Creutzfeldt-Jakob Disease

Creutzfeldt-Jakob (KROYTZ-felt YAH-kub) disease is a rapidly progressing fatal disorder of the brain caused by an abnormal protein called a prion (FREE-on).

What Is Creutzfeldt-Jakob Disease?

First described in 1920 by two German neurologists * , Hans Gerhard Creutzfeldt (1885–1964) and Alfons Maria Jakob (1884–1931), Creutzfeldt-Jakob disease (CJD) is a very rare, progressive, and fatal disease of the brain. It is a form of transmissible * spongiform encephalopathy (SPUN-ji-form en-sef-a-LOP-a-thee), which means that the disease causes the brain to become a sponge-like mass as it deteriorates. Creutzfeldt-Jakob disease destroys the tissues of the brain, causing a rapid decline in mental function and muscle coordination, eventually leading to death.

Although 90 percent of people who contract CJD die within several months, a few patients decline more slowly and may survive between one and two years after they are diagnosed. Creutzfeldt-Jakob disease usually affects people over 60 years of age, but a form of the disease known as variant Creutzfeldt-Jakob disease (vCJD) strikes younger people. Because CJD affects the brain, its primary symptom is dementia * . Some signs of dementia are disorientation, neglect of personal hygiene and grooming, and irritability. Other symptoms of the disease include fatigue, insomnia * , and muscle twitching or sudden contractions of the muscles. Because there is no known cure, medical treatment focuses on palliative * care, which is designed to make people with CJD as comfortable as possible.




A tiny transmissible protein called a prion triggers Creutzfeldt-Jakob disease. The protease-resistant protein (PrP) is found throughout the body in healthy people and in animals.





A tiny transmissible protein called a prion triggers Creutzfeldt-Jakob disease. The protease-resistant protein (PrP) is found throughout the body in healthy people and in animals. It has, however, two basic configurations, one diseased and one healthy. The diseased configuration of PrP is thought to be the agent of Creutzfeldt-Jakob disease.
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MAD COW DISEASE AND CREUTZFELDT-JAKOB DISEASE IN HUMANS

In 1986, the brain disease called bovine spongiform encephalopathy (BSE) was first identified in cows in the United Kingdom. Termed “mad cow disease” because the infected cows lost muscular coordination and stumbled, BSE had been transmitted to the cows from feed made from ground sheep bones and body parts. The sheep disease called scrapie had been passed on to the cattle in their feed. (Scrapie is another form of spongiform encephalopathy found in sheep that causes them to feel itchy and scrape or rub against the fences of their pastures.)

Doctors thought at first that the infectious agent of mad cow disease could not be passed on to people, but the British Ministry of Health discovered a variant form of CJD (vCJD) in people younger than the average age of patients with classical CJD. BSE was subsequently linked to variant CJD. The practice of feeding sheep parts to cows may have caused an epidemic * of BSE among cattle in the United Kingdom, and this feeding practice was banned in 1998. Countries all over Europe and other parts of the world began to ban the import of beef from Britain in 1996, and millions of cattle in Britain were killed in order to avoid spreading the disease. Some people turned to vegetarian diets, and many restaurants stopped serving beef. The number of new BSE cases dropped sharply, and the ban on beef coming from the United Kingdom was lifted by the European Union in 2006.

To further prevent the transmission of mad cow disease to humans, surveillance programs were put in place to test cows for the disease before they are allowed to enter the human food chain. The number of cows tested varies by country, as does the type of cow tested. Some countries test only cows that have been classified as “downer cows,” or cows that cannot walk, for BSE. Other countries test a selection of seemingly healthy cows as well as downer cows and test a greater number of cows than are examined in the United States. The U.S. government practices what is known as targeted surveillance, meaning that only a sample of cows from the population is tested for BSE. BSE-infected cattle have never been detected below the age of 20 months, and 88 percent of the cows slaughtered for food in the United States are under this age. The U.S. Department of Agriculture (USDA) allows only animals that look healthy to be used as food, and it maintains meat removal practices that keep brain and spinal cord matter from getting into processed meat. The USDA prohibits the use of downer cows in food processing.

ARE PRIONS INFECTIOUS?

