Human Prion Diseases in the Czech Republic –  10 Years of Experience with the Diagnosis

Authors: Z. Rohan 1;  E. Parobková 1;  S. Johanidesová 2;  F. Koukolík 1;  R. Matěj 1;  R. Rusina 2
Authors‘ workplace: Thomayerova nemocnice, Praha Národní referenční laboratoř lidských TSE/CJN při oddělení patologie a molekulární medicíny 1;  Thomayerova nemocnice, Praha Neurologické oddělení 2
Published in: Cesk Slov Neurol N 2013; 76/109(3): 300-306
Category: Review Article


Human prion diseases are rare neurodegenerative diseases. Since 2001, their diagnosis in the Czech Republic is performed at the National Reference Laboratory for human TSE/ CJD, a part of the Department of Pathology and Molecular Medicine, Thomayer Hospital in Prague. The most common is the sporadic form of Creutzfeldt‑ Jakob disease with 111 diagnosed definitive cases during 2002–2012. In addition, an increasing number of genetic forms is being diagnosed, with 24 confirmed cases during 2002–2012. Three cases of Gerstmann‑Sträussler‑ Scheinker syndrome were confirmed in 2009 a 2012. No case of new variant CJD has been diagnosed in the Czech Republic yet. Since 2007, the laboratory also performs obligatory testing of cornea transplant donors. This article recapitulates the ten years of existence of the National Reference Laboratory and summarizes human prion disease incidence and diagnosis in the Czech Republic.

Key words:
prion diseases – Creutzfeldt-Jakob disease – neuropathology – diagnostics


1. Aguzzi A, Falsig J. Prion propagation, toxicity and degradation. Nat Neurosci2012; 15(7): 936– 939.

2. Pastore A, Zagari A. A structural overview of the vertebrate prion proteins. Prion2007; 1(3): 185– 197.

3. Capellari S, Strammiello R, Saverioni D, Kretzschmar H, Parchi P. Genetic Creutzfeldt‑ Jakob disease and fatal familial insomnia: insights into phenotypic variability and disease pathogenesis. Acta Neuropathol 2011; 121(1): 21– 37.

4. Zerr I, Kallenberg K, Summers DM, Romero C, Taratuto A, Heinemann U et al.Updated clinical diagnostic criteria for sporadic Creutzfeldt‑ Jakob disease. Brain 2009; 132(Pt 10): 2659– 2668.

5. Heath CA, Cooper SA, Murray K, Lowman A, Henry C,MacLeod MA et al.Validation of diagnostic criteria for variant Creutzfeldt‑ Jakob disease. Ann Neurol 2010; 67(6): 761– 770.

6. WHO. WHO manual for surveillance of human transmissible spongiform encephalopathies including variant Cretzfeldt‑ Jakob disease. 2003. Available from: http:/ / publications/ 2003/ 9241545887.pdf.

7. Cordery RJ, Alner K, Cipolotti L, Ron M, Kennedy A,Collinge J et al.The neuropsychology of variant CJD: a comparative study with inherited and sporadic forms of prion disease. J Neurol Neurosurg Psychiatry 2005; 76(3): 330– 336.

8. Snowden JS, Mann DM, Neary D. Distinct neuropsychological characteristics in Creutzfeldt‑ Jakob disease. J Neurol Neurosurg Psychiatry 2002; 73(6): 686– 694.

9. Alner K, Hyare H, Mead S, Rudge P, Wroe S, Rohrer JD et al. Distinct neuropsychological profiles correspond to distribution of cortical thinning in inherited prion disease caused by insertional mutation. J Neurol Neurosurg Psychiatry 2012; 83(1): 109– 114.

10. Steinacker P, Aitken A, Otto M. 14‑3‑3 Proteins in neurodegeneration. Semin Cell Dev Biol 2011; 22(7): 696– 704.

11. Matej R, Novakova J, Fiala J, Koukolik F, Rusina R. Vyšetřování proteinu 14‑3‑3 v mozkomíšním moku –  klinicko‑patologická korelace. Cesk Slov Neurol N 2008; 71/ 104(6): 695– 699.

12. Hamlin C, Puoti G, Berri S, Sting E, Harris C, Cohen M et al.A comparison of tau and 14‑3‑3 protein in the diagnosis of Creutzfeldt‑ Jakob disease. Neurology 2012; 79(6): 547– 552.

13. Muayqil T, Gronseth G, Camicioli R. Evidence‑based guideline: diagnostic accuracy of CSF 14‑3‑3 protein in sporadic Creutzfeldt‑ Jakob disease: report of the guideline development subcommittee of the American Academy of Neurology. Neurology 2012; 79(14): 1499– 1506.

