What is Creutzfeldt-Jakob disease?
Creutzfeldt-Jakob disease (CJD) is a rare, rapidly worsening brain disorder that causes unique changes in brain tissue and affects muscle coordination thinking, and memory. There are about 350 cases per year in the U.S.
The two main symptoms of CJD are:
- Severe mental deterioration and dementia
- Involuntary (unwanted) muscle jerks (myoclonus) or muscle movement
Early symptoms of the disease may include:
- Lack of coordination
- Problems with walking and balance
- Impaired thinking, memory, and judgment
- Behavior changes
- Depression, mood swings, and anxiety
- Insomnia or changes in sleeping patterns
- Unusual sensations
- Changes in vision
As CJD progresses, symptoms may include:
- Weakness of the arms and legs
- Loss of ability to move or speak
- Pneumonia and other infections
Some symptoms of CJD can be similar to symptoms of other progressive (continuing to worsen) neurological disorders, such as Alzheimer's and Huntington's disease. However, these symptoms tend to worsen faster in CJD than in Alzheimer's disease or most other types of dementia.
There are three major categories of CJD, including:
- Sporadic CJD—The disease develops in someone when the cause is unknown. This accounts for at least 85 percent of cases.
- Hereditary CJD—There may be a known gene mutation that occurs in a family. About 10 to 15 percent of cases of CJD in the United States are hereditary.
- Acquired CJD—Rarely, the disease is transmitted by exposure to brain or nervous system tissue, usually through certain medical procedures such as surgical grafts of dura mater (a tissue that covers the brain), transplanted corneas, and implantation of inadequately sterilized electrodes in the brain. Doctors call these iatrogenic cases. Fewer than one percent of cases have been acquired CJD.
- A type of CJD called variant CJD (or vCJD) can be acquired by eating meat from cattle affected by a disease similar to CJD called bovine spongiform encephalopathy (BSE, or “mad cow” disease). Variant CJD begins primarily with psychiatric symptoms, affects younger people than other types of CJD, and has a longer than usual duration from onset of symptoms to death. Fortunately, government regulations have basically eliminated this chance of transmission.
Who is more likely to get Creutzfeldt-Jakob disease?
CJD usually appears in later life, typically around age 60, and quickly gets worse. About 70 percent of people having CJD die within one year. A person cannot get CJD through the air or by touching something like a doorknob or being close to someone who has CJD. Still, doctors recommend that people with suspected or confirmed CJD or who have a family history of CJD should not donate blood, organs, or tissue.
There is a very small risk that a surgeon or others who handle brain tissue following a brain biopsy or autopsy may become accidentally infected. Special surgical and disinfection procedures can markedly reduce this risk. There is no evidence that caregivers, healthcare workers, and those who prepare bodies for funerals and cremation have an increased risk of prion disease when compared to the general population.
CJD is caused by abnormal forms of proteins called prions. Proteins are long chains of amino acids that fold together into a unique shape or conformation to help a cell function in a particular way. The normal and harmless prion protein is found throughout the body but is most abundant in the nervous system. Its overall role is not fully understood. This abnormal folding or conformation is “transmitted” to normal prion proteins in surrounding nerve cells, causing them to become infective and changed to one that results in the disease. Once they are formed, abnormal prion proteins aggregate, or clump together, which may lead to the nerve cell loss and other brain damage seen in CJD.
CJD belongs to a family of human and animal diseases known as the transmissible spongiform encephalopathies (TSEs) or prion diseases. The infective prion causes CJD and related disorders in people and TSEs in animals. Spongiform refers to the characteristic appearance of infected brains, which become filled with holes until they resemble sponges when examined under a microscope.
Human prion diseases include:
- CJD and variant CJD
- Gerstmann-Straussler-Schenker Disease
- Fatal Familial Insomnia
Animal prion diseases include:
- Bovine spongiform encephalopathy (also known as “mad cow” disease)
- Mink encephalopathy
- Feline encephalopathy
- Scrapie (which affects sheep and goats)
- Chronic wasting disease (which affects elk and deer)
The normal, harmless prion protein is usually designated as PrPC ("C" stands for cellular) and the abnormal, infectious form (which causes the disease) is PrPSc ("Sc" stands for prototypical prion disease–scrapie).
- In the acquired form of the disease, the infectious PrPSc comes from the outside the body, for example, through contaminated meat as is seen in variant CJD.
- In the hereditary form, infectious prions can arise when a mutation occurs in the gene for the body's normal prion protein. As the mutated PrPC duplicates itself, it spontaneously changes shape into the infectious form. (Prions themselves do not contain genetic information and do not require genes to reproduce themselves.) If the prion protein gene is changed in a person's sperm or egg cells, the changed gene can be transmitted to the person's children. Specific changes found in each family affects how often the disease appears and what symptoms are most noticeable. However, not all people with mutations in the prion protein gene develop CJD.
- In the sporadic form, the infectious prions are believed to be made by an error in the cell's machinery that makes proteins and controls their quality. These errors are more likely to occur with aging.
How is Creutzfeldt-Jakob disease diagnosed and treated?
There are a few tests a doctor can use to help diagnose CJD:
- Electroencephalography (EEG)—This test records the brain's electrical pattern and find a specific type of abnormality in major types of CJD.
- Cerebrospinal fluid-based tests—This testing looks for the 14-3-3 protein (a marker for some prion diseases, such as CJD) to detect the abnormal prion protein in the fluid that surrounds the brain and spinal cord.
- Magnetic resonance imaging (MRI)—This type of brain imaging is accurate in about 90 percent of cases.
The only way to confirm a diagnosis of CJD is by brain biopsy or an autopsy. In a brain biopsy, a neurosurgeon removes a small piece of tissue from the living person's brain so it can be examined by a neuropathologist. This procedure may be dangerous for the individual and is generally discouraged unless it is needed to rule out a treatable disorder. In an autopsy, the whole brain is examined after death.
Currently there is no cure for CJD, although some drugs are being tested to control it. Today's treatments are aimed at making the person comfortable and easing symptoms. Medications may help relieve pain and muscle jerks. During later stages of the disease, intravenous fluids and machine feeding also may be used.
What are the latest updates on Creutzfeldt-Jakob disease?
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.
For research articles and summaries on CJD, search PubMed, which contains citations from medical journals and other sites.
How can I or my loved one help improve care for people with Creutzfeldt-Jakob disease?
Consider participating in a clinical trial so clinicians and scientists can learn more about CJD. Clinical research uses human volunteers to help researchers learn more about a disorder and perhaps find better ways to safely detect, treat, or prevent disease.
All types of volunteers are needed—those who are healthy or may have an illness or disease—of all different ages, sexes, races, and ethnicities to ensure that study results apply to as many people as possible, and that treatments will be safe and effective for everyone who will use them.
For information about participating in clinical research visit NIH Clinical Research Trials and You. Learn about clinical trials currently looking for people with CJD at Clinicaltrials.gov, a database of federal and privately funded trials and research results.
Scientists are conducting biochemical analyses of brain tissue, blood, spinal fluid, urine, and serum in the hope of determining the nature of the transmissible agent or agents causing CJD. To help with this research, they are seeking biopsy and autopsy tissue, blood, and cerebrospinal fluid from individuals with CJD and related diseases. The following investigators have expressed an interest in receiving such material:
Dr. Brian Appleby, Director
National Prion Disease Pathology Surveillance Center
Case Western Reserve University
Dr. Laura Manuelidis
Manuelidis TSE Laboratory
Yale University School of Medicine
Where can I find more information about Creutzfeldt-Jakob disease?
Information may be available from the following organizations: