Download PDF
Anästhesiol Intensivmed Notfallmed Schmerzther 2001; 36(1): 15-24
DOI: 10.1055/s-2001-10236
DER BESONDERE BEITRAG
© Georg Thieme Verlag Stuttgart · New York

Prion-Krankheiten

H . HossainT. Chakraborty
  • Institut für Medizinische Mikrobiologie Klinikum der Justus-Liebig-Universität, Gießen
Further Information

Publication History

Publication Date:
31 December 2001 (online)

Also available at
    Permissions and Reprints

Zusammenfassung.

Transmissible spongiforme Enzephalopathien (TSE) sind bei Mensch und Tier bekannt. Wissenschaftlich wird eine selbst-propagierende Konformationsänderungen von infektiösen Proteinpartikel, den Prionen, als ursächlich für die TSE erachtet. Gesichert ist eine genetische Komponente bei Infektionsempfänglichkeit sowie die Übertragbarkeit über Artgrenzen hinweg. Große Aufmerksamkeit in der Öffentlichkeit erlangten die TSE durch die Erstbeschreibung der neuen Variante der Creutzfeld-Jakob-Krankheit im Zusammenhang mit einer möglichen Übertragung der Bovinen Spongiformen Enzephalitis (BSE) des Rindes auf den Menschen. Dies führt zu einer zunehmenden Unsicherheit von klinischem Personal im Umgang mit Patienten mit einer TSE. Diese Darstellung fasst in einer Übersicht alle bekannten TSE bei Mensch und Tier zusammen und gibt einen Überblick über jüngste Entwicklungen, sowohl was den Stand der Diagnostik und Therapie anbelangt als auch den Ausschluss von möglichen iatrogenen Übertragungswegen.

Prion Diseases.

Transmissible spongiform encephalopathies (TSEs) are clinical entities recognized both in humans and animals. Current evidence suggests that TSEs are caused by a self-propagating alteration of infectious protein particles known as prions. In addition, there is strong evidence for a genetic predisposition for the disease and documentation that transmission can cross species borders. The current public awareness of TSEs has resulted from the clinical symptoms observed in bovine spongiform encephalopathy (BSE) and the demonstration that a new variant of the Creutzfeld-Jacobs syndrome is probably the result of transmission from animals to humans. This has led to uncertainity amongst clinical personnel when dealing with patients presenting with TSEs. We review briefly the spectrum of TSEs known both in animals and humans, report on recent developments in the diagnostics and therapy, and discuss iatrogenic sources of infection.

Schlüsselwörter:

TSE - Prion - Creutzfeld-Jakob - BSE - Therapie

Key words:

