Creutzfeldt-Jakob Disease
Creutzfeldt-Jakob Disease (CJD) is a rare, degenerative brain disorder that leads to rapid mental deterioration and loss of physical control. It is caused by abnormal infectious proteins called prions. Symptoms include memory loss, personality changes, and impaired coordination. CJD has no cure and is ultimately fatal, with most patients succumbing to the disease within a year of onset.
6 Key excerpts on "Creutzfeldt-Jakob Disease"
eBook - ePubNeurology
A Visual Approach
- Sunjay Parmar(Author)
- 2017(Publication Date)
- CRC Press(Publisher)
...Creutzfeldt–Jakob Disease Definition A rare, transmissible prion neurodegenerative illness Aetiology Pathophysiology: PrP exists in two forms: native, α-helical state (PrP c) that is present in healthy neurons, which can be converted (either sporadic, inherited or transmitted) into abnormal, protease- resistant β-pleated sheet state (PrP sc). This non- degradable, misfolded PrP sc prion propagates refolding of native PrP c protein into the diseased PrP sc form, disrupting neuronal function and even- tually causing cell death (spongiform changes) and astrogliosis (a glial response to neuronal loss and tissue damage) Variant CJD types: Sporadic CJD: 85%; is the most common. No risk factors Hereditary CJD: <15%; autosomal dominant Iatrogenic CJD: prion transmission in con- taminated tissue, e.g. organ transplants (corneal), growth hormone from cadaveric donors and blood transfusion nvCJD: prion ingestion from infected cattle (bovine spongiform encephalopathy aka ‘mad cow disease’); the fi case appeared in 1996; earlier onset → ↑psychiatric symptoms and longer duration Kuru : among Fore people of Papua New Guinea there was a funeral custom of ritualistic eating of the deceased person’s brain. The practice has now ceased Epidemiology Rare; 1/1,000,000 Peak incidence (of sporadic): 50–70 y/o Presentation Neurological features: rapidly progressive dementia, ataxia and myoclonic jerks with pyramidal signs Initial presentation: sporadic CJD: neurological fea- tures; nvCJD: psychiatric/behavioural changes Time course: sporadic CJD: rapid, over weeks to months; nvCJD: over years Investigations Best initial test: EEG ; may show characteristic periodic sharp waves LP: 14-3-3 protein is detected in the CSF...
eBook - ePub- Ronald G. Labbé, Santos García, Ronald G. Labbé, Santos García(Authors)
- 2013(Publication Date)
- Wiley-Blackwell(Publisher)
...Two prion disease characteristics have contributed to iatrogenic CJD: the presence of CJD-infectivity in preclinical patients and the resistance of these disease agents to inactivation. Iatrogenic CJD has been documented primarily by exposure to central nervous system tissue from infected individuals, specifically dura mater, corneal transplants, and cadaveric pituitary growth hormone treatment. Kuru is a prion disease that affected the Fore cultural group of Papua New Guinea. The disease was perpetuated by ritualistic cannibalistic practices with, at its height, approximately 1% of the population affected. The incidence of Kuru declined dramatically upon the cessation of cannibalism in the late 1950s; however, due to the long incubation periods that characterize all TSEs, a few cases were still observed in the 1980s. It can now be considered a historical prion disease. Variant CJD (vCJD) was first identified in 1995. As will be described below, vCJD can be distinguished from CJD based upon clinical, biochemical, and rodent transmission studies. Whereas sporadic CJD affects individuals in their 50s or 60s, vCJD affects primarily teenagers and young adults. Biological and biochemical studies have tightly linked vCJD with BSE. It is assumed that consumption of beef products is the source of the infection. Combined with the BSE exposure risk, there is a strong genetic component to this disease. vCJD patients typically have a specific prion protein allele, met/met, at position 129. Uncertainties over the length of the incubation period, route of infection, impact of genetics and number of individuals exposed to contaminated bovine products have resulted in very disparate estimates of the future course of this prion disease. 24.2 Nature of illness caused Prion diseases are inevitably fatal, inducing a progressive neurological disease after a long incubation period...
- Amy E. Wenzel(Author)
- 2017(Publication Date)
- SAGE Publications, Inc(Publisher)
...In particular, this entry reviews the diagnostic criteria for mild and major NCD due to prion disease, as stipulated by the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). History and Terminology The most common human prion disease is sporadic Creutzfeldt-Jakob Disease, also referred to as Jakob-Creutzfeldt disease. According to Geschwind, human prion disease is more appropriately referred to as Jakob-Creutzfeldt disease than as Creutzfeldt-Jakob Disease, based on historical context. German neurologist Alfons Jakob described the first prion disease cases in the early 1920s, and the case of the seminal patient described by Hans Creutzfeld actually did not fit the modern criteria for prion disease. Despite this history, the term Creutzfeldt-Jakob Disease is in common usage in the published literature, including the DSM-5. For this reason, the term Creutzfeldt-Jakob Disease is used in this entry and is abbreviated as CJD. Epidemiology In the developed world, the incidence of human prion disease is 1 to 1.5 cases per million per year. Approximately 400 cases are diagnosed in the U.S. population of 330 million per year, yielding an incidence of 1.2 per million per year in the United States. Regarding the frequency of the three forms of human prion disease: sporadic CJD constitutes 80% to 95%, genetic cases constitute 10% to 15%, and acquired cases make up less than 1%. The sporadic form of human prion disease consists of sporadic CJD. Genetic human prion disease include genetic CJD (also called familial CJD), Gerstmann-Sträussler-Scheinker syndrome, and fatal familial insomnia. The acquired forms of human prion disease consist of kuru, variant CJD, and iatrogenic CJD...
