Journal of Neurology

, Volume 255, Issue 10, pp 1464–1472 | Cite as

Heightened incidence of sporadic Creutzfeldt-Jakob disease is associated with a shift in clinicopathological profiles

  • Katharina Stoeck
  • Klaus Hess
  • Lorenz Amsler
  • Tobias Eckert
  • Dieter Zimmermann
  • Adriano AguzziEmail author
  • Markus GlatzelEmail author


Incidences of human transmissible spongiform encephalopathies are monitored by national registries in the majority of countries in Western Europe. During the past 13 years incidences for Creutzfeldt-Jakob disease (CJD) in Switzerland fluctuated between 0.4 and 2.63 cases/106 inhabitants. We have compared clinicpathological patient profiles including geographic and gender distribution, age at disease onset, duration of disease, clinical symptoms, and recognized or hypothetical risk factors for CJD, genetic risk factors, biochemical and histopathological data for two cohorts of Swiss sporadic CJD patients from years of regular sporadic CJD incidence (1996–2000, mean incidence 1.3 cases/106 inhabitants, n = 47) to Swiss sporadic CJD patients from years of elevated sporadic CJD incidence (2001–2004, mean incidence 2.3 cases/106 inhabitants, n = 73). Sporadic CJD patients from the cohort with elevated sporadic CJD incidence presented with a higher frequency of rare sporadic CJD subtypes. Patients of these subtypes were significantly older and showed a skewed male/female ratio when compared to published patients of identical sporadic CJD-types or to patients from the 1996–2000 cohort and indicates that improved detection of rare sporadic CJD subtypes may have contributed to increased incidence.

Key words

Creutzfeldt-Jakob disease prions dementia epidemiology 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Supplementary material

415_2008_900_MOESM1_ESM.pdf (38 kb)
Tabele 1 (pdf format 40 KB)


