Creutzfeldt-Jakob Disease

Creutzfeldt-Jakob disease is a rare encephalopathy, or brain disease, that causes a swift, progressive dementia and neuromuscular changes. It was first described by German psychiatrist Alfons Maria Jakob (1884–1931) in 1921. He gave credit to Hans Gerhard Creutzfeldt (1885–1964), also a German psychiatrist, for describing the syndrome first without realizing he had stumbled onto a repeating set of symptoms that constitute a syndrome. Although it is now known that what Creutzfeldt described was not the same syndrome that Jakob had discovered, the disease retains its compound name.

Creutzfeldt-Jakob disease is the more common of two known human spongiform encephalopathies, the other being kuru. Both encephalopathies are thought to be caused by prions, infectious agents made up of genelacking proteins.

The early stages of Creutzfeldt-Jakob disease include symptoms similar to those of Alzheimer disease. Disturbances in vision and other senses, confusion, and inappropriate behavior patterns are the usual early signs. During the following months the patient will invariably progress first to dementia and then into a coma. Jerking movements of the arms and legs are common, and convulsions are less common. Muscle spasms and rigidity occur in the late stages of the disease. Usually, the patient will deteriorate and die in less than a year, although some will live for as long as two years.

Creutzfeldt-Jakob disease occurs throughout the world, usually equally among men and women at about age 60. Rarely do young people get the disease. Three forms of the disease have been identified, classified by virtue of transmission. About 10% of Creutzfeldt-Jakob patients in the United States have a positive family history of Creutzfeldt-Jakob disease (hereditary form). About 85% have no identifiable risk factors for the disease, and yet have developed Creutzfeldt-Jakob disease (sporadic form). Only 1% are thought to have contracted the disease through exposure to infective materials (acquired form).

There are no laboratory tests to help diagnose Creutzfeldt-Jakob disease. Many tests which are performed when a patient is suspected of having Creutzfeldt-Jakob disease are done to make sure that the patient does not have some other, potentially treatable disease. A brain scan using magnetic resonance imaging (MRI) will usually show the degeneration of the cerebrum and enlargement of the brain ventricles (fluid-filled openings in the center of the brain) which characterize encephalopathy. A definitive diagnosis can be made only when a specimen (biopsy) of the brain tissue is stained and studied under a microscope. Biopsying the brain, however, is a highly invasive procedure and is rarely done to diagnose Creutzfeldt-Jakob disease, as information gained from the biopsy does not lead to any change in treatment. Other neurological measurements are less directly correlated to diagnosing the disease. The electroencephalogram (which monitors the pattern of electric brain waves) may show certain repeated signs, but not always. The cerebrospinal fluid (which fills spaces in the brain and surrounds the spinal cord) may have an elevated level of protein when tested; this measurement is currently being investigated to determine whether the presence or elevation of specific proteins is diagnostic of this disease. The changes seen in brain tissue are not found in any organ outside the central nervous system. The etiologic agent that causes the disease can be found in other organs, but evidently it has no effect on their structure or function.

The etiologic agent of Creutzfeldt-Jakob disease has unique characteristics. The agent can withstand heat, ionizing radiation, and ultraviolet light—immunities that documented viruses do not possess. Most scientists consider the agent to be a unique, nonviral pathogen that does not contain any DNA or RNA, the nucleic acids containing the reproductive code for any organism. Thus, a new theory emerged and gained widespread acceptance and the infectious agent is now though to be an unconventional proteinaceous particle called a "prion", ("proteinaceous infectious agent). Prion proteins are believed to be proteins that are able to exist in two forms: a normal form, performing some unknown but presumably necessary physiological function in the host, and an abnormal, infectious form, which can cause the disease. When a substantial amount of the normal host protein is converted to the abnormal form (by processes which are not understood fully to date) prion disease can ensue.

The means of transmitting this disease is unknown. A case has been documented in which a patient who received a transplanted cornea from the eye of a person with Creutzfeldt-Jakob disease also developed the disease. Another person contracted the disease when electrodes previously used on an infected patient were used in an electroencephalogram. Even the spread of the disease within families is the result of a mysterious mechanism. It is not always seen and may be the result of more than one family member having a genetic predisposition to the disease.

There is no cure for Creutzfeldt-Jakob disease. Symptoms are treated to make the patients more comfortable, but nothing has been found that will interfere with the progress of the disease or kill the causal agent. In fact, very special precautions are required around these patients because the means of spreading the disease is not known. Only three means of sterilization of instruments or other objects that have touched the patient are known—lye, bleach, and intense heat. It is recommended that clothing and bed linens of the patient be burned, as washing will not kill the etiologic agent.

Researchers are very interested in more clearly identifying the infective agent, and defining its characteristics and the methods of transmission. Concern has been raised regarding the chance that the disease could potentially be passed through contaminated blood transfusions. No such case has been identified, but the issue has been raised. Contaminated beef has been held resonsible for a related disease called bovine spongiform encephalopathy, leading researchers to question whether Creutzfeldt-Jakob disease could also be spread through contaminated food products.

Recently in the United Kingdom, there have been several unusual cases of CJD in younger people. These cases surfaced in 1994 and 1995, with a disease that differed significantly from classical sporadic CJD and has been termed variant CJD (vCJD). The patients were all under the age of 42, with an average age of 28, as opposed to the typical age of 63 for classical CJD. The average course of the duration of vCJD was 13 months, in contrast to the average four to six month duration for classical CJD. The electroencephalographic (EEG) electrical activity in the brain for vCJD was different from classical CJD. While the brain pathology of the vCJD cases was identifiable as CJD, the pattern differed because of the presence of large aggregates of prion protein plaques. Scientists ascertained a likely connection between this new form of CJD and bovine spongiform encephalopathy (BSE), a prion disease in cattle, which reached epidemic proportions in the 1980s in the United Kingdom. There have now been over 100 cases of vCJD, most of which have occurred in the United Kingdom, and the numbers are still rising. A few cases of vCJD have been found in France, Ireland, Italy, and Hong Kong. Because the incubation period between exposure to the agent and the onset of symptoms may be as long as 40 years, it is uncertain whether these vCJD cases may signal the beginning of an epidemic or whether the incidence of vCJD will remain low.

Creutzfeldt-Jakob disease remains a medical mystery, since scientists are not yet certain about its means of transmission, its cure, or its prevention. Much work is being done to collect brain, tissue, and body fluid samples from all sufferers, in order to advance research into the disease.