eBook - ePub- Douglas D. Richman, Richard J. Whitley, Frederick G. Hayden, Douglas D. Richman, Richard J. Whitley, Frederick G. Hayden(Authors)
- 2016(Publication Date)
- ASM Press(Publisher)
...Experimental injection of the kuru-affected brain into macaques was subsequently shown to cause a spongiform encephalopathy and led to the realization that kuru was spreading among the Fore as an infectious disease from endocannibalistic practices (9). For these findings, Gadjusek was awarded the Nobel Prize in Medicine or Physiology in 1976 for “discoveries concerning new mechanisms for the origin and dissemination of infectious diseases.” The pioneering discovery of kuru as an infectious disease set the stage for the recognition of other rapidly progressive neurodegenerative diseases as part of a family of prion diseases, including Creutzfeldt-Jakob Disease (CJD) in humans, bovine spongiform encephalopathy (BSE) or “mad cow” disease in cattle, scrapie in sheep and goats, and chronic wasting disease (CWD) of deer and elk. The history of the nomenclature for CJD is complicated. Alfons Jakob published four papers in 1921 and 1923 describing five uncommon cases of rapidly progressive dementia, stating that his cases were quite similar to a previously published case reported by his professor, Hans Creutzfeldt, in 1920. This disease was referred to as Jakob’s or Jakob–Creutzfeldt disease for many decades until a prominent researcher in the field, Clarence J. Gibbs, began using the term Creutzfeldt–Jakob disease, as its acronym, CJD, was closer to his own initials (12). Interestingly, the cases Jakob described were in fact very different than Creutzfeldt’s case, in that only two of Jakob’s five cases had pathological evidence of the disease that we now consider to be prion disease, whereas Creutzfeldt’s case did not have prion disease (13). Thus, the name for human clinical prion disease should be Jakob’s disease or possibly Jakob–Creutzfeldt disease...
eBook - ePubA Matter of Life and Death
Inside the Hidden World of the Pathologist
- Sue Armstrong(Author)
- 2010(Publication Date)
- Canongate Books(Publisher)
...It’s like a domino effect: once you have the first conversion from normal to abnormal, then you get a sort of chain reaction building up as more and more normal protein is converted. The abnormal protein is toxic and damages the brain and eventually causes death. This is biologically heretical because all other types of transmissible diseases rely on genetic material in order to spread, and there seems to be no need for this here. Anyway, I moved from Leeds to Edinburgh in 1990 and it so happened that that was the year the National CJD Surveillance Project was starting. My colleague, Bob Will, was the physician responsible for the clinical part of the project. We had managed to get funding, and the biggest challenge at that stage was finding space in the hospital where we could work: everyone thought it was genuinely interesting, but they didn’t want it anywhere near them because of the perceived risk of ‘these prions floating down the corridors and jumping down your throat’, or whatever! After lots of negotiation with the hospital, we were offered accommodation – with very few windows! We started with a small team, just five of us, and at that time it was sold to me as ‘a very interesting but very rare’ disease that probably wouldn’t entail a great deal of extra work. There had been previous surveillance of CJD, which Bob had been involved in at Oxford when he was a trainee. They’d been particularly interested then in looking at the risk factors for CJD, because the disease, in the mid-1980s, had just emerged in recipients of human growth hormone, and the question was whether any other kind of treatment might predispose patients to the disease. Aren’t there different forms of CJD: ‘sporadic’, where it happens out of the blue, as it were; and ‘familial’, where it’s inherited? That’s right. There’s also the so-called ‘iatrogenic CJD’ – that is, transmitted accidentally by medical procedures – and the human growth hormone recipients are in that category...
- Barbara Detrick, John L. Schmitz, Robert G. Hamilton, Barbara Detrick, Robert G. Hamilton, John L. Schmitz(Authors)
- 2016(Publication Date)
- ASM Press(Publisher)
...The peak age of onset of sCJD is ~68 years, with a wide range of 12 to 98 years (162, 163). However, sCJD patients that are < 30 years old are rarely presented (164). The median duration of disease is from 4 to 6 months, with death occurring within 1 year in 90% of cases and another 5% dying in the second year of disease (165). Jakob initially described CJD in 1921 (166); ironically, the case reported by Creutzfeldt a year earlier is probably unrelated to the disease that carries his name. An issue that has not been fully resolved is how sCJD arises. This has been suggested to be the result of either a random somatic mutation in the PRNP gene or more commonly a spontaneous conformational conversion of PrP C to PrP Sc (167, 168). Aging is recognized to contribute to protein quality control failure in the CNS, and this may be a factor in sCJD being an age-related disease. In fact, a recent therapeutic avenue for prion disease, which has shown some promise in mouse models, is ameliorating an aberrant unfolded protein response (169, 170). An argument in favor of the spontaneous-conversion hypothesis is the uniform worldwide occurrence of sCJD with no convincing geographic clustering, with the exception being areas with an increased incidence of genetic forms of CJD (i.e., gCJD). However, some case-control studies suggest that at least a portion of “sporadic” CJD can in fact be related to surgical procedures much earlier in life (hence in fact representing acquired CJD, i.e., iCJD). In a comparison of 241 patients with sCJD from the Australian CJD registry to 784 controls, there was an association with past surgical treatments that increased with the number to a maximum of three procedures producing an odds ratio of 2.13 (171). In another case-control study, using Danish and Swedish registries of 167 CJD patients compared to 3,059 controls, a similar association was found with past surgical procedures (172)...
