Preclinical Detection of Variant CJD and BSE †MyAssignmenthelp.com

Question: Discuss about the Preclinical Detection of Variant CJD and BSE. Answer: Introduction: JCD is a neurodegenerative disorder which is caused due to the altered folding of the host prion proteins. People suffering from CJD suffer from severe dementia, slurred speech, twitching of muscles and tremors, slurred speech, loss of speech, blindness. Finally the person becomes bedridden. Most of the people end up dying due to pneumonia (Head and Ironside 2012). Human prion diseases can be hereditary, acquired or sporadic. The cause of the sporadic Creutzfeldt-Jakob disease (CJD) is not known, but hereditary cases are associated with mutations in the prion protein gene (PRNP) (Siroska et al.2012). The infections can also be transferred from infected humans to other. vCJD is a new form of prion disease and resembles Bovine spongioform encephalopathy (Lacroux et al. 2014). Kuru, vCJD, iCJD all are caused by the proteinacious infected particle formed due to the altered folding of the host prion protein PrPc to infectious PrPsc (Siroska et al.2012). The common signs and symptoms of al the prion diseases are almost same such as severe dementia, insomnia, twitching of muscles, neuronal loss, loss of physical coordination, distorted speaking, loss of speech, blindness, coma followed by death. Symptoms of Kuru involve compulsive crying or laughing (Sikorska and Liberski 2012). Kuru is a fatal nervous system disease and is highly prevalent during the 1950s and 1960 in people residing in the highlands of New Guinea. The fore people contracted this disease on eating the infected brains of the dead people as the funeral rites (Siroska et al.2012). Kuru mainly occurs as a result of cannibalism or coming in to contact with open wounds or sores of somebody with kuru. Many years later it was found that in this disease the infected brain resembles sponges with holes (Sikorska and Liberski 2012). Iatrogenic CJD is a neurodegenerative disorder that occurs due to the exposure to prion infections (Siroska et al.2012). Exposure to the prion particles may occur due to medical treatment that involves blood products or tissues from an infected individual. It can occur during the organ transplants, preparation of hormones (Sikorska and Liberski 2012). One can be contracted to this by unexpected incidents such as stab wounds by a needle that was in contact with a brain or tissue infected with CJD. Symptoms of Iatrogenic CJD are almost similar to that of sporadic CJD. It involves depression, memory lapse with a rapid progression to dementia. iCJD is very rare in comparison to kuru or variant CJD. Less than 1 percent of the cases have been found to contract acquired CJD (Siroska et al.2012). vCJD is a rare and fatal neurodegenerative disease. It belonged to the family of diseases known as the transmissible spongiform encephalopathy (Lacroux et al.2014). vCJD is differentiated from kuru and other CJD in the context that vCJd shows its onset at a much younger age than that of CJD. In vCJD the amount of the amyloid plaques is much more than that of classical CJD (Siroska et al.2012). Unlike Kuru and iCJD, vCJD is caused from the consumption of contaminated meat products from cattle having a disease called bovine Spongiform encephalopathy or ' mad cow disease'. According to findings, the infectious particle responsible for the BSE in cattles is the same as the causative agent of vCJD. Symptoms are same as that of the other classes of CJD. vCJD as first discovered in 1996, and was prevalent mainly in Great Britain along with many other European countries. The initial symptom of vCJD is different from the other forms of CJD. It occurs in typically younger patients as compared to the other forms, whereas in the other forms, the median age is about 68 years (Urwin et al.2016). The incubation period of vCJD is unknown (Siroska et al.2012). vCJD have typical unique features, having prominent clinical manifestations. The neurologic abnormalities are delayed. The duration of the illness lasts for about 6 months after which the patient dies. The presence of florid plaques is rarely found in other forms of CJD, but in vCJD it is present in large numbers (Lacroux et al.2014). The infectious agent is usually not determined in the other two forms of CJD but is readily found in the lymphoid tissues (Sikorska and Liberski 2012). Variant Creutzfeldt-Jakob disease vCJD is a rare neurodegenerative disorder caused by the infectious prior protein that was discovered in the United Kingdom in the year 1996. It is characterized by the formation of holes in the brain due to the accumulation of the amyloid plaques in the brain (Davidson et al.2014). The agent responsible for the prion diseases in cows, Bovine spongiform encephalopathy is the same agent for causing vCJD in humans (Siroska et al.2012). vCJD is exclusively caused by the prion protein designated as PrPsc without any encoding nucleic acid. PrPSc is nothing but an altered form of the normal host functional prion protein PrPc. Abnormal prion proteins are generated due to the abnormal folding of the PrPc protein (Sikorska and Liberski 2012). PrPc is protinease sensitive but PrPsc are resistant to proteases and hence deposit as amyloid plaques. The infectious prion proteins are transmissible and self propagating. More abnormal prion proteins are produced; it converts rest of the normal proteins to its abnormal isoforms rapidly (Lacroux et al.2014). It has been found that the conformational change in the PrPc is caused due to the mutation in the PRNP gene, which modifies the sequence of the amino acids. A valine or methionine polymorphism at the codon number 129 of the PRNP gene is the probable cause of the disease (Lacroux et al.2014). Normally the host protein contains alpha helical structures, but in the altered protein beta sheets are present. Biological mechanism According to Siroska et al.(2012) the time of the incubation period PrPsc is present in all the tissue fluids, especially in the spinal fluids. At first intracytoplasmic vacuoles are formed in the neurons. With the progression of the disease the vacuolization becomes more prominent and the cortical neurophil resembles a sponge (Manix et al.2015). Advanced stage progresses with neuronal loss, brain atrophy and gliosis. The purkinje cells of the brain are lost. In some diseases related to prion infection, the PrPsc protein deposits as amyloid palques. Variant CJD is normally diagnosed by neuropathology examination. At the initial stage the disease remains asymptomatic with irreversible neurodegenerative loss (Siroska et al.2012). The disease is diagnosed by autopsy, tonsil biopsy that exploits a vast tissue distribution of the infectious protein compared to other prion diseases. Biopsy is a 100% specific test for vCJD and is specific and sensitive (Paterson et al.2012). Preclinical diagnosis is normally done by the tonsil biopsy. Neuropathologic examination reveals amyloid plaques surrounded by vacuoles in the brain which are known as florid plaques. References Davidson, L.R.R., Llewelyn, C.A., Mackenzie, J.M., Hewitt, P.E. and Will, R.G., 2014. Variant CJD and blood transfusion: are there additional cases?.Vox sanguinis,107(3), pp.220-225. Hall, J.E., 2015.Guyton and Hall Textbook of Medical Physiology E-Book. Elsevier Health Sciences. Head, M.W. and Ironside, J.W., 2012. CreutzfeldtJakob disease: prion protein type, disease phenotype and agent strain.Neuropathology and applied neurobiology,38(4), pp.296-310. Lacroux, C., Comoy, E., Moudjou, M., Perret-Liaudet, A., Lugan, S., Litaise, C., Simmons, H., Jas-Duval, C., Lantier, I., Bringue, V. and Groschup, M., 2014. Preclinical detection of variant CJD and BSE prions in blood.PLoS pathogens,10(6), p.e1004202. Manix, M., Kalakoti, P., Henry, M., Thakur, J., Menger, R., Guthikonda, B. and Nanda, A., 2015. Creutzfeldt-Jakob disease: updated diagnostic criteria, treatment algorithm, and the utility of brain biopsy.Neurosurgical focus,39(5), p.E2. Paterson, R.W., Torres-Chae, C.C., Kuo, A.L., Ando, T., Nguyen, E.A., Wong, K., DeArmond, S.J., Haman, A., Garcia, P., Johnson, D.Y. and Miller, B.L., 2012. Differential diagnosis of Jakob-Creutzfeldt disease.Archives of neurology,69(12), pp.1578-1582. Sikorska, B. and Liberski, P.P., 2012. Human prion diseases: from Kuru to variant Creutzfeldt-Jakob disease. InProtein Aggregation and Fibrillogenesis in Cerebral and Systemic Amyloid Disease(pp. 457-496). Springer Netherlands. Sikorska, B., Knight, R., Ironside, J.W. and Liberski, P.P., 2012. Creutzfeldt-Jakob disease.Neurodegenerative Diseases, pp.76-90. Urwin, P.J.M., Mackenzie, J.M., Llewelyn, C.A., Will, R.G. and Hewitt, P.E., 2016. CreutzfeldtJakob disease and blood transfusion: updated results of the UK Transfusion Medicine Epidemiology Review Study.Vox sanguinis,110(4), pp.310-316.