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Prion disease





BSE

Causes of Creutzfeldt-Jakob disease

Creutzfeldt-Jakob disease (CJD) is caused by an abnormal infectious protein in the brain called a prion.

Proteins are molecules, made up of amino acids, which help the cells in our body to function. They begin as a string of amino acids that then fold themselves into a three-dimensional shape. This ‘protein folding’ allows them to perform useful functions within our cells.

Normal prion proteins (thought to be the precursors of the infectious prions that cause CJD) are found in almost all body tissues, but at highest levels in brain and nerve cells. The exact role of the normal prion proteins is unknown, but it is thought they may play a role in transporting messages between certain brain cells.

How prions cause CJD 

Sometimes, mistakes happen during protein folding and the prion protein cannot be used by the body. Normally these misfolded prion proteins are recycled by the body, but if they are not they can build up in the brain.

Prions are misfolded prion proteins that surround brain cells and cause normal prion proteins to misfold as well. This causes the brain cell to die, releasing more prions to infect other brain cells.

Eventually, clusters of brain cells are killed and areas where prions have built up, called plaques, may appear in the brain.

Prion infections also result in the appearance of small holes in the brain, causing it to become sponge-like. The damage to the brain causes the mental and physical impairment and eventual death associated with CJD.

Prions can survive in nerve tissue, such as the brain or spinal cord, for a very long time, even after death.

Types of CJD

There are a number of different types of CJD. They are all caused by a build-up of prions in the brain, but the reason why this happens is different for each type.

The causes of the main types of CJD are described below.

Sporadic CJD

Sporadic CJD is the most common type of CJD, accounting for around 8 in every 10 cases, although it is still very rare.

It is not known what triggers sporadic CJD, but it may be that a normal prion protein spontaneously changes into a prion or a normal gene spontaneously changes into a faulty gene that produces prions. 

At present, nothing has been identified that increases your risk of developing sporadic CJD.

Variant CJD

There is clear evidence that variant CJD (vCJD) is caused by the same strain of prions that causes bovine spongiform encephalopathy (BSE or ‘mad cow disease’).

A government inquiry in 2000 concluded that the prion was spread through cattle that were fed meat-and-bone mix containing traces of infected brains or spinal cords. The prion then ended up in processed meat products, such as beef burgers, and entered the human food chain.

Strict controls have been in place since 1996 to prevent BSE from entering the human food chain and the use of meat-and-bone mix has since been outlawed.

It appears that not everyone who is exposed to BSE-infected meat will go on to develop vCJD.

All definite cases of vCJD occurred in people with a specific version of a gene called codon 129, which affects how the body makes a number of amino acids. It is estimated that up to one half of the UK population have this version of the gene.

Cases of vCJD peaked in the year 2000, in which there were 28 deaths from vCJD. There were no confirmed deaths in 2012. Some experts believe that the food controls have worked and that further cases of vCJD will continue to decline, but this does not rule out the possibility that other cases may be identified in future.

It is also possible for vCJD to be transmitted by blood transfusion, although this is very rare and measures have been put in place to reduce the risk of this happening.

There is considerable uncertainty about how many people in the UK population could develop vCJD in the future and how long it will take for symptoms to appear, if they ever will.

A study published in October 2013 that involved testing random tissue samples suggested that around 1 in 2,000 of the UK population may be infected with vCJD, but show no symptoms to date.

Familial or inherited CJD

This very rare form of CJD is caused by an inherited mutation (abnormality) in the gene that produces the prion protein. The altered gene seems to produce misfolded prions that cause CJD.

Everyone has two copies of the prion protein gene, but the mutated gene is dominant. This means you only need to inherit one mutated gene to develop the illness. So if one of the parents has the mutated gene, there is a 50% chance it will be passed on to each of their children.

As the symptoms of familial CJD do not usually begin until a person is in their 50s many people with familial CJD are unaware that their children are also at risk of inheriting this condition when they decide to start a family.

Iatrogenic CJD

Iatrogenic CJD (iCJD) is when the infection is spread from someone with CJD through medical or surgical treatment.

