Infectious Diseases, Pathogen of the Month

Creutzfeldt Jakob Disease (CJD): Uncurable Brain Infection Caused by Prions

Author Chandana Balasubramanian , 02-Dec-2022

Telling someone they are “one in a million” should be a compliment. But for many, this phrase is accompanied by a devastating diagnosis of Creutzfeldt-Jakob Disease (CJD). CJD leads to dementia and has a 100% fatality rate; death usually occurs within a year from when symptoms first appear [1]. 

 

Creutzfeldt-Jakob Disease is a rapidly progressive disease of the central nervous system caused by abnormal proteins called prions. They are a unique class of pathogens that cause normal proteins to fold abnormally, affecting their ability to function [1,2].  

 

Like other prion diseases, CJD can lead to a global public health crisis because it is transmissible and highly fatal. Additionally, studies on mice show that prions can be aerosolized, making them a potential biosafety threat [3]. As a result, stringent surveillance is needed to prevent the spread of the disease.  

 

The disease may be rare, but its rapidly degenerative nature is devastating for infected individuals and their loved ones. Hopefully, research can lead to better ways to diagnose, treat, and even prevent prion diseases [4]. 

History

 

CJD was first described in 1920 by Hans Creutzfeldt, a German neurologist and neuropathologist [2]. The condition was described as a “peculiar focal illness of the central nervous system” discovered in a 23-year-old woman.

In 1921, Alfons Jakob, a German neurologist, published two articles on the anatomical findings of the disease. In 1923, he published another article describing a few cases that turned out to be fatal due to rapidly progressive dementia [5]. At the time, Dr. Jakob felt that his patient’s symptoms were similar to Dr. Creutzfeldt’s reported case. As a result, this condition was later named Creutzfeldt-Jakob disease (CJD) in honor of the two doctors by Clearance J. Gibbs, an American microbiologist [2]. Even though Dr. Creutzfeldt eventually did not agree that his cases matched those of Dr. Jakob’s, his name continues to be associated with the disease [2, 12] 

In 1982, Stanley Prusiner, an American neurologist and biochemist, isolated prions and found that they were also present in healthy people and animals. Prusiner learned that prions were folded differently from regular proteins but could ‘infect’ the normal proteins, causing neurodegenerative diseases in humans. 

For this landmark discovery, Prusiner was awarded the Nobel Prize in Physiology or Medicine in 1997, but he faced intense opposition. At the time, many in the medical community refused to accept the concept of infectious proteins causing degenerative diseases of the central nervous system. However, in time, Dr. Prusiner was proved right, and research on prions continued. Not one to rest on his laurels, he and his team established the role of prions in the spread of mad cow disease in 2004 [2,7]. 

Research on prions led to more understanding of CJD and many other neurodegenerative disorders. Although there has been progress, CJD is 100% fatal, and there is much left to uncover about prion diseases.

Epidemiology

 

CJD, although rare, occurs worldwide. According to the Centers for Disease Control and Prevention (CDC), around 1 to 1.5 cases per million are reported worldwide each year. In the US alone, about 350 cases are reported per year. The elderly are at a higher risk of developing CJD [1]. According to data gathered from 1979 to 2020 in the United States, the incidence of CJD in people over 50 was 3.6 cases per million [1].

The average age of people who die due to CJD is 68 years, and the average duration of illness is between four and five months [2].

There are different types of CJD – sporadic, variant, familial, and acquired.

Sporadic Creutzfeldt-Jakob Disease (sCJD)

 

Sporadic CJD or sCJD is one of the most common types of Creutzfeldt-Jakob Disease. It accounts for almost 85% of cases reported. sCJD has been found worldwide, including in North America, Central America, Europe, Asia, Africa, Australia, and more. The global incidence is about 1-2 million people a year. But many more may be undiagnosed based on the level of awareness and surveillance in different countries. 

This condition is called ‘sporadic’ because people with sCJD develop the disease spontaneously or sporadically. Most of those affected were between 55 to 75 years of age, and almost 90% died within one year from when symptoms appeared [2,4,9]. 

The cause of sCJD remains unknown, although there are several hypotheses regarding its origins. 

Familial CJD or Inherited CJD

 

Familial CJD is a rare genetic disease accounting for 10% to 15% of CJD cases reported in the United States. Infected individuals inherit the prion protein gene from one of their parents. For familial CJD, even if one of the parents has a mutated gene, there is a 50% probability that their children might develop the disease. But, symptoms usually begin when people are in their fifties or older [2,4, 9]. 

Acquired CJD or Iatrogenic CJD

 

It is also referred to as iatrogenic CJD (caused by medical or surgical treatment) and accounts for less than 1% of cases. It is transmitted from one person to another through shared medical equipment used in surgical procedures. 

