Source: http://www.asmscience.org/content/book/10.1128/9781555817831.chap15
Timestamp: 2019-04-24 12:06:54+00:00

Document:
Creutzfeldt-Jakob disease (CJD) is a rare, progressive, fatal, degenerative disease of the central nervous system (CNS) with the pathological features of multifocal neuronal loss, gliosis, and parenchymal spongy change. A further pathological feature seen occasionally in sporadic CJD (sCJD), more commonly in scrapie and kuru, and invariably in some inherited forms of prion disease and vCJD is the presence of microscopic plaques of amyloidlike material. Abnormalities in the eponymic forms of inherited CJD, fatal familial insomnia (FFI) and GSS , include sleep disturbance and dysautonomia for FFI and ataxia and dementia for GSS. Iatrogenic forms that have sufficient numbers of cases to review include patients who have received cadaveric growth hormone or cadaveric dura mater. A consolidated table of clinical features found across the several forms of human prion disease is presented and provides a basis for the descriptions of the specific types of prion disorders. However, across all types of prion disorders, subacute dementia, ataxia, and psychiatric disorders are the triad of most common clinical features. Familial CJD , FFI, and GSS will be considered next, followed by transmission associated with ingestion of contaminated proteins which includes cannibalism and consumption of bovine spongiform encephalopathy (BSE)-contaminated beef. Although the risk of transmissibility in most health care settings is negligible, comprehensive institutionwide evaluation for risk and implementation of infection control guidelines for the human prion disorders are necessary.
Coronal slice through fixed brain from a case of CJD. There is only minimal cerebral atrophy with ventricular dilation and prominent sulci.
Low-power view of cerebral cortex in CJD showing mild patchy spongiform change, mainly in layers 2 and 3. Hematoxylin and eosin stain.
Low -power view of cerebral cortex showing more extensive spongiform change. PTAH stain.
Low-power view of cerebral cortex from a healthy control (a) and a case of C JD (b). In CJD, neurons are lost and the cortical organization is haphazard. Small nuclei are those of glial cells. Arrows in (a) and (b) indicate the pial surface. Nissl stain.
Reactive gliosis in the putamen in a case of CJD. Cajal&apos;s stain.
Cerebellar cortex containing kuru plaques in the molecular layer (above). Thioflavine T stain photographed under fluorescent light.
“Florid” plaque in vCJD surrounded by spongiform vacuoles.
PrP immunostained deposits (arrows) in cortex in sCJD.
PrP immunostained plaques in cerebellum in inherited ataxic form of CJD.
PrP immunostaining of vCJD cerebellar cortex.
Peridendritic pattern of immunostaining for PrP in the basal ganglia from a case of vCJD.
Electron micrograph of cerebral cortex in CJD. Vacuolar distension of a postsynaptic neuritic process is seen. Courtesy of I. Janota.
EEG in sCJD: a 72-year-old woman with a history of progressive dementia and myoclonus. EEG shows periodic complexes predominantly over the left hemisphere. Courtesy of Huned Patwa, Yale University School of Medicine.
Axial FLAIR MRI of sCJD with graded hyperintensity more marked in the anterior putamen relative to the posterior half of the nucleus. N o significant pulvinar or dorsal thalamic hyperintensity. There is also some cortical hyperintensity in the right insula. Courtesy of David Summers, U.K. National CJD Surveillance Unit, Edinburgh, Scotland.
Axial FLAIR MRI of vCJD demonstrating symmetrical hyperintensity of the pulvinar nuclei of the thalamus relative to the caudate head and other gray matter. Courtesy of David Summers, U.K. National CJD Surveillance Unit, Edinburgh, Scotland.
1. Aksamit, A. J., , C. M. Preissner,, and H. A. Homburger. 2001. Quantitation of 14-3-3 and neuron specific enolase proteins in CSF in Creutzfeldt-Jakob disease. Neurology 57: 728– 730.
2. Alper, T.,, W. A. Cramp,, D. A. Haig,, and M. C. Clarke. 1967. Does the agent of scrapie replicate without nucleic acid? Nature 214: 764– 766.
3. Alperovitch, A.,, I. Zerr,, M. Pocchiari,, E. Mitrova,, J. de P. Cuesta,, I. Hegyi,, S. Collins,, H. Kretzschmar,, C. Van Duijn,, and R. G. Will. 1999. Codon 129 prion protein genotype and sporadic Creutzfeldt-Jakob disease. Lancet 353: 1673– 1674.
