Part 5: Creutzfeldt-Jakob disease
In this series we are taking an in-depth look at the various types of dementia and how to improve treatment in a long-term care setting. There are several lesser known dementias affecting our seniors. As part of their care team we need to educate ourselves on how to better understand and meet their needs.
Today we’ll take a look at Creutzfeldt-Jakob disease. If you’re interested in reading more about this lesser-known dementia, the National Institute of Neurological Disorders and Stroke (NINDS) offers an excellent overview of the disease.
What is Creutzfeldt-Jakob Disease?
Creutzfeldt-Jakob disease (CJD) is a rare, degenerative, invariably fatal brain disorder. It affects about one person in every one million per year worldwide. In the United States there are about 300 cases per year. CJD usually appears in later life and runs a rapid course. Typically, onset of symptoms occurs around age 60 and approximately 90 percent of individuals die within one year. In the early stages of the disease, people 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 CJD:
In sporadic CJD, the disease appears even though the person has no known risk factors. This is by far the most common type of CJD and accounts for at least 85 percent of cases.
In hereditary CJD, the person has a family history of the disease and/or tests positive for a genetic mutation associated with CJD. About 5 to 10 percent of cases of CJD in the United States are hereditary.
In acquired CJD, the disease is transmitted by exposure to brain or nervous system tissue, usually through certain medical procedures. There is no evidence CJD is contagious through casual contact with a patient who has it. Since it was first described in 1920, fewer than 1 percent of cases have been acquired CJD.
CJD 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. CJD 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 nearly disappeared. FFI 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.
What are the Symptoms of the Disease?
CJD is characterized by rapidly progressive dementia. Initially, individuals experience 1) problems with muscular coordination, 2) personality changes, including impaired memory, judgment and thinking and 3) impaired vision. People with the disease also may experience insomnia, depression or unusual sensations. CJD does not cause a fever or other flu-like symptoms. As the illness progresses, mental impairment becomes severe. Individuals often develop involuntary muscle jerks called myoclonus, and may go blind. They eventually lose the ability to move and speak and enter a coma. Pneumonia and other infections often occur in these individuals and can lead to death.
Amnesia, mental confusion, dementia, delusion, disorientation, inability to speak or understand, lack of concentration
Rhythmic muscle contractions, slow bodily movement, jerking muscle spasms, problems with coordination, overactive reflexes
Anxiety or apathy
Depression or hallucinations
Blurred vision, difficulty speaking, insomnia, personality change, rapid involuntary eye movement
There are several known variants of CJD. These variants differ somewhat in the symptoms and course of the disease. For example, a variant form called new variant or variant (nv-CJD, v-CJD), described in Great Britain and France, begins primarily with psychiatric symptoms, affects younger individuals than other types of CJD 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.
Some symptoms of CJD can be similar to symptoms of other progressive neurological disorders, such as Alzheimer’s or Huntington’s disease. However, CJD 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 CJD Diagnosed?
There is currently no single diagnostic test for CJD. When a doctor suspects CJD, 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 CJD. 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 can also reveal characteristic patterns of brain degeneration that can help diagnose CJD.
The only way to confirm a CJD diagnosis is by brain biopsy or autopsy. In a brain biopsy, a neurosurgeon removes a small piece of tissue from the patient’s brain for a neuropathologist’s examination. This procedure may be dangerous for the individual, and the operation does not always obtain tissue from the affected part of the brain. Because a correct diagnosis of CJD does not help the person, 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 National Institute of Neurological Disorders and Stroke and the World Health Organization.
Scientists are working to develop laboratory tests for CJD. 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 CJD 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. They are also working to develop other tests for this disorder.
How is the Disease Treated?
There is no treatment that can cure or control CJD. Researchers have tested many drugs, including amantadine, steroids, interferon, acyclovir, antiviral agents and antibiotics. Studies of a variety of other drugs are now in progress. So far none of these treatments have shown any consistent benefit in humans.
Current treatment for CJD is aimed at alleviating symptoms and making the individual 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 help prevent bedsores. A catheter can be used to drain urine if the individual cannot control bladder function, and intravenous fluids and artificial feeding may also be used.
What Causes Creutzfeldt-Jakob Disease?
Some researchers believe an unusual "slow virus" or another organism causes CJD. However, they have never been able to isolate a virus or other organism in people with the disease. Furthermore, the agent which causes CJD has several characteristics unusual for known organisms such as viruses and bacteria. It is difficult to kill, does not appear to contain any genetic information in the form of nucleic acids (DNA or RNA) and usually has a long incubation period before symptoms appear. In some cases, the incubation period may be as long as 50 years. The leading scientific theory at this time maintains that CJD and other TSEs are caused by a type of protein called a prion.
Prion proteins occur in both a normal form, as a harmless protein found in the body’s cells, and an infectious form, which causes disease. The harmless and infectious forms of the prion protein have the same sequence of amino acids (the building blocks of proteins) but the infectious form of the protein takes a different folded shape than the normal protein. Sporadic CJD 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 aggregate, or clump together. Investigators think these protein aggregates may lead to the neuron loss and other brain damage seen in CJD, but do not know exactly how this damage occurs.
About 5 to 10 percent of all CJD 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 prion protein. If the prion protein gene is altered in a person’s sperm or egg cells, the mutation can be transmitted to the person’s offspring. All mutations in the prion protein gene are inherited as dominant traits. Therefore, family history is helpful in considering the diagnosis. 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 protein gene develop CJD.
How is CJD Transmitted?
CJD cannot be transmitted through the air, touch or most other forms of casual contact. Spouses and other household members of sporadic CJD patients have no higher risk of contracting the disease than the general population. However, exposure to brain tissue and spinal cord fluid from infected individuals should be avoided to prevent transmission of the disease through these materials.
In some cases, CJD 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 the pituitary glands of 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 CJD by this route.
The appearance of the new variant of CJD (nv-CJD or v-CJD) in several younger-than-average people in Great Britain and France has led to concern that BSE (bovine spongiform encephalopathy) 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-CJD, there is no direct proof to support this theory.
Many people are concerned that it may be possible to transmit CJD 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 CJD, so they do not know whether these fluids are potentially infectious or not. We do know that, even though millions of people receive blood transfusions each year, there are no reported cases of someone contracting CJD from a transfusion. Even among people with hemophilia, who sometimes receive blood plasma concentrated from thousands of donors, there are no reported cases of CJD.
While there is no evidence that blood from people with sporadic CJD is infectious, studies have found that infectious prions from BSE and v-CJD may accumulate in the lymph nodes (which produce white blood cells), the spleen and the tonsils. These findings suggest that blood transfusions from people with v-CJD might transmit the disease. The possibility that blood from people with v-CJD may be infectious has led to a policy preventing people in the United States from donating blood if they have resided for more than three months in a country or countries where BSE is common.
How Can People Avoid Spreading the Disease?
To reduce the already very low risk of CJD transmission from one person to another, people should never donate blood, tissues or organs if they have suspected or confirmed CJD, 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, healthcare workers and undertakers should take the following precautions when working with a person with CJD:
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, and 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.
Fact sheets listing additional precautions for healthcare workers and morticians are available from the NINDS and the World Health Organization.