About Creutzfeldt-Jakob disease

Creutzfeldt-Jakob disease (CJD) is a degenerative brain disorder that eventually leads to dementia. Symptoms of CJD sometimes resemble those of other brain disorders such as Alzheimer’s and Huntington’s disease, but Creutzfeldt-Jakob disease usually progresses much more rapidly than do other diseases associated with dementia.

Creutzfeldt-Jakob disease captured public attention in the 1990s when a form of the disease — variant CJD (vCJD) — developed among a number of people in the United Kingdom who had eaten meat from cattle suspected of having mad cow disease.

Although serious, the disease is rare. Worldwide, doctors typically diagnose one case of Creutzfeldt-Jakob disease per million people each year, most commonly in older adults. Treatment of Creutzfeldt-Jakob disease focuses on relieving symptoms and maximizing comfort.

Symptoms

Creutzfeldt-Jakob disease is marked by rapid mental deterioration, usually within the span of a few months. Initial signs and symptoms of CJD typically include:

  • Personality changes
  • Anxiety
  • Depression
  • Memory loss
  • Impaired thinking
  • Impaired muscle coordination
  • Blurred vision
  • Insomnia
  • Speech impairment

As the diseases progress, mental symptoms become more severe. Most people eventually lapse into a coma. Heart failure, respiratory failure, pneumonia or other infections are generally the cause of death. The disease usually runs its course in about seven months, although a few people may live up to one or two years after diagnosis.

In people with vCJD, psychiatric symptoms may be more prominent in the beginning, with dementia — the loss of the ability to think, reason and remember — developing later in the course of the illness. In addition, this variant affects people at a younger age than classic CJD does, and appears to have a slightly longer duration — 12 to 14 months.

Causes

Creutzfeldt-Jakob disease and its variants belong to a broad group of human and animal diseases known as transmissible spongiform encephalopathies (TSEs). The name derives from the spongy holes, visible under a microscope, that develop in affected brain tissue.

The cause of Creutzfeldt-Jakob disease and other TSEs appears to be abnormal versions of a kind of protein called a prion.

The nature of prions
Prions are proteins that occur naturally in the brains of animals and people. Normally, these proteins are harmless, but when they’re misshapen they can wreak havoc on normal biological processes.

All proteins start out as loose strings of amino acids. But proteins can’t perform their intended function until the amino acids fold into a specific three-dimensional shape. The shape a particular protein assumes is determined by the sequence of its amino acids. Most proteins fold spontaneously during or just after they’re synthesized inside cells.

But some prions don’t fold as intended. Not only do they misfold, but also they may enter brain cells and force normal proteins to misfold as well. When the infected cells die, the defective prions are released into normal tissue and go on to infect more cells. Eventually, large clusters of cells die, leaving the brain riddled with holes. This is a prolonged process, and symptoms of disease may not appear for years.

Defective prions also seem capable of crossing species barriers, jumping, for example, from sheep to cows to humans. Although transmission may occur more readily when proteins have the same amino acid sequence and exist within a single species, evidence is strong that prions can move from one species to another.

How CJD is transmitted
Researchers have identified three basic ways that CJD may develop:

  • Spontaneously. Most people with classic CJD develop the disease for no apparent reason. CJD that occurs without explanation is termed spontaneous CJD or sporadic CJD and accounts for the great majority of all cases.
  • By genetic mutation. In the United States, about 5 percent to 10 percent of people with CJD have a family history of the disease or test positive for a genetic mutation associated with CJD. This type is referred to as familial CJD.
  • By contamination. The risk of being contaminated with CJD-related prions is low. CJD can’t be transmitted through airborne droplets of fluid (coughing or sneezing), casual contact, such as touching, or even through sexual contact.

    A small number of people have developed the disease after being exposed to infected human tissue during a medical procedure, such as a cornea or skin transplant, or grafts of dura mater, the membrane that covers the brain. Some adults have developed CJD decades after receiving injections of contaminated human growth hormone (HGH) derived from human pituitary glands. Since 1985, HGH in the U.S. is made from genetically engineered synthetic materials, avoiding the risk of contaminated tissue. Cases of CJD related to medical procedures are referred to as iatrogenic CJD.

