What are other Names for this Condition? (Also known as/Synonyms)

• Acquired Creutzfeldt-Jakob Disease (Iatrogenic)
• Iatrogenic Prion Disease
• iCJD (Iatrogenic Creutzfeldt-Jakob Disease)

What is Iatrogenic Creutzfeldt-Jakob Disease? (Definition/Background Information)

• Creutzfeldt-Jakob disease (CJD) is a rare, progressive degenerative disease of the brain that occurs following infection with certain protein types, called prions. Iatrogenic Creutzfeldt-Jakob Disease (iCJD) develops as a result of acquiring rogue prion proteins during or after a medical procedure
• These prions may be acquired from an individual, who has or has had any type of CJD, by coming into contact with certain bodily fluids or tissues, either through direct contact or via contaminated medical supplies
• Prions are infectious pathogens, but are very different from other pathogens, such as bacteria, viruses, and fungi. They are unusual, because they lack both DNA and RNA molecules. Instead, prions are normal cellular proteins that take on an abnormal configuration
• Prions are able to multiply by converting similar normal proteins in the brain into infectious abnormal forms, ultimately leading to the destruction of brain tissue. As a result, individuals with CJD develop dementia, involuntary muscle jerks (myoclonus), loss of motor coordination, and psychiatric symptoms
• There is no cure for iCJD and the treatment provided is often symptomatic. The prognosis of Creutzfeldt-Jakob Disease is poor

Creutzfeldt-Jakob Disease is also known as subacute or transmissible spongiform encephalopathy. Several types of CJD exist. All types involve an abnormal form of a naturally-occurring protein in the central nervous system.

• Sporadic Creutzfeldt-Jakob Disease (sCJD) is the most common form of the disorder and accounts for approximately 85% of all cases
• Familial Creutzfeldt-Jakob Disease (fCJD) is an inherited form caused by genetic mutations on chromosome 20
• Iatrogenic Creutzfeldt-Jakob Disease (iCJD) is an unintended consequence of medical therapy
• New Variant (or Variant) Creutzfeldt-Jakob Disease (nvCJD or vCJD) is due to the consumption of contaminated beef from cattle affected by a similar disease, called bovine spongiform encephalopathy (BSE)

Who gets Iatrogenic Creutzfeldt-Jakob Disease? (Age and Sex Distribution)

• Creutzfeldt-Jakob Disease is found worldwide with an incidence of approximately 1 case per 1,000,000 people. Iatrogenic Creutzfeldt-Jakob Disease accounts for less than 1% of these cases
• Iatrogenic Creutzfeldt-Jakob Disease can affect individuals of any age depending on the incubation period, but most individuals are 50-75 years old, at the time of symptom onset
• Both males and females are equally affected and no particular preference is observed
• Iatrogenic Creutzfeldt-Jakob Disease does not show higher prevalence in any specific ethnic or geographical group

What are the Risk Factors for Iatrogenic Creutzfeldt-Jakob Disease? (Predisposing Factors)

The only known risk factor for Iatrogenic Creutzfeldt-Jakob Disease is exposure to infectious prions following medical treatments. However, the rate of transmission is thought to be very low. An exposure may occur during:

• Medical treatments involving tissues or blood products from an infected donor with unknown CJD, such as during an organ transplant/graft, treatment with a hormone preparation, etc.
• An infection due to an unexpected circumstance, such as a stab wound from a needle that has come into contact with a CJD-infected individual’s brain tissue or spinal fluid

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one's chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Iatrogenic Creutzfeldt-Jakob Disease? (Etiology)

• Iatrogenic Creutzfeldt-Jakob Disease is caused by accidental transmission of prion proteins during or after organ transplants (e.g. corneas, dura mater grafts), electroencephalogram (EEG) electrode implantation, and other surgeries. In such cases, it is believed that insufficiently decontaminated equipment may have been responsible

Three common methods of transmission of Iatrogenic Creutzfeldt-Jakob Disease have been observed historically, which include:

