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transmissible spongiform encephalopathy (prion disease)

Transmissible spongiform encephalopathies are a group of prion- associated diseases. Classification: 1) animal spongiform encephalopathies 2) human diseases a) kuru b) Creutzfeldt-Jakob disease (CJD) - sporadic form - familial form - new variant Creutzfeldt-Jakob disease (Mad Cow disease) - iatrogenic c) Gerstmann-Straussler-Scheinker disease d) fatal familial insomnia Epidemiology: - CJD most common human prion disease Biochemistry: - down-regulated of CHST8 (17-fold) in prion-infected cells Pathology: 1) incubation period of years to months 2) none evoke an inflammatory process 3) disease is largely restricted to the CNS 4) potentially transmitted across species Clinical manifestations: - rapid cognitive decline - myoclonus - pyramidal signs & extrapyramidal signs - visual impairment - cerebellar dysfunction, ataxia - akinetic mutism - cortical signs - neglect, aphasia, acalculia, apraxia - symptomatic progression refractory to any therapy Laboratory: - cerebrospinal fluid appears normal - transmissible spongiform encephalopathy in brain by light microscopy [9] - abnormal prion protein in brain - abnormal prion protein in tissue - abnormal prion protein in brain by electron microscopy [9] - 14-3-3 protein in CSF (disease duration < 2 years) - insufficiently sensitive or specific [2] - CSF real time quaking-induced conversion assay is the most sensitive & specific test for prion proteins in CSF (MKSAP19) [2] Special laboratory: - electroencephalogram Radiology: - MRI of brain Management: - uniformly fatal, no specific treatment - advance directives - end of life planning Comparative biology: - inhibitor of PERK halts progression of prion disease in mice, but does not reverse deficits [6]

Related

prion

Specific

animal spongiform encephalopathy Creutzfeldt-Jakob [CJ] disease fatal familial insomnia Gerstmann-Straussler-Scheinker disease Huntington disease like 1 kuru

General

encephalopathy neurodegenerative disease

Database Correlations

Kegg hsa/hsa05060

References

  1. Johnson RT & Gibbs CJ Creutzfeldt-Jakob disease and related transmissible spongiform encephalopathies. N Engl J Med. 1998 Dec 31;339(27):1994-2004. Review. PMID: 9869672
  2. Medical Knowledge Self Assessment Program (MKSAP) 15, 16, 18, 19. American College of Physicians, Philadelphia 2009, 2012, 2018, 2021.
  3. Holman RC, Belay ED, Christensen KY et al Human prion diseases in the United States. PLoS One. 2010 Jan 1;5(1):e8521 PMID: 20049325
  4. Rosenbloom MH, Atri A. The evaluation of rapidly progressive dementia. Neurologist. 2011 Mar;17(2):67-74. PMID: 21364356
  5. Ryou C. Prions and prion diseases: fundamentals and mechanistic details. J Microbiol Biotechnol. 2007 Jul;17(7):1059-70. PMID: 18051314
  6. Moreno JA et al Oral Treatment Targeting the Unfolded Protein Response Prevents Neurodegeneration and Clinical Disease in Prion- Infected Mice. PMID: 24107777 http://stm.sciencemag.org/content/5/206/206ra138
  7. Imran M, Mahmood S. An overview of human prion diseases. Virol J. 2011 Dec 24;8:559. Review. PMID: 22196171 Free PMC Article
  8. Sikorska B, Liberski PP. Human prion diseases: from Kuru to variant Creutzfeldt-Jakob disease. Subcell Biochem. 2012;65:457-96. Review. PMID: 23225013
  9. Loinc
  10. National Institute of Neurological Disorders and Stroke (NINDS) NINDS Transmissible Spongiform Encephalopathies Information Page https://www.ninds.nih.gov/Disorders/All-Disorders/Transmissible-Spongiform-Encephalopathies-Information-Page