- TSE - Prions - Creutzfeld-Jakob - BSE

Literatur

  • 1 Sigurdson B. Rida, a chronic encephalitis of sheep. With general remarks of infections which develop slowly and some of their special characteristics.  Br Vet J. 1954;  110 341-354
    PubMedGoogle Scholar
  • 2 Serpell L C, Sunde M, Blake C CF. The molecular basis of amyloidosis.  CML Cell Mol Life Sci. 1997;  53 871-887
    PubMedGoogle Scholar
  • 3 Prusiner S B, DeArmond S J. Prion disease and neurodegeneration.  Annu Rev Neurosci. 1994;  17 311-339
    CrossrefPubMedGoogle Scholar
  • 4 Kimberlin R H. et al . Desinfection studies with two strains of mouse-passaged scrapie agent. Guidelines for Creutzfeld-Jakob disease in mice.  J Neurol Sci. 1983;  59 355-369
    CrossrefPubMedGoogle Scholar
  • 5 Prusiner S B. Novel proteinaceous infections particles cause scrapie.  Science. 1982;  216 136-144
    CrossrefPubMedGoogle Scholar
  • 6 Prusiner S B, Hsiao K K. Human prion diseases.  Ann Neurol. 1994;  35 385-395
    CrossrefPubMedGoogle Scholar
  • 7 Alper T, Cramp W A, Haig D A, Clarke M C. Does the agent of scrapie replicate without nucleic acid?.  Nature. 1967;  214 764-766
    PubMedGoogle Scholar
  • 8 Griffith J S. Self-replication and scrapie.  Nature. 1967;  215 1043-1044
    PubMedGoogle Scholar
  • 9 Prusiner S B, Bolton D C, Groth D F, Bowman K A, Cochran S P, McKinley M P. Further purification and characterization of scrapie prions.  Biochemistry. 1982;  21 6942-6950
    CrossrefPubMedGoogle Scholar
  • 10 Kretschmar H A. Neuropathology of human prion diseases.  Arch Virol (Suppl). 1993;  7 261-293
    PubMedGoogle Scholar
  • 11 Kretschmar H A, Neumann M, Riethmüller G, Prusiner S B. Molecular cloning of a mink prion protein gene.  J Gen Virol. 1982;  73 2757-2761
    PubMedGoogle Scholar
  • 12 Lehmann S, Harris D A. Two mutant prion proteins expressed in cultured cells acquire biochemical properties reminiscent of the scrapie isoforms.  Proc Natl Acad Sci USA;. 1996;  93 5610-5614
    CrossrefPubMedGoogle Scholar
  • 13 Tobler I. et al . Altered circadian activity rhythmus and sleep in mice devoid of prion protein.  Nature. 1996;  380 639-642
    CrossrefPubMedGoogle Scholar
  • 14 Rogers M, Taraboulos A, Scott M, Groth D, Prusiner S B. Intracellular accumulation of the cellular prion protein after mutagenesis of ist Asn-linked glycosylation sites.  Glycobiology. 1990;  1 1101-109
    PubMedGoogle Scholar
  • 15 Borchelt D R, Taraboulos A, Prusiner S B. Evidence of synthesis of scrapie prion protein in the endocytic pathway.  J Biol Chem. 1992;  267 16 188-16 199
    PubMedGoogle Scholar
  • 16 Riek R, Hornemann S, Wider G, Billeter M, Glockshuber R, Wüthrich K. Structure of prion protein.  Nature. 1996;  382 180-182
    CrossrefPubMedGoogle Scholar
  • 17 Parchi P. et al . Molecular basis of phenotypic variability in sporadic Creutzfeld-Jakob disease.  Ann Neurol. 1996;  39 767-778
    CrossrefPubMedGoogle Scholar
  • 18 Gambetti P, Parchi P, Petersen R B, Chen S G, Lugaresi E. Fatal familial insomnia and familial Creutzfeld-Jakob disease: clinical, pathological and molecular features.  Brain Pathol. 1995;  5 43-51
    PubMedGoogle Scholar
  • 19 Baldwin M A, Cohen F E, Prusiner S B. Prion protein isoforms, a convergence of biological and structural investigations.  J Biol Chem. 1995;  27 19 197-19 200
    PubMedGoogle Scholar
  • 20 Forloni G. et al . Neurotoxicity of a prion protein fragment.  Nature. 1993;  362 543-546
    CrossrefPubMedGoogle Scholar
  • 21 Weissmann C. A unified theory of prion propagation.  Nature. 1991;  352 679-683
    CrossrefPubMedGoogle Scholar
  • 22 Kellings K, Meyer N, Mirenda C, Prusiner S B, Riesner D. Further analysis of nucleic acids in purified scrapie prion preparations by improved return refocusing gel electrophoresis.  J Gen Virol. 1992;  73 1025-1029
    PubMedGoogle Scholar
  • 23 Diringer H. Proposed link between transmissible spongiform encephalopathies of man and animals.  Lancet. 1995;  346 1208-1210
    CrossrefPubMedGoogle Scholar
  • 24 Diener T O, McKinley M P, Prusiner S B. Viroids and prions.  Proc Natl Acad Sci USA. 1982;  79 5220-5224
    PubMedGoogle Scholar
  • 25 Hope J. The nature of the scrapie agent: the evolution of the virino.  Ann NY Acad Sci. 1994;  724 282-289
    PubMedGoogle Scholar
  • 26 Diringer H. Creutzfeld-Jakob-Disease.  Lancet. 1996;  347 1332-1333
    CrossrefPubMedGoogle Scholar
  • 27 Rubinstein R. et al . Scrapie strain infection in vitro induces changes in neuronal cells.  Mol Neurobiol. 1994;  8 129-138
    PubMedGoogle Scholar
  • 28 Manuelidis L, Sklaviadis T, Akowitz A, Fritsch W. Virus particles are required for infection in neurodegenerative Creutzfeld-Jakob disease.  Proc Natl Acad Sci USA. 1995;  92 5124-5128
    PubMedGoogle Scholar
  • 29 Narang H K. The nature of the scrapie agent: The virus theory.  Proc Soc Exp Biol Med. 1996;  212 208-224
    PubMedGoogle Scholar
  • 30 Özel M, Diringer H. Small virus-like structure in fractions from scrapie hamster brain.  Lancet. 1994;  343 894-895
    CrossrefPubMedGoogle Scholar
  • 31 Lasmezas C L, Deslys J P, Robain O. et al . Transmission of the BSE agent to mice in the abscence of detectable abnormal prion protein.  Science. 1997;  275 402
    CrossrefPubMedGoogle Scholar
  • 32 Bueler H, Aguzzi A, Sailer A, Greiner R A. et al . Mice devoid of PrP are resistent to scrapie.  Cell. 1993;  73 1339
    CrossrefPubMedGoogle Scholar
  • 33 Mestel R. Putting prions to the test.  Science. 1996;  273 184-189
    CrossrefPubMedGoogle Scholar
  • 34 Brandner S. et al . Normal host prion protein necessary for scrapie-induced neurotoxicity.  Nature. 1996;  379 339-343
    CrossrefPubMedGoogle Scholar
  • 35 Kümper H. Scrapie aus klinischer Sicht. Tierärztl Kl 1994: 115-120
    Google Scholar
  • 36 Anderson R M, Donnelly C A, Ferguson N M, Woolhouse M EJ. et al . Transmission dynamics and epidemiology of BSE in British cattle.  Nature. 1996;  382 779
    CrossrefPubMedGoogle Scholar
  • 37 Bruce M E, Will R G, McConnell I. et al . Transmission to mice indicate that the new variant CJD is caused by the BSE agent.  Nature. 1997;  389 498
    CrossrefPubMedGoogle Scholar
  • 38 Collinge J, Sidle K CL, Meads J, Ironside J, Hill A F. Molecular analysis of prion strain variation and the aetiology of new variant CJD.  Nature. 1996;  388 685
    PubMedGoogle Scholar
  • 39 Wyatt J M. et al . Spongiform encephalopathy in a cat.  Vet Rec. 1990;  126 513
    PubMedGoogle Scholar
  • 40 Hewicker-Trautwein M. Die feline spongiforme Enzephalopathie.  Kleintierpraxis. 1994;  39 821-844
    PubMedGoogle Scholar
  • 41 Rabenau H. Die subakute spongiforme Enzephalitis (SSE) bei Mensch und Tier: Aktueller Stand der Epidemiologie unter Berücksichtigung von Creutzfeld-Jakob-Syndrom und BSE.  Mikrobiologe. 1995;  5 153
    PubMedGoogle Scholar
  • 42 Williams E S, Young S. Chronic Wasting Disease of captive mule deer: A spongiform encephalopathy.  J Wildlife Dis. 1980;  16 89-98
    PubMedGoogle Scholar
  • 43 Williams E S, Young S. Spongiform encephalopathy of Rocky Mountain elk.  J Wildlife Dis. 1982;  18 465-471
    PubMedGoogle Scholar
  • 44 Wallach J D, Boever W J. Diseases in exotic animals. Philadelphia; Saunder Comp 1982
    Google Scholar
  • 45 Schoon H A. et al . Spongiforme Enzephalopathie beim RothaIsstrauß.  Tierärztl Praxis. 1991;  19 263-265
    PubMedGoogle Scholar
  • 46 Gajdusek D C. Unconventional viruses and the origin and disappearance of Kuru.  Science. 1977;  197 943
    PubMedGoogle Scholar
  • 47 King A O. Kuru. Epidemiological developments.  Lancet. 1975;  2 761-763
    PubMedGoogle Scholar
  • 48 Holman G, Khan A S, Kent J, Strine T W, Schonberger L B. Epidemiology of Creutzfeld-Jakob disease in the United States.  Neuroepiderniology. 1995;  14 174
    PubMedGoogle Scholar
  • 49 Alperovitch A. et al . The incidence of Creutzfeld-Jakob disease in Europe in 1993.  Lancet. 1994;  334 918
    PubMedGoogle Scholar
  • 50 Goldfarb L G, Brown P. The transmissible spongiform encephalopathies.  Annu Rev Med. 1995;  46 57
    CrossrefPubMedGoogle Scholar
  • 51 Masters C L. et al . Creutzfeld-Jakob disease: patterns of worldwide occurence and the significance of familial and sporadic clustering.  Ann Neurol. 1979;  5 177-188
    CrossrefPubMedGoogle Scholar
  • 52 Poser S, Zerr I, Weidehaas K. Epidemiological and clinical features of Creutzfeld-Jakob disease (CJD). In: Doerr HW, Rabenau HF, Sonneborn HH (ed) Contributions to the epidemiology of viral diseases. Biotest Bull 1997 5: 359
    Google Scholar
  • 53 Weber T, Zerr I, Bodemer M, Poser S. Erweitertes Krankheitsspektrum humaner spongiformer Enzephalopathien oder Prionkrankheiten.  Nervenarzt. 1997;  68 309-323
    CrossrefPubMedGoogle Scholar
  • 54 Rabenau H F, Preiser W, Doerr H W. Übertragbare spongiforme Enzephalopathien: die Creutzfeld-Jakob-Krankheit.  Chirurg. 1998;  69 511-521
    CrossrefPubMedGoogle Scholar
  • 55 Collinge J, Palmer M S, Dryden A J. Genetic predisposition to iatrogenic Creutzfeld-Jakob disease.  Lancet. 1991;  337 1441
    CrossrefPubMedGoogle Scholar
  • 56 Allan B, Tuft S. Transmission of Creutzfeld-Jakob disease in corneal grafts.  BMJ. 1997;  315 1553
    PubMedGoogle Scholar
  • 57 Centers for Disease Control and Prevention (CDC) . Creutzfeld-Jakob disease associated with cadaveric dura mater grafts - Japan, January 1979 - May 1996.  MMWR. 1997;  46 1066
    PubMedGoogle Scholar
  • 58 Heye N, Hensen S, Müller N. Creutzfeld-Jakob disease and blood transfusion.  Lancet. 1994;  343 298
    CrossrefPubMedGoogle Scholar
  • 59 Hill A F, Zeidler M, Ironside J, Collinge J. Diagnosis of new variant Creutzfeld-Jakob disease by tonsil biopsy.  Lancet. 1997;  349 99
    CrossrefPubMedGoogle Scholar
  • 60 Ricketts M N, Cashman N R, Stratton E E, ElSaadany S. Is Creutzfeld-Jakob disease transmitted in blood?.  Emerging Infect Dis. 1997;  3 155
    PubMedGoogle Scholar
  • 61 Weller R O. latrogenic transmission of Creutzfeld-Jakob disease.  Pyschol Med. 1989;  19 1-4
    PubMedGoogle Scholar
  • 62 Brown P. et al . ”Friendly fire” in medicine: hormones, homografts and Creutzfeld-Jakob disease.  Lancet. 1992;  34 24-27
    PubMedGoogle Scholar
  • 63 Doudelet V. et al . Emerging problems in prion disease.  Can Med Assoc L. 1996;  155 549-551
    PubMedGoogle Scholar
  • 64 Kozak R W. et al . Transmissible spongiform encephalpathies (TSE)-minimizing the risk of transmission by biological/biopharmaceutical products: an industry perspective.  Dev Biol Stand. 1996;  88 257-264
    PubMedGoogle Scholar
  • 65 Palmer M S, Dryden A J, Hughes J T, Collinge J. Homozygous prion protein genotype predisposes to sporadic Creutzfeld-Jakob disease.  Nature. 1991;  352 340
    CrossrefPubMedGoogle Scholar
  • 66 Esmonde T F, Will R G, Slattery J M, Knight R. et al . Creutzfeld-Jakob disease and blood transfusion.  Lancet. 1993;  341 205-207
    CrossrefPubMedGoogle Scholar
  • 67 Will R G, Zeidler M, Brown P, Harrington M. et al . A new variant Creutzfeld-Jakob disease in the UK.  Lancet. 1996;  347 921
    CrossrefPubMedGoogle Scholar
  • 68 Zeidler M, Johnstone E C, Bamber R WK, Dickens C M. et al . New Creutzfeld-Jakob disease: psychiatric features.  Lancet. 1997;  350 908