4. Beck, E.,, and P. M. Daniel,. 1979. Kuru and Creutzfeldt-Jakob disease: neuropathological lesions and their significance, p. 253— 270. In S. B. Prusiner, and W. J. Hadlow (ed.), Slow Transmissible Diseases of the Nervous System. Academic Press, New York, N.Y.
5. Belay, E. D.,, P. Gambetti,, L. B. Schonberger,, P. Parchi,, D. R. Lyon,, S. Capellari,, J . H. McQuiston,, K. Bradley,, G. Dowdle,, J. M. Crutcher,, and C. R. Nichols. 2001. Creutzfeldt-Jakob disease in unusually young patients who consumed venison. Arch. Neurol. 58: 1673– 1678.
6. Bell, J. E.,, and J. W. Ironside. 1993. How to tackle a possible Creutzfeldt-Jakob disease necropsy. J. Clin. Pathol. 46: 193– 197.
7. Bockman, J. M.,, D. T. Kingsbury,, M. P. McKinley,, P. E. Bendheim,, and S. B. Prusiner. 1985. Creutzfeldt-Jakob disease prion proteins in human brains. N. Engl. J. Med. 312: 73– 78.
8. Boellard, W.,, and W. Scholte. 1980. Subacute spongiforme Encephalopathie mit multi-former Plaquebildung. Acta Neuropathol. 49: 205– 212.
9. Brandner, S.,, A. Raeber,, A. Sailer,, T. Blaettler,, M. Fischer,, C. Weissmann,, and A. Aguzzi. 1996. Normal host prion protein (PrPc) required for scrapie spread within the central nervous system. Proc. Natl. Acad. Sci. USA 93: 13148– 13151.
10. Brown, P.,, P. Rodgers-Johnson,, F. Carthala,, C. J. Gibbs Jr.,, and D. C. Gajdusek. 1984 - Creutzfeldt-Jakob disease of long duration: clinicopathological characteristics, transmissibility, and differential diagnosis. Ann. Neurol. 16: 295– 304.
11. Brown, D. R.,, W. J . Schulz-Schaeffer,, B. Schmidt,, and H. A. Kretzschmar. 1997. Prion protein-deficient cells show altered response to oxidative stress due to decreased SOD-1 activity. Exp. Neurol. 146: 104– 112.
12. Brown, P.,, M. A. Preece,, and R. G. Will. 1992. "Friendly fire" in medicine: hormones, homografts and Creutzfeldt-Jakob disease. Lancet 340: 24– 27.
13. Brown, P.,, C. J. Gibbs Jr.,, P. Rodgers-Johnson,, D. M. Asher,, M. P. Sulima,, A. Bacote,, L. G. Goldfarb,, and D. C. Gajdusek. 1994. Human spongiform encephalopathy: the National Institutes of Health series of300 cases of experimentally transmitted disease. Ann. Neurol. 35: 513– 529.
14. Brown, P.,, M. Preece,, J. -P Brandel,, T. Sato,, L . McShane,, I. Zerr,, A. Fletcher,, R. G. Will,, M. Pocchiari,, N. R. Cashman,, J . H. d'Aignaux,, L. Cervenáková,, J. Fradkin,, L. B. Schonberger,, and S. J. Collins. 2000. Iatrogenic Creutzfeldt-Jakob disease at the millennium. Neurology 55: 1075– 1081.
15. Brownell, B.,, and D. R. Oppenheimer. 1965. An ataxic form of subacute presenile polioencephalopathy (Creutzfeldt-Jakob Disease). J. Neurol. Neurosurg. Psychiatr. 28: 350– 361.
16. Bruce, M. E.,, R. G. Will,, J. W. Ironside,, I. McDonell,, D. Drummond,, A. Suttie,, L. McCardle,, A. Chree,, J . Hope,, C. Birkett,, S. Cousens,, H. Fraser,, and C. J. Bostock. 1997. Transmissions to mice indicate that1 'new variant' CJD is caused by the BSE agent. Nature 389: 498– 501.
17. Büeler, H.,, A. Aguzzi,, A. Sailer,, R. A. Greiner,, P. Autenried,, M. Aguet,, and C. Weissman. 1993. Mice devoid of PrP are resistant to scrapie. Cell 73: 1339– 1347.
