Diseases and Disorders

Creutzfeldt-Jakob Disease: An Overview

Vaishnavi Peyyety, Shamika Yemula


Introduction

Creutzfeldt-Jakob disease (CJD), or spongiform encephalopathy, is a neurodegenerative disorder that affects the brain similar to dementia and Alzheimer’s, but proceeds more rapidly. This condition ultimately leads to death. It is extremely rare, affecting one in a million worldwide and there are several different types of CJD, all of them being caused by prions.
 

Prion Diseases

A prion is an abnormal protein that can disrupt the biological processes of the body and cause infection [1]. The discovery of prions was very strange, as all other infectious agents have nucleic acids in order to reproduce once they have infected cells, but prions do not [2]. Later, it was observed that the protein could be coded properly in the nucleus and their conformation can spontaneously change in the cytoplasm [2]. The change in the protein shape forces it to bond with other proteins that it is not likely to bond with and causes a domino effect which results in the biological processes of the cell to be hindered [2].                                                                                        

 

Types of CJD

CJD has four main ways of developing in an individual.

Sporadic CJD

Sporadic CJD affects around 85% of all individuals that have CJD, making it the most common type [4]. There is no concrete way to prevent it. In cases of Sporadic CJD, proteins fold abnormally in the cytoplasm of the cell after being coded in the nucleus [4]. Those affected by this type of CJD, tend to live up to a year after being diagnosed [4]. 

Genetic CJD

Genetic CJD accounts in around 5% to 15% of all people with this degenerative disorder [4]. As per fertilization, individuals get one copy of the PrP gene from the maternal parent and one from the paternal parent. CJD exhibits autosomal dominant behavior [5]. This means that only one parent needs to pass down a dominant form of the allele in order  to have the offspring exhibit the phenotype for CJD at some point in their life. Sometimes people are unaware that they have a familial history of CJD, because in the past it was diagnosed as dementia or another degenerative neurological disease [5].

Iatrogenic CJD

Iatrogenic CJD is caused by prions being introduced into a person’s tissue [4]. This type of CJD can develop in an individual who comes in contact with surgical instruments even though they may be sterilized [4]. The exact procedure when sterilizing equipment  depends on the instruments, but it tends to be through high-heat or low-temperature techniques.

However, if these sterilization methods are implemented, why may there be prions on the surgical equipment? These sterilization techniques are designed to inactivate microorganisms by affecting their nucleic acids – but prions do not have nucleic acids, so they are unaffected by the common means of chemical and physical sterilization [6]. Instead, prions can be removed from equipment by soaking the equipment for long periods of time in a solution like sodium hydroxide [6]. These conditions may be too much for the tools to handle, so it is impractical to do this every time [6]. Additionally, it can be transmitted through blood donated by a person with CJD [4]. In the past, people have gotten CJD from hormones that were harvested from the pituitary gland of someone who had CJD, and so in order to prevent that, hospitals are required to use a synthetic human growth hormone instead [4].

Variant CJD

Variant CJD (vCJD) and CJD have several differences [7].   In comparison to classic CJD, Variant CJD (vCJD) appears to have a larger quantity of florid plaques and a longer life expectancy [8].  However, classic CJD tends to occur at an older age in contrast to vCJD [8].

 

Diagnosis and Important Characteristics

There are many different tests that can be performed to diagnose CJD. In major types of CJD, an individual's brain’s electrical pattern displays a specific abnormal sequence, which can be detected by an EEG [10]. Secondly, a test known as the Real Time-Quaking Induced Conversion (RT-QuiC) “is based on an ultrasensitive detection of the pathogenic prion protein in the cerebrospinal fluid of individuals affected by CJD and other forms of human prion diseases” [10].  RT-Quic is different from other markers of Creutzfeldt-Jakob as “it directly detects a disease-defining pathogenic prion protein as opposed to a surrogate marker of rapid neurodegeneration” [10].  The major way to confirm a diagnosis of CJD, however, is by utilizing a brain biopsy that involves a neurosurgeon removing a small amount of tissue from an individual's brain that is later studied by a neuropathologist [10].