    CrossrefPubMedGoogle Scholar
  • 69 Gerstmann J, Sträussler E, Scheinker I. Über eine eigenartige hereditär-familiäre Erkrankung des Zentralnervensystems. Zugleich ein Beitrag zur Frage des vorzeitigen lokalen Alterns.  Z Neurol. 1936;  154 736-762
    PubMedGoogle Scholar
  • 70 Masters C L, Gajdusek D C, Gibbs C J. Creutzfeld-Jakob disease virus isolation from the Gerstmann-Sträussler syndrome with an analysis of the various forms of amyloid plaque deposition in the virus-induced spongiform encephalopathies.  Brain. 1981;  104 559-588
    PubMedGoogle Scholar
  • 71 Manetto V. et al . Fatal Familial Insomnia: clinical and pathological study of five new cases.  Neurology. 1992;  42 312-319
    PubMedGoogle Scholar
  • 72 Goldfarb L G. et al . Fatal Familial Insomnia and familial Creutzfeld-Jakob disease: disease phenotype determined by a DNA polymorphism.  Science. 1992;  258 806-808
    CrossrefPubMedGoogle Scholar
  • 73 Reder A T. et al . Clinical and genetic studies of Fatal Familial Insomnia.  Neurology. 1995;  45 1068-1075
    PubMedGoogle Scholar
  • 74 Zerr I, Bodemer M, Gefeller O, Otto M. et al . Detection of 14-3-3 brain protein in cerebrospinal fluid supports the diagnosis of Creutzfeld-Jakob disease.  Ann Neurol. 1998;  43 32
    CrossrefPubMedGoogle Scholar
  • 75 Klein M A, Frigg R, Flechsig E, Raeber A J. et al . A crucial role for B cells in neuroinvasive scrapie.  Nature. 1997;  390 687
    PubMedGoogle Scholar
  • 76 Korth C, Stierli B, Streit P, Moser M. et al . Prion-specific epitope defined by a monoclonal antibody.  Nature. 1997;  390 74
    CrossrefPubMedGoogle Scholar
  • 77 Lee K H, Harrington M G. Premortem diagnosis of Creutzfeld-Jakob disease by cerebrospinal fluid analysis.  Lancet. 1996;  348 887
    PubMedGoogle Scholar
  • 78 Otto M, Wiltfang J, Schütz E, Zerr I. et al . Diagnosis of Creutzfeld-Jakob disease by measurement of S100 protein in serum: prospective case-control study.  BMJ. 1998;  316 577
    PubMedGoogle Scholar
  • 79 Otto M, Wiltfang J, Tumani H, Zerr I. et al . Elevated levels of tau-protein in cerebrospinal fluid of patients with Creutzfeld-Jakob disease.  Neuro Sci Lett. 1997;  225 210
    CrossrefPubMedGoogle Scholar
  • 80 Zerr I, Bodemer M, Racker S, Grosche S. et al . Cerebrospinal fluid concentration of neuron-specific enolase in diagnosis of Creutzfeld-Jakob disease.  Lancet. 1995;  345 1609
    CrossrefPubMedGoogle Scholar
  • 81 Priola S A, Caughey B, Caughey W S. Novel therapeutic uses for porphyrins and phthalocyanines in the transmissible spongiform encephalopathies.  Curr Op Microbiol. 1999;  2 563-566
    PubMedGoogle Scholar
  • 82 Soto C. Alzheimer's and prion disease as disorders of protein conformation: implications for the design of novel therapeutic approaches.  J Mol Med. 1999;  77 412-418
    CrossrefPubMedGoogle Scholar
  • 83 Poser S, Kretzschmar H A. Prion-Erkrankungen. Aus: Marre R, Trautmann M, Mertens T, Vanek E Klinische Infektiologie. Urban & Fischer München, Jena; 2000: 703-713
    Google Scholar
  • 84 Hilton D A, Fathers E, Edwards P, Ironside J W, Zajicek J. Prion immunoreactivity in appendix before clinical onset of variant Creutzfeld-Jakob disease.  Lancet. 1998;  392 703-704
    PubMedGoogle Scholar
  • 85 Aguzzi A. Prion diseases, blood and the immune system: concerns and reality.  Haematologica. 2000;  85 3-10
    PubMedGoogle Scholar
  • 86 Colling S B, Collinge J, Jeffreys J G. Hypocampal slices from prion protein null mice: disrupted Ca++-activated K+ currents.  Neurosci Lett. 1996;  209 49-52
    CrossrefPubMedGoogle Scholar

Dr. med. Hamid Hossain

Institut für Medizinische Mikrobiologie Klinikum der Justus-Liebig-Universität

Frankfurter Str. 107

35392 Giessen

      >