    Misshapen prions aren’t affected by standard sterilization methods, including heat, radiation, alcohol, benzene and formaldehyde. As a result, a few people have developed CJD after undergoing brain surgery with instruments contaminated by previous use in a person with CJD. Now, instruments used during brain surgery on a person with suspected CJD are destroyed.

    Variant CJD has been linked primarily to the consumption of beef infected with bovine spongiform encephalopathy (BSE), the medical term for mad cow disease. Not everyone who becomes infected with the abnormal prion protein develops vCJD.

    To date, four cases of vCJD have occurred in the United Kingdom as a result of blood transfusions. All four cases involved transfusions received in the 1990s.

Most cases of Creutzfeldt-Jakob disease occur for unknown reasons and no risk factors can be identified. However, a few factors seem to be associated with different kinds of CJD.

  • Age. Sporadic CJD tends to develop later in life, usually around the age of 60. Onset of familial CJD occurs only slightly earlier. On the other hand, vCJD has affected people at a much younger age, usually in their late 20s. This suggests that older adults may not be as susceptible to vCJD as children and young adults are.
  • Genetics. People with familial CJD have a genetic mutation that causes the disease. The disease is inherited in an autosomal dominant fashion, which means you only need to inherit one copy of the mutated gene, from either parent, to develop the disease. If you have the mutation, the chance of passing it on to your children is 50 percent.

    Genetic analysis in people with iatrogenic and variant CJD suggest that inheriting identical copies of certain variants of the prion gene may predispose a person to developing CJD if exposed to contaminated tissue.

  • Exposure to contaminated tissue. People who’ve received human growth hormone derived from human pituitary glands or who’ve had dura mater grafts may be at risk of iatrogenic CJD.

    The risk of contracting vCJD from eating contaminated beef is difficult to determine. In general, if countries are effectively implementing public health measures, the risk is very low. For example, in the United Kingdom the current estimated risk of acquiring vCJD from beef and beef products appears to be about one case per 10 billion servings. The risk from beef in other high-incidence countries is estimated to be very low, as well.

Diagnosis

Only a brain biopsy or an examination of brain tissue after death (autopsy) can confirm the presence of Creutzfeldt-Jakob disease. But doctors often can make an accurate diagnosis based on your medical and personal history, a neurological exam, and certain diagnostic tests.

The exam is likely to reveal such characteristic symptoms as muscle twitching and spasms, abnormal reflexes, and coordination problems. People with CJD also may have areas of blindness and changes in visual-spatial perception.

In addition doctors commonly use these tests to help detect CJD:

  • Electroencephalogram (EEG). Using electrodes placed on your scalp, this test measures your brain’s electrical activity. People with CJD and vCJD show a characteristically abnormal pattern.
  • Magnetic resonance imaging (MRI). This technique uses radio waves and a magnetic field to create cross-sectional images of your head and body. It’s especially useful in diagnosing brain disorders because of its high-resolution images of the brain’s white matter and gray matter.
  • Spinal fluid tests. Cerebral spinal fluid surrounds and cushions your brain and spinal cord. In a test called a lumbar puncture — popularly known as a spinal tap — doctors use a needle to withdraw a small amount of this fluid for testing. The presence of a particular protein in spinal fluid is often an indication of CJD or vCJD.
  • Tonsil biopsy. Scientists have learned that tissue from the tonsils tends to harbor evidence of vCJD. Examination of a sample of tonsil tissue may help diagnose vCJD, but this method seems less reliable for other forms of CJD.

Complications

As with other causes of dementia, Creutzfeldt-Jakob disease profoundly affects the mind as well as the body, although CJD and its variants usually progress much more rapidly. People with CJD usually withdraw from friends and family and eventually lose the ability to recognize or relate to them in any meaningful way. They also lose the ability to care for themselves, and many eventually slip into a coma.