18. CJD Incidents Panel. 2001. Management of possible exposure to CJD through medical procedures.[Online.]http:// www.doh.gov.uk/cjdconsultation.
19. Collie, D. A.,, R. J . Sellar,, M. Zeidler,, A. C. F. Colchester,, R. Knight,, and R. G. Will. 2001. MRI of Creutzfeldt-Jakob disease: imaging features and recommended MRI protocol. Clin. Radiol. 56: 726– 739.
20. Collinge, J. 1999. Variant Creutzfeldt-Jakob disease. Lancet 354: 317– 323.
21. Collinge, J.,, and M. Rossor. 1996. A new variant of prion disease. Lancet 347: 916– 917.
22. Collinge, J.,, M. S. Palmer,, and A. J. Dryden. 1991. Genetic predisposition to iatrogenic Creutzfeldt-Jakob disease. Lancet 337: 1441– 1442.
23. Collinge, J.,, M. S. Palmer,, K. C. L. Sidle,, I. Gowland,, R. Medori,, J. Ironside,, and P. Lantos. 1995. Transmission of fatal familial insomnia to laboratory animals. Lancet 346: 569– 570.
24. Collinge, J., , K. C L. Sidle,, J. Meads,, J. Ironside,, and A. F. Hill. 1996. Molecular analysis of prion strain variation and the aetiology of "new variant" CJD. Nature 383: 685– 690.
25. Collins, S.,, M. G. Law,, A. Fletcher,, A. Boyd,, J . Kaldor,, and C. L. Masters. 1999. Surgical treatment and risk of sporadic Creutzfeldt-Jakob disease: a case-control study. Lancet 353: 693– 697.
26. Collins, S. J.,, V. Lewis,, M. Brazier,, A. E. Hill,, A. Fletcher,, and C. L. Masters. 2002. Quinacrine does not prolong survival in a murine Creutzfeldt-Jakob disease model. Ann. Neurol. 52: 503– 506.
27. Cousens, S. N.,, E. Vynnycky,, M. Zeidler,, R. G. Will,, and P. G. Smith. 1997. Predicting the CJD epidemic in humans. Nature 385: 197– 198.
28. Cuille, J.,, and P. L. Chelle. 1936. Pathologie animale—la maladie dite trémblante du mouton est-elle inoculable. C R . Hebd. Seances Acad. Sci. 203: 1552– 1554.
29. DeArmond, S. J.,, H. A. Kretzschmar,, and S. B. Prusiner,. 2002. Priondiseases, p. 273– 323. In D. I. Graham, and P. Lantos (ed.), Greenfield's Neuropathology. Arnold, London, United Kingdom.
30. Derkatch, I. L.,, Y. O. Chernoff,, V. V. Kushnirov,, S. G. Inge-Vechtomov,, and W. Leibman. 1996. Genesis and variability of [PSI] prion factors in Saccharomyces cerevisiae. Genetics 144: 1375– 1386.
31. de Silva, R.,, and R. G. Will,. 2000. Human prion diseases, p. 215– 230. In L. E. Davis, and P. G. E. Kennedy (ed.), Infectious Diseases of the Nervous System. Butterworth-Heinemann, Oxford, United Kingdom.
32. Dickinson, A. G.,, and V. M. H. Meikle. 1969. A comparison of some biological characteristics of the mouse-passed scrapie agents, 22A and ME7. Genet. Res. 13: 213– 225.
33. Dickinson, A. G.,, and V. M. H. Meikle. 1971. Host-genotype and agent effects in scrapie incubation: change in allelic interaction with different strains of agent. Mol. Gen. Genet. 112: 73– 79.
34. Dormont, D., 1999. Bovine spongiform encephalopathy and the new variant of Creutzfeldt-Jakob disease, p. 177– 191. In D. A. Harris (ed.), Prions: Molecular and Cellular Biology. Horizon Scientific Press, Norfolk, United Kingdom.
35. Enari, M.,, E. Flechsig,, and C. Weissmann. 2001. Scrapie prion protein accumulation by scrapie-infected neuroblastoma cells abrogated by exposure to a prion protein antibody. Proc. Natl. Acad. Sci. USA 98: 9295– 9299.
36. Enserink, M. 2001. U.S. gets tough against chronic wasting disease. Science 294: 978– 979.
37. Ernst, D. R.,, and R. E. Race. 1993. Comparative analysis of scrapie agent inactivation methods. J. Virol. Methods 41: 193— 201.
