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Variant Creutzfeldt-Jakob disease

Henry G Brown, MD, PhD
John M Lee, MD, PhD
Section Editor
Michael J Aminoff, MD, DSc
Deputy Editor
Janet L Wilterdink, MD


Prion diseases are neurodegenerative diseases that have long incubation periods and progress inexorably once clinical symptoms appear. Five human prion diseases are currently recognized: kuru, Creutzfeldt-Jakob disease (CJD), variant Creutzfeldt-Jakob disease (vCJD), Gerstmann-Sträussler-Scheinker syndrome (GSS), and fatal familial insomnia (FFI).

These human prion diseases share certain common neuropathologic features including neuronal loss, proliferation of glial cells, absence of an inflammatory response, and the presence of small vacuoles within the neuropil, which produces a spongiform appearance.

Variant CJD (vCJD) may be distinguished from cases of typical sporadic Creutzfeldt-Jakob disease (sCJD) by the following features:

A considerably younger age at the onset of symptoms

Less rapid progression of illness

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Literature review current through: Oct 2017. | This topic last updated: Jun 16, 2017.
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  1. Will RG, Ironside JW, Zeidler M, et al. A new variant of Creutzfeldt-Jakob disease in the UK. Lancet 1996; 347:921.
  2. Collinge J, Rossor M. A new variant of prion disease. Lancet 1996; 347:916.
  3. Britton TC, al-Sarraj S, Shaw C, et al. Sporadic Creutzfeldt-Jakob disease in a 16-year-old in the UK. Lancet 1995; 346:1155.
  4. Chazot G, Broussolle E, Lapras Cl, et al. New variant of Creutzfeldt-Jakob disease in a 26-year-old French man. Lancet 1996; 347:1181.
  5. National Creutzfeldt-Jakob Disease Surveillance Unit. Edinburgh, Scotland http://www.cjd.ed.ac.uk/documents/worldfigs.pdf (Accessed on June 28, 2013).
  6. La Bella V, Collinge J, Pocchiari M, Piccoli F. Variant Creutzfeldt-Jakob disease in an Italian woman. Lancet 2002; 360:997.
  7. Turner ML, Ludlam CA. An update on the assessment and management of the risk of transmission of variant Creutzfeldt-Jakob disease by blood and plasma products. Br J Haematol 2009; 144:14.
  8. Gill ON, Spencer Y, Richard-Loendt A, et al. Prevalent abnormal prion protein in human appendixes after bovine spongiform encephalopathy epizootic: large scale survey. BMJ 2013; 347:f5675.
  9. Brandel JP, Heath CA, Head MW, et al. Variant Creutzfeldt-Jakob disease in France and the United Kingdom: Evidence for the same agent strain. Ann Neurol 2009; 65:249.
  10. Hilton DA, Ghani AC, Conyers L, et al. Accumulation of prion protein in tonsil and appendix: review of tissue samples. BMJ 2002; 325:633.
  11. Hilton DA, Ghani AC, Conyers L, et al. Prevalence of lymphoreticular prion protein accumulation in UK tissue samples. J Pathol 2004; 203:733.
  12. Ironside JW, Hilton DA, Ghani A, et al. Retrospective study of prion-protein accumulation in tonsil and appendix tissues. Lancet 2000; 355:1693.
  13. Frosh A, Smith LC, Jackson CJ, et al. Analysis of 2000 consecutive UK tonsillectomy specimens for disease-related prion protein. Lancet 2004; 364:1260.
  14. Clewley JP, Kelly CM, Andrews N, et al. Prevalence of disease related prion protein in anonymous tonsil specimens in Britain: cross sectional opportunistic survey. BMJ 2009; 338:b1442.
  15. Collinge J. Variant Creutzfeldt-Jakob disease. Lancet 1999; 354:317.
  16. Colchester AC, Colchester NT. The origin of bovine spongiform encephalopathy: the human prion disease hypothesis. Lancet 2005; 366:856.
  17. Johnson CJ, Phillips KE, Schramm PT, et al. Prions adhere to soil minerals and remain infectious. PLoS Pathog 2006; 2:e32.
