transmit the disease. The possibility that
blood from people with vCJD may be infectious has led to a policy
preventing people in the United States from donating blood if they have
resided for more than 3 months in a country or countries where BSE is
common.
HOW CAN PEOPLE AVOID
SPREADING THE DISEASE?
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 smoking.
Cover 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 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.
- 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.
Fact sheets listing
additional precautions for healthcare workers and morticians are available
from the NINDS and the World Health Organization.
WHAT RESEARCH IS TAKING
PLACE?
Many researchers are
studying CJD. They are examining whether the transmissible agent is, in
fact, a prion or a product of the infection, and are 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.
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 Creutzfeldt-Jakob disease. To help with this research, they
are seeking biopsy and autopsy tissue, blood, and cerebrospinal fluid from
patients with CJD and related diseases.
Click here to find out more.
IS THERE
INFORMATION ON THE WEB ABOUT CJD?
There is a great deal of CJD information on
the web. CJD Voice, is an e-mail based support and discussion group. Most
members of the group have lost a loved one to CJD. Many of the members are
very active in lobbying for increased awareness as well as increased
budget appropriations for CJD research. The website address is
www.cjdvoice.org This website features information about the support group, statistical
information compiled from clinical and pathological information submitted
by members, facilities currently performing CJD research (used also as a
reference for families seeking facilities to send memorials or donations),
programs currently underway by various entities such as the CDC, a
chat room, message board and a CJD information ring as well as links to
other websites with CJD information. For further information contact the
founders of CJD Voice: Dolly Campbell at DBC006@aol.com, Pat Ewanitz
at Ape826@aol.com
or Liz Armstrong at
LArmstr853@aol.com.
