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Volume 21, Number 5—May 2015
CME ACTIVITY - Perspective

Recent US Case of Variant Creutzfeldt-Jakob Disease—Global Implications

Atul MaheshwariComments to Author , Michael Fischer, Pierluigi Gambetti, Alicia Parker, Aarthi Ram, Claudio Soto, Luis Concha-Marambio, Yvonne Cohen, Ermias D. Belay, Ryan A. Maddox, Simon Mead, Clay Goodman, Joseph S. Kass, Lawrence B. Schonberger, and Haitham M. Hussein
Author affiliations: Baylor College of Medicine, Houston, Texas, USA (A. Maheshwari, A. Parker, A. Ram, C. Goodman, J.S. Kass); Harris Health System, Houston (A. Maheshwari, A. Parker, A. Ram, J.S. Kass); Texas Department of State Health Services, Austin, Texas, USA (M. Fischer); Case Western Reserve University School of Medicine, Cleveland, Ohio, USA (P. Gambetti, Y. Cohen); University of Texas Medical School at Houston, Houston (C. Soto, L. Concha-Marambio); Universidad de los Andes, Santiago, Chile (L. Concha-Marambio); Centers for Disease Control and Prevention, Atlanta, Georgia, USA (E.D. Belay, R.A. Maddox, L.B. Schonberger); University College London Institute of Neurology, London, UK (S. Mead); HealthPartners Clinics & Services, St. Paul, Minnesota, USA (H.M. Hussein)

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Figure 4

Results of biochemical testing of a US patient with variant Creutzfeldt-Jakob disease (vCJD). A) Immunoblot of vCJD patient and controls. All the PK-treated preparations show similar electrophoretic profiles characterized by 3 bands displaying different mobilities according to number of the linked sugar moieties. The samples from this case and another vCJD case used as positive control (third lane) show the overrepresentation of the diglycosylated band, whereas in sCJD cases, the monoglycosylate

Figure 4. Results of biochemical testing of a US patient with variant Creutzfeldt-Jakob disease (vCJD). A) Immunoblot of vCJD patient and controls. All the PK-treated preparations show similar electrophoretic profiles characterized by 3 bands displaying different mobilities according to number of the linked sugar moieties. The samples from this case and another vCJD case used as positive control (third lane) show the overrepresentation of the diglycosylated band, whereas in sCJD cases, the monoglycosylated band is the most prominent. In both vCJD cases, the unglycosylated band co-migrates with type 2 (sixth lane) as indicated by the type 1 and 2 controls. The PK-untreated preparation (first lane) is used as control of PK digestion. Total brain homogenate, antibody 3F4. B) PrPSc detection in urine by protein misfolding cyclic amplification (PMCA). A urine sample from the patient was processed as previously described (6), and the supernatant fraction was run in duplicate (S1, S2). Samples were subjected to 96 PMCA cycles in the presence of 10% TgHuM brain homogenate, used as the substrate for PMCA. PrPSc signal was assessed by Western blot after PK digestion. As a positive control, vCJD brain homogenate was spiked at 10−5, 10−7, and 10−9 dilutions into urine from a healthy person and processed at the same time and in the same manner for PMCA. Lane C, PMCA-negative control (no sample); lane H, urine from a healthy person; sCJD, urine from an sCJD patient. CJD, Creutzfeldt-Jakob disease; Contr, control; MonoGly, monoglycosylated; NBH, normal brain homogenate without PK treatment used as an electrophoretic migration marker; Pres, present; PK, proteinase K; PrPSc, scrapie prion protein; sCJD, sporadic CJD; Unglyc, unglycosylated.