Most iatrogenic CJD cases have occurred through the use of human growth hormone, which is used to treat children who have restricted growth. Between 1958 and 1985, thousands of children were treated with the hormone, which at the time was extracted from the pituitary glands (a gland at the base of the skull) of human corpses.

A minority of those children developed CJD, as the hormones they received were taken from glands infected with CJD. Since 1985, all human growth hormone in the UK has been artificially manufactured, so there is now no risk.

A few other cases of iCJD occurred when people received transplants of infected dura (tissue that covers the brain) or came into contact with surgical instruments that were contaminated with CJD. This happened because prions are tougher than viruses or bacteria, so the normal process of sterilising surgical instruments had no effect.

Once the risk was recognised, the Department of Health tightened the guidelines on organ donation and the reuse of surgical equipment. As a result, cases of iCJD are now extremely rare.

Published Date
2013-10-27 21:08:00Z
Last Review Date
2013-10-15 00:00:00Z
Next Review Date
2015-10-15 00:00:00Z
Classification
Blood,Blood transfusion,Brain,CJD,Proteins






BSE

Diagnosing Creutzfeldt-Jakob disease

A diagnosis of Creutzfeldt-Jakob disease (CJD) is normally based on medical history, symptoms and a series of tests.

A neurologist (a doctor who specialises in conditions of the nervous system) will carry out the tests to rule out other conditions with similar symptoms, such as Alzheimer’s diseaseParkinson’s disease or a brain tumour.

The only way to confirm a diagnosis of CJD is to examine the brain tissue with a brain biopsy or, after death, by post-mortem examination of the brain.

Specialist services to advise local teams in diagnosis are available at the National CJD Research and Surveillance Unit in Edinburgh and the National Prion Clinic in London.

Tests for CJD

A clinical neurologist will rule out other diseases with similar symptoms and check for some common signs of CJD by carrying out the tests below:

  • Magnetic resonance imaging (MRI) brain scan – This uses strong magnetic fields and radio waves to produce a detailed image of the brain and can show up abnormalities that are particular to CJD.
  • Electroencephalogram (EEG) – This records brain activity and may pick up abnormal electrical patterns seen in sporadic CJD.
  • Lumbar puncture – During a lumbar puncture a needle is inserted into the lower part of the spine to draw out a sample of cerebrospinal fluid (which surrounds your brain and spinal cord) to be tested for a certain protein that indicates you may have CJD.
  • A prototype blood test for variant CJD has also been developed by the prion unit at the Medical Research Council (MRC). This is available through the National Prion Clinic.
  • Tonsil biopsy – A small piece of tissue can be taken from the tonsils and checked for the abnormal prions found in variant CJD (they are not present in other types of CJD).
  • Genetic test – This is a simple blood test to see if you have a mutation (fault) in the gene that produces normal protein. A positive result may indicate familial (inherited) prion disease.

Brain biopsy

During a brain biopsy, a surgeon drills a tiny hole into the skull and removes a small piece of brain tissue using a very thin needle. This is done under general anaesthetic, which means that the patient will be asleep during the procedure.

As a brain biopsy carries the risk of causing brain damage or seizures (fits), it is only performed in a few cases where there is a concern that someone does not have CJD but some other treatable condition.

Read more about biopsies.

Glossary

Biopsy
A biopsy is a test that involves taking a small sample of tissue from the body so it can be examined.
EEG
EEG stands for electroencephalogram. It is a painless test that records the electrical messages from the brain.
MRI
MRI stands for magnetic resonance imaging. It is the use of magnets and radio waves to take detailed pictures of inside the body.
Tissue
Body tissue is made up of groups of cells that perform a specific job, such as protecting the body against infection, producing movement or storing fat.  
Published Date
2013-10-27 21:36:45Z
Last Review Date
2013-10-15 00:00:00Z
Next Review Date
2015-10-15 00:00:00Z
Classification
Brain tumours,CJD,Neurological (nerve and brain) diseases






BSE

Introduction

Creutzfeldt-Jakob disease (CJD) is a rare and fatal condition that affects the brain. It causes brain damage that worsens over time.

