Creutzfeldt-Jakob disease (CJD) is the most common human
form of a group of rare, fatal brain disorders known as prion diseases.
About Creutzfeldt-Jakob disease
Prion diseases, such as Creutzfeldt-Jakob disease, occur
when prion protein, which is found throughout the body but whose normal
function isn't yet known, begins folding into an abnormal three-dimensional
shape. This shape change gradually triggers prion protein in the brain to fold
into the same abnormal shape.
Creutzfeldt-Jakob disease causes a type of dementia that
gets worse unusually fast. More common causes of dementia, such as Alzheimer's,
dementia with Lewy bodies and frontotemporal dementia, typically progress more
slowly.
Through a process scientists don't yet understand,
misfolded prion protein destroys brain cells. Resulting damage leads to rapid
decline in thinking and reasoning as well as involuntary muscle movements,
confusion, difficulty walking and mood changes.
Creutzfeldt-Jakob disease is rare, occurring in about one
in 1 million people annually worldwide. The disease most often affects older
adults.
Types of Creutzfeldt-Jakob disease
Experts generally recognize the following main types of
Creutzfeldt-Jakob disease:
·
Sporadic Creutzfeldt-Jakob disease develops
spontaneously for no known reason. It accounts for 85 percent of cases. On
average, sporadic Creutzfeldt-Jakob disease first appears between ages 60 and
65.
·
Familial Creutzfeldt-Jakob disease is
caused by certain changes in the chromosome 20 gene coding the biological
blueprint for prion protein. People who develop familial Creutzfeldt-Jakob
disease do so because they inherited the genetic changes from a parent.
Familial Creutzfeldt-Jakob disease accounts for about 10 to 15 percent of
cases. It develops, on average, at a younger age than sporadic
Creutzfeldt-Jakob disease, with some genetic types appearing as early as ages
20 to 40.
·
Acquired Creutzfeldt-Jakob disease results
from exposure to an external source of abnormal prion protein. These sources
are estimated to account for about 1 percent of Creutzfeldt-Jakob disease
cases. The two most common outside sources are:
1.
Medical procedures involving instruments used in
neurosurgery, growth hormone from human sources or certain transplanted human
tissues, including corneas (the clear outer covering of the eye) and dura mater
(the fibrous membrane covering the brain and spinal cord). This type of
acquired CJD is also known as iatrogenic CJD (iCJD). The risk of iCJD from
medical procedures has been greatly reduced by improved neurosurgical
instruments sterilization techniques, new single-use instruments and synthetic
sources of growth hormone and dura mater.
2.
Meat or other products from cattle infected with
bovine spongiform encephalopathy (BVE) or "mad cow disease,"
recognized in the mid-1990s as the cause of variant CJD (vCJD). Scientists
traced this new type of CJD to consumption of beef from cattle whose feed
included processed brain tissue from other animals. Since then, experts have
diagnosed about 200 cases of vCJD, primarily in the United Kingdom and other
European countries. Variant CJD tends to occur at a younger age than sporadic
or familial forms, sometimes even in teenagers. New cases of vCJD have slowed
significantly, most likely due to changes in animal feeding practices.
Symptoms
Specific Creutzfeldt-Jakob disease symptoms experienced
by an individual and the order in which they appear can differ significantly.
Some common symptoms include:
·
Depression.
·
Agitation, apathy and mood swings.
·
Rapidly worsening confusion.
·
Disorientation.
·
Problems with memory, thinking, planning and
judgment.
·
Difficulty walking.
·
Muscle stiffness, twitches and involuntary jerky
movements.
·
Vision problems, such as double vision and
hallucinations
Complications
Creutzfeldt-Jakob disease has serious effects on the
brain and body. The disease usually progresses quickly. Over time, people with
CJD withdraw from friends and family. They also lose the ability to care for
themselves. Many slip into a coma. The disease is always fatal.
Rapid symptom progression is one of the most important
clues that a person may have Creutzfeldt-Jakob disease.