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References
  1. Prusiner  SB. Cell biology. A unifying role for prions in neurodegenerative diseases. Science. 2012;336:1511–3. DOIPubMedGoogle Scholar
  2. Barria  MA, Ironside  JW, Head  MW. Exploring the zoonotic potential of animal prion diseases: in vivo and in vitro approaches. Prion. 2014;8:85–91. DOIPubMedGoogle Scholar
  3. Diack  AB, Head  MW, McCutcheon  S, Boyle  A, Knight  R, Ironside  JW, Variant CJD: 18 years of research and surveillance. Prion. 2014;8:286–95. DOIPubMedGoogle Scholar
  4. Sanchez-Juan  P, Cousens  SN, Will  RG, van Duijn  CM. Source of variant Creutzfeldt-Jakob disease outside United Kingdom. Emerg Infect Dis. 2007;13:1166–9. DOIPubMedGoogle Scholar
  5. Food and Drug Administration. 2011 Meeting materials, Transmissible Spongiform Encephalopthies Advisory Committee [cited 2014 Oct 1]. http://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/BloodVaccinesandOtherBiologics/TransmissibleSpongiformEncephalopathiesAdvisoryCommittee/ucm261283.htm
  6. Moda  F, Gambetti  P, Notari  S, Concha-Marambio  L, Catania  M, Park  K-W, Prions in the urine of patients with variant Creutzfeldt-Jakob disease. N Engl J Med. 2014;371:530–9. DOIPubMedGoogle Scholar
  7. Heath  CA, Cooper  SA, Murray  K, Lowman  A, Henry  C, MacLeod  MA, Diagnosing variant Creutzfeldt-Jakob disease: a retrospective analysis of the first 150 cases in the UK. J Neurol Neurosurg Psychiatry. 2011;82:646–51. DOIPubMedGoogle Scholar
  8. Will  RG, Ironside  JW, Zeidler  M, Cousens  SN, Estibeiro  K, Alperovitch  A, A new variant of Creutzfeldt-Jakob disease in the UK. Lancet. 1996;347:921–5. DOIPubMedGoogle Scholar
  9. Barash  J. Identification of Creutzfeldt-Jakob disease variants. [author reply 1045–6]. Arch Neurol. 2009;66:1045. DOIPubMedGoogle Scholar
  10. Appleby  BS, Appleby  KK, Crain  BJ, Onyike  CU, Wallin  MT, Rabins  PV. Characteristics of established and proposed sporadic Creutzfeldt-Jakob disease variants. Arch Neurol. 2009;66:208–15 .PubMedGoogle Scholar
  11. Heath  CA, Cooper  SA, Murray  K, Lowman  A, Henry  C, MacLeod  MA, Validation of diagnostic criteria for variant Creutzfeldt-Jakob disease. Ann Neurol. 2010;67:761–70 .PubMedGoogle Scholar
  12. World Health Organization Department of Communicable Disease Surveillance and Response. WHO recommended surveillance standards, 1999 [cited 2015 Mar 8]. http://www.who.int/csr/resources/publications/surveillance/whocdscsrisr992.pdf
  13. Zerr  I, Kallenberg  K, Summers  DM, Romero  C, Taratuto  A, Heinemann  U, Updated clinical diagnostic criteria for sporadic Creutzfeldt-Jakob disease. Brain. 2009;132:2659–68 . DOIPubMedGoogle Scholar
  14. Collie  DA, Summers  DM, Sellar  RJ, Ironside  JW, Cooper  S, Zeidler  M, Diagnosing variant Creutzfeldt-Jakob disease with the pulvinar sign: MR imaging findings in 86 neuropathologically confirmed cases. AJNR Am J Neuroradiol. 2003;24:1560–9 .PubMedGoogle Scholar
  15. Ugnon-Café  S, Dorey  A, Bilheude  JM, Streichenberger  N, Viennet  G, Meyronet  D, Rapid screening and confirmatory methods for biochemical diagnosis of human prion disease. J Virol Methods. 2011;175:216–23. DOIPubMedGoogle Scholar
  16. Hill  AF, Butterworth  RJ, Joiner  S, Jackson  G, Rossor  MN, Thomas  DJ, Investigation of variant Creutzfeldt-Jakob disease and other human prion diseases with tonsil biopsy samples. Lancet. 1999;353:183–9. DOIPubMedGoogle Scholar
  17. Lukic  A, Mead  S, Rudge  P, Collinge  J. Comment on validation of diagnostic criteria for variant Creutzfeldt-Jakob disease. [author reply 212–3]. Ann Neurol. 2011;69:212. DOIPubMedGoogle Scholar
  18. Green  AJ, Thompson  EJ, Stewart  GE, Zeidler  M, McKenzie  JM, MacLeod  MA, 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;70:744–8. DOIPubMedGoogle Scholar
