Creutzfelt-Jakob Disease

Index

• Dementia
• Historical Note
• Occurance
• Other spongiform encephalopathies
• Common Factors in these Conditions
• Transmission
• Significant Characteristics of CJD
• Diagnosis
• Research
• Common questions about CJD
  Can you catch it from somebody? Why did my friend/relative get CJD? Can you catch it from food or animals? Is the person with CJD in Pain? What can the medical profession do?
• What is being done to investigate the disease at present?
• Precautions to be taken by Nurses and other Carers

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  Dementia

  The term dementia is used to describe conditions which are characterised by the progressive loss of mental abilities. Alzheimer's disease is the most common form of dementia followed by vascular dementia.
  Among the other types of dementia is a small group of conditions known as 'transmissible dementias' or 'prion diseases'. They include Creutzfeldt-Jacob disease, Kuru and Gerstmann-Straussler-Schenker syndrome.

  Historical Note

  Creutzfeldt-Jacob disease is named after the two German neurologists who in the early 1920's separately described a total of six patients with peculiar and previously unrecorded neurological illnesses. Although the symptoms of these patients were diverse, when their brains were examined under the microscope after their deaths there were a number of features which appeared very similar. They had all lost many of the nerve cells: these had been replaced by a network of fine fibres and there was a generalised appearance of microscopic holes resembling a sponge. Thus was born the term 'spongiform encephalopathy', or spongy brain disease (encephalon meaning brain and pathos meaning disease).

  Occurrence

  During the decades following its discovery similar cases were recorded all over the world and it is now recognised that Creutzfeldt-Jakob disease is worldwide in its distribution. It is a rare disease which is estimated to occur at the rate of about one new case per million people each year. The number of identified cases of CJD in the UK over the last three or four decades has been between 30 and 50 cases per year with a tendency for the numbers to rise slightly in the 1980s and 1990s, probably because the medical profession has become much more aware of the disease. The commonest age of onset is over 55. It seems to be unusual among people under 40 or over 80. However, in March 1996, researchers identified what appears to be a new form of CJD which has so far affected fewer than 20 individuals with an average age of 28. , see later: New variant CJD. In certain circumstances CJD appears to be inherited from generation to generation within a family. In these rare circumstances family members will often be aware that the disease has already occurred in a close relative.

  Other spongiform encephalopathies

  Scrapie

  This spongy brain disease of sheep was first described in 1732. It owes its name to the habit of affected animals to scrape themselves against posts in the more advanced stages of the disease. The animals 'go off their feet' (become unsteady) and eventually die. Microscopic examination of the brain reveals many of the same changes as seen in CJD.

  Kuru

  This was a disease that occurred among the Fore people in New Guinea and showed similar features to some cases of CJD. Kuru afflicted those who consumed the brains of deceased members of the tribe as part of ritual cannibalism. It mainly affected the women who consumed the brains. The men usually ate other parts such as muscle and did not develop the disease. The Fore people were persuaded to abandon cannibalism in 1959 and Kuru has since gradually died out.

  BSE (bovine spongiform encephalopathy or 'mad cow disease')

  This affliction was first recognised in 1986. Affected animals begin to exhibit a change in their behaviour. They go 'off their feet', that is become very unsteady, lose weight and eventually, if not destroyed, die of the disease. This condition is sometimes referred to, not always appropriately, as 'mad cow disease'.

  Other spongy brain disease

  Many other mammals ranging from the smallest (mice) to the largest (cattle and antelopes), including apes, have been recorded as suffering from spongy brain diseases which have occurred either naturally or in the course of research.

  Common factors in these conditions

  All the spongiform encephalopathies are transmissible diseases. They are a kind of infection with a germ or micro-organism. They share three main features:
  • The causative agents, whatever they are, remain remarkably resistant to the usual sterilising techniques.
  • The diseases have very long incubation periods. This means that the time between acquiring the infection and developing signs of the disease is measured in years rather than days or weeks. Affected people or animals appear outwardly normal throughout the incubation period. The possible extent of the incubation period is not known for certain in CJD but in Kuru it can exceed 30 years. Because of this long incubation period these diseases are sometimes called 'slow virus diseases', a term which some researchers feel is more appropriate than the now fashionable 'prion diseases'.
  • The organisms involved in these conditions do not give rise to any immunological responses so there is no test as yet which can reveal which people or animals are incubating these diseases.

  Transmission

  These diseases are caused by an unusual infectious agent which is quite distinct from the usual form of virus or bacterium.
  All the spongiform encephalopathies can be transmitted in the laboratory but only scrapie is known to be naturally transmissible among sheep. It is not yet clear whether cows with BSE can transmit the disease to their offspring.
  Although these diseases are transmissible across certain species it is not through the normal process of infection. Thus scrapie has not over the centuries infected cattle although sheep and cattle shared the same pasture. It was not till cows were fed the carcasses of sheep with scrapie, including their infected brains, that they finally caught the disease.
  It is most important to realise that CJD is not 'catching' in the usual way and that there is no danger whatever of becoming infected by nursing or otherwise caring for a person with CJD.

  Significant Characteristics of CJD

  Many of the early signs of CJD are similar to those occurring in other neurological and psychiatric illnesses such as Alzheimer's disease and depression. In the early stages the person may have the odd lapse of memory and mood swings and may feel inclined to withdraw from social activities. Fairly soon they are likely to become far more forgetful and rather unsteady on their feet and they may have problems in finding the right word so that conversation becomes difficult.
  There is usually a rapid downhill course with the development of uncontrollable, jerky movements, progressive stiffness of the limbs and incontinence. As the disease progresses the person loses awareness of their surroundings and becomes unable to recognise members of their own family.
  The person with CJD often appears very agitated, which is very distressing for everyone, but some of this may be due to the uncontrollable tremor and jerky movements which are physical symptoms of the illness.
  Mercifully, it seems that it is only in the very early stages of the illness that people with CJD are aware that anything is amiss. As a consequence they may complain of being muddled or not being able to see clearly. As the disease pursues its relentless course they lose insight and seem unaware of their condition.
  Although most people with CJD die within six months or so, in about 10 per cent of cases it can last for between two and five years.
  There is unfortunately no known cure for CJD, although a considerable amount of research is being carried out. There are some medicines which can help to make the last few weeks easier for the person with CJD.

  Diagnosis

  This condition can be very difficult to distinguish from certain other neurological and psychiatric illnesses in its very early stages. However, it usually progresses so rapidly that a diagnosis can very soon be made through observing symptoms. However, there are some investigations which might prove helpful, particularily in excluding other possible conditions.
  
  • CT scan
    These initials stand for "computerised axial tomography." It is a special three dimensional X ray enabling examination of the brain but not showing the "spongy" changes since these are microscopic. It is useful in excluding other conditions.
  • MRI scan
    MRI stands for "magnetic resonance imaging." It is another three-dimensional way of looking at the brain, this time without using X-rays. It cannot detect "spongy" changes but is also useful in excluding other conditions.
  • EEG
    The electro-encephalogram records the electrical activity which takes place in the brain. A number of small electrodes are placed on the scalp and the tracings are recorded. Theses sometimes show abnormalities which may assist in reaching a diagnosis.
  • Lumbar puncture
    The brain and the spinal cord are bathed in a clear fluid - the cerebro spinal fluid (CSF). Using a fine hollow needle and as local anaesthetic it is possible to withdraw a small quantity of this fluid for examination. This test is often used to see whether there is a condition that might respond to treatment.
    Recently, researchers in the USA and Germany have described a test for a protein (14-3-3 protein) in the CSF that may be useful in the diagnosis of CJD. However, more work to evaluate this test is needed before it is introduced into routine use.
  • Microscopy
    The only certain way to diagnose CJD is to examine part of the brain under a microscope after the person's death.
    In some cases a brain biopsy may be performed while the person is alive by removing a tiny portion of the brain while they are under anaesthetic for examination under a microscope. However, the biopsy may yield a negative result if the disease process has not yet reached the fragment taken. Brain biopsies are in many cases unreliable and therefore are not usually an appropriate way of confirming a clinical diagnosis. This method should only be used as a last resort after a full explanation to the nearest relatives and with their agreement.

