Creutzfeldt-Jakob Disease: Symptoms, Causes & Risk Factors

What Is Creutzfeldt-Jakob Disease?

Creutzfeldt-Jakob disease (CJD) is a rare, degenerative, and invariably fatal brain disorder that progresses rapidly, affecting memory, behaviour, and physical coordination. It is caused by misfolded proteins known as prions, which induce normal brain proteins to misfold, leading to widespread neuronal damage and spongiform changes.

While the disease is uncommon, affecting about 1 to 2 people per million each year, usually between the ages of 50 and 80, genetic forms can appear earlier in life. Understanding the signs, risk factors, and causes can help you recognise the condition early and seek timely support.

Types of CJD

Sporadic CJD (sCJD)

Sporadic CJD is the most common form, accounting for about 85% of all cases. It occurs spontaneously without any known cause or risk factors. Symptoms of sCJD worsen rapidly over a few months, and most patients die within a year of diagnosis.

Familial CJD (fCJD)

Familial CJD is an inherited form of the disease caused by genetic mutations in the prion protein gene (PRNP). This type of CJD tends to progress more slowly than sporadic CJD, often over two years. However, it is still a devastating and fatal condition.

Variant CJD (vCJD)

Variant CJD is a rare form linked to eating beef products contaminated with the prion that causes bovine spongiform encephalopathy (BSE), also known as “mad cow disease". People with vCJD are typically younger than those with other forms of CJD. While the disease may progress slightly more slowly, it remains universally fatal.

Iatrogenic CJD

Iatrogenic CJD occurs through accidental transmission of prion-contaminated tissues or surgical instruments during medical procedures, such as transplants or hormone treatments. The incubation period and progression of iatrogenic CJD are highly variable and unpredictable.

Early Symptoms of Creutzfeldt-Jakob Disease

The initial CJD symptoms can be subtle and may include:

• Personality changes
• Memory loss
• Impaired thinking
• Blurred or double vision
• Difficulty walking and balance problems
• Slurred speech
• Numbness or tingling sensations
• Dizziness
• Changes in mood or behaviour
• Sleep disturbances or insomnia

Progressive Symptoms of CJD

• Rapidly progressive dementia
• Muscle stiffness and jerking movements (myoclonus)
• Loss of coordination and inability to move
• Difficulty swallowing
• Unclear speech
• Visual hallucinations
• Blindness or severe vision impairment
• Inability to speak or communicate

Causes of Creutzfeldt-Jakob Disease

The underlying cause of Creutzfeldt-Jakob disease is the accumulation of abnormally folded prion proteins in the brain. These misfolded proteins trigger a cascade of events that lead to the destruction of brain cells. Prions can form spontaneously, be inherited through genetic mutations, or be acquired from external sources.

The main causes of Creutzfeldt-Jakob disease include:

• Spontaneous misfolding of the prion protein (in sporadic CJD)
• Genetic mutations in the PRNP gene (in familial CJD)
• Ingestion of prion-contaminated beef (in variant CJD)
• Exposure to prion-infected tissues during medical procedures (in iatrogenic CJD)

How CJD Spreads (Transmission)

1. Sporadic CJD is not contagious and arises spontaneously, without any identifiable exposure to prion sources.
2. Familial CJD is inherited through genetic mutations and tends to run in families.
3. Variant CJD is primarily acquired by consuming beef products from cattle infected with BSE (mad cow disease). According to the WHO, in rare cases, vCJD can be transmitted through contaminated blood products.
4. Iatrogenic CJD can be transmitted during medical procedures that involve exposure to prion-contaminated surgical instruments, transplanted tissues, or hormone extracts derived from human sources.

Risk Factors for CJD

Several factors can increase the risk of developing Creutzfeldt-Jakob disease:

• Age: Most cases of CJD occur in people between the ages of 50 and 80.
• Family history: Having a family member with familial CJD increases the risk of inheriting the genetic mutation.
• Exposure to human-derived growth hormone or dura mater grafts: These treatments, if derived from prion-infected donors, can transmit CJD.
• Consuming beef from BSE-infected cattle: This is a risk factor for variant CJD.
• Undergoing certain medical procedures: Procedures involving prion-contaminated instruments or tissues can rarely transmit CJD.
• Having specific mutations in the PRNP gene: These genetic changes are associated with familial forms of CJD.

Diagnosis of Creutzfeldt-Jakob Disease

Diagnosing CJD can be challenging, as the early symptoms may resemble those of other dementia-causing conditions. However, the rapid progression of symptoms often raises suspicion of CJD. The diagnostic process typically involves several steps:

1. Medical History and Physical Examination

Doctors assess the onset and progression of symptoms, as well as any neurological signs, to differentiate CJD from other forms of dementia.

2. Imaging Tests

• MRI scans often show hyperintense signals in the caudate nucleus, putamen, or cortical ribboning — findings highly suggestive of CJD.
• CT scans, while less sensitive, may help rule out other potential causes of symptoms.