The key features of CJD are similar to other ongoing neurological disorders such as Alzheimer’s and Huntington’s but occur more rapidly [11]. The main symptom of CJD is rapidly progressive dementia [12]. Individuals affected by this disease “experience problems with muscle coordination, personality changes (including impaired memory, judgment, and thinking), and impaired vision” [10].  Some may even experience insomnia, depression, or ‘unusual sensations’[10]. In addition, myoclonus or involuntary muscle jerks may develop and in rare cases, individuals may even go blind [10]. As the disease progresses, patients are unable to speak, move, and eventually enter a coma [10]. 

 

Possible Treatments and Research

Antibodies, which are proteins produced by the immune system and bond to foreign materials, are potential treatment options as they can bind to the prions and prevent them from infecting more cells. The difficulty in utilizing antibodies is that scientists would have to make antibodies that are able to bind to these specific proteins [14][15]. Furthermore, gene silencing may be a promising treatment that involves inhibiting the ability of a gene to express its phenotype [14]. Nevertheless, there are difficulties for both gene silencing and antibody treatment because researchers would have to figure out how to get past the blood-brain barrier [14].

Institutes such as the NIH, National Institute of Allergy and Infectious Diseases and the National Institute on Aging, are conducting research on CJD [10]. In particular, “researchers are examining and characterizing the prions associated with CJD and other human and animal prion diseases” and how this condition affects the brain [10]. Results from these studies may help identify medicines that can treat prion diseases. Individuals affected by CJD may aid in research by donating “autopsy tissue, blood, and cerebrospinal fluid” [10]. 

 

Case Study

A 66-year old woman-with no familial history of CJD underwent tests to further evaluate her dementia that had been diagnosed five months prior [16]. Initially, the patient experienced memory loss, anorexia, and unplanned weight loss [16]. As time progressed, her symptoms worsened and her husband reported that she was having issues with short-term memory, emotional changes, sight, and every-day functional abilities [16]. During her physical evaluation, doctors observed that she did not have issues with sensations and coordinations. Her reflexes were regular, she did not have Babinski reflexes, and her blood work was normal [16]. However, she repeated phrases even after the stimulus that had prompted it, ceased. As a result, this did not allow her to complete the MMSE and more difficult tasks [16].

The physical exam of the patient alone could not be used to determine if the patient had CJD because it showed that her cognitive abilities had decreased sharply which is consistent with people who have CJD patients and other neurological conditions [16]. The brain scans showed restricted diffusion, indicating that there were dead brain cells [16]. This is consistent with CJD since prions kill neurons [16]. When images of the patient’s brain were taken, there were several areas of restricted diffusion and an EEG showed no periodic discharges [16]. The lack of period discharges in the EEG is also a sign of CJD [16].

Though the brain images and scans indicated that the patient has CJD, similar results (rapid dementia, visual issues, Cerebellar ataxia, etc.) are exhibited by patients affected by other diseases, which makes CJD difficult to diagnose [16]. A definite diagnosis of CJD can be achieved by finding prion proteins in the brain, which was performed on the patient [16].

After being diagnosed for CJD, the patient opted for an experimental oxygen treatment and passed away seven months after the onset of symptoms [16].

 

Correlation Between CJD and BSE

Scientists have discovered a correlation between bovine spongiform encephalopathy or BSE and the variant form of CJD or vCJD [17]. BSE is a progressive, deadly neurological disorder similar to CJD that affects cows [17]. In the years of 1984 to 1986, beef was contaminated by the BSE agent, which resulted in a spike in the vCDJ in the years of 1994 to 1996 [17]. This indicated that the two are linked because the incubation period of vCDJ matches up with the contamination of the meat [17]. This outbreak took place primarily in Britain [17].

