Creutzfeldt-Jakob disease

Creutzfeldt-Jakob disease (CJD) is a rare and fatal condition that affects the brain.

Contents

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 memory
  • loss of balance and co-ordination
  • slurred speech
  • visual problems and blindness
  • abnormal jerking movements
  • progressive deterioration and immobility

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 patients vulnerable to infection.

Read more about the symptoms of Creutzfeldt-Jakob disease.

What causes CJD?

CJD is a rare disorder that appears to be caused by an abnormal protein called a prion. Prions accumulate at high levels in the brain and cause irreversible damage to nerve cells, causing the neurological symptoms described above.

Prions are infectious particles made of abnormally folded protein. They are very different in their behaviour to conventional viruses and bacteria, and are not destroyed by the extremes of heat and radiation used to kill bacteria and viruses.

Antibiotic and antiviral medicines have no effect on prions, and there is no effective treatment for CJD (see below).

Read more about the causes of Creutzfeldt-Jakob disease.

Treating CJD

There is currently no cure for CJD so treatment involves helping to relieve symptoms and making a patient feel as comfortable as possible.

This can include using medication such as antidepressants to improve mood and painkillers to relieve pain. Assistance with feeding may also be required.

Read more about the treatment of Creutzfeldt-Jakob disease.

Types of CJD

There are four main types of CJD, which are described below.

Sporadic CJD

Sporadic CJD is the most common type of CJD.

For reasons that are still unclear it appears that in cases of sporadic CJD a normal protein undergoes an abnormal change (mutation) and turns into a prion.

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

Despite being the most common type of CJD, sporadic CJD is still very rare, affecting only one in every million people in any given year in the UK.

There were 74 deaths due to sporadic CJD in the UK during 2011.

Variant CJD

Variant CJD is caused by eating 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 there have been strict controls, that have proved extremely effective, to prevent meat from infected cattle from entering the food chain.

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 in some people. So people who were exposed to infected meat before the food controls were introduced continue to develop variant CJD.

There were five deaths due to variant CJD in the UK during 2011.

Familial CJD

Familial CJD is a rare genetic condition where the genes a person inherits from one of their parents cause a protein to mutate into a prion in later life, triggering the onset of symptoms of CJD.

Most cases of familial CJD first develop in people who are in their early 50s.

There were nine deaths due to familial CJD in the UK during 2011.

Iatrogenic CJD

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

For example, in the past a common cause of iatrogenic CJD was that a person was given growth hormone treatment with hormones extracted from somebody 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 or nerve surgery are not properly cleaned between each surgical procedure.

Due to increased awareness of these risks, iatrogenic CJD is now very rare. There were only three deaths due to iatrogenic CJD in the UK during 2011.

Symptoms

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

In cases of 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 cases of 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, again, get worse over the course of a 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 CJD prion.

Initial neurological symptoms

Initial neurological symptoms of sporadic CJD include:

  • difficulties with walking – which can be in terms of balance, co-ordination, rhythm or all three
  • slurred speech
  • numbness or pins and needles in different parts of the body
  • dizziness
  • visual problems such as double vision and hallucinations (seeing things that are not really there)

Initial psychological symptoms

Initial psychological symptoms of variant CJD include:

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

Advanced neurological symptoms

Advanced neurological symptoms of CJD include:

  • loss of physical co-ordination, which can affect a wide range of functions, such as walking, speaking and balance (the medical term for this type of symptom is ataxia)
  • muscle twitches and spasms (myoclonus)
  • loss of bladder control and bowel control
  • blindness
  • difficulties swallowing (dysphagia)

Advanced psychological symptoms

Advanced psychological symptoms of CJD include:

  • loss of memory, which can often be severe, for example someone with CJD may be unable to remember who is the current prime minister
  • impaired concentration
  • mental confusion
  • agitation
  • becoming very tearful
  • 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 patients with 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 medicine (the treatment of incurable conditions) mean than people with CJD often have a peaceful death.

Causes

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

Role of proteins in the brain

Proteins are molecules, made up of amino acids, that help the cells in our body to function.

Proteins begin as a string of amino acids which then fold themselves into a three-dimensional shape. This 'protein folding' allows them to perform useful functions within our cells.

Prion proteins (which are not the same as the infectious prions that cause CJD) are a type of protein found in the brain and several other tissues of the nervous system. The exact role of prion proteins in our brain is unknown, but it is thought they may have something to do with our long-term memory.

Protein folding

Sometimes, mistakes happen during protein folding and the prion protein cannot be used by the body. These misfolded prion proteins are normally recycled by the body, but sometimes they can build up. This can cause problems, such as Alzheimer's disease.

Prions are misfolded prion proteins that enter brain cells and cause normal 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 replaced with deposits of prions, called plaques.

These plaques produce 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 the person or animal has died.

Sporadic CJD

Sporadic CJD is the most common type of CJD, although it is still very rare.

It is not known what triggers sporadic CJD, but it may be that a normal 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, also known as 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 gene called codon 129 which affects how the body makes a number of amino acids.

It is estimated that around one half of the UK population have this gene.

Cases of vCJD peaked in the year 2000, in which there were 28 deaths from vCJD. There were only five confirmed deaths in 2011. Some experts believe that the food controls have worked and that further cases of vCJD will continue to decline. As of January 2012 there were no patients with vCJD, but this does not rule out the possibility that other cases may be identified in future.

There is considerable uncertainty about how many people in the UK population are incubating vCJD.

A recent study based on random tissue samples suggested that around 1 in 4,000 might be infected with vCJD, but show no symptoms to date.

Familial CJD

This very rare form of CJD is caused by an inherited mutation (abnormality) of 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.

Most forms of familial CJD are inherited as dominant diseases, with a 50% chance of being passed on to the children of an affected individual. However, as the symptoms of familial CJD do not usually begin until a person is in their 50s many patients with familial CJD are unaware that their children are also at risk of inheriting this condition.

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.

Diagnosis

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 disease, Parkinson'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, when the patient is dead, during a post-mortem.

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:

  • A 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.
  • An electroencephalogram (EEG). This records brain activity and may pick up abnormal electrical patterns seen in sporadic CJD.
  • A 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. If a protein called 14-3-3 is found in the fluid, it indicates that you may have CJD (this protein is found in almost all cases of sporadic CJD and half of variant CJD cases).
  • A prototype blood test for variant CJD has 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 inherited prion disease.

Brain biopsy

During a brain biopsy, a surgeon drills a tiny hole into your skull and removes a small piece of brain tissue using a very thin needle. This is done under general anaesthetic (you are put to sleep).

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 the patient 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.

Treatment

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

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
  • other medicines, such as clonazepam and sodium valproate, can be used to treat muscle jerks and tremors
  • opiate-based painkillers can provide effective pain relief

Advance directive

Many people with CJD draw up an advance directive. This is where you make your treatment preferences known in advance, in case you can't communicate your decisions later because you're too ill.

Issues that can be covered by an advance directive include:

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

A doctor and nurse from these services will be assigned to the patient to liaise with local services, including the patient's doctor, 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.

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

Nursing care and support

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 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.

Rather than coping at home, many carers prefer to use the services of a hospital or hospice.

Prevention

Since the link between bovine spongiform encephalopathy (BSE) 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 for transfusion becoming contaminated.

These steps include:

  • not allowing people potentially at risk from CJD to donate blood, tissue or organs
  • 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

Expert view

Professor John Collinge of the National Prion Clinic explains different variants of CJD, a rare neurological illness that causes damage to the brain and for which there is no cure.

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