  Research

  Scrapie, the spongy brain disease affecting sheep, has been the subject of most of the research undertaken into this group of diseases since in 1938 it was the first one to be shown to be an infection, albeit one with a very long incubation period.
  Important experiments carried out on scrapie between 1950 and 1970 revealed that it can be transmitted to a number of mammals, including primates, that the causal agent is highly resistant to sterilisation, that the infection can spread from ewe to lamb and that the disease can be experimentally transmitted using brain material but that many other tissues do not seem to carry infection.
  By 1959 it was suspected that Kuru was also an infection. This was proved in 1967 when Kuru brain material was injected into a monkey. The monkey developed a similar disease after a couple of years and its brain showed the characteristic spongy pathology.
  One of the important observations about Kuru was that although cannibalism, which transmitted the disease, stopped in 1959, some recent cases have taken as long as 30 years to develop.
  Following the 1967 experiment that revealed that Kuru was transmissible a similar experiment was carried out with CJD. In 1968 a preparation of brain tissue from a CJD patient was inoculated into various laboratory animals and they developed a similar disease, their brains also showing characteristic spongy changes.
  It gradually became clear that the various spongiform encephalopathies are caused by closely related organisms.
  The next advance was the identification of a particular protein in the brain which was found to occur in much larger amounts in patients with CJD. Using an electron microscope it is possible to see this protein forming stick-like structures, known as 'scrapie-associated fibrils'. It is the presence of these fibrils, that seem to be a sort of trail left by the organism, which helped to identify these diseases.
  There is at the time of publication a dispute amongst researchers as to the precise nature of the agent which causes these diseases. Since it has been found to resist all sorts of techniques which are known to destroy DNA and RNA (nucleic acids) a hypothesis known as the 'prion theory', first proclaimed by British scientists in 1967/68, has become very popular. This states that the agent might be capable of replicating without the benefit of nucleic acid.
  A different view is that this is an ordinary virus which has a tough jacket or capsule around it which is able to resist all 'disinfectants'. Crack the capsule and the virus inside may be more vulnerable. A similar situation occurs with the bacillus which causes tuberculosis.

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  Common questions about Creutzfeldt-Jakob disease.

  Can you catch it from somebody?

  It is not a 'catching' disease like measles or mumps. People who look after, come into contact with, or eat off the same plate as those with CJD will not get the disease any more frequently than members of the general public. Indeed, doctors and nurses who would be expected to come into contact with people with the disease are no more likely to develop CJD than anyone else.

  Why did my friend or relative get CJD?

  The truth is that no one knows. Without knowing what causes the condition, we do not have an answer to this question. However, a number of cases have occurred in particular circumstances with a logical explanation.

  Some known causes of CJD

  • Some people who received treatment with human growth hormone developed CJD. In the past, growth hormone was obtained from the pituitary gland (a small gland at the base of the brain) of people who had died.
    It is suspected that one or more people from whom the glands were obtained had died from CJD. At that time it was not known that CJD could be passed on from one person to another in this way. Since 1985 the hormone has been made artificially and there are now no risks of acquiring the disease in this way.

  • Although there is no direct evidence that CJD is transmitted through blood transfusions, it is now recommended as a precautionary measure that individuals who have received human pituitary hormones or individuals with a family history of CJD should not act as blood donors.

  • One case of CJD was described in an individual who contracted the disease after receiving corneal transplants from someone who had died, to replace their own damaged cornea. Other cases have occurred due to the implantation of human dura mater grafts at neurosurgery (the dura mater is the tough outer membrane enclosing the brain and spinal cord). These tragic medical accidents occurred at a time when it was now known that CJD could be transmitted from one person to another in this way. No organs or tissues of any type are now taken from people who have died from CJD for use in donations.

  • Four cases of CJD occurred in people who had undergone brain surgery and it is likely that transmission of the infectious agent occurred from case to case by the use of contaminated surgical instruments. It is now standard practice for all instruments used in neurosurgical or eye operations on a patient with CJD to be destroyed.

  Can you catch it from food or animals?