              

Conclusion

In summary, Creutzfeldt-Jakob Disease, a neurodegenerative disorder, is caused by prions. There are four main types: Sporadic CJD, Genetic CJD, Iatrogenic CJD, and Variant CJD. This condition can be diagnosed using the results of an EEG, Real Time-Quaking Induced Conversion or, brain biopsy. Antibodies are a potential treatment option; however, much more research needs to be conducted before a more effective treatment can be identified. Lastly, scientists have found a correlation between BSE and vCJD as the incubation period of vCJD coincides with that of the beef that was contaminated with BSE. This discovery can aid researchers in finding out more about this condition and potential treatments for the future. 


References


  1. (09/10/2019). Centers for Disease Control and Prevention. www.cdc.gov/prions/index.html. Retrieved: 20/07/2020.

  2. (1/21/2012). https://www.ucsfhealth.org/conditions/creutzfeldt-jakob-disease#:~:text=Creutzfeldt%2DJakob%20disease%20(CJD),CJD%20die%20within%20a%20year.  Retrieved: 21/07/2020.

  3. (04/10/2018). Mayo Clinic. www.mayoclinic.org/diseases-conditions/creutzfeldt-jakob-disease/symptoms-causes/syc-20371226. Retrieved: 20/07/2020.

  4. (04/10/2018). Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/creutzfeldt-jakob-disease/diagnosis-treatment/drc-20371230. Retrieved: 20/07/2020.

  5. Abby. Creutzfeldt-Jakob Disease Foundation. cjdfoundation.org/genetic-1. Retrieved: 29/7/2020.

  6. Weinstein, Robert et al. Oxford Academic. https://academic.oup.com/cid/article/32/9/1348/291736. Retrieved: 29/07/2020.

  7. (3/12/2018). Centers for Disease Control and Prevention. www.cdc.gov/prions/vcjd/clinical-pathologic-characteristics.html. Retrieved: 21/07/2020.

  8. The Creutzfeldt-Jakob Disease Foundation. Creutzfeldt-Jakob Disease and other Prion Diseases, https://cjdfoundation.org/files/pdf/Booklet%20-%20CJD%20and%20Other%20Prion%20Diseases.pdf.  Retrieved: 31/07/2020.

  9. (18/07/2015). CJD Support Network. https://www.cjdsupport.net/what-is-cjd/types-symptoms-of-cjd. Retrieved: 21/07/2020.

  10. National Institute of Neurological Disorders and Stroke https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-Sheets/Creutzfeldt-Jakob-Disease-Fact-Sheet. Retrieved: 20/07/2020.

  11. (04/10/2018). Mayo Clinic. www.mayoclinic.org/diseases-conditions/creutzfeldt-jakob-disease/symptoms-causes/syc-20371226. Retrieved: 25/07/2020.

  12. (9/10/2018).  Centers for Disease Control and Prevention. www.cdc.gov/prions/cjd/index.html. Retrieved: 24/07/2020.

  13. Zanusso, Gianluigi. Nature Reviews Neurology. www.nature.com/articles/nrneurol.2016.65. Retrieved: 30/07/2020.

  14. (04/02/2014). National Institute of Neurological Disorders and Stroke. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4008459.  Retrieved: 30/07/2020.

  15. Proceedings of the National Academy of Sciences. https://www.pnas.org/content/103/10/3875. Retrieved: 20/07/2020.

  16. Kohima, Gotaro et al. (01/04/2013). US National Library of Medicine National Institutes of Health. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3689509/. Retrieved: 31/07/2020.

  17. (29/09/1997). Science News. https://www.sciencemag.org/news/1997/09/bse-and-vcjd-same-disease#:~:text=But%20vCJD%20tends%20to%20strike,infectious%20protein%20called%20a%20prion. Retrieved: 31/07/2020.

  18. (26/07/2017). European Center for Disease Prevention and Control. https://www.ecdc.europa.eu/en/vcjd/facts. Retrieved: 31/07/2020.

Vaishnavi Peyyety

Vaishnavi Peyyety


A highschool senior living in the US!

Shamika Yemula

Shamika Yemula


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