14. Stoeck K, Sanchez‑ Juan P, Gawinecka J, Green A,Ladogana A, Pocchiari M et al. Cerebrospinal fluid bio­marker supported diagnosis of Creutzfeldt‑ Jakob disease and rapid dementias: a longitudinal multicentre study over 10 years. Brain 2012; 135(Pt 10): 3051– 3061.

15. Shiga Y, Miyazawa K, Sato S, Fukushima R, Shibuya S, Sato Y et al. Diffusion‑ weighted MRI abnormalities as an early diagnostic marker for Creutzfeldt‑ Jakob disease. Neurology 2004; 63(3): 443– 449.

16. Young GS, Geschwind MD, Fischbein NJ, Martindale JL, Henry RG, Liu S et al. Diffusion‑ weighted and fluid‑ attenuated inversion recovery imaging in Creutzfeldt‑ Jakob disease: high sensitivity and specificity for diagnosis. AJNR Am J Neuroradiol 2005; 26(6): 1551– 1562.

17. Wang LH, Bucelli RC, Patrick E, Rajderkar D, Alvarez Iii E, Lim MM et al. Role of magnetic resonance imaging, cerebrospinal fluid, and electroencephalogram in diagnosis of sporadic Creutzfeldt‑ Jakob disease. J Neurol 2013; 260(2): 498– 506.

18. Tschampa HJ, Zerr I, Urbach H. Radiological asses­sment of Creutzfeldt‑ Jakob disease. Eur Radiol 2007; 17(5): 1200– 1211.

19. Vitali P, Maccagnano E, Caverzasi E, Henry RG, Haman A, Torres‑ Chae C et al. Diffusion‑ weighted MRI hyperintensity patterns differentiate CJD from other rapid dementias. Neurology 2011; 76(20): 1711– 1719.

20. Matej R, Rusina R, Koukolik F. 5 let činnosti Národní referenční laboratoře lidských prionových onemocnění při Oddělení patologie a molekulární medicíny FTNsP: naše zkušenosti a přehled literatury. Cesk Slov Neurol N 2007; 70/ 103(6): 637– 642.

21. Will RG, Ironside JW, Zeidler M, Cousens SN, Estibeiro K, Alperovitch A et al. A new variant of Creutzfeldt‑ Jakob disease in the UK. Lancet1996; 347(9006): 921– 925.

22. Shinde A, Kunieda T, Kinoshita Y, Wate R, Nakano S, Ito H et al.The first Japanese patient with variant Creutzfeldt‑ Jakob disease (vCJD). Neuropathology 2009; 29(6): 713– 719.

23. Zeidler M, Sellar RJ, Collie DA, Knight R, Stewart G,Macleod MA et al.The pulvinar sign on magnetic resonance imaging in variant Creutzfeldt‑ Jakob disease. Lancet 2000; 355(9213): 1412– 1418.

24. Hill AF, Butterworth RJ, Joiner S, Jackson G, Rossor MN, Thomas DJ et al. Investigation of variant Creutzfeldt‑ Jakob disease and other human prion diseases with tonsil bio­psy samples. Lancet 1999; 353(9148): 183– 189.

25. Hill AF, Zeidler M, Ironside J, Collinge J. Diagnosis of new variant Creutzfeldt‑ Jakob disease by tonsil bio­psy. Lancet 1997; 349(9045): 99– 100.

26. Bruce ME, McConnell I, Will RG, Ironside JW. Detection of variant Creutzfeldt‑ Jakob disease infectivity in extraneural tissues. Lancet 2001; 358(9277): 208– 209.

27. Brown P, Brandel JP, Sato T, Nakamura Y, MacKenzie J, Will RG et al. Iatrogenic Creutzfeldt‑ Jakob disease, final assessment. Emerg Infect Dis 2012; 18(6): 901– 907.

28. Hewitt PE, Llewelyn CA, Mackenzie J, Will RG. Three reported cases of variant Creutzfeldt‑ Jakob disease transmission following transfusion of labile blood components. Vox Sang 2006; 91(4): 348.

29. Jirsova K, Krabcova I, Novakova J, Hnathova I, Koukolik F, Kubesova B et al. The assessment of pathogenic prions in the brains of eye tissue donors: 2‑years experience in the Czech Republic. Cornea 2010; 29(9): 996– 999.

30. Schuette AJ, Taub JS, Hadjipanayis CG, Olson JJ. Open bio­psy in patients with acute progressive neurologic decline and absence of mass lesion. Neurology 2010; 75(5): 419– 424.

31. Tahiri‑ Alaoui A, Gill AC, Disterer P, James W. Methionine 129 variant of human prion protein oligomerizes more rapidly than the valine 129 variant: implications for disease susceptibility to Creutzfeldt‑ Jakob disease. J Biol Chem 2004; 279(30): 31390– 31397.

