Creutzfeldt-Jakob Disease: Causes, Symptoms, Diagnosis, Treatment

Creutzfeldt-Jakob Disease: Causes, Symptoms, Diagnosis, Treatment

What is Creutzfeldt-Jakob Disease?

Creutzfeldt-Jakob disease  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. Creutzfeldt-Jakob disease 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 Creutzfeldt-Jakob disease: 

  • In sporadic Creutzfeldt-Jakob disease, the disease appears even though the person has no known risk factors for the disease. This is by far the most common type of Creutzfeldt-Jakob disease and accounts for at least 85 percent of cases. 
  • In hereditary Creutzfeldt-Jakob disease, the person has a family history of the disease and/or tests positive for a genetic mutation associated with Creutzfeldt-Jakob disease. About 5 to 10 percent of cases of Creutzfeldt-Jakob disease in the United States are hereditary. 
  • In acquired Creutzfeldt-Jakob disease, the disease is transmitted by exposure to brain or nervous system tissue, usually through certain medical procedures. There is no evidence that Creutzfeldt-Jakob disease is contagious through casual contact with a Creutzfeldt-Jakob disease patient. Since Creutzfeldt-Jakob disease was first described in 1920, fewer than 1 percent of cases have been acquired Creutzfeldt-Jakob disease.

Creutzfeldt-Jakob disease 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. Creutzfeldt-Jakob disease 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 goats, mink encephalopathy, and feline encephalopathy. Similar diseases have occurred in elk, deer, and exotic zoo animals.

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What Causes Creutzfeldt-Jakob Disease?

Some researchers believe an unusual "slow virus" or another organism causes Creutzfeldt-Jakob Disease. However, they have never been able to isolate a virus or other organism in people with the disease. Furthermore, the agent that causes Creutzfeldt-Jakob disease 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 Creutzfeldt-Jakob disease 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 Creutzfeldt-Jakob disease 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 Creutzfeldt-Jakob disease 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 percent of all Creutzfeldt-Jakob disease 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 Creutzfeldt-Jakob Disease. This suggests that the mutations merely increase susceptibility to Creutzfeldt-Jakob disease and that other, still-unknown factors also play a role in the disease.

How is Creutzfeldt-Jakob disease Transmitted?

Creutzfeldt-Jakob disease is not a contagious disease. Although it can be transmitted to other people, the risk of this happening is extremely small. Creutzfeldt-Jakob disease cannot be transmitted through the air or through touching or most other forms of casual contact. Spouses and other household members of sporadic Creutzfeldt-Jakob disease 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 materials.

In a few very rare cases, Creutzfeldt-Jakob disease 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 Creutzfeldt-Jakob disease by this route.

The appearance of the new variant of CCreutzfeldt-Jakob disease  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-Creutzfeldt-Jakob disease, there is no direct proof to support this theory. Furthermore, BSE has never been found in the United States, and importation 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 Creutzfeldt-Jakob disease 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 Creutzfeldt-Jakob disease, 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 Creutzfeldt-Jakob disease from a transfusion. Even among hemophiliacs, who sometimes receive blood plasma concentrated from thousands of people, there are no reported cases of Creutzfeldt-Jakob disease. This suggests that, if there is a risk of transmitting Creutzfeldt-Jakob disease through blood or plasma, it is extremely small.

What are the Symptoms of the Disease?

Creutzfeldt-Jakob disease is characterized as a 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. Creutzfeldt-Jakob Disease 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 Creutzfeldt-Jakob disease. 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-Creutzfeldt-Jakob disease, v-Creutzfeldt-Jakob disease), described in Great Britain and France - begins primarily with psychiatric symptoms, affects younger patients than other types of Creutzfeldt-Jakob disease, 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 and course of the disease. Some symptoms of Creutzfeldt-Jakob disease can be similar to symptoms of other progressive neurological disorders, such as Alzheimer's or Huntington's disease. However, Creutzfeldt-Jakob disease 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 Creutzfeldt-Jakob Diseasee Diagnosed?

There is currently no single diagnostic test for Creutzfeldt-Jakob disease. When a doctor suspects Creutzfeldt-Jakob disease, 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 Creutzfeldt-Jakob disease. 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 Creutzfeldt-Jakob disease.

The only way to confirm a diagnosis of Creutzfeldt-Jakob disease 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 Creutzfeldt-Jakob disease 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 Creutzfeldt-Jakob disease. 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 Creutzfeldt-Jakob disease 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. There have been reports of other ways of diagnosing the disease, including tonsil biopsies, which may lead to other tests.

How 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.

Current treatment for Creutzfeldt-Jakob disease 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.

Keeping in tune with your disease or condition not only makes treatment less intimidating but also increases its chance of success, and has been shown to lower a patients risk of complications. As well, as an informed patient, you are better able to discuss your condition and treatment options with your physician.

How Can People Avoid Spreading the Disease?

To reduce the already very low risk of Creutzfeldt-Jakob disease transmission from one person to another, people should never donate blood, tissues, or organs if they have suspected or confirmed Creutzfeldt-Jakob disease, 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 Creutzfeldt-Jakob disease:

  • 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.
A fact sheet listing additional precautions for healthcare workers and morticians is available from the NINDS and the World Health Organization.