Like bacteria, viruses, and parasites, prions, which are abnormal forms of widely occurring protein particles, have been linked to certain transmissible diseases. Yet prions are different from other infectious agents. Microorganisms * contain genetic material but prions do not, which means that prions are not alive. According to the theory of prion disease, the prion protein (PrP, also called the protease-resistant protein) at first cannot cause or transmit disease. Instead, it undergoes a change that causes it to fold into a different and abnormal shape, which it can transmit to other proteins. When one of these abnormal proteins enters a brain cell in the course of CJD, it attaches itself to normal proteins, causing them to adopt its misfolded shape. This shape-changing sets off a chain reaction that leads to the death of the brain cell and the release of more prions that will in turn enter and affect still other cells.

As the cells die, holes form in brain tissue, giving it the characteristic sponge-like appearance of CJD. Prions can be acquired during a medical procedure or from some other exposure to brain tissue or fluids containing brain tissue. In the inherited form of CJD, a mutation in the PRNP gene on chromosome 20 affects the ability of this gene to form the normal form of the prion protein, abbreviated as PrPC. Instead, the mutated gene produces PrPSc, the disease-causing form of the protein.

  1. Familial CJD, which accounts for up to about 5 to 10 percent of cases in the United States. In these instances, there is a family history of the disease caused by a mutation * in the gene * that codes for PrP. This gene, the PRNP gene, is located on human chromosome 20. As of 2016, there were 30 known mutations of this gene that can cause familial CJD.
  2. Sporadic * (spoh-RAD-ik) CJD, in which afflicted people have no known risk factors for the disease. Sporadic cases make up about 85 percent of cases of CJD in the United States.
  3. Acquired or iatrogenic (ee-ah-tro-JEN-ik) CJD, in which the defective protein is transmitted to an uninfected person due to exposure to infected brain or spinal tissue. Acquired CJD is the rarest form; less than 1 percent of all cases result from exposure to infected brain or spinal tissue. Iatrogenic means that a disease or other problem is caused by the actions of a healthcare professional, and most of these cases of acquired CJD occur during a medical procedure.
* ; bovine spongiform encephalopathy (BSE), which infects cattle and is known as mad cow disease; and scrapie * , which affects sheep, goats, and other animals. Creutzfeldt-Jakob disease generally affects people over the age of 60 years. But scientists have identified a new form of CJD, called variant CJD or new variant CJD (vCJD), which typically affects people under the age of 30 years and causes a different set of symptoms. Cases of vCJD have been limited mostly to the United Kingdom and France, and all the people in whom vCJD developed were exposed to areas where BSE had been found.

How Common Is Creutzfeldt-Jakob Disease?

CJD is rare. It occurs in only one person per one million people worldwide. In the United States, about 300 cases are diagnosed annually, according to the National Institute of Neurological Disorders and Stroke. The age of onset for classical CJD is between 50 and 75 years, with the average age of onset about 60 years of age. About 90 percent of cases end in death within one year after symptoms begin, whereas the remaining 10 percent of people with CJD survive for one to two years.

Variant CJD is very rare, with about 170 cases reported in the United Kingdom between 1996 and 2012, and about 30 cases in the rest of the world. People with variant CJD live somewhat longer than patients with classical CJD.

Is Creutzfeldt-Jakob Disease Contagious?

People cannot get Creutzfeldt-Jakob disease from casual contact with a friend or loved one diagnosed with the disease, nor is CJD spread through the air like many viral infections. It is transmitted from human to human primarily through contact with infected tissue from the brain or central nervous system * , contact that usually arises only during a medical procedure. For example, CJD has been reported to have been transmitted by cornea * transplants and dura mater * grafts * taken from infected persons; by injection of growth hormone * derived from pituitary * glands taken from cadavers (corpses); and by contact with medical instruments that were used during brain surgery or other surgery performed on a person with the disease. Cerebrospinal fluid * can transmit CJD, but there is no evidence that other bodily fluids, including saliva, blood, or urine, can transmit the defective protein.

Variant CJD has occurred only where cases of BSE also have been found, leading researchers to theorize that eating beef from cattle with BSE could spread the defective prion protein and lead to CJD in humans. This theory has not been proven as of 2016, however, partly because the number of people who have been diagnosed with vCJD since 1996 is very small compared to the number of people who ate beef from cows with BSE. Some researchers think that small variations in the PRNP gene may make some people more susceptible than others to developing vCJD from eating contaminated beef.

What Are the Signs and Symptoms of CreutzfeldtJakob Disease?

The most characteristic symptom of CJD is quickly worsening dementia, including memory loss and impaired thinking. Family members often say that they can see the patient's loss of mental functions worsen literally from one day to the next. In addition, patients with CJD often have problems with vision and muscle coordination. Insomnia (inability to sleep), unusual sensations, and depression can also occur. Many patients experience muscle jerking known as myoclonus (my-AH-kloh-nus), which consists of brief rapid muscle contractions; they may also go blind. Toward the end, patients with CJD are no longer able to move or speak, and go into a coma * . If the disease was contracted from infected human tissue (such as from a transplanted cornea), symptoms may not appear for decades after exposure to the contaminated tissue.

The early symptoms of variant CJD are psychiatric (sy-kee-AH-trik) in nature, and usually include depression, anxiety (ang-ZY-e-tee), or personality changes. Dementia and myoclonus typically occur later in vCJD than in classic CJD.

How Do Doctors Diagnose and Treat CreutzfeldtJakob Disease?

Creutzfeldt-Jakob disease can be diagnosed by a brain biopsy (BI-op-see), which requires removing a small piece of brain tissue during surgery to look for signs of the disease, or at autopsy * . Other less invasive tests may point to a diagnosis of CJD or help to exclude such other diagnoses as meningitis or encephalitis. During a physical examination, the doctor checks the patient for muscle twitching and spasms. An eye examination may show areas of blindness that the patient may not have noticed, and a spinal tap * and blood tests may identify certain proteins associated with CJD. An electroencephalogram (EEG) is a test that records patterns of electrical activity in the brain; it may show a pattern of brain waves seen in many patients with CJD, although the EEG findings typical of CJD are not present in vCJD. Some people with CJD have negative test results, making a diagnosis difficult without a brain biopsy.

Because there was no cure for CJD as of 2016, the goal of treatment is to keep the patient as comfortable as possible. Medications can help control aggressive behavior, lessen pain, and ease muscle contractions. As the dementia progresses to loss of speech, the patient loses the ability to take care of him- or herself, and eventually slips into a coma. As patients with CJD become bedridden, they are vulnerable to infections, particularly pneumonia, and most eventually require hospital treatment. Most patients with classic CJD die within a year after symptoms appear.

Can Creutzfeldt-Jakob Disease Be Prevented?

Relatives of a person diagnosed with CJD may wish to have genetic counseling to learn whether they have any of the PRNP mutations associated with the disease and whether they are at risk of transmitting these mutations to the next generation. There were two laboratories in the United States, as of 2016, that offer genetic testing for mutations in the PRNP gene.

With regard to acquired or iatrogenic CJD, special techniques for handling and sterilizing surgical instruments limit the chance of transmitting the disease during certain medical procedures, particularly those involving the brain.

See also Dementia • Genetic Diseases: Overview • Global Health Issues: Overview • Prion Diseases

Resources

Books and Articles

Ingram, Jay. Fatal Flaws: How a Misfolded Protein Baffled Scientists and Changed the Way We Look at the Brain. New Haven, CT: Yale University Press, 2013.

Prusiner, Stanley B. Madness and Memory: The Discovery of Prions—A New Biological Principle of Disease. New Haven, CT: Yale University Press, 2014.

Websites

Centers for Disease Control and Prevention. “Bovine Spongiform Encephalopathy (BSE), or Mad Cow Disease.” http://www.cdc.gov/prions/bse/ (accessed March 20, 2016).

Centers for Disease Control and Prevention. “Creutzfeldt-Jakob Disease, Classic (CJD).” http://www.cdc.gov/prions/cjd/index.html (accessed March 20, 2016).

National Institute of Neurological Disorders and Stroke. “CreutzfeldtJakob Disease Fact Sheet.” http://www.ninds.nih.gov/disorders/cjd/detail_cjd.htm (accessed March 20, 2016).

University of California, San Francisco Memory and Aging Center. “Creutzfeldt-Jakob Disease.” http://memory.ucsf.edu/cjd (accessed March 20, 2016).

Organizations

Centers for Disease Control and Prevention. 1600 Clifton Rd., Atlanta, GA 30329. Toll-free: 800-232-4636. Website: http://www.cdc.gov (accessed March 20, 2016).

CJD Aware! 2527 South Carrollton Ave., New Orleans, LA 70118. Telephone: 504-861-4627. Website: http://www.cjdaware.com/index.html (accessed March 20, 2016).

Creutzfeldt-Jakob Disease Foundation. 341 W. 38th St., Suite 501, New York, NY 10018. Toll-free: 800-659-1991. Website: http://cjdfoundation.org (accessed March 20, 2016).

National Institute of Neurological Disorders and Stroke. PO Box 5801, Bethesda, MD 20824. Telephone: 301-496-5751. Website: http://www.ninds.nih.gov/ (accessed March 20, 2016).

U.S. Food and Drug Administration. 10903 New Hampshire Ave., Silver Spring, MD 20993. Toll-free: 888-463-6332. Website: http://www.fda.gov (accessed March 20, 2016).

* neurologist (new-RHAL-eh-jist) is a physician who specializes in diagnosing and treating diseases of the nervous system.

* transmissible (trans-MIH-sih-bul) refers to any disease that can be transferred or spread.

* dementia (dih-MEN-sha) is a loss of mental abilities, including memory, understanding, and judgment.

* insomnia is the inability to get adequate sleep; the person may have difficulty falling asleep or staying asleep long enough to get needed rest.

* epidemic (eh-pih-DEH-mik) is an outbreak of a disease (generally an infectious disease) in which the number of cases suddenly becomes far greater than usual.

* palliative (PAL-ee-at-iv) means to ease or relieve the symptoms of a disease without curing it.

* microorganism is a tiny organism that can be seen only under a microscope. Types of microorganisms include fungi, bacteria, protozoa, and viruses.

* mutation (myoo-TAY-shun) is a change in an organism's gene or genes.

* genes (JEENS) are chemical structures composed of deoxyribonucleic acid (DNA) that help determine a person's body structure and such physical characteristics as hair or eye color. Inherited from a person's parents, genes are contained in the chromosomes found in the body's cells.

* sporadic (spoh-RAD-ik) means occurring at random or in scattered instances, with no apparent pattern.

* kuru (KUR-ew) is a progressive, fatal brain disease characterized by tremors and loss of muscle coordination. It is caused by eating contaminated brain tissue from other humans who had the disease.

* scrapie (SKRAY-pee) is a fatal brain disorder of sheep characterized by itching of the skin and difficulty walking. It takes its name from the way in which affected animals rub or scrape themselves against a fence or tree.

* central nervous system (SEN-trul NER-vus SIS-tem) is the part of the nervous system that includes the brain and spinal cord.

* cornea (KOR-nee-uh) is the transparent circular layer of cells over the central colored part of the eye (the iris) through which light enters the eye.

* dura mater (DUR-uh MAY-ter) is the outermost of the three membranes that cover the brain and spinal cord.

* grafts are tissue or organ transplants.

* growth hormone is a chemical substance produced by the pituitary gland that regulates growth and other body functions.

* pituitary (pih-TOO-ih-tare-e) is a small oval-shaped gland at the base of the skull that produces several hormones—chemicals that affect various body functions, including growth.

* cerebrospinal fluid (SEH-ree-broSPY-nuhl) is the fluid that surrounds the brain and spinal cord.

* coma (KO-ma) is an unconscious state like a very deep sleep. A person in a coma cannot be awakened, and cannot move, see, speak, or hear.

* autopsy (AW-top-see) is an examination of a body after death to look for the cause of death or the effects of a disease.

* spinal tap also called a lumbar puncture, is a medical procedure in which a needle is used to withdraw a sample of the fluid surrounding the spinal cord and brain. The fluid is then tested, usually to detect signs of infection caused by meningitis or other diseases.

Disclaimer:   This information is not a tool for self-diagnosis or a substitute for professional care.

(MLA 8th Edition)