WHAT IS CREUTZFELDT-JAKOB DISEASE? SYMPTOMS, CAUSES, MYTHS, AND MORE

Medically Reviewed by Dr. Rae Osborn, Ph.D., 1 July, 2024

Creutzfeldt-Jakob disease (CJD) is a terminal, degenerative brain disorder that affects an average of one in every million people worldwide. It falls under the category of prion diseases, which are caused by abnormal proteins called prions that damage brain cells. CJD advances rapidly and can lead to significant disability and even be fatal within a year of being diagnosed.

This article uncovers the causes, symptoms, diagnosis, and management of CJD.

What is CJD?

CJD is a rare and fatal prion disorder that affects the central nervous system when abnormal prion proteins accumulate in the brain and destroy brain cells.

Normal prion proteins reside on the surface of several types of cells, with higher concentrations seen on neurons and glial cells. Research shows that prion proteins may play a role in many cellular functions, helping to regulate neuronal growth, survival, nerve insulation (myelination), and nervous transmission.^[1]

Diseased prion proteins, called "prions", are misfolded prion proteins that can rapidly self-replicate. They can attach to normal prion proteins and other proteins, transforming them into diseased prions. Diseased prions make it difficult for the body to break down proteins, disrupting brain protein production, energy metabolism, and neuronal function. They also injure glial cells in the brain, causing brain tissue to develop holes and giving it a sponge-like appearance, hence the name "spongiform encephalopathy".

The accumulation of infectious prions gives rise to the classic dementia and other neurological symptoms of prion disease.^[2]

The condition progresses much faster compared to other neurodegenerative disorders, like Alzheimer's Disease, and can lead to severe disability. Up to 90% with sporadic CJD succumb to mortality within a year of onset. However, the exact life expectancy can vary depending on the type of CJD and the individual's overall health.

CJD affects one person per million per year worldwide. It is the most common prion disease, with an average onset age of 62.

Types and Causes: How is Creutzfeldt Jakob Disease transmitted?

There are three prominent types of CJD: sporadic, hereditary, and acquired.^[3]

Sporadic CJD: This is the most common form of CJD, accounting for about 85% of cases. It occurs spontaneously without any known cause.

Hereditary CJD: This type is also known as Familial Creutzfeldt–Jakob disease (fCJD)^[4] and is heritable from a parent carrying a CJD gene mutation. It accounts for about 10-15% of cases. There are more than 50 gene mutations associated with CJD. Gene mutations may also make one more susceptible to acquiring variant CJD.

Acquired CJD: This type is rare, caused by exposure to tissue infected with prions. Stringent safety measures are ensured to prevent their transmission.

There are two primary forms of acquired CJD:

• Iatrogenic CJD transmits through medical procedures such as corneal transplants, neurosurgery, or contaminated surgical instruments. In some cases, human growth hormone extracted from the brains of deceased patients with the condition transmits prion disease.
• Variant CJD (vCJD) infects individuals who consume contaminated meat products. vCJD is linked to eating^[5] beef from cows with bovine spongiform encephalopathy (BSE), commonly called "mad cow disease". The occurrence is rare, as the cow must consume animal feed containing infected cow matter in the first year of life.^[6] While all forms of CJD share common symptoms, vCJD may also present with additional features such as psychiatric symptoms, sensory abnormalities, and a longer duration of illness.

Risk Factors

The exact cause of sporadic CJD is unknown, and there are no known risk factors for this type of CJD.

However, there are some risk factors associated with hereditary and acquired CJD.

• A family history can predispose one to hereditary CJD.
• Specific gene mutations may make one more susceptible to acquired CJD.
• Those exposed to contaminated proteins are at a higher risk, yet the odds are very low due to stringent protection measures.

Early Signs and Symptoms

The early signs and symptoms of CJD can vary depending on the type of CJD and the individual. Those with sporadic CJD tend to experience symptoms between the ages of 45 and 75, while those with hereditary CJD acquire symptoms between the ages of 20 and 40.

However, some common symptoms include:^[7]

• Rapidly progressive dementia: This is the first and most common symptom of CJD. Those affected progressively become more confused and disorientated, experiencing a decline in memory, thinking, and behavior.
• Psychiatric symptoms: In vCJD, anxiety, depression, or other psychiatric symptoms are the first to occur, with dementia following at a later stage.
• Difficulty with movement and coordination: This manifestation can include muscle stiffness, jerky movements, and difficulty walking. Those affected may startle easily.
• Vision problems: CJD can induce blurred vision, double vision, and visual disturbances.

Other symptoms can include vertigo, headaches, fatigue, and sleep disorders. Those with CJD are vulnerable to pneumonia as the condition affects the muscles used for breathing.

In Variant CJD, the disease course may take up to 14 months^[8], whereas it can take up to a year in other cases.