38. Ferrer, I.,, F. Costa,, and J. M. Grau Veciana. 1981. Creutzfeldt- Jacob disease: a Golgi study. Neuropathol. Appl. Neurobiol. 7: 237– 242.
39. Finkenstaedt, M.,, A. Szudra,, I. Zerr,, S. Poser,, J. H. Hise,, J. M. Stoebner,, and T. Weber. 1996. MR imaging of Creutzfeldt-Jakob disease. Radiology 199: 793– 798.
40. Fradkin, J. E.,, L. B. Schonberger,, J . L. Mills,, W. J. Gunn,, J . M. Piper,, D. K. Wysowski,, R. Thomson,, S. Durako,, and P. Brown. 1991. Creutzfeldt-Jakob disease in pituitary growth hormone recipients in the United States. JAMA 265: 880– 884.
41. Fraser, H. 1973. Scrapie in mice: agent-strain differences in the distribution and intensity of grey matter vacuolation. J. Comp. Pathol. 83: 29– 40.
42. Fraser, H.,, M. E. Bruce,, D. Davies,, C. F. Farguhar,, and P. A. McBridge,. 1992. The lymphoreticular system in the pathogenesis of scrapie, p. 308– 317. In S. B. Prusiner,, J. Collinge,, J. Powell,, and B. Anderton (ed.), Prion Diseases of Humans and Animals. Ellis Horwood, London, United Kingdom.
43. Gajdusek, D. C.,, and V. Zigas. 1957. Degenerative disease of the central nervous system in New Guinea. The endemic occurrence of 'kuru' in the native population. N. Engl. J. Med. 257: 974– 978.
44. Gajdusek, D. C.,, C. J. Gibbs,, and M. Alpers. 1966. Experimental transmission of a kuru-like syndrome to chimpanzees. Nature 209: 794– 796.
45. Gambetti, P.,, and E. Jugaresi. 1998. Conclusions of the symposium. Brain Pathol. 8: 571– 575.
46. Ghani, A. C.,, N. M. Ferguson,, C. A. Donnelly,, T. J. Hagenaars,, and R. M. Anderson. 1999. Epidemiological determinants of the pattern and magnitude of the vCJD epidemic in Great Britain. Proc. R. Soc. London Ser B. Biol. Sci. 265: 2243– 2252.
47. Gibbs, C. J.,, D. C. Gajdusek,, D. M. Asher,, M. P. Alpers,, E. Beck,, R. M. Daniel,, and W. B. Matthews. 1968. Creutzfeldt- Jakob disease (spongiform encephalopathy): transmission to the chimpanzee. Science 161: 388– 389.
48. Goldfarb, L. G.,, R. B. Petersen,, M. Tabaton,, P. Brown,, A. C. Leblanc,, P. Montagna,, P. Cortelli,, J . Julien,, C. Vital,, W. W. Pendelbury,, M. Haltia,, P. R. Wills,, J. J. Hauw,, P. E. McKeever,, L. Monari,, B. Schrank,, G. D. Swergold,, L. Autilio-Gambetti,, D. C. Gajdusek,, E. Lugaresi,, and P. Gambetti. 1992. Fatal familial insomnia and familial Creutzfeldt-Jakob disease—disease phenotype determined by a DNA polymorphism. Science 258: 806– 808.
49. Griffiths, J . 1967. Self-replication and scrapie. Nature 215: 1043– 1044.
50. Hadlow, W. J. 1959. Scrapie andkuru. Lancet ii: 289– 290.
51. Hill, A. F.,, M. Desbrulais,, S. Joiner,, K. C. Sidle,, I. Gowland,, J. Collinge,, L. J. Doey,, and P. Lantos. 1997. The same prion strain causes vCJD and BSE. Nature 389: 448– 450, 526.
52. Hill, A. F.,, R. J. Butterworth,, S. Joiner,, G. Jackson,, M. N. Rossor,, D. J. Thomas,, A. Frosh,, N. Folley,, J. E. Bell,, M. Spencer,, A. King,, S. Al-Sarraj,, J. W. Ironside,, P. L. Lantos,, and J. Collinge. 1999a. Investigation of variant Creutzfeldt- Jakob disease and other human prion disease with tonsil biopsy samples. Lancet 353: 183– 189.
53. Hill, A.,, M. Antoniou,, and J . Collinge. 1999b. Protease-resistant prion protein produced in vitro lacks detectable infectivity. J . Gen. Virol. 80: 11– 14.