There is no single test — or any combination of tests — that can conclusively
diagnose sporadic Creutzfeldt-Jakob disease in a living person, but the
following tests may help determine whether an individual has Creutzfeldt-Jakob
disease:
·
Electroencephalogram (EEG) measures the brain's
patterns of electrical activity similar to the way an electrocardiogram (ECG)
measures the heart's electrical activity.
·
Brain magnetic resonance imaging (MRI) can
detect certain brain changes consistent with Creutzfeldt-Jakob disease.
·
Lumbar puncture (spinal tap) tests spinal fluid
for the presence of certain proteins.
·
Protein misfolding cyclic amplification (PMCA):
PMCA is an amplification
technique for the detection of misfolded protein aggregates.
Causes and risks
Sporadic CJD has no known cause. Most scientists believe
the disease begins when prion protein somewhere in the brain spontaneously
misfolds, triggering a "domino effect" that misfolds prion protein
throughout the brain. Genetic variation in the prion protein gene at a location
called "codon 129" may increase risk of this spontaneous misfolding.
Variation at codon 129 in the prion protein gene may also
play a role in making people susceptible to acquired CJD from external sources.
Scientists don’t yet know why acquired CJD seems to be transmitted through such
a limited number of external sources. Researchers have found no evidence that
the abnormal protein is commonly transmitted through sexual activity or blood
transfusions, although a few cases of vCJD seem to have been spread through
blood transfusions. Professionals who regularly encounter blood from a human or
animal, such as surgeons, pathologists or butchers, have not been shown to have
a higher-than-normal risk through occupational exposure.
Familial CJD is caused by variations in the prion protein
gene that increase the likelihood an individual will develop CJD. Researchers
have identified more than 50 prion protein mutations in those with inherited
CJD. Genetic testing can determine whether family members at risk have
inherited a CJD-causing mutation. Experts strongly recommend professional
genetic counseling both before and after genetic testing for hereditary CJD.
Age has an influence on sporadic CJD, which tends to
develop later in life, usually around age 60. Onset of familial CJD occurs
slightly earlier and vCJD has affected people at a much younger age, usually in
their late 20s.
Chronic wasting disease is a prion disease similar to mad
cow disease that’s been found in wild deer, elk and moose in certain U.S.
states, Canadian provinces, Korea and Norway. According to the U.S. Centers for
Disease Control and Prevention (CDC), there’s no evidence to date that chronic
wasting disease has been transmitted to humans, including hunters who eat meat
from affected animals. There’s also no evidence that rates of CJD have
increased in states or provinces where chronic wasting disease has been
identified. Additional studies are under way to understand what risk, if any,
chronic wasting disease poses to humans. The CDC recommends that hunters who
plan to eat meat from deer, elk or moose in areas where chronic wasting disease
occurs consider having the meat tested by their local state wildlife agency.
The CDC also recommends wearing gloves while field dressing these animals to
avoid handling the brain or spinal column.
Treatment and outcomes
There is no treatment that can slow or stop the
underlying brain cell destruction caused by Creutzfeldt-Jakob disease and other
prion diseases. Various drugs have been tested but have not shown any benefit.
Clinical studies of potential Creutzfeldt-Jakob disease treatments are
complicated by the rarity of the disease and its rapid progression.
Current therapies focus on treating symptoms and on
supporting individuals and families coping with Creutzfeldt-Jakob disease.
Doctors may prescribe painkillers such as opiates to treat pain if it occurs.
Muscle stiffness and twitching may be treated with muscle-relaxing medications
or antiseizure drugs. In the later stages of the disease, individuals with
Creutzfeldt-Jakob disease become completely dependent on others for their daily
needs and comfort.
Creutzfeldt-Jakob disease progresses rapidly. Those
affected lose their ability to move or speak and require full-time care to meet
their daily needs. An estimated 90 percent of those diagnosed with sporadic
Creutzfeldt-Jakob disease die within one year. Those affected by familial
Creutzfeldt-Jakob disease tend to develop the disorder at an earlier age and
survive somewhat longer than those with the sporadic form, as do those
diagnosed with variant Creutzfeldt-Jakob disease. Scientists have not yet
learned the reason for these differences in survival.
