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{{‪Creutzfeldt-Jakob disease‬}}
{{‪Creutzfeldt-Jakob disease‬}}
{{CMG}}
{{CMG}} {{AE}}, {{MMJ}}
==Overview==
The majority of cases of Creutzfeldt-Jakob disease are thought to occur sporadically from [[prions]] by an unknown route of transmission. Reports on transmission by [[human growth hormone]] products, [[grafting]], [[Electrode|surgical electrode implantation]], and consumption of infected products have been described. Once transmitted, the CJD [[prion]] promotes refolding of the native proteins into the diseased state. The number of misfolded [[protein]] molecules increases exponentially, and the process leads to a large quantity of insoluble [[prions]] in the affected cells, resulting in [[cell death]]. On gross histopathological analysis, the brain tissue appears "spongy" with areas of perforation within the brain tissue. On microscopic histopathological analysis, spongiform changes, neuronal loss, [[astrocyte]] proliferation, and deposition of [[prion]] proteins in the brain are characteristic findings.
 
==Pathophysiology==
==Pathophysiology==
The CJD prion is dangerous because it promotes refolding of native proteins into the diseased state. The number of misfolded [[protein]] molecules will increase exponentially, and the process leads to a large quantity of insoluble prions in affected cells. This mass of misfolded [[protein]]s disrupts cell function and causes cell death. Once the prion is transmitted, the defective proteins invade the brain and are produced in a self-sustaining feedback loop, causing exponential spread of the prion, death within a few months, although a few patients have been known to live as long as two years.


The defective protein can be transmitted by [[human growth hormone]] (hGH) products, [[cornea]]l grafts, dural grafts or [[electrode]] implants (acquired or [[Iatrogenesis|iatrogenic]] form: iCJD); it can be inherited (hereditary or familial form: fCJD); or it may appear for the first time in the patient (sporadic form: sCJD). In the hereditary form, a [[mutation]] occurs in the [[gene]] for PrP, [[PRNP]]. 10 to 15% of CJD cases are inherited. (CDC)
===Transmission===
* The majority of cases of Creutzfeldt-Jakob disease are thought to occur sporadically from prions by an unknown route of transmission.
* The defective protein associated with Creutzfeldt-Jakob disease can be inherited (familial form) or transmitted ([[Iatrogenesis|iatrogenic]] form) through the following:
** [[Human growth hormone]] (hGH) products
** [[Corneal grafting]]
** Dural grafts or [[electrode]] implants<ref>{{cite web|title =Questions and Answers: Creutzfeldt-Jakob Disease Infection-Control Practices|work =Infection Control Practices/CJD (Creutzfeldt-Jakob Disease, Classic)|publisher =Centers for Disease Control and Prevention|date =[[January 4]][[2007]]|url = http://www.cdc.gov/ncidod/dvrd/cjd/qa_cjd_infection_control.htm#sterilization|accessdate = 2007-06-09}}</ref><ref>{{cite web|title =WHO Infection Control Guidelines for Transmissible Spongiform Encephalopathies|Publisher =World Health Organization: Communicable Disease Surveillance and Control|date =[[26 March]] [[1999]]|url =http://www.who.int/csr/resources/publications/bse/WHO_CDS_CSR_APH_2000_3/en/|accessdate = 2007-06-09}}</ref><ref>{{cite journal |author=McDonnell G, Burke P. | title=The challenge of prion decontamination | journal=Clin Infect Dis | year=2003 | volume=36 | pages=1152&ndash;4 }}</ref>
** Use of [[Human growth hormone|HGH]] drawn from the [[pituitary gland]]s of [[cadaver]]s<ref name="titleHGH Linked to Brain Eater">{{cite web |url=http://www.wired.com/news/medtech/0,1286,62998,00.html |title=HGH Linked to Brain Eater |accessdate=2007-12-02 |format= |work=}}</ref>
** Consumption of infected animals
** Cannibalism
*The incubation period of prions is unknonw, but it is speculated that the disease may develop many years (up to 30-50 years) after initial exposure. However, these reports remain controversial.<ref>{{cite web|url=http://www.nature.com/nature/journal/v407/n6800/full/407025a0.html|title=Diamond, J.M. (2000)"Archaeology: Talk of cannibalism" ''Nature'' 407, 25-26<!--INSERT TITLE-->}}</ref>
=== Pathogenesis ===
* The CJD prion promotes refolding of the native [[proteins]] into the diseased state.
* The number of misfolded [[protein]] molecules increases exponentially, and the process leads to a large quantity of insoluble [[prions]] in the affected cells.
* This mass of misfolded [[protein]]s disrupts cell function and causes cell death.
* Once the prion is transmitted, the defective proteins invade the brain and are produced in a self-sustaining [[feedback loop]], causing exponential spread of the prion.
[[cadaver|<nowiki/>]]
===Mutations===
* [[Mutations]] in the gene responsible for the production of prion protein can cause misfolding of the alpha helical regions into beta pleated sheets.
* This change in the conformation disables the ability of the protein to undergo digestion.
* Individuals may also acquire CJD genetically through the [[mutation]] occurring [[PRNP|''PRNP'']] gene.
 