Symptoms of CJD include:

  • loss of intellect and memory
  • change in personality
  • loss of balance and co-ordination
  • slurred speech
  • vision problems and blindness
  • abnormal jerking movements
  • progressive loss of brain function and mobility

Most people with CJD will die within a year of the symptoms starting, usually from infection. This is because the immobility caused by CJD can make people with the condition vulnerable to infection.

Read more about the symptoms of Creutzfeldt-Jakob disease and diagnosing Creutzfeldt-Jakob disease.

What causes CJD?

CJD appears to be caused by an abnormal infectious protein called a prion. These prions accumulate at high levels in the brain and cause irreversible damage to nerve cells, causing the symptoms described above.

While the abnormal prions are technically infectious, they are very different to viruses and bacteria. For example, prions are not destroyed by the extremes of heat and radiation used to kill bacteria and viruses, and antibiotics or antiviral medicines have no effect on them.

Read more about the causes of Creutzfeldt-Jakob disease.

Types of CJD

There are four main types of CJD.

Sporadic CJD

Sporadic CJD is the most common type of CJD.

The precise cause of spradic CJD is unclear, but it has been suggested that in some people a normal brain protein undergoes an abnormal change (misfolding) and turns into a prion.

Most cases of sporadic CJD occur in older adults aged between 45 and 75 years, with the average age of symptoms developing being around 60-65 years.

Despite being the most common type of CJD, sporadic CJD is still very rare, affecting only 1-2 in every million people each year in the UK.

There were 83 recorded deaths from sporadic CJD in the UK during 2012.

Variant CJD

Variant CJD is likely to be caused by consuming meat from a cow that has been infected with a similar prion disease called bovine spongiform encephalopathy (BSE) – also known as ‘mad cow disease’.

Since the link between variant CJD and BSE was discovered in 1996, strict controls have proved extremely effective in preventing meat from infected cattle from entering the food chain (see preventing Creutzfeldt-Jakob disease for more information).

However, the average time it takes for the symptoms of variant CJD to occur after initial infection (the incubation period) is still unclear. The incubation period could be very long (over 10 years) in some people, so people who were exposed to infected meat before the food controls were introduced can still develop variant CJD.

The prion that causes variant CJD can also be transmitted by blood transfusion, although this has only happened four times in the UK.

There have been 177 recorded cases of variant CJD in the UK to date and there were no recorded deaths from the condition in the UK during 2012.

Familial or inherited CJD

Familial CJD is a very rare genetic condition where one of the genes a person inherits from their parent (the prion protein gene) carries a mutation that causes the formation of prions in their brain during adulthood, triggering the symptoms of CJD. It affects about 1 in every 9 million people in the UK.

The symptoms of familial CJD usually first develop in people aged in their early 50s.

There were ten deaths from familial CJD and similar inherited prion diseases in the UK during 2012.

Iatrogenic CJD

Iatrogenic CJD is where the infection is accidentally spread from someone with CJD through medical or surgical treatment.

For example, a common cause of iatrogenic CJD in the past was growth hormone treatment using human pituitary growth hormones extracted from deceased individuals, some of whom were infected with CJD. Synthetic versions of growth hormones are now used, so this is no longer a risk.

Cases of iatrogenic CJD can also occur if instruments used during brain surgery on a person with CJD are not properly cleaned between each surgical procedure before re-use on another person.

Increased awareness of these risks, however, means iatrogenic CJD is now very rare. There were five deaths from iatrogenic CJD in the UK during 2012.

How CJD is treated

There is currently no cure for CJD, so treatment involves helping to relieve symptoms and making the affected person feel as comfortable as possible.

This can include using medication such as antidepressants to improve anxiety and depression, and painkillers to relieve pain. Assistance with feeding and nursing care for bedridden patients may also be needed.

Read more about treating Creutzfeldt-Jakob disease.

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Published Date
2013-12-19 15:33:56Z
Last Review Date
2013-10-15 00:00:00Z
Next Review Date
2015-10-15 00:00:00Z
Classification
Brain,CJD,Neurological (nerve and brain) diseases






BSE

Preventing Creutzfeldt-Jakob disease

Although the condition is very rare, it can be difficult to prevent Creutzfeldt-Jakob disease (CJD).