  18. Bencsik A, Baron T. Bovine spongiform encephalopathy agent in a prion protein (PrP)ARR/ARR genotype sheep after peripheral challenge: complete immunohistochemical analysis of disease-associated PrP and transmission studies to ovine-transgenic mice. J Infect Dis 2007; 195:989.
  19. Ward HJ, Everington D, Cousens SN, et al. Risk factors for variant Creutzfeldt-Jakob disease: a case-control study. Ann Neurol 2006; 59:111.
  20. Centers for Disease Control and Prevention (CDC). Bovine spongiform encephalopathy in a dairy cow--Washington state, 2003. MMWR Morb Mortal Wkly Rep 2004; 52:1280.
  21. The United States Department of Agriculture Animal and Plant Health Inspection Service www.aphis.usda.gov/animal_health/animal_diseases/bse/downloads/BSE_Summary_Report.pdf (Accessed on August 01, 2013).
  22. Llewelyn CA, Hewitt PE, Knight RS, et al. Possible transmission of variant Creutzfeldt-Jakob disease by blood transfusion. Lancet 2004; 363:417.
  23. Peden AH, Head MW, Ritchie DL, et al. Preclinical vCJD after blood transfusion in a PRNP codon 129 heterozygous patient. Lancet 2004; 364:527.
  24. Wilson K, Ricketts MN. Transfusion transmission of vCJD: a crisis avoided? Lancet 2004; 364:477.
  25. Wroe SJ, Pal S, Siddique D, et al. Clinical presentation and pre-mortem diagnosis of variant Creutzfeldt-Jakob disease associated with blood transfusion: a case report. Lancet 2006; 368:2061.
  26. Editorial team. Fourth case of transfusion-associated vCJD infection in the United Kingdom. Euro Surveill 2007; 12:E070118.4.
  27. Chohan G, Llewelyn C, Mackenzie J, et al. Variant Creutzfeldt-Jakob disease in a transfusion recipient: coincidence or cause? Transfusion 2010; 50:1003.
  28. Bishop MT, Hart P, Aitchison L, et al. Predicting susceptibility and incubation time of human-to-human transmission of vCJD. Lancet Neurol 2006; 5:393.
  29. Bishop MT, Diack AB, Ritchie DL, et al. Prion infectivity in the spleen of a PRNP heterozygous individual with subclinical variant Creutzfeldt-Jakob disease. Brain 2013; 136:1139.
  30. Collinge J, Whitfield J, McKintosh E, et al. Kuru in the 21st century--an acquired human prion disease with very long incubation periods. Lancet 2006; 367:2068.
  31. Jackson GS, Burk-Rafel J, Edgeworth JA, et al. A highly specific blood test for vCJD. Blood 2014; 123:452.
  32. Mead S, Wadsworth JD, Porter MC, et al. Variant Creutzfeldt-Jakob disease with extremely low lymphoreticular deposition of prion protein. JAMA Neurol 2014; 71:340.
  33. Jackson GS, Burk-Rafel J, Edgeworth JA, et al. Population screening for variant Creutzfeldt-Jakob disease using a novel blood test: diagnostic accuracy and feasibility study. JAMA Neurol 2014; 71:421.
  34. Bird SM. Attributable testing for abnormal prion protein, database linkage, and blood-borne vCJD risks. Lancet 2004; 364:1362.
  35. Williamson LM. Leucocyte depletion of the blood supply - how will patients benefit? Br J Haematol 2000; 110:256.
  36. Ludlam CA, Turner ML. Managing the risk of transmission of variant Creutzfeldt Jakob disease by blood products. Br J Haematol 2006; 132:13.
  37. Gregori L, Gurgel PV, Lathrop JT, et al. Reduction in infectivity of endogenous transmissible spongiform encephalopathies present in blood by adsorption to selective affinity resins. Lancet 2006; 368:2226.
  38. Wiltshire M, Thomas S, Scott J, et al. Prion reduction of red blood cells: impact on component quality. Transfusion 2010; 50:970.
  39. Sowemimo-Coker SO, Demczyk CA, Andrade F, Baker CA. Evaluation of removal of prion infectivity from red blood cells with prion reduction filters using a new rapid and highly sensitive cell culture-based infectivity assay. Transfusion 2010; 50:980.
  40. Guntz P, Walter C, Schosseler P, et al. Feasibility study of a screening assay that identifies the abnormal prion protein PrPTSE in plasma: initial results with 20,000 samples. Transfusion 2010; 50:989.