3. Cerebrospinal Fluid (CSF) Tests

• CSF analysis for proteins such as 14-3-3, tau, or neuron-specific enolase (NSE) can support diagnosis, though these are not definitive.
• The RT-QuIC (Real-Time Quaking-Induced Conversion) assay is the current gold-standard laboratory test for detecting misfolded prion protein in CSF or nasal brushings for detecting misfolded prion proteins in CSF.

4. Electroencephalogram (EEG)

An EEG measures the electrical activity of the brain. In CJD, the EEG often shows a characteristic pattern known as periodic sharp wave complexes, which can help in the diagnostic process.

5. Genetic Testing

For individuals with a family history of CJD or presenting with symptoms at a younger age, genetic testing can identify mutations in the PRNP gene associated with familial forms of the disease.

Treatment and Management of CJD

Currently, there is no cure or effective disease-modifying treatment for Creutzfeldt-Jakob disease. Treatment approaches may include:

• Pain management with appropriate medications
• Anti-seizure drugs to control muscle jerks and spasms
• Medications to manage psychiatric symptoms, such as depression or agitation
• Nutritional support to ensure adequate intake of fluids and nutrients
• Physical therapy to help maintain mobility and prevent complications related to immobility.
• Occupational therapy to assist with daily activities and adapt the living environment.
• Psychological support for patients and their families to cope with the emotional impact of the disease.

Complications of CJD

• Severe dementia and loss of independence
• Difficulty swallowing, which can lead to aspiration pneumonia
• Infections due to immobility and weakened immune function
• Heart or lung failure
• Falls and related injuries

Prognosis for CJD Patients

Unfortunately, the prognosis for individuals with CJD is poor, as the disease is invariably fatal. Most patients with sporadic CJD die within 6–12 months of symptom onset; familial forms may progress slightly more slowly. Those with Patients with variant CJD often survive 12–24 months, with rare cases exceeding 3 years. The most common causes of death in CJD patients are pneumonia, heart or lung failure, or secondary infections.

Prevention of Creutzfeldt-Jakob Disease

While sporadic CJD cannot be prevented, measures can be taken to reduce the risk of acquired forms of the disease:

• Strict decontamination protocols for surgical instruments (using sodium hypochlorite or autoclaving at 134°C for ≥18 min) and safe disposal of contaminated materials.
• Screening and restricting the use of human-derived tissues in medical procedures.
• Surveillance and control of BSE in cattle populations to prevent the spread of variant CJD.
• Excluding individuals with a history of possible prion exposure (e.g., dura mater graft, human pituitary hormone treatment, or residence in BSE-affected regions) from blood or organ donation.
• Maintaining a balanced and varied diet and being cautious about consuming beef products from countries with a history of BSE.

When to Seek Medical Help

If you or your loved one experiences any of the following symptoms, it is essential to seek medical attention promptly:

• Sudden or unexplained dementia-like symptoms
• Rapidly progressive memory loss or cognitive decline
• Significant changes in personality, mood, or behaviour
• Difficulty with coordination or movement
• Problems with speech or swallowing
• Sudden visual disturbances or vision loss

Conclusion

Creutzfeldt-Jakob disease is a rare and devastating neurodegenerative condition. If you or your loved one is experiencing symptoms that are related to CJD or other neurological conditions, it is essential to seek prompt medical advice from a qualified healthcare provider.

At Metropolis Healthcare, we bring together 220 state-of-the-art diagnostic laboratories and over 4,600 service centres across India to make advanced testing more accessible. Our wide range of neurological and genetic testing services is designed to support your doctor in accurately diagnosing complex brain conditions, like CJD, helping you take proactive steps to protect your cognitive health and quality of life.

FAQs

1. What are the first signs of Creutzfeldt-Jakob disease?

The initial signs of CJD can be subtle and may include personality changes, memory loss, impaired thinking, vision problems, and difficulties with movement or coordination.

2. How quickly does CJD progress?

CJD is known for its rapid progression compared to other neurodegenerative diseases. CJD symptoms tend to worsen rapidly over a period of weeks to months.

3. Is CJD contagious?

CJD is not contagious. It does not spread through casual contact, such as hugging, kissing, or sharing meals with an affected person.

4. Can CJD be treated or cured?

Currently, there is no cure or effective treatment that can slow or stop the progression of CJD. Creutzfeldt-Jakob disease treatment focuses on providing supportive care, managing symptoms, and ensuring the patient's comfort.

5. What is the difference between CJD and Alzheimer's disease?

CJD typically progresses much more rapidly, with most patients dying within a year of diagnosis. In contrast, Alzheimer's disease advances more slowly. Additionally, CJD is caused by prion proteins, while Alzheimer's disease is associated with the accumulation of beta-amyloid plaques and tau protein tangles in the brain.

References

• https://cdn.who.int/media/docs/default-source/biologicals/transmissible-spongiform-encephalopathies/tsepublishedreport.pdf?sfvrsn=c73b7b7f_3&download=true
• https://my.clevelandclinic.org/health/diseases/6001-creutzfeldt-jakob-disease
• https://cjdfoundation.org/types-of-prion-disease/
• https://www.nhs.uk/conditions/creutzfeldt-jakob-disease-cjd/
• https://www.mountsinai.org/health-library/diseases-conditions/creutzfeldt-jakob-disease