This is because most cases occur spontaneously for an unknown reason (sporadic CJD) and some are caused by an inherited genetic fault (familial CJD).

Sterilisation methods used to help prevent bacteria and viruses spreading are also not completely effective against the infectious protein (prion) that causes CJD, although tightened guidelines on the reuse of surgical equipment mean that cases of CJD spread through medical treatment (iatrogenic CJD) are now extremely rare.

There are also measures in place to prevent variant CJD spreading through the food supply or via the supply of blood used for blood transfusions. These are described below.

Protecting the food supply

Since the link between bovine spongiform encephalopathy (BSE or ‘mad cow disease’) and variant CJD was confirmed, strict controls have been in place to stop BSE entering the human food chain.

These controls include:

  • a ban on feeding meat-and-bone mix to farm animals
  • the removal and destruction of all parts of an animal’s carcass that could be infected with BSE
  • a ban on mechanically recovered meat (meat residue left on the carcass that is pressure-blasted off the bones)
  • testing on all cattle more than 30 months old (experience has shown that infection in cattle under 30 months of age is rare, and even cattle that are infected have not yet developed dangerous levels of infection)

Blood transfusions

In the UK, there have been four cases where variant CJD has been transmitted by blood transfusion. In each case, the person received a blood transfusion from a donor who later developed variant CJD.

Three of the four recipients went on to develop variant CJD, while the fourth recipient died before developing variant CJD, but was found to be infected following a post-mortem examination.

It is not certain whether the blood transfusion was the cause of the infection, as those involved could have contracted variant CJD through dietary sources.

Nevertheless, steps were taken to minimise the risk of the blood supply becoming contaminated.

These steps include:

  • not allowing people potentially at risk from CJD to donate blood, tissue or organs (including eggs and sperm for fertility treatments)
  • not accepting donations from people who have received a blood transfusion in the UK since 1980
  • removing white blood cells, which may carry the greatest risk of transmitting CJD, from all blood used for transfusions
Published Date
2013-10-27 21:32:01Z
Last Review Date
2013-10-15 00:00:00Z
Next Review Date
2015-10-15 00:00:00Z
Classification
Blood,Blood transfusion,CJD






BSE

Symptoms of Creutzfeldt-Jakob disease

The pattern of symptoms of Creutzfeldt-Jakob disease (CJD) can vary depending on the type.

In sporadic CJD, the symptoms mainly affect the workings of the nervous system (neurological symptoms) and these symptoms rapidly worsen in the space of a few months.

In variant CJD, a person will usually first develop symptoms affecting their behaviour and emotions (psychological symptoms). These are then followed by additional neurological symptoms around four months later, which get worse over the following few months.

Familial CJD has the same sort of pattern as sporadic CJD, though it often takes longer for the symptoms to progress – usually around two years rather than a few months.

The pattern of iatrogenic CJD is unpredictable, as it depends on how a person becomes exposed to the infectious protein (prion) that causes CJD.

Read more about the types of Creutzfeldt-Jakob disease and causes of Creutzfeldt-Jakob disease.

Initial neurological symptoms

Initial neurological symptoms of sporadic CJD can include:

  • difficulty walking, caused by problems of balance and co-ordination
  • slurred speech
  • numbness or pins and needles in different parts of the body
  • dizziness
  • vision problems such as double vision and hallucinations (seeing things that are not really there)

Initial psychological symptoms

Initial psychological symptoms of variant CJD can include:

  • severe depression
  • intense feelings of despair
  • withdrawal from your family, friends and the world around you
  • anxiety
  • irritability
  • difficulties sleeping (insomnia)

Advanced neurological symptoms

Advanced neurological symptoms of all forms of CJD can include:

  • loss of physical co-ordination, which can affect a wide range of functions, such as walking, speaking and balance (ataxia)
  • muscle twitches and spasms (myoclonus)
  • loss of bladder control and bowel control
  • blindness
  • swallowing difficulties (dysphagia)
  • loss of speech
  • loss of voluntary movement (akinesia)