• Transmission to younger individuals during human growth hormone injections to correct growth problems
  • In some cases, the human growth hormones were derived from the pituitary glands of deceased individuals
  • A very small amount of these growth hormones were derived from individuals who likely had unknown CJD
• Transmission to a wide age range of individuals who received dura matter implantations from cadavers
  • Dura matter is from a strong membrane, which protects the brain lies directly under the skull
  • Individuals who received dura matter had defects in their dura that needed repairs, likely due to brain surgery in the past
  • A very small amount of the dura matter obtained from deceased individuals happened to come from individuals with some form of CJD. Consequently, individuals who received the infected dura developed Iatrogenic Creutzfeldt-Jakob Disease later in life
• Individuals have acquired CJD rarely from additional surgical procedures:
  • Surgery on the brain of an individual using incorrectly sterilized instruments which were previously used on an individual with a known case of CJD
  • Surgery to implant corneal grafts from deceased individuals to healthy individuals, in order to improve vision. In rare cases, the corneal grafts were taken from someone who had a form of Creutzfeldt-Jakob Disease that went unnoticed; this led to an infection in those who received the contaminated graft

What are the Signs and Symptoms of Iatrogenic Creutzfeldt-Jakob Disease?

The signs and symptoms of Iatrogenic Creutzfeldt-Jakob Disease may include:

• Some individuals may initially experience fatigue, sleep disturbances, hallucinations, weight loss, headaches, and pain
• The initial symptoms in most individuals are mainly cognitive and include memory loss, confusion, and impaired judgment
• Some have vision, speech, or gait disturbances
• Other possible symptoms include rigidity, uncontrollable limb movements, poor coordination, and seizures
• Sudden, loud noises or bright light may trigger myoclonus (involuntary twitching of muscles). This may also occur during sleep
• Depression and sensory disturbances are common in nvCJD
• In all cases, the symptoms progress to profound dementia

How is Iatrogenic Creutzfeldt-Jakob Disease Diagnosed?

A diagnosis of Iatrogenic Creutzfeldt-Jakob Disease may involve:

• Complete medical history and a thorough physical examination; a positive family history may help diagnose CJD in a minority of cases
• Symptoms of dementia, myoclonus, and an abnormal EEG, in a middle-aged individual can suggest a diagnosis of Creutzfeldt-Jakob Disease
• Brain MRI may be helpful in diagnosing CJD
• CJD may be confirmed by brain tissue biopsy and assays that detect abnormal prion proteins. If a biopsy is negative, the diagnosis of CJD may not be ruled out, because prion proteins may be absent from a small tissue sample. In such cases, a final diagnosis may not be made until autopsy

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Iatrogenic Creutzfeldt-Jakob Disease?

The complications of Iatrogenic Creutzfeldt-Jakob Disease may include:

• Development of pneumonia during the later stages of the disease which is often fatal
• Severe dementia that may cause significant stress and social issues for the individual with CJD, as well as for their caretakers

How is Iatrogenic Creutzfeldt-Jakob Disease Treated?

There are currently no effective treatments available for any form of Iatrogenic Creutzfeldt-Jakob Disease.

• Quinacrine has shown to slow the rate of decline in some patients
• The affected individuals receive supportive care and may be given medications to control myoclonus and pain, if present
• Treatments in development for CJD include the use of antibodies against prions and several drugs with potential therapeutic efficacy

How can Iatrogenic Creutzfeldt-Jakob Disease be Prevented?

Iatrogenic Creutzfeldt-Jakob Disease is not a ‘readily’ contagious disease, but it may be transmitted to others while not exercising due care, when handling infected brain tissue. iCJD can be prevented in the following ways:

• Since prions may be transmitted to healthcare workers through accidental needle sticks or stab wounds, it is important to maintain proper safety standards and ensure that suitable disposal techniques are in place
• It is very important to sterilize by autoclave, any equipment that has had contact with brain tissue from patients with CJD

What is the Prognosis for Iatrogenic Creutzfeldt-Jakob Disease? (Outcomes/Resolutions)

• There is a highly variable incubation period in Creutzfeldt-Jakob Disease, following the transmission of prions. Symptoms have been observed in as few as 1-2 years, or after as many as 30 years, especially in the case of nvCJD
• Individuals diagnosed with CJD may live 3 months to 5 years following onset of symptoms. However with CJD, in a majority of cases, death usually results in less than 1 year
• 5-10% of the patients survive more than 2 years.  Patients with fCJD tend to live longer than those with sCJD

Additional and Relevant Useful Information for Iatrogenic Creutzfeldt-Jakob Disease:

There are voluntary organizations and support groups that provide counsel, help, and understanding to the individuals and families affected by Creutzfeldt-Jakob Disease.