  1. 1.
    Alperovitch A, Zerr I, Pocchiari M, Mitrova E, de Pedro Cuesta J, Hegyi I, Collins S, Kretzschmar H, van Duijn C, Will RG (1999) Codon 129 prion protein genotype and sporadic Creutzfeldt-Jakob disease. Lancet 353:1673–1674PubMedCrossRefGoogle Scholar
  2. 2.
    Brown P, Preece M, Brandel JP, Sato T, McShane L, Zerr I, Fletcher A, Will RG, Pocchiari M, Cashman NR, d’Aignaux JH, Cervenakova L, Fradkin J, Schonberger LB, Collins SJ (2000) Iatrogenic Creutzfeldt-Jakob disease at the millennium. Neurology 55:1075–1081PubMedGoogle Scholar
  3. 3.
    Bruce ME, Will RG, Ironside JW, McConnell I, Drummond D, Suttie A, McCardle L, Chree A, Hope J, Birkett C, Cousens S, Fraser H, Bostock CJ (1997) Transmissions to mice indicate that ‘new variant’ CJD is caused by the BSE agent Nature 389:498–501PubMedCrossRefGoogle Scholar
  4. 4.
    Budka H, Aguzzi A, Brown P, Brucher JM, Bugiani O, Collinge J, Diringer H, Gullotta F, Haltia M, Hauw JJ, et al. (1995) Tissue handling in suspected Creutzfeldt-Jakob disease (CJD) and other human spongiform encephalopathies (prion diseases). Brain Pathol 5:319–322PubMedCrossRefGoogle Scholar
  5. 5.
    Cali I, Castellani R, Yuan J, Al-Shekhlee A, Cohen ML, Xiao X, Moleres FJ, Parchi P, Zou WQ, Gambetti P (2006) Classification of sporadic Creutzfeldt-Jakob disease revisited. Brain 129:2266–2277PubMedCrossRefGoogle Scholar
  6. 6.
    Castellani RJ, Colucci M, Xie Z, Zou W, Li C, Parchi P, Capellari S, Pastore M, Rahbar MH, Chen SG, Gambetti P (2004) Sensitivity of 14-3-3 protein test varies in subtypes of sporadic Creutzfeldt-Jakob disease. Neurology 63:436–442PubMedGoogle Scholar
  7. 7.
    Collinge J, Sidle KC, Meads J, Ironside J, Hill AF (1996) Molecular analysis of prion strain variation and the aetiology of ‘new variant’ CJD. Nature 383:685–690PubMedCrossRefGoogle Scholar
  8. 8.
    Collins SJ, Sanchez-Juan P, Masters CL, Klug GM, van Duijn C, Poleggi A, Pocchiari M, Almonti S, Cuadrado-Corrales N, de Pedro-Cuesta J, Budka H, Gelpi E, Glatzel M, Tolnay M, Hewer E, Zerr I, Heinemann U, Kretszschmar HA, Jansen GH, Olsen E, Mitrova E, Alperovitch A, Brandel JP, Mackenzie J, Murray K, Will RG (2006) Determinants of diagnostic investigation sensitivities across the clinical spectrum of sporadic Creutzfeldt-Jakob disease. Brain 129:2278–2287PubMedCrossRefGoogle Scholar
  9. 9.
    Glatzel M, Ott PM, Lindner T, Gebbers JO, Gmur A, Wuest W, Huber G, Moch H, Podvinec M, Stamm B, Aguzzi A (2003) Human prion diseases: epidemiology and integrated risk assessment. The Lancet Neurology 2:757–763CrossRefGoogle Scholar
  10. 10.
    Glatzel M, Rogivue C, Ghani A, Streffer JR, Amsler L, Aguzzi A (2002) Incidence of Creutzfeldt-Jakob disease in Switzerland. Lancet 360:139–141PubMedCrossRefGoogle Scholar
  11. 11.
    Glatzel M, Stoeck K, Seeger H, Luhrs T, Aguzzi A (2005) Human prion diseases: molecular and clinical aspects. Arch Neurol 62:545–552PubMedCrossRefGoogle Scholar
  12. 12.
    Head MW, Ritchie D, Smith N, McLoughlin V, Nailon W, Samad S, Masson S, Bishop M, McCardle L, Ironside JW (2004) Peripheral tissue involvement in sporadic, iatrogenic, and variant Creutzfeldt-Jakob disease: an immunohistochemical, quantitative, and biochemical study. Am J Pathol 164:143–153PubMedGoogle Scholar
  13. 13.
    Hill AF, Desbruslais M, Joiner S, Sidle KC, Gowland I, Collinge J, Doey LJ, Lantos P (1997) The same prion strain causes vCJD and BSE (letter). Nature 389:448–450PubMedCrossRefGoogle Scholar
  14. 14.
    Hill AF, Joiner S, Wadsworth JD, Sidle KC, Bell JE, Budka H, Ironside JW, Collinge J (2003) Molecular classification of sporadic Creutzfeldt-Jakob disease. Brain 126:1333–1346PubMedCrossRefGoogle Scholar
  15. 15.
    Kovacs GG, Puopolo M, Ladogana A, Pocchiari M, Budka H, van Duijn C, Collins SJ, Boyd A, Giulivi A, Coulthart M, Delasnerie-Laupretre N, Brandel JP, Zerr I, Kretzschmar HA, de Pedro-Cuesta J, Calero-Lara M, Glatzel M, Aguzzi A, Bishop M, Knight R, Belay G, Will R, Mitrova E (2005) Genetic prion disease: the EUROCJD experience. Hum Genet 118:166–174PubMedCrossRefGoogle Scholar
  16. 16.
    Krasnianski A, Schulz-Schaeffer WJ, Kallenberg K, Meissner B, Collie DA, Roeber S, Bartl M, Heinemann U, Varges D, Kretzschmar HA, Zerr I (2006) Clinical findings and diagnostic tests in the MV2 subtype of sporadic CJD. Brain 129:2288–2296PubMedCrossRefGoogle Scholar
  17. 17.
    Meissner B, Kortner K, Bartl M, Jastrow U, Mollenhauer B, Schroter A, Finkenstaedt M, Windl O, Poser S, Kretzschmar HA, Zerr I (2004) Sporadic Creutzfeldt-Jakob disease: magnetic resonance imaging and clinical findings. Neurology 63:450–456PubMedGoogle Scholar
  18. 18.
    Mollenhauer B, Zerr I, Ruge D, Krause G, Mehnert WH, Kretzschmar HA, Poser S (2002) Epidemiology and clinical symptomatology of Creutzfeldt-Jakob disease. Dtsch Med Wochenschr 127:312–317PubMedCrossRefGoogle Scholar
  19. 19.
    Parchi P, Giese A, Capellari S, Brown P, Schulz-Schaeffer W, Windl O, Zerr I, Budka H, Kopp N, Piccardo P, Poser S, Rojiani A, Streichemberger N, Julien J, Vital C, Ghetti B, Gambetti P, Kretzschmar H (1999) Classification of sporadic Creutzfeldt-Jakob disease based on molecular and phenotypic analysis of 300 subjects. Ann Neurol 46:224–233PubMedCrossRefGoogle Scholar
  20. 20.
    Peden AH, Head MW, Ritchie DL, Bell JE, Ironside JW (2004) Preclinical vCJD after blood transfusion in a PRNP codon 129 heterozygous patient. Lancet 364:527–529PubMedCrossRefGoogle Scholar
  21. 21.
    Polymenidou M, Stoeck K, Glatzel M, Vey M, Bellon A, Aguzzi A (2005) Coexistence of multiple PrPSc types in individuals with Creutzfeldt-Jakob disease. Lancet Neurol 4:805–814PubMedCrossRefGoogle Scholar
  22. 22.
    Prusiner SB (1982) Novel proteinaceous infectious particles cause scrapie. Science 216:136–144PubMedCrossRefGoogle Scholar
  23. 23.
    Prusiner SB (2001) Shattuck lecture – neurodegenerative diseases and prions. N Engl J Med 344:1516–1526PubMedCrossRefGoogle Scholar
  24. 24.
    Saiz A, Nos C, Yague J, Dominguez A, Graus F, Munoz P (2001) The impact of the introduction of the 14-3-3 protein assay in the surveillance of sporadic Creutzfeldt-Jakob disease in Catalonia. J Neurol 248:592–594PubMedCrossRefGoogle Scholar
  25. 25.
    Schoch G, Seeger H, Bogousslavsky J, Tolnay M, Janzer RC, Aguzzi A, Glatzel M (2005) Analysis of Prion Strains by PrP(Sc) Profiling in Sporadic Creutzfeldt-Jakob Disease. PLoS Med 3:e14PubMedCrossRefGoogle Scholar
  26. 26.
    Steinhoff BJ, Zerr I, Glatting M, Schulz-Schaeffer W, Poser S, Kretzschmar HA (2004) Diagnostic value of periodic complexes in Creutzfeldt-Jakob disease. Ann Neurol 56:702–708PubMedCrossRefGoogle Scholar
  27. 27.
    Ukisu R, Kushihashi T, Kitanosono T, Fujisawa H, Takenaka H, Ohgiya Y, Gokan T, Munechika H (2005) Serial diffusion-weighted MRI of Creutzfeldt-Jakob disease. AJR Am J Roentgenol 184:560–566PubMedGoogle Scholar
  28. 28.
    Van Everbroeck B, Michotte A, Sciot R, Godfraind C, Deprez M, Quoilin S, Martin JJ, Cras P (2006) Increased incidence of sporadic Creutzfeldt-Jakob disease in the age groups between 70 and 90 years in Belgium. Eur J Epidemiol 21:443–447PubMedCrossRefGoogle Scholar
  29. 29.
    Will RG, Ironside JW, Zeidler M, Cousens SN, Estibeiro K, Alperovitch A, Poser S, Pocchiari M, Hofman A, Smith PG (1996) A new variant of Creutzfeldt-Jakob disease in the UK. Lancet 347:921–925PubMedCrossRefGoogle Scholar
  30. 30.
    Windl O, Giese A, Schulz-Schaeffer W, Zerr I, Skworc K, Arendt S, Oberdieck C, Bodemer M, Poser S, Kretzschmar HA (1999) Molecular genetics of human prion diseases in Germany. Hum Genet 105:244–252PubMedCrossRefGoogle Scholar
  31. 31.
    Zerr I, Bodemer M, Gefeller O, Otto M, Poser S, Wiltfang J, Windl O, Kretzschmar HA, Weber T (1998) Detection of 14-3-3 protein in the cerebrospinal fluid supports the diagnosis of Creutzfeldt-Jakob disease (In Process Citation). Ann Neurol 43:32–40PubMedCrossRefGoogle Scholar
  32. 32.
    Zerr I, Schulz-Schaeffer WJ, Giese A, Bodemer M, Schroter A, Henkel K, Tschampa HJ, Windl O, Pfahlberg A, Steinhoff BJ, Gefeller O, Kretzschmar HA, Poser S (2000) Current clinical diagnosis in Creutzfeldt-Jakob disease: identification of uncommon variants. Ann Neurol 48:323–329PubMedCrossRefGoogle Scholar

Copyright information

© Springer 2008

Authors and Affiliations

  • Katharina Stoeck
    • 1
    • 6
  • Klaus Hess
    • 2
  • Lorenz Amsler
    • 3
    • 7
  • Tobias Eckert
    • 3
  • Dieter Zimmermann
    • 4
  • Adriano Aguzzi
    • 1
    • 8
    Email author
  • Markus Glatzel
    • 5
    • 8
    Email author
  1. 1.Institute of NeuropathologyUniversity Hospital of ZürichZurichSwitzerland
  2. 2.Dept. of NeurologyUniversity Hospital ZurichZurichSwitzerland
  3. 3.Swiss Federal Office of Public HealthBernSwitzerland
  4. 4.Institute of Surgical PathologyUniversity Hospital ZurichZurichSwitzerland
  5. 5.Institute of NeuropathologyUniversity Hospital Hamburg-EppendorfHamburg-EppendorfGermany
  6. 6.Dept. of NeurologyUniversity Hospital Hamburg-EppendorfHamburg-EppendorfGermany
  7. 7.CSL BehringBernSwitzerland
  8. 8.Institute of NeuropathologyUniversity Hospital Hamburg-EppendorfHamburgGermany

Personalised recommendations