In the past, a common source was growth hormone treatment. The therapy involved using human growth hormones from deceased individuals. If some of them had been infected with CJD, there was a risk of spreading the disease. Fortunately, this method is no longer in use, which greatly reduces the risk of acquiring CJD [9].  

Iatrogenic CJD mainly occurs in young adults whose mean age is less than 29 years [2,9].

Variant Creutzfeldt-Jakob Disease (vCJD)

 

First detected in 1996, vCJD is caused by the same types of prions responsible for Bovine Spongiform Encephalopathy (BSE) or mad cow disease in cows. After investigation, the UK government determined that infected beef was the issue. Prions spread from cattle that had been fed a mixture of meat and bones that had parts of brains and spinal cords in them. These prions end up in humans when eaten as burgers or other processed meats. 

Thanks to international surveillance programs and public health control measures, vCJD cases have declined [4]. Using a meat-and-bone mix to feed cattle is now illegal, lowering the risk of spreading diseases like vCJD.  

Most human vCJD cases occurred in the UK and France. In the UK, cases were high in 2000, with 28 related deaths [2,9,10].

How is it spread?

 

CJD is not a communicable disease. It cannot be transmitted through air or physical contact with an infected person [11]. It is also not caused by a virus, as previously assumed. 

Most CJD cases are developed spontaneously, and the cause is unknown. Some vascular conditions like strokes or hypertensive encephalopathy can also lead to rapidly progressive neurological disorders in humans [2]. Other known ways of transmission include:

  • Contact with contaminated human growth hormone, dura mater and corneal grafts, or neurosurgical equipment during a surgical procedure.
  • Mutation in the prion protein gene
  • Consuming beef infected with prion disease [2,6,11].

Biology of the disease

 

Creutzfeldt-Jakob disease is a part of a group of diseases known as TSEs – transmissible spongiform encephalopathies. The ‘spongiform’ term comes from sponge-like holes found in the brain tissue of people with an abnormal, infectious version of the prion protein. 

All prions are not harmful. In fact, our body makes prion proteins, and they are found on the surface of many of our cells. But as the structure of proteins is critical to how they function, problems arise when proteins become misshapen. These misfolded prions act like bad apples. They convert normal prion proteins into abnormal ones by changing their structure, eventually leading to neurological disorders. 

Abnormal prion proteins are called ‘scrapie prion proteins’ (PrPSc). The term ‘scrapie’ comes from observing infected sheep. These animals would behave in strange ways, including scraping themselves against trees and other surfaces, even when their wool tore off [2,5].

Symptoms

 

The symptoms of CJD are similar to commonly-known neurological disorders that cause dementia, like Alzheimer’s and Huntington’s disease. But, what distinguishes CJD from these illnesses is that it is rapidly progressive, which means the patient’s physical abilities deteriorate very quickly from when symptoms appear [11]. 

CJD symptoms onset begin with:

  • Vertigo
  • Headache
  • Fatigue
  • Sleep disorders

Other secondary symptoms experienced during the initial stages include:

  • Memory problems
  • Behavioral changes – agitation, irritability, depression, apathy, and mood swings
  • Sensory changes –  incoordination and loss of vision.

During advanced stages, people experience:

  • Confusion
  • Disorientation
  • Severe memory problems
  • Quick and involuntary muscle jerks
  • Muscle stiffness
  • Muscle twitching
  • Slow movement of limbs (less common)
  • Muscle contractions (less common) 
  • Rigidity (less common)
  • Blindness (less common) 

 

Over time, the infected person may gradually lose mobility, speech, and enter into a coma [2]. CJD is especially frightening because the incubation period can last years and even decades.

Diagnosis

 

The following screening tests are performed to diagnose CJD:

  • Complete Blood Count (CBC)
  • Magnesium level
  • Liver function tests
  • Rapid plasma reagin
  • Erythrocyte sedimentation rate
  • Antinuclear antibody 
  • C-reactive protein
  • Thyroid function tests
  • Vitamin B-12 
  • HIV
  • Lyme disease titer 
  • Autoimmune antibodies
  • Urinalysis
  • Cerebrospinal (CSF) studies – including glucose, oligoclonal bands, cell count & differential
  • VDRL 
  • MRI brain (including FLAIR & DWI) – with and without contrast
  • EEG [2].

 

While these tests may help healthcare providers eliminate other neurological disorders, the only way to truly confirm a CJD diagnosis is through a brain biopsy during post-mortem analysis [13]. 

Treatment

 

There is no cure for CJD, but treatment involves supportive care to address the symptoms [2]. Opiate drugs can help relieve pain. Other drugs like clonazepam and sodium valproate may help patients deal with their quick and involuntary muscle jerks. As the disease progresses, intravenous fluids and artificial feeding may be used [11].  

In most cases, patients will need admission to intensive care units (ICUs). Unfortunately, most of them may die within a few weeks or months. Extensive research and clinical trials are needed to find an effective treatment for this fatal condition [2]. 