== Pathology ==


The disease has also been shown to result from usage of [[Human growth hormone|HGH]] drawn from the [[pituitary gland]]s of [[cadaver]]s who died from Creutzfeldt-Jakob Disease,<ref name="titleHGH Linked to Brain Eater">{{cite web |url=http://www.wired.com/news/medtech/0,1286,62998,00.html |title=HGH Linked to Brain Eater |accessdate=2007-12-02 |format= |work=}}</ref> though the known incidence of this cause is (as of April 2004) quite small. The risk of infection through cadaveric HGH usage in the US only ceased when the medication was withdrawn in 1985.
===Gross Pathology===
* On gross histopathological analysis, the brain tissue appears "spongy" with areas of perforation within the brain tissue.


It is thought that humans can contract the disease by consuming material from animals infected with the bovine form of the disease. The only suspected cases to arise thus far have been vCJD, although there are fears; based on animal studies &mdash; that consuming beef or beef products containing [[prion]]particles can also cause the development of classic CJD.
=== Microscopic Pathology ===
* CJD is associated with the build-up of abnormal [[prion]] [[proteins]].


[[Cannibalism]] has also been implicated as a transmission mechanism for abnormal [[prion]]s, causing the disease known as [[Kuru (disease)|kuru]], found primarily among women and children of the Fore tribe in Papua New Guinea. While the men of the tribe ate the body of the deceased and were not affected, the women and children ate the brain and contracted the disease from infected brain tissue.
* The following microscopic findings may be present in CJD:
** Presence of florid plaques, defined as round, packed deposits of abnormal prion protein (in variant CJD)
** Spongiform changes
** Neuronal loss
** [[Astrocyte]] proliferation
** Deposition of prion protein throughout the brain<ref name="Sellars-2002">{{Cite journal  | last1 = Sellars | first1 = RJ. | last2 = Collie | first2 = DA. | last3 = Will | first3 = RJ. | title = Progress in understanding Creutzfeldt-Jakob disease. | journal = AJNR Am J Neuroradiol | volume = 23 | issue = 7 | pages = 1070-2 | month = Aug | year = 2002 | doi =  | PMID = 12169459 }}</ref>


[[Prion]]s, the [[infectious agent]] of CJD, may not be inactivated by means of routine [[surgical instrument]] [[Autoclave|sterilization]] procedures. The [[World Health Organization]] and the US [[Centers for Disease Control and Prevention]] recommend that heat and chemical decontamination be used in combination to process instruments that come in contact with high-infectivity tissues. No cases of [[iatrogenic]] transmission of CJD have been reported subsequent to the adoption of current sterilization procedures, or since 1976.<ref>{{cite web|title =Questions and Answers: Creutzfeldt-Jakob Disease Infection-Control Practices|work =Infection Control Practices/CJD (Creutzfeldt-Jakob Disease, Classic)|publisher =Centers for Disease Control and Prevention|date =[[January 4]][[2007]]|url = http://www.cdc.gov/ncidod/dvrd/cjd/qa_cjd_infection_control.htm#sterilization|accessdate = 2007-06-09}}</ref><ref>{{cite web|title =WHO Infection Control Guidelines for Transmissible Spongiform Encephalopathies|Publisher =World Health Organization: Communicable Disease Surveillance and Control|date =[[26 March]] [[1999]]|url =http://www.who.int/csr/resources/publications/bse/WHO_CDS_CSR_APH_2000_3/en/|accessdate = 2007-06-09}}</ref><ref>{{cite journal |author=McDonnell G, Burke P. | title=The challenge of prion decontamination | journal=Clin Infect Dis | year=2003 | volume=36 | pages=1152&ndash;4 }}</ref>[[Copper]]-[[hydrogen peroxide]] has been suggested as an alternative to the current recommendation of [[sodium hydroxide]] or [[sodium hypochlorite]].<ref>{{cite journal | author=Solassol J, Pastore M, Crozet C, ''et al.'' | title=A novel copper-hydrogen peroxide formulation for prion decontamination | journal=J Infect Dis | year=2006 | volume=194 | pages=865&ndash;869 }}</ref> [[Thermal depolymerization]] also destroys [[prion]]s in infected organic and inorganic matter, since the process dissolves protein at the molecular level.
[[Image:Spongiform changes in CJD.jpg|left|220px|Spongiform changes in brain in CJD]]
===Mutations===
<br style="clear:left">
The CJD prion is dangerous because it promotes [[Protein folding|refolding]] of native proteins into the diseased state. The number of misfolded protein molecules will [[exponential growth|increase exponentially]], and the process leads to a large quantity of insoluble prions in affected [[cell (biology)|cells]]. This mass of misfolded proteins disrupts cell function and causes cell death. Mutations in the gene for the prion protein can cause a misfolding of the dominantly alpha helical regions into beta pleated sheets. This change in conformation disables the ability of the protein to undergo digestion. Once the prion is transmitted, the defective proteins invade the brain and are produced in a self-sustaining [[feedback loop]], causing exponential spread of the prion, death within a few months, although a few patients have been known to live as long as two years.
===Microscopic Pathology===
The symptoms of CJD are caused by the progressive [[cell death|death]] of the brain's [[neuron|nerve cells]], which is associated with the build-up of abnormal [[prion]] [[proteins]]. When brain tissue from a CJD patient is examined under a [[microscope]], many tiny holes can be seen where whole areas of nerve cells have died. The word 'spongiform' in '[[transmissible spongiform encephalopathies]]' refers to the 'spongy' appearance of the [[brain]] tissue.


==References==
==References==
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[[Category:Infectious disease]]
[[Category:Neurology]]
[[Category:Neurology]]
[[Category:Disease]]
[[Category:Disease]]
[[Category:Transmissible spongiform encephalopathies]]
[[Category:Transmissible spongiform encephalopathies]]
[[Category:Needs overview]]
[[Category:Needs overview]]

Latest revision as of 19:44, 7 July 2020

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: , Mohamadmostafa Jahansouz M.D.[2]

Overview

The majority of cases of Creutzfeldt-Jakob disease are thought to occur sporadically from prions by an unknown route of transmission. Reports on transmission by human growth hormone products, grafting, surgical electrode implantation, and consumption of infected products have been described. Once transmitted, the CJD prion promotes refolding of the native proteins into the diseased state. The number of misfolded protein molecules increases exponentially, and the process leads to a large quantity of insoluble prions in the affected cells, resulting in cell death. On gross histopathological analysis, the brain tissue appears "spongy" with areas of perforation within the brain tissue. On microscopic histopathological analysis, spongiform changes, neuronal loss, astrocyte proliferation, and deposition of prion proteins in the brain are characteristic findings.

Pathophysiology

Transmission

  • The majority of cases of Creutzfeldt-Jakob disease are thought to occur sporadically from prions by an unknown route of transmission.
  • The defective protein associated with Creutzfeldt-Jakob disease can be inherited (familial form) or transmitted (iatrogenic form) through the following:
  • The incubation period of prions is unknonw, but it is speculated that the disease may develop many years (up to 30-50 years) after initial exposure. However, these reports remain controversial.[5]

Pathogenesis

  • The CJD prion promotes refolding of the native proteins into the diseased state.
  • The number of misfolded protein molecules increases exponentially, and the process leads to a large quantity of insoluble prions in the affected cells.
  • This mass of misfolded proteins disrupts cell function and causes cell death.
  • Once the prion is transmitted, the defective proteins invade the brain and are produced in a self-sustaining feedback loop, causing exponential spread of the prion.

Mutations

  • Mutations in the gene responsible for the production of prion protein can cause misfolding of the alpha helical regions into beta pleated sheets.
  • This change in the conformation disables the ability of the protein to undergo digestion.
  • Individuals may also acquire CJD genetically through the mutation occurring PRNP gene.

Pathology

Gross Pathology

  • On gross histopathological analysis, the brain tissue appears "spongy" with areas of perforation within the brain tissue.

Microscopic Pathology

  • The following microscopic findings may be present in CJD:
    • Presence of florid plaques, defined as round, packed deposits of abnormal prion protein (in variant CJD)
    • Spongiform changes
    • Neuronal loss
    • Astrocyte proliferation
    • Deposition of prion protein throughout the brain[6]
Spongiform changes in brain in CJD
Spongiform changes in brain in CJD


References

  1. ↑ "Questions and Answers: Creutzfeldt-Jakob Disease Infection-Control Practices". Infection Control Practices/CJD (Creutzfeldt-Jakob Disease, Classic). Centers for Disease Control and Prevention. January 42007. Retrieved 2007-06-09. Check date values in: |date= (help)
  2. ↑ "WHO Infection Control Guidelines for Transmissible Spongiform Encephalopathies". 26 March 1999. Retrieved 2007-06-09. Unknown parameter |Publisher= ignored (|publisher= suggested) (help); Check date values in: |date= (help)
  3. ↑ McDonnell G, Burke P. (2003). "The challenge of prion decontamination". Clin Infect Dis. 36: 1152&ndash, 4.
  4. ↑ "HGH Linked to Brain Eater". Retrieved 2007-12-02.
  5. ↑ "Diamond, J.M. (2000)"Archaeology: Talk of cannibalism" Nature 407, 25-26".
  6. ↑ Sellars, RJ.; Collie, DA.; Will, RJ. (2002). "Progress in understanding Creutzfeldt-Jakob disease". AJNR Am J Neuroradiol. 23 (7): 1070–2. PMID 12169459. Unknown parameter |month= ignored (help)


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