  41. Edgeworth JA, Farmer M, Sicilia A, et al. Detection of prion infection in variant Creutzfeldt-Jakob disease: a blood-based assay. Lancet 2011; 377:487.
  42. Center for Biologics Evaluation and Research, Food and Drug Administration: Guidance for Industry. Revised precautionary measures to reduce the possible risk of transmission of Creutzfeldt-Jacob disease and new variant Creutzfeldt-Jacob disease by blood and blood products. November 1999.
  43. Dietz K, Raddatz G, Wallis J, et al. Blood transfusion and spread of variant Creutzfeldt-Jakob disease. Emerg Infect Dis 2007; 13:89.
  44. Murray K, Peters J, Stellitano L, et al. Is there evidence of vertical transmission of variant Creutzfeldt-Jakob disease? J Neurol Neurosurg Psychiatry 2011; 82:729.
  45. Zeidler M, Stewart GE, Barraclough CR, et al. New variant Creutzfeldt-Jakob disease: neurological features and diagnostic tests. Lancet 1997; 350:903.
  46. Lorains JW, Henry C, Agbamu DA, et al. Variant Creutzfeldt-Jakob disease in an elderly patient. Lancet 2001; 357:1339.
  47. Barbot C, Castro L, Oliveira C, Carpenter S. Variant Creutzfeldt-Jakob disease: the first confirmed case from Portugal shows early onset, long duration and unusual pathology. J Neurol Neurosurg Psychiatry 2010; 81:112.
  48. Heath CA, Cooper SA, Murray K, et al. Diagnosing variant Creutzfeldt-Jakob disease: a retrospective analysis of the first 150 cases in the UK. J Neurol Neurosurg Psychiatry 2011; 82:646.
  49. Zeidler M, Johnstone EC, Bamber RW, et al. New variant Creutzfeldt-Jakob disease: psychiatric features. Lancet 1997; 350:908.
  50. Spencer MD, Knight RS, Will RG. First hundred cases of variant Creutzfeldt-Jakob disease: retrospective case note review of early psychiatric and neurological features. BMJ 2002; 324:1479.
  51. Cordery RJ, Alner K, Cipolotti L, et al. The neuropsychology of variant CJD: a comparative study with inherited and sporadic forms of prion disease. J Neurol Neurosurg Psychiatry 2005; 76:330.
  52. Mead S, Poulter M, Uphill J, et al. Genetic risk factors for variant Creutzfeldt-Jakob disease: a genome-wide association study. Lancet Neurol 2009; 8:57.
  53. Kaski D, Mead S, Hyare H, et al. Variant CJD in an individual heterozygous for PRNP codon 129. Lancet 2009; 374:2128.
  54. Parchi P, Castellani R, Capellari S, et al. Molecular basis of phenotypic variability in sporadic Creutzfeldt-Jakob disease. Ann Neurol 1996; 39:767.
  55. Parchi P, Giese A, Capellari S, et al. Classification of sporadic Creutzfeldt-Jakob disease based on molecular and phenotypic analysis of 300 subjects. Ann Neurol 1999; 46:224.
  56. Collinge J, Sidle KC, Meads J, et al. Molecular analysis of prion strain variation and the aetiology of 'new variant' CJD. Nature 1996; 383:685.
  57. Wadsworth JD, Jackson GS, Hill AF, Collinge J. Molecular biology of prion propagation. Curr Opin Genet Dev 1999; 9:338.
  58. Hill AF, Joiner S, Wadsworth JD, et al. Molecular classification of sporadic Creutzfeldt-Jakob disease. Brain 2003; 126:1333.
  59. Head MW, Bunn TJ, Bishop MT, et al. Prion protein heterogeneity in sporadic but not variant Creutzfeldt-Jakob disease: UK cases 1991-2002. Ann Neurol 2004; 55:851.
  60. Hill AF, Butterworth RJ, Joiner S, et al. Investigation of variant Creutzfeldt-Jakob disease and other human prion diseases with tonsil biopsy samples. Lancet 1999; 353:183.
  61. Wadsworth JD, Joiner S, Hill AF, et al. Tissue distribution of protease resistant prion protein in variant Creutzfeldt-Jakob disease using a highly sensitive immunoblotting assay. Lancet 2001; 358:171.
  62. Glatzel M, Abela E, Maissen M, Aguzzi A. Extraneural pathologic prion protein in sporadic Creutzfeldt-Jakob disease. N Engl J Med 2003; 349:1812.