Advanced psychological symptoms

Advanced psychological symptoms of all forms of CJD include:

  • loss of memory, which is often severe
  • problems concentrating
  • confusion
  • feeling agitated
  • aggressive behaviour
  • loss of appetite, which can lead to weight loss
  • paranoia, which is when you feel that people are secretly out to harm you 
  • unusual and inappropriate emotional responses, such as laughing when you hear bad news or bursting into tears for no apparent reason

Final stages

As the disease progresses to its final stages, people with all forms of CJD will become totally bedridden. They often become totally unaware of their surroundings and require around-the-clock care. They also often lose the ability to speak and cannot communicate with their carers.

Death will then inevitably follow, usually in one of two ways:

  • due to infection – such as the lung infection pneumonia
  • due to respiratory failure – where the lungs stop working and a person is unable to breathe

Nothing can be done to prevent death in these circumstances.

Advancements in palliative care (the treatment of incurable conditions) mean than people with CJD often have a peaceful death.

Read more about treating Creutzfeldt-Jakob disease.

Published Date
2013-10-27 21:03:34Z
Last Review Date
2013-10-15 00:00:00Z
Next Review Date
2015-10-15 00:00:00Z
Classification
Behavioural changes,Brain,CJD,Memory problems,Neurological (nerve and brain) diseases,Urinary incontinence






BSE

Treating Creutzfeldt-Jakob disease

There is no proven cure for any type of Creutzfeldt-Jakob disease (CJD), although clinical studies are under way at the National Prion Clinic to investigate possible treatments.

Instead, treatment involves trying to keep the person as comfortable as possible and reducing symptoms through the use of medicines.

For example, psychological symptoms of CJD (such as anxiety and depression) can be treated with sedatives and antidepressants and muscle jerks or tremors can be treated with medicines such as clonazepam and sodium valproate

Any pain experienced can be relieved using powerful, opiate-based painkillers

Advance directive

Many people with CJD draw up an advance directive (also known as an advance decision). This is where they make their treatment preferences known in advance, in case they can’t communicate their decisions later because they are too ill.

Issues that can be covered by an advance directive include:

  • whether they want to be treated at home, in a hospice or in a hospital once they reach the final stages of CJD
  • what type of medications they would be willing to take in certain circumstances
  • whether they would be willing to use a feeding tube if they were no longer able to swallow food and liquid
  • whether they’re willing to donate any of their organs for research after they die (the brains of people with CJD are particularly important for ongoing research)
  • if they have respiratory failure (loss of lung function), whether they would be willing to be resuscitated by artificial means, for example by having a breathing tube inserted into their neck

Your care team can provide more advice about making an advance directive.

Specialist team

When somebody is diagnosed with CJD, they are referred to the National Care Team for CJD in the National CJD Research and Surveillance Unit, or the National Prion Clinic, for diagnosis and care.

A doctor and nurse from these services will be assigned to liaise with local services, including the person’s GP, social worker, physiotherapist and occupational therapist.

Specialist teams are available to diagnose and offer clinical and emotional support to patients and their families, and to work alongside the local care team. A local care team may include doctors and nurses, occupational therapists, dietitians, incontinence advisers and social workers.

Treating symptoms of CJD

For more information on how some of the specific symptoms of CJD may be treated see:

Care and support in the advanced stages of CJD

As the condition progresses, people with CJD will need significant nursing care and practical support.

As well as help with feeding, washing and mobility, some people may need help with urinating. Often, the use of a catheter (a tube that is inserted into the bladder and used to drain off urine) is required.

Many people will also have problems swallowing, so they may have to be given nutrition and fluids through a feeding tube.

It may be possible to treat people with CJD at home, but this will depend on the progression and severity of the condition.

Caring for someone with CJD can be distressing and difficult to cope with, so many carers prefer to use the specialist services of a hospital or hospice.

Read more about end of life issuesend of life care and your own emotional wellbeing if you are caring for someone else.  

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Published Date
2013-10-27 21:20:36Z
Last Review Date
2013-10-15 00:00:00Z
Next Review Date
2015-10-15 00:00:00Z
Classification
CJD