  19. Zeidler  M, Stewart  GE, Barraclough  CR, Bateman  DE, Bates  D, Burn  DJ, New variant Creutzfeldt-Jakob disease: neurological features and diagnostic tests. Lancet. 1997;350:903–7. DOIPubMedGoogle Scholar
  20. Beck  JA, Poulter  M, Campbell  TA, Adamson  G, Uphill  JB, Guerreiro  R, PRNP allelic series from 19 years of prion protein gene sequencing at the MRC Prion Unit. Hum Mutat. 2010;31:E1551–63. DOIPubMedGoogle Scholar
  21. Jackson  GS, Burk-Rafel  J, Edgeworth  JA, Sicilia  A, Abdilahi  S, Korteweg  J, Population screening for variant Creutzfeldt-Jakob disease using a novel blood test: diagnostic accuracy and feasibility study. JAMA Neurol. 2014;71:421–8. DOIPubMedGoogle Scholar
  22. Edgeworth  JA, Farmer  M, Sicilia  A, Tavares  P, Beck  J, Campbell  T, Detection of prion infection in variant Creutzfeldt-Jakob disease: a blood-based assay. Lancet. 2011;377:487–93. DOIPubMedGoogle Scholar
  23. Parchi  P, Giese  A, Capellari  S, Brown  P, Schulz-Schaeffer  W, Windl  O, Classification of sporadic Creutzfeldt-Jakob disease based on molecular and phenotypic analysis of 300 subjects. Ann Neurol. 1999;46:224–33. DOIPubMedGoogle Scholar
  24. Gambetti  P, Kong  Q, Zou  W, Parchi  P, Chen  SG. Sporadic and familial CJD: classification and characterisation. Br Med Bull. 2003;66:213–39. DOIPubMedGoogle Scholar
  25. Gambetti  P, Cali  I, Notari  S, Kong  Q, Zou  W-Q, Surewicz  WK. Molecular biology and pathology of prion strains in sporadic human prion diseases. Acta Neuropathol. 2011;121:79–90. DOIPubMedGoogle Scholar
  26. Sikorska  B, Knight  R, Ironside  JW, Liberski  PP. Creutzfeldt-Jakob disease. Adv Exp Med Biol. 2012;724:76–90. DOIPubMedGoogle Scholar
  27. Mihara  M, Sugase  S, Konaka  K, Sugai  F, Sato  T, Yamamoto  Y, The “pulvinar sign” in a case of paraneoplastic limbic encephalitis associated with non-Hodgkin’s lymphoma. J Neurol Neurosurg Psychiatry. 2005;76:882–4. DOIPubMedGoogle Scholar
  28. Ryan  AM, Ryan  J, Wan-Ahmed  M, Hardiman  O, Farrell  MA, McNamara  B, Vacuolar leucoencephalopathy and pulvinar sign in association with coeliac disease. BMJ Case Rep. 2009;2009:pii: bcr08.2008.0650. PMID: 20414170
  29. Schmidt  C, Plickert  S, Summers  D, Zerr  I. Pulvinar sign in Wernicke’s encephalopathy. CNS Spectr. 2010;15:215–8 .PubMedGoogle Scholar
  30. US Census Bureau. The foreign-born population in the United States [cited 2014 Aug 27]. https://www.census.gov/newsroom/pdf/cspan_fb_slides.pdf
  31. Garske  T, Ghani  AC. Uncertainty in the tail of the variant Creutzfeldt-Jakob disease epidemic in the UK. PLoS ONE. 2010;5:e15626. DOIPubMedGoogle Scholar
  32. Ghani  AC, Donnelly  CA, Ferguson  NM, Anderson  RM. Updated projections of future vCJD deaths in the UK. BMC Infect Dis. 2003;3:4. DOIPubMedGoogle Scholar
  33. Valleron  AJ, Boelle  PY, Will  R, Cesbron  JY. Estimation of epidemic size and incubation time based on age characteristics of vCJD in the United Kingdom. Science. 2001;294:1726–8. DOIPubMedGoogle Scholar
  34. Brown  P, Brandel  J-P, Sato  T, Nakamura  Y, MacKenzie  J, Will  RG, Iatrogenic Creutzfeldt-Jakob disease, final assessment. Emerg Infect Dis. 2012;18:901–7. DOIPubMedGoogle Scholar
  35. Collinge  J, Whitfield  J, McKintosh  E, Beck  J, Mead  S, Thomas  DJ, Kuru in the 21st century—an acquired human prion disease with very long incubation periods. Lancet. 2006;367:2068–74. DOIPubMedGoogle Scholar
  36. Boëlle  P-Y, Cesbron  J-Y, Valleron  A-J. Epidemiological evidence of higher susceptibility to vCJD in the young. BMC Infect Dis. 2004;4:26 . DOIPubMedGoogle Scholar
  37. Gill  ON, Spencer  Y, Richard-Loendt  A, Kelly  C, Dabaghian  R, Boyes  L, Prevalent abnormal prion protein in human appendixes after bovine spongiform encephalopathy epizootic: large scale survey. BMJ. 2013;347:f5675. DOIPubMedGoogle Scholar

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Page created: April 19, 2015
Page updated: April 19, 2015
Page reviewed: April 19, 2015
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