32. Alperovitch A, Zerr I, Pocchiari M, Mitrova E, de Pedro Cuesta J, Hegyi I et al. Codon 129 prion protein genotype and sporadic Creutzfeldt‑ Jakob disease. Lancet1999; 353(9165): 1673– 1674.

33. Mackay GA, Knight RS, Ironside JW. The molecular epidemiology of variant CJD. Int J Mol Epidemiol Genet 2011; 2(3): 217– 227.

34. Zeidler M, Stewart G, Cousens SN, Estibeiro K, Will RG. Codon 129 genotype and new variant CJD. Lancet 1997; 350(9078): 668.

35. Mitrová E, Belay G. Creutzfeldt‑ Jakob disease with E200K mutation in Slovakia: characterization and development. Acta Virol 2002; 46(1): 31– 39.

36. Hsiao K, Meiner Z, Kahana E, Cass C, Kahana I, Avrahami D et al. Mutation of the prion protein in Libyan Jews with Creutzfeldt‑ Jakob disease. N Engl J Med 1991; 324(16): 1091– 1097.

37. D‘Alessandro M, Petraroli R, Ladogana A, Pocchiari M.High incidence of Creutzfeldt‑ Jakob disease in rural Calabria, Italy. Lancet 1998; 352(9145): 1989– 1990.

38. Ladogana A, Puopolo M, Poleggi A, Almonti S, Mellina V, Equestre M et al. High incidence of genetic human transmissible spongiform encephalopathies in Italy. Neurology 2005; 64(9): 1592– 1597.

39. Chapman J, Ben‑ Israel J, Goldhammer Y, Korczyn AD. The risk of developing Creutzfeldt‑ Jakob disease in subjects with the PRNP gene codon 200 point mutation. Neurology 1994; 44(9): 1683– 1686.

40. Goldfarb LG, Petersen RB, Tabaton M, Brown P, LeBlanc AC, Montagna P et al. Fatal familial insomnia and familial Creutzfeldt‑ Jakob disease: disease phenotype determined by a DNA polymorphism. Science 1992; 258(5083): 806– 808.

41. Mastrianni JA, Iannicola C, Myers RM, DeArmond S,Prusiner SB. Mutation of the prion protein gene at codon 208 in familial Creutzfeldt‑ Jakob disease. Neurology 1996; 47(5): 1305– 1312.

42. Capellari S, Cardone F, Notari S, Schinina ME, Maras B, Sita D et al.Creutzfeldt‑ Jakob disease associated with the R208H mutation in the prion protein gene. Neurology 2005; 64(5): 905– 907.

43. Matej R, Kovacs GG, Johanidesova S, Keller J, Matejckova M, Novakova J et al. Genetic Creutzfeldt‑ Jakob disease with R208H mutation presenting as progressive supranuclear palsy. Mov Disord 2012; 27(4): 476– 479.

44. Rusina R, Fiala J, Holada K, Matejckova M, Novakova J, Ampapa R et al.Gerstmann‑Sträussler‑ Scheinker syndrome with the P102L pathogenic mutation presenting as familial Creutzfeldt‑ Jakob disease: a case report and review of the literature. Neurocase 2013; 19(1): 41– 53.

45. Rowe DB, Lewis V, Needham M, Rodriguez M, Boyd A, McLean C et al. Novel prion protein gene mutation presenting with subacute PSP‑like syndrome. Neurology 2007; 68(11): 868– 870.

46. Majtenyi C, Brown P, Cervenakova L, Goldfarb LG, Tateishi J. A three‑ sister sibship of Gerstmann‑Sträussler‑ Scheinker disease with a CJD phenotype. Neurology 2000; 54(11): 2133– 2137.

47. Lugaresi E, Medori R, Montagna P, Baruzzi A, Cortelli P, Lugaresi A et al. Fatal familial insomnia and dysautonomia with selective degeneration of thalamic nuclei. N Engl J Med 1986; 315(16): 997– 1003.

48. Montagna P, Gambetti P, Cortelli P, Lugaresi E. Familial and sporadic fatal insomnia. Lancet Neurol 2003; 2(3): 167– 176.

49. Parchi P, de Boni L, Saverioni D, Cohen ML, Ferrer I,Gambetti P et al.Consensus classification of human prion disease histotypes allows reliable identification of molecular subtypes: an inter‑ rater study among surveillance centres in Europe and USA. Acta Neuropathol 2012; 124(4): 517– 529.

50. Ironside JW, Head MW. Neuropathology and molecular bio­logy of variant Creutzfeldt‑ Jakob disease. Curr Top Microbio­l Immunol 2004; 284: 133– 159.

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