Prevention
There's no known way to prevent sporadic CJD. If you
have a family history of neurological disease, you may benefit from talking
with a genetics counselor. A counselor can help you sort through your risks.
Preventing Creutzfeldt-Jakob disease related to
medical procedures
Hospitals and other medical institutions follow clear
policies to prevent CJD related to medical procedures, known as
iatrogenic CJD. These measures have included:
·
Using only human-made human growth hormone. This
is used instead of taking the hormone from human pituitary glands.
·
Destroying surgical instruments that may have
been exposed to CJD. This includes instruments used in procedures that
involve the brain or nervous tissue of someone with known or suspected
Creutzfeldt-Jakob disease.
·
Single-use kits for spinal taps, also known as
lumbar punctures.
To help ensure the safety of the blood supply, people
with a risk of exposure to CJD or vCJD aren't eligible to
donate blood in the United States. This includes people who:
·
Have a blood relative who has been diagnosed
with familial CJD. Blood relatives include parents, aunts, uncles,
grandparents and cousins.
·
Have received a dura mater brain graft. Dura
mater is the tissue that covers the brain.
·
Have received human growth hormone from
cadavers.
The United Kingdom (U.K.) and certain other countries
also have specific restrictions regarding blood donations from people with a
risk of exposure to CJD or vCJD.
Preventing variant Creutzfeldt-Jakob disease
The risk of getting vCJD in the United States
remains very low. Only four cases have been reported in the U.S. According to
the U.S. Centers for Disease Control and Prevention (CDC), strong evidence
suggests that these cases were acquired in other countries outside of the U.S.
In the United Kingdom, where the majority
of vCJD cases have occurred, fewer than 200 cases have been
reported. CJD incidence peaked in the U.K. between 1999 and
2000 and has been declining since. A very small number of
other vCJD cases also have been reported in other countries
worldwide.
To date, there is no evidence that people can develop
Creutzfeldt-Jakob disease from consuming the meat of animals infected with
chronic wasting disease (CWD). However, the CDC recommends that
hunters strongly consider taking precautions. The CDC recommends
having deer and elk tested before eating the meat in areas
where CWD is known to be present. Hunters also should avoid shooting
or handling meat from deer or elk that appear sick or are found dead.
Regulating potential sources of variant
Creutzfeldt-Jakob disease
Most countries have taken steps to prevent meat infected
with bovine spongiform encephalopathy (BSE) from entering the food supply.
Steps include:
·
Tight restrictions on importing cattle from
countries where BSE is common.
·
Restrictions on animal feed.
·
Strict procedures for dealing with sick animals.
·
Surveillance and testing methods for tracking
cattle health.
·
Restrictions on which parts of cattle can be
processed for food.
Latest Research
Researchers are examining and characterizing the prions
associated with CJD and other human and animal prion diseases. A better
understanding of these diseases may help scientists discover factors that
influence prion infectivity and transmission, and how the disorder damages the
brain. Researchers are investigating the cellular mechanisms involved in
abnormal prion formation and accumulation, as well as their replication by
select cellular subsets in the brain. Other projects are examining how
abnormal prions cross the protective blood-brain barrier and spread throughout
the central nervous system, and tests that measure the biological activity of
prions. Findings may identify new therapeutic targets to treat prion
diseases.
Other NIH Institutes, including the National Institute of
Allergy and Infectious Diseases, also conduct research on CJD. More information
about CJD research supported by NINDS and other NIH Institutes and Centers can
be found using NIH RePORTER, a searchable database of current and past
research projects supported by NIH and other federal agencies. RePORTER also
includes links to publications and resources from these projects.
Sources and Additional Information:
https://www.alz.org/alzheimers-dementia/what-is-dementia/types-of-dementia/creutzfeldt-jakob-disease
https://www.ninds.nih.gov/health-information/disorders/creutzfeldt-jakob-disease