54. Hilton, D. A.,, E. Fathers,, P. Edwards,, J. W. Ironside,, and J. Zajicek. 1998. Prion immunoreactivity in appendix before clinical onset of variant Creutzfeldt-Jakob disease. Lancet 352: 703– 704.
55. Hornabrook, R. W., 1978. Slow virus infections of the central nervous system, p. 275– 290. In P. J. Vinken, and G. W. Bruyn, (ed.), in collaboration with H. L. Klawans, Handbook of Clinical Neurology, Part II, Infections of the Nervous System, vol. 34. North- Holland Publishing Co., Amsterdam, The Netherlands.
56. Hsiao, K.,, H. F. Baker,, T. J . Crow,, M. Poulter,, F. Owen,, J . Tewiliger,, D. Westaway,, J . Ott,, and S. Prusiner. 1989. Linkage of a prion protein missense variant to Gerstmann-Straussler syndrome. Nature 338: 342– 345.
57. Hsiao, K. K.,, M. Scott,, D. Foster,, D. F. Groth,, S. J. DeArmond,, and S. B. Prusiner. 1990. Spontaneous neurodegeneration in transgenic mice with mutant prion protein. Science 250: 1587– 1590.
58. Ironside, J . W.,, and J . E. Bell,. 1997. Pathology of prion diseases, p. 57– 88. In J. Collinge, and M. S. Palmer (ed.), Prion Diseases. Oxford University Press, Oxford, United Kingdom.
59. Kim, J . H.,, and E. E. Manuelidis. 1983. Pathology of human and experimental Creutzfeldt-Jakob disease. Pathol. Annu. 18: 359– 373.
60. Kimberlin, R. H.,, and C. A. Walker. 1986. Pathogenesis of scrapie (strain 263K) in hamsters infected intracerebrally, intraperitoneally or intraocularly. J. Gen. Virol. 67: 255– 263.
61. Kirschbaum, W. R. 1968. Jakob-Creutrfeldt Disease. American Elsevier Publishing Co., New York, N.Y.
62. Kitagawa, Y.,, F. Gotoh,, A. Koto,, S. Ebihara,, H. Okayasu,, T. Ishii,, and H. Matsuyama. 1983. Creutzfeldt-Jakob disease: a case with extensive white matter degeneration and optic atrophy. J . Neurol. 229: 97– 101.
63. Kitamoto, T.,, R. W. Shin,, K. Doh-ura,, N. Tomokane,, M. Miyazono,, T. Muramoto,, and J . Tateishi. 1992. Abnormal isoform of prion protein accumulates in synaptic structures of the central nervous system in patients with Creutzfeldt-Jakob disease. Am. J. Pathol. 140: 1285– 1289.
64. Klatzo, I.,, D. C. Gajdusek,, and V. Zigas. 1959. Pathology of kuru. Lab. Investig. 8: 799– 847.
65. Klein, M. A.,, R. Frigg,, E. Flechsig,, A. J. Raeber,, U. Kalinke,, H. Bluethmann,, F. Bootz,, M. Suter,, R. M. Zinkermagel,, and A. Aguzzi. 1997. A crucial role for B cells in neuroinvasive scrapie. Nature 390: 687– 690.
66. Knopman, D. S.,, S. T. DeKosky,, J . L. Cummings,, H. Chui,, J . Corey-Bloom,, N . Relkin,, G. W. Small,, B . Miller,, and J . C. Stevens. 2001. Practice parameter: diagnosis of dementia (an evidence based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 56: 1143– 1153.
67. Kocisko, D. A.,, J . H. Come,, S. A. Priola,, B. Chesebro,, G. J . Raymond,, P. T. Lansbury,, and B. Caughy. 1994. Cell-free formation of protease-resistant prion protein. Nature 370: 471– 474.
68. Korth, C.,, B. C. H. May,, F. E. Cohen,, and S. B. Prusiner. 2001. Acridine and phenothiazine derivatives as pharmacotherapeutics for prion disease. Proc. Natl. Acad. Sci. USA 98: 9836– 9841.
69. Kretzschmar, H. A.,, G. Honold,, F. Seitelberger,, M. Feucht,, P. Wessely,, P. Mehraein,, and H. Budka. 1991. Prion protein mutation in family first reported by Gerstmann, Straussler, and Scheinker. Lancet 337: 1160.