  Classical CJD

  The classical form off CJD occurs at a relatively standard rate in all countries around the world. One possible explanation for the cause of classical CJD is that it is transmitted to humans when they eat meat or other products from animals infected by animal spongiform encephalopathy. However, CJD occurs in countries where there is no scrapie or BSE and there is, as yet, no evidence that this form of CJD is caused by transmission from animals. Studies have not shown any common link between patients with CJD and there does not appear to be any increased risk through dietary or occupational exposure to sheep.
  The cause of classical CJD is unknown, although one possible but unproven explanation is that the disease results from a random and chance alteration of the form of the brain protein, prion protein, which then multiplies and eventually causes disease. If this theory is correct, classical CJD may not be due to any form of infection from the environment.
  

  New variant CJD

  Although the risk from eating meat from BSE affected animals has always been considered to be remote, there has been a theoretical risk that some of us may have been exposed to infection prior to the banning of many adult cattle tissues, including brain and spinal cord, from the human food chain in November 1989.
  Research carried out by the CJD Surveillance Unit in Edinburgh early in 1996 identified a number of younger people, average age 28, in the UK with a new clinical pathological type of CJD. Researchers believe that a new variant of the disease has been identified and that there have now been 15 cases of this type of CJD in the UK and one case in France.
  The new cases do not appear to be linked to known risk factors for CJD such as earlier treatment with human growth hormone or exposure to surgical instruments contaminated with CJD. It also seems that the new cases examined to date are not genetic in origin.
  The occurrence of a new and unexplained form of CJD in a country with a high incidence of BSE suggests the possibility of a causal link. Recent evidence has also shown that the protein that accumulates in the brains of patients with the new variant is different from other forms of CJD and similar to BSE. Although this is not proof, the evidence strengthens the possibility that new variant CJD is caused by BSE. If these cases have arisen as a result of eating infected animal tissue, given the probable ten to twenty year incubation period, there may be many more people at risk.

  Is the person with CJD in pain?

  Individuals with CJD may sometimes feel discomfort from, for example, sitting in one position too long, but there is no pain associated with the disease itself. However, it is very distressing for others to see someone they care about seriously ill.

  What can the medical profession do?

  There are ways to alleviate some of the features which can accompany the illness. For example, frequent changes of position of an immobile person are necessary to ensure comfort and prevent the development of pressure sores. A catheter to drain urine is often necessary if incontinence of urine is a problem. A catheter is a narrow rubber tube which is painlessly inserted into the bladder. Sometimes the ability to swallow may be lost, and then the patient can be fed via a tube through the nose or receive fluid by means of a plastic needle in their vein (a "drip").
  The shakiness or jerks which some patients experience can be treated with sedative drugs or painkillers. The object is to keep the person with CJD as comfortable as possible up to the time of death.

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  What is being done to investigate the disease at present ?

  A great deal of research is being carried out all over the world to try to find the cause of CJD.
  The Department of Health in this country has set up a nationwide survey to identify all cases of the condition. Information is gathered from a close relative or friend, wherever possible, regarding the person's past medical history, work, places of residence and dietary history so that any factors which might link people with the disease can be identified. The number of cases each year and where in the UK they occur are then recorded to see if there is any change with time.
  It is vital that research into the spongiform encephalopathies of CJD and BSE are pursued vigorously. The difficulty with such research is that the only way to confirm the presence of the infectious agent is by means of a laboratory transmission experiment and that in such experiments the very long incubation period means that there is a wait of a least a year before results can be expected.
  If these experimental hurdles can be overcome, swifter progress will be achieved in understanding and eradicating CJD and related conditions.

  Precautions to be taken by nurses and other carers.

  There is no requirement for nurses or other carers to take special precautions when nursing CJD patients. Normal good practice regarding procedures involving the handling of body fluids, for example, will suffice and in any case will be subject to the existing guidelines issued by health authorities and professional bodies.
  The local guidelines are issued by the Consultant in Communicable Disease Control and will be based on two documents:

  Advisory group on the management of patients with spongiform encephalopathy (CJD), HMSO 1981
  Precautions for work with human and animal transmissible spongiform encephalopathies, HMSO 1994