Prevention

 

It is hard to protect against CJD as it is impossible to destroy prions through standard sterilization techniques like boiling, cooking, and washing [11]. Prevention is even more difficult because over 99% of cases are either sporadic or familial [2,9]. 

But, the spread of acquired or variant CJDs can be minimized to a certain degree by: 

  • Covering cuts and abrasions with waterproof dressings.
  • Wearing surgical gloves while handling a patient’s tissues and fluids and dressing their wounds.
  • Avoiding direct contact with surgical instruments contaminated with blood and tissue.
  • Using face protection – including face masks and goggles while performing a surgical procedure – to avoid the risk of contaminated blood or cerebrospinal fluid being splashed on the face.
  • Using disposable bedclothes after the surgical procedure. If regular clothes are used, they must be soaked in undiluted chlorine bleach for over an hour before being washed and reused.
  • Similarly, other surgical instruments that got in contact with blood or other body fluids can be soaked in undiluted chlorine bleach for an hour or more. They can then be sterilized under pressure for over an hour at 132 – 134 degrees celsius.  
  • Receiving blood, tissue, or organ transplants from people who have or are suspected of having CJD has to be avoided [8,11].
  • People visiting places with indigenous cases of BSE or Mad Cow Disease should consider avoiding beef or beef products [8]. 

 

Prion diseases include CJD, kuru, and Gerstmann-Straussler-Scheinker Syndrome. Although we understand much more about prions than we did a century ago, there is a vast chasm of knowledge to cross before we can find a cure for these deadly diseases. As with all research efforts, adequate funding is critical. As awareness about CJD and other prion diseases grows, let us hope for life-saving diagnostics, therapies, or ways to prevent them. 

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References

[1] CDC, “Occurrence and transmission,” Centers for Disease Control and Prevention, 23-Feb-2022. [Online]. Available: https://www.cdc.gov/prions/cjd/occurrence-transmission.html?CDC_AA_refVal=https%3A%2F%2Fwww.cdc.gov%2Fprions%2Fcjd%2Foccurance-transmisison.html

[2] K. K. Sitammagari and W. Masood, “Creutzfeldt Jakob Disease,” in StatPearls [Internet], StatPearls Publishing, 2022. Available: https://www.ncbi.nlm.nih.gov/books/NBK507860/ 

[3] A. Aguzzi and C. Zhu, “Five questions on prion diseases,” PLoS Pathog., vol. 8, no. 5, p. e1002651, 2012.

[4] N. Watson et al., “The importance of ongoing international surveillance for Creutzfeldt-Jakob disease,” Nat. Rev. Neurol., vol. 17, no. 6, pp. 362–379, 2021.

[5] M. da Mota Gomes, “Creutzfeldt-Jakob disease: one hundred years of participation in the design of the transmissible spongiform encephalopathies,” Rev Bras Neurol, vol. 56, no. 3, p. 25-28, 2020.

[6] F. Katscher, “It’s Jakob’s disease, not Creutzfeldt’s,” Nature, vol. 393, no. 6680, p. 11, 1998.

[7] CDC, “Infection control,” Centers for Disease Control and Prevention, 12-Nov-2021. [Online]. Available: https://www.cdc.gov/prions/cjd/infection-control.html 

[8] NHS, “Creutzfeldt-Jakob Disease – Causes,” National Health Service. [Online]. Available: https://www.nhs.uk/conditions/creutzfeldt-jakob-disease-cjd/causes/ 

[9] A. Clifton, “Prions: Understanding Proteins Role in Neurodegenerative Diseases,” Stellar. [Online]. Available: http://www.okcu.edu/uploads/arts-and-sciences/english/docs/stellar2016.pdf#page=58 

[10] NHS. “Creutzfeldt-Jakob Disease – Prevention,” National Health Service. [Online]. Available: https://www.nhs.uk/conditions/creutzfeldt-jakob-disease-cjd/prevention/

[11] CDC, “Relationship with BSE (mad cow disease),” Centers for Disease Control and Prevention, 13-Oct-2021. [Online]. Available: https://www.cdc.gov/prions/vcjd/relationship-with-bse.html 

[12] NINDS, “Creutzfeldt-Jakob Disease Fact Sheet,” National Institute of Neurological Disorders and Stroke. [Online]. Available: https://www.ninds.nih.gov/creutzfeldt-jakob-disease-fact-sheet 

[13] “Creutzfeldt-Jakob disease – diagnosis,” nhs.uk. [Online]. Available: https://www.nhs.uk/conditions/creutzfeldt-jakob-disease-cjd/diagnosis/. [Accessed: 28-Nov-2022].

Author
Chandana Balasubramanian

Chandana Balasubramanian is an experienced healthcare executive who writes on the intersection of healthcare and technology. She is the President of Global Insight Advisory Network, and has a Masters degree in Biomedical Engineering from the University of Wisconsin-Madison, USA.

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