What is Creutzfeldt Jakob disease?

Overview

Creutzfeldt-Jakob disease (CJD) is a rare neurodegenerative disease; a disease that affects the brain cells, ultimately causing them to die. There are different types of CJD which, in all cases, are caused by prions. The CDC defines prions as agents that have the ability to cause normal, healthy prion protein (abundant in the brain) to fold abnormally and cause disease. Normally, misfolded prion protein is recycled in the body and doesn’t cause harm, but in the case of CJD, they build up and cause brain cell death which then releases more prions and so on.

Eventually, a large number of brain cells die and plaques can build up within the brain. Holes also develop, giving the brain a sponge-like appearance. Unfortunately, the damage rapidly expands and causes a range of devastating symptoms such as a change in personality and memory loss. CJD is fatal in 100% of cases.

Although prions are infectious proteins, they differ from viruses and bacteria because they do not contain any genetic information; therefore, treatments such as antibiotics do not affect them in the same way. Prions can cause diseases in both animals and humans, including Chronic Wasting Disease and Bovine Spongiform Encephalopathy in animals and Creutzfeldt-Jakob disease (CJD) in humans.

Causes of creutzfeldt jakob disease

There are 4 main types of CJD that affect humans::

• Sporadic/Classic CJD

In around 85% of cases, CJD occurs sporadically with no known cause and no family history. Although the cause isn’t clear, it has been hypothesised that misfolds in normal brain proteins turn into prions. Another theory is that one or more brain cells might have developed a somatic mutation in the gene that encodes the prion protein, resulting in the development of faulty, abnormal prion proteins.

• Variant CJD 

This type is caused by consuming meat from a cow with mad cow disease (bovine spongiform encephalopathy). Although both diseases cause fatal brain degeneration, variant CJD is not the same disease as sporadic CJD. In some people, it can take around 10 years to develop symptoms which means that the actual prevalence of the disease is hard to predict. However, regulations that prevent sale of infected cattle as food products have lowered the number of infected individuals.  

Blood transfusions have also caused variant CJD in some patients. In 2003, a patient received a transfusion from a donor that developed variant CJD, and unfortunately, the recipient developed the disease.⁵ In the UK, there have been 5 confirmed cases of variant CJD being transmitted in this manner.

• Familial/Inherited CJD

This is another rare condition in which an individual inherits a faulty prion protein gene (PRNP gene) from one of their parents. Around 5-10% of CJD cases are of this type. The gene is dominant, meaning that you would only need to inherit the mutated gene from one parent to develop CJD. If a parent has the condition, there is a 50% chance it will be passed on. Symptoms of CJD don’t usually develop until a person is in their 50s, so patients might have chosen to start a family without knowing the risks of passing on the gene to their children. The forms of CJD that are inherited include Gerstmann-Straussler-Scheinker Syndrome and fatal familial insomnia. 

• Iatrogenic CJD 

This type of CJD occurs when the infection is spread accidentally through medical equipment and procedures. There have been less than 300 cases reported. In the past, it has been linked to the injection of human pituitary growth hormone sourced from deceased individuals, but nowadays, synthetic versions of the hormone are used to eliminate such risks. Now, with more awareness about the risks, iatrogenic CJD is rare. However, it could still occur if instruments used in brain surgery which are infected with CJD do not get cleaned properly. This highlights the difference between prions and bacteria/viruses; normal sterilisation that would kill bacteria and viruses do not work on prions.

Signs and symptoms of creutzfeldt jakob disease

The first symptoms that develop are different depending on the type of CJD but all usually appear around middle age. 

• Sporadic CJD
  • Symptoms mostly begin at ages 45-75
  • Neurological symptoms are usually the first to appear, including:
    • Difficulty walking
    • Balance problems
    • Slurred speech
    • Numbness
    • Tingling or prickling
    • Dizziness
    • Changes in vision 
    • Confusion 
    • Hallucinations

Symptoms generally develop quickly over a few months and the patient usually deteriorates rapidly. 

• Variant CJD 
  • For patients with vCJD, the behaviour, emotions and personality are usually the first noticeable changes/symptoms, which include:
    • Depression
    • General lack of interest
    • Disinterest in activities they used to enjoy
    • Anxiety
    • Irritability and impatience 
    • Insomnia

The more advanced stages of CJD have symptoms that are similar across all different disease types:

• Lack of coordination causing inability to walk, speak or maintain balance
• Muscle twitching and spasms
• Incontinence (lack of voluntary control over urination or defecation)
• Severe visual disturbance and blindness
• Difficulty swallowing
• Loss of speech 
• Lack of voluntary movements
• Severe loss of memory 
• Confusion and lack of concentration
• Loss of appetite
• Paranoia
• Continued hallucinations
• Inappropriate emotional reactions

In the final stages of the disease, patients suffering from any kind of CJD will become bed bound and totally reliant on caregivers. Unfortunately, nothing can be done to prevent death from CJD and the patient usually passes away due to an infection such as pneumonia. Patients usually die within one year of the symptom onset.

Management and treatment for creutzfeldt jakob disease

Currently, there is no treatment for CJD. Although the disease is ultimately fatal, there are ways to keep a patient comfortable and achieve a peaceful and dignified death. There are plenty of painkillers available for patients suffering from any pain, and drugs such as antidepressants can be used to ease the psychological discomfort associated with the disease. 

The NHS provides a comprehensive guide on the best ways to treat the individual symptoms associated with CJD. 

Research has been carried out to determine the best antidepressant medication for a patient with CJD. It has been reported that patients prescribed SNRIs to assist with the symptoms of sporadic CJD actually had a reduction in survival time compared to patients that had been prescribed first generation antidepressants. The research suggests that this could be due to different kinds of medications targeting different neurotransmitters within the brain. Similar studies have the potential to give an insight into the mechanisms behind the development of CJD and provide ideas for the best ways to treat the symptoms.²

Other studies have investigated treating the disease as a whole. Scientists at the University College London Hospitals’ biomedical research centre developed a monoclonal antibody called PRN100; monoclonal antibodies are man-made proteins that act as human antibodies. The antibody was given to 6 patients between October 2018 and July 2019. The treatment was deemed safe with no side effects and antibodies were able to reach the brain. In half of the patients, the progression of the disease stabilised. Although the disease was fatal for all of the patients in this small research group and the results cannot be generalised to the wider population of patients with CJD, this research has provided an encouraging development in the treatment of prion diseases.³

Diagnosis of creutzfeldt jakob disease

If a GP suspects that a patient has CJD, they will usually be referred to a neurologist (a brain specialist). The symptoms of CJD are similar to other neurodegenerative diseases like dementia and Parkinson’s disease, therefore tests are needed to confirm CJD diagnosis. 

Tests that are carried out to investigate whether a person has variant CJD include:

• A prototype blood test 
• A biopsy of the tonsils to check for the presence of prions associated with vCJD⁴

Other tests that can help with diagnosis of other CJD types include an MRI scan of the brain that looks for abnormalities associated with CJD, a sample of cerebrospinal fluid can be taken during a spinal tap to look for proteins commonly found in patients with CJD and an EEG to look for unusual patterns of activity within the brain. Genetic testing can also be used in cases where there is a suspicion of the inherited form of CJD. 

In order to be 100% sure of a CJD diagnosis, a biopsy of brain tissue is needed which is carried out under general anaesthesia. It is more common to confirm a CJD diagnosis with an autopsy after death.  

Risks factors

Sporadic CJD develops for an unknown reason, there isn’t currently any known way to reduce the risk for its development. 

Having a family history of inherited CJD means that there is a higher risk for other members of the family and any future offspring. 

Although strict regulations have massively reduced the risk of this occurring, if contaminated beef is eaten, there is a risk of developing variant CJD,. The NHS outlines some of the regulations in place including the ban on feeding meat and bone mixtures to farm animals and the destruction of all animal carcass parts that could be infected with bovine spongiform encephalopathy. There are also regulations in place to reduce the risk of variant CJD developing from blood transfusions. These include removing all white blood cells from all blood used for transfusions because these cells carry the highest risk of transmitting CJD. Another measure in place is not allowing people that are more at risk of CJD to donate any organs or blood. 

To reduce the risk of iatrogenic CJD, medical instruments that might be contaminated with CJD must be destroyed. 

According to gov.uk, people at a higher risk of developing CJD are:

• People who have received multiple blood transfusions (from 300 or more donors since 1990)
• People who receive blood from a donor who later developed variant CJD
• People who had surgery using instruments that had previously been used on a patient who developed vCJD
• People who received growth hormone from a human source before 1985

Complications

Most people diagnosed with CJD will die within one year. This usually happens because they have contracted an infection such as pneumonia or their inability to swallow,  increased risk of falls and heart or lung issues that might develop. 

FAQs

How common is creutzfeldt jakob disease?

CJD is a rare condition. It’s estimated that there is one case per million people in the USA.However, researchers have suggested other neurodegenerative diseases such as Alzheimer’s disease be misdiagnosed prion disease.⁵

Is creutzfeldt jakob disease contagious?

CJD is not contagious through personal contact or through the air. However, it can be transmitted among people  through surgical instruments or blood transfusions. 

Can creutzfeldt jakob disease be prevented?

There’s no way to prevent sporadic CJD. Inherited CJD is passed on through families and similarly cannot be prevented if someone already possesses the dominant gene. The risk of variant CJD can be reduced before consumption of infected food but cannot be prevented after infection. 

When should I see a doctor?

If you think that there is any chance you could have CJD, a doctor should be contacted as soon as possible. They will be able to give you the best advice and information about what could be causing your symptoms. You should also contact your doctor if somebody else in your family has the disease and you are worried about inheriting it. 

Summary

Creutzfeldt-Jakob disease is a rare condition caused by prions. The condition can appear sporadically or a person can become infected through eating infected meat or other ways. The symptoms result in severe neurodegeneration and ultimately death within a short span of time compared to similar diseases. Although the risk of infection can be reduced there is currently no treatment for CJD; however, there are measures that could keep the patient as comfortable as possible while research is ongoing.