70. Kuzuhara, S.,, I. Kanazawa,, H. Sasaki,, T. Nakanishi,, and K. Shimamura. 1983. Gerstmann-Sträussler-Scheinker's disease. Ann. Neurol 14: 216– 225.
71. Lampert, P. W.,, D. C. Gajdusek,, and C. J. Gibbs Jr. 1971. Experimental spongiform encephalopathy (Creutzfeldt-Jakob disease) in chimpanzees. Electron microscopic studies. J . Neuropathol Exp. Neurol. 30: 20– 32.
72. Lampert, P. W.,, D. C Gajdusek,, and C. J. Gibbs Jr. 1975. Pathology of dendrites in subacute spongiform virus encephalopathies. Adv. Neurol. 12: 465– 470.
73. Landis, D. M.,, R. S. Williams,, and C. L. Masters. 1981. Golgi and electron microscopic studies of spongiform encephalopathy. Neurology 31: 538– 549.
74. Lemstra, A. W.,, M. T. van Meegen,, J. P. Vreyling,, P. H. S. Meijerink,, G. H. Jansen,, S. Bulk,, F. Baas,, and W. A. van Gool. 2000. 14-3-3 testing in diagnosing Creutzfeldt-Jakob disease. A prospective study. Neurology 55: 514– 516.
75. Lugaresi, E.,, R. Medori,, P. Montagna,, A. Baruzzi,, P. Cortelli,, A. Lugaresi,, P. Tinnper,, M. Zucconi,, and P. Gambetti. 1986. Fatal familial insomnia and dysautonomia with selective degeneration of thalamic nuclei. N. EngL J. Med. 315: 997– 1003.
76. Manuelidis, E. E.,, E. J . Gorgacz,, and L. Manuelidis. 1978. Transmission of Creutzfeldt-Jakob disease with scrapie-like syndromes to mice. Nature 271: 778– 779.
77. Masters, C. L.,, and E. P. Richardson Jr. 1978. Subacute spongiform encephalopathy (Creutzfeldt-Jakob disease). The nature and progression of spongiform change. Brain 101: 333– 344.
78. Masters, C. L.,, and D. C. Gajdusek,. 1982. The spectrum of Creutzfeldt-Jakob disease and the virus-induced subacute spongiform encephalopathies, p. 139– 162. In W. T. Smith, and J. B. Cavanagh (ed.), Recent Advances in Neuropathology. Churchill Livingstone, Edinburgh, Scotland.
79. Masters, C. L.,, J. O. Harris,, C. Gajdusek,, C. J. Gibbs Jr.,, C. Bernoulli,, and D. M. Asher. 1979. Creutzfeldt-Jakob disease: patterns of worldwide occurrence and the significance of familial and sporadic clustering. Ann. Neurol. 5: 177– 188.
80. Masters, C. L.,, D. C. Gajdusek,, and C. J. Gibbs, Jr. 1981. Creutzfeldt-Jakob disease virus isolations from the Gerstmann- Straussler syndrome with an analysis of the various forms of amyloid plaque deposition in the virus-induced spongiform encephalopathies. Brain 104: 559– 588.
81. Matthews, W. B. 1978. Creutzfeldt-Jakob disease. Postgrad. Med. J. 54: 591– 594.
82. Medori, R.,, H.-J. Tritschler,, A. LeBlanc,, F. Villare,, V. Manetto,, H. Y. Chen,, R. Xue,, S. Leal,, P. Montagna,, P. Cortelli,, P. Tinuper,, P. Avoni,, M. Mochi,, A. Baruzzi,, J. J. Hauw,, J . Ott,, E. Lugaresi,, L . Autilio-Gambetti,, and P. Gambetti. 1992. Fatal familial insomnia, a prion disease with a mutation at codon 178 of the prion protein gene. N. Engl. J. Med. 326: 444– 449.
83. Milhavet, O.,, M. E. M. McMahon,, W. Rachidi,, N. Nishida,, S. Katamine,, A. Mange,, M. Arlotto,, D. Casanova,, J . Riondel,, A. Favier,, and S. Lehmann. 2000. Prion infection impairs the cellular response to oxidative stress. Proc. Natl. Acad. Sci. USA 97: 13937– 13942.
84. Miller, M. W.,, E. S. Williams,, C. W. McCarty,, T. R. Spraker,, T. J. Kreeger,, C. T. Larsen,, and E. T. Thorne. 2000. Epizootiology of chronic wasting disease in free-ranging cervids in Colorado and Wyoming. J. Wildlife Dis. 36: 676– 690.