Physical complications, all of which may become life-threatening, include:

  • Infection
  • Heart failure
  • Respiratory failure

Treatment

No effective treatment exists for Creutzfeldt-Jakob disease or any of its variants. A number of drugs have been tested — including steroids, antibiotics and antiviral agents — and have not shown benefits. For that reason, doctors focus on alleviating pain and other symptoms and on making people with these diseases as comfortable as possible.

Prevention

There is no known way to prevent sporadic CJD from developing. If you have a family history of neurological disease, you may benefit from talking with a genetics counselor, who can help you sort through the risks associated with your particular situation.

Caregivers
If you’re caring for someone with CJD or vCJD, the National Institutes of Health recommend the following basic precautions:

  • Wash your hands and exposed skin before eating, drinking or smoking
  • Protect your hands and face from exposure to the person’s blood or fluids
  • Cover cuts or wounds with water-proof bandages

Preventing iatrogenic CJD
Because some cases of CJD have been associated with certain medical procedures, policies have been set in place in an effort to prevent these sorts of cases from developing. Prevention measures have included:

  • Exclusive use of synthetic human growth hormone, rather than the kind derived from human pituitary glands
  • Destruction of surgical instruments used on the brain or nervous tissue of someone with known or suspected CJD
  • Single-use kits for spinal taps (lumbar punctures)

Organ transplants typically must be done before a full autopsy can be conducted. Hence, it’s possible that someone may contract CJD from an organ transplant if the donor was in the incubation stage of CJD and not yet showing signs and symptoms. However, this scenario is very unlikely and the benefits obtained from an organ transplant are generally much greater than the risk of contracting CJD.

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. This includes people who:

  • Have a biological relative who has been diagnosed with CJD
  • Have received a dura mater brain graft
  • Have received human growth hormone
  • Spent a total of at least three months in the U.K. from 1980 to 1996
  • Spent five years or more in France from 1980 to the present
  • Received a blood transfusion in the U.K. between 1980 and the present
  • Have injected bovine insulin at any time since 1980

Preventing vCJD
The risk of contracting vCJD in the United States remains extremely low. So far, a total of three cases have been reported in the U.S. According to the Centers for Disease Control and Prevention, strong evidence suggests that these cases were acquired abroad — two in the United Kingdom and one in Saudi Arabia.

In the United Kingdom, where the majority of vCJD cases have occurred, the total number of reported cases had reached 165 in early 2007. New cases were first reported in 1995, peaked between 1999 and 2000 and have been declining since. In France, on the other hand, reported cases of vCJD have been increasing since 2005. Future patterns of disease incidence are difficult to predict. Computer models estimate that the number of people who develop the disease is likely to be much lower than the number of carriers of the defective protein.

Most countries have adopted stringent measures to prevent BSE-infected tissue from entering the food supply, including severe restrictions on importation of 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; and restrictions on which parts of cattle can be processed for food.

If you’re concerned about the possibility of contracting vCJD from contaminated beef while abroad, you may consider avoiding beef altogether. Or you may opt for solid pieces of muscle meats, such as steak, which are less likely to harbor infectious BSE agents than are meats such as brains or ground beef. Still, the risk is low.

Other methods of transmission
The best way to protect yourself from products that may harbor infection is to become as well informed as possible. The risk of vCJD from the following sources is estimated to be extremely low:

  • Vaccines. Some parts of cows, including blood, enzymes and amino acids, are used to grow the bacteria and viruses needed to make certain vaccines. Not all vaccines are grown in cattle parts, however, and the Food and Drug Administration (FDA) recommends that companies producing such vaccines use cattle parts only from low-risk countries. These recommendations apply to cosmetics as well. The FDA keeps a listing on its Web site of companies that use cattle from countries that aren’t classified as low-risk.
  • Insulin. Insulin sold in the United States isn’t derived from cows, but you’re allowed to import beef insulin from other countries if you follow specific guidelines. Because there’s no way to guarantee the safety of imported insulin, talk to your doctor about the best way to obtain insulin from sources outside the United States.