Complications

CJD is a rapidly progressive disease that can lead to severe disability and death within a year of onset. As the disease progresses, individuals may experience a range of complications, including:

• Loss of motor function: Difficulty walking, speaking, and performing daily activities are frequent complications in those with CJD.
• Infections: Individuals with CJD are more susceptible to diseases and pneumonia as the immune system weakens.
• Respiratory failure: This can occur in the later stages of the disease as the muscles responsible for breathing become affected.
• Coma: In the final stages of the disease, individuals may enter a coma.

How is Creutzfeldt Jakob Disease Diagnosed?

Diagnosing CJD can be challenging as the symptoms can be similar to other neurological disorders. There is no specific test that definitively detects and diagnoses CJD. A doctor will ask about the individual's medical history and perform a physical examination to look for signs of CJD. A combination of tests is necessary to make a diagnosis.

These tests may include:^[9]

1. Electroencephalogram (EEG): EEG measures electrical activity in the brain, helping to detect abnormal brain wave patterns characteristic of CJD.
2. Magnetic Resonance Imaging (MRI): MRI scans provide detailed images of the brain, enabling the identification of structural changes associated with CJD, such as brain atrophy.
3. Cerebrospinal Fluid Analysis: Analysis of cerebrospinal fluid obtained through a lumbar puncture, also known as a spinal tap, helps detect specific proteins associated with CJD, such as 14-3-3 and tau proteins.
4. Genetic Testing: Genetic tests can pinpoint mutations in the PRNP gene and others associated with hereditary forms of CJD, providing valuable diagnostic information.
5. Brain Biopsy: In some instances, a small sample of brain tissue may be taken and examined under a microscope to detect abnormal prion proteins, aiding in diagnosing CJD. This is the only way to definitively confirm diagnosis.^[10]

Creutzfeldt-Jakob Disease Treatment

Unfortunately, there is no cure for CJD. Treatment aims to manage symptoms and provide supportive care to improve the individual's quality of life until the disease runs its course.

Treatment options may include:

• Medications: These may manage symptoms such as anxiety, depression, and muscle stiffness.
• Physical therapy: Targeted exercises can assist with improving mobility and muscle strength.
• Speech therapy: Practising aspects of speech with a qualified therapist can help individuals with speech and language problems.
• Nutritional support: Individuals may have difficulty eating as the disease progresses and require a feeding tube to ensure proper nutrition.
• Ventilation: If suffering severe pneumonia or respiratory failure, an affected person may need ventilator support to breathe optimally.
• Palliative care: This focuses on providing comfort and support to individuals with a terminal illness.

Individuals with a family history of CJD might wish to undergo genetic testing to determine if they are carriers of hereditary CJD. Genetic screening can help the affected and their families to plan ahead.

Research Advances in CJD Treatment

Research efforts are investigating the deeper causes of prion diseases like CJD and attempting to develop treatment options that can extend the lifespan of patients. These include:

• Gene therapies that target the PRNP gene, causing it to function optimally.^[11]
• Monoclonal Antibody therapy slows the rapid development of the disease, leading to diminished concentrations of prions in the brain. One minimal clinical trial performed on three patients has shown promising results in this regard.^[12]

Prevention

Without a known cause, there are no specific prevention methods for sporadic CJD. 

In general, one can avoid contaminated transplantation of donor brain tissue or nerves by ensuring one attends a clinic with high hygiene standards that properly sterilizes surgical equipment. Healthcare professionals can follow these measures and opt for synthetic human growth hormone when required.

It is also necessary to follow food safety guidelines and avoid consuming meat from sick mammals. Most food regulatory boards are aware of prion diseases and prevent the sale of high-risk animal meat.^[13] Cook meat properly to destroy any potential prions or other infectious agents.

Myths and misconceptions about "mad cow disease" and CJD

There are many myths and misconceptions surrounding CJD and its link to "mad cow disease." 

Some common myths include:

Myth: CJD is a contagious disease, transmissible through casual contact.

Fact: CJD is not infectious and is not transmissible through casual contact or airborne particles.

Myth: All types of CJD are caused by eating contaminated meat.

Fact: Only one type of CJD, variant CJD (vCJD), has been linked to consuming contaminated meat. The prevalence of vCJD is less than 1%, making it exceptionally rare. The other types of CJD are not caused by eating contaminated meat.

Takeaways

Creutzfeldt-Jakob disease is a rare, terminal brain disorder that affects about one in every one million people worldwide. Abnormal prion proteins cause the disease when they damage brain cells. The condition leads to severe disability and eventual death within an average of a year from onset. While there is no cure for CJD, treatments can assist with managing symptoms and providing supportive care. Individuals can reduce their risk of acquiring CJD by leading a healthy lifestyle, following food safety guidelines, and avoiding exposure to infected tissue.