  63. Glatzel M, Giger O, Seeger H, Aguzzi A. Variant Creutzfeldt-jakob disease: between lymphoid organs and brain. Trends Microbiol 2004; 12:51.
  64. Adjou KT, Demaimay R, Deslys JP, et al. MS-8209, a water-soluble amphotericin B derivative, affects both scrapie agent replication and PrPres accumulation in Syrian hamster scrapie. J Gen Virol 1999; 80 ( Pt 4):1079.
  65. Hilton DA, Sutak J, Smith ME, et al. Specificity of lymphoreticular accumulation of prion protein for variant Creutzfeldt-Jakob disease. J Clin Pathol 2004; 57:300.
  66. Glatzel M. Testing for prions: a novel protocol for vCJD prevalence studies. Lancet 2004; 364:1196.
  67. Ironside JW, Head MW. Neuropathology and molecular biology of variant Creutzfeldt-Jakob disease. Curr Top Microbiol Immunol 2004; 284:133.
  68. Goodall CA, Head MW, Everington D, et al. Raised CSF phospho-tau concentrations in variant Creutzfeldt-Jakob disease: diagnostic and pathological implications. J Neurol Neurosurg Psychiatry 2006; 77:89.
  69. Green AJ, Thompson EJ, Stewart GE, et al. Use of 14-3-3 and other brain-specific proteins in CSF in the diagnosis of variant Creutzfeldt-Jakob disease. J Neurol Neurosurg Psychiatry 2001; 70:744.
  70. Macfarlane RG, Wroe SJ, Collinge J, et al. Neuroimaging findings in human prion disease. J Neurol Neurosurg Psychiatry 2007; 78:664.
  71. Zeidler M, Sellar RJ, Collie DA, et al. The pulvinar sign on magnetic resonance imaging in variant Creutzfeldt-Jakob disease. Lancet 2000; 355:1412.
  72. Collie DA, Summers DM, Sellar RJ, et al. Diagnosing variant Creutzfeldt-Jakob disease with the pulvinar sign: MR imaging findings in 86 neuropathologically confirmed cases. AJNR Am J Neuroradiol 2003; 24:1560.
  73. Yamada M, Variant CJD Working Group, Creutzfeldt-Jakob Disease Surveillance Committee, Japan. The first Japanese case of variant Creutzfeldt-Jakob disease showing periodic electroencephalogram. Lancet 2006; 367:874.
  74. de Silva R, Patterson J, Hadley D, et al. Single photon emission computed tomography in the identification of new variant Creutzfeldt-Jakob disease: case reports. BMJ 1998; 316:593.
  75. Binelli S, Agazzi P, Giaccone G, et al. Periodic electroencephalogram complexes in a patient with variant Creutzfeldt-Jakob disease. Ann Neurol 2006; 59:423.
  76. Will RG, Zeidler M, Stewart GE, et al. Diagnosis of new variant Creutzfeldt-Jakob disease. Ann Neurol 2000; 47:575.
  77. Hill AF, Zeidler M, Ironside J, Collinge J. Diagnosis of new variant Creutzfeldt-Jakob disease by tonsil biopsy. Lancet 1997; 349:99.
  78. Quadrio I, Ugnon-Café S, Dupin M, et al. Rapid diagnosis of human prion disease using streptomycin with tonsil and brain tissues. Lab Invest 2009; 89:406.
  79. Moda F, Gambetti P, Notari S, et al. Prions in the urine of patients with variant Creutzfeldt-Jakob disease. N Engl J Med 2014; 371:530.
  80. Heath CA, Cooper SA, Murray K, et al. Validation of diagnostic criteria for variant Creutzfeldt-Jakob disease. Ann Neurol 2010; 67:761.
  81. Todd NV, Morrow J, Doh-ura K, et al. Cerebroventricular infusion of pentosan polysulphate in human variant Creutzfeldt-Jakob disease. J Infect 2005; 50:394.
  82. Parry A, Baker I, Stacey R, Wimalaratna S. Long term survival in a patient with variant Creutzfeldt-Jakob disease treated with intraventricular pentosan polysulphate. J Neurol Neurosurg Psychiatry 2007; 78:733.
  83. Whittle IR, Knight RS, Will RG. Unsuccessful intraventricular pentosan polysulphate treatment of variant Creutzfeldt-Jakob disease. Acta Neurochir (Wien) 2006; 148:677.
  84. Newman PK, Todd NV, Scoones D, et al. Postmortem findings in a case of variant Creutzfeldt-Jakob disease treated with intraventricular pentosan polysulfate. J Neurol Neurosurg Psychiatry 2014; 85:921.