85. Mitzutani, T.,, A. Okumura,, M. Oda,, and H. Shirki. 1981. Panencephalitic type of Creutzfeldt-Jakob disease: primary involvement of the cerebral white matter. J. Neurol. Neurosurg. Psychiat. 44: 103– 115.
86. Montagna, P.,, P. Cortelli,, P. Avoni,, P. Tinuper,, G. Plazzi,, R. Galassi,, F. Portaluppi,, J. Julien,, C. Vital,, M. B. Delisle,, P. Gambetti,, and E. Lugaresi. 1998. Clinical features of fatal familial insomnia: phenotypic variability in relation to a polymorphism at codon 129 of the prion protein. Brain Pathol 8: 515– 520.
87. Muramoto, T.,, S. J . DeArmond,, M. Scott,, G. C. Telling,, F. E. Cohen,, and S. B. Prusiner. 1997. Heritable disorder resembling neuronal storage disease in mice expressing prion protein with deletion of an alpha-helix. Nat. Med. 3: 750– 755.
88. Ohta, M.,, M. Koga,, J . Tateishi,, S. Motomara,, and S. Yamashita. 1978. An autopsy report of spongiform encephalopathy associated with kuru plaques and leucomalacia. Adv. Neurol. Sci. 22: 487– 496.
90. Palmer, M. S.,, A. J . Dryden,, J. T. Hughes,, and J . Collinge. 1991. Homozygous prion protein genotype predisposes to sporadic Creutzfeldt-Jakob disease. Nature 352: 340– 342.
91. Parchi, P.,, A. Giese,, S. Capellari,, P. Brown,, W. Schulz-Schaeffer,, O. Windl,, I. Zerr,, H. Budka,, N . Kopp,, P. Piccardo,, S. Poser,, A. Rojiani,, N. Streichemberger,, J . Julien,, C. Vital,, B . Ghetti,, P. Gambetti,, and H. Kretzschmar. 1999. Classification of sporadic Creutzfeldt-Jakob disease based on molecular and phenotypic analysis of 300 subjects. Ann. Neurol. 46: 224– 233.
92. Park, T. S.,, G. M. Kleinman,, and E. P. Richardson. 1980. Creutzfeldt-Jakob disease with extensive degeneration of white matter. Acta Neuropathol. 52: 239– 242.
93. Peretz, D.,, R. A. Williamson,, K. Kaneke,, J . Vergara,, E. Leclerc,, G. Schmitt-Ulms,, I. R. Mehlhorn,, G. Legname,, M. R. Wormald,, P. M. Rudd,, R. A. Dwek,, D. R. Burton,, and S. B. Prusiner. 2001. Antibodies inhibit prion propagation and clear cell cultures of prion infectivity. Nature 412: 739– 743.
94. Poser, S.,, B. Mollenhauer,, A. Krauss,, I. Zerr,, B. J. Steinhoff,, A. Schroeter,, M. Finkenstaedt,, W. J. Schulz-Schaeffer,, H. A. Kretzschmar,, and K. Felgenhauer. 1999. How to improve the clinical diagnosis of Creutzfeldt-Jakob disease. Brain 122: 2345– 2351.
95. Prusiner, S. B. 1982. Novel proteinaceous infectious particles cause scrapie. Science 216: 136– 144.
96. Prusiner, S. B. 2001. Shattuck lecture—neurodegenerative diseases and prions. N. Engl. J. Med. 344: 1516– 1526.
97. Prusiner, S. B.,, K. K. Hsiao,, D. E. Bredesen,, and S. J. DeArmond,. 1989. Prion disease, p. 543– 580. In R. R. McKendall (ed.), Handbook of Clinical Neurology, vol. 12(56): Viral Disease. Elsevier Science, Amsterdam, The Netherlands.
98. Richardson, E. P., Jr.,, and C. L. Masters. 1995. The nosology of Creutzfeldt-Jakob disease and conditions related to the accumulation of PrP CJD in the nervous system. Brain Pathol. 5: 33– 41.
99. Ricketts, M. N.,, N. R. Cashman,, E. E. Stratton,, and S. E. L. Saadany. 1997. Is Creutzfeldt-Jakob disease transmitted in blood. Emerg. Infect. Dis. 3: 155– 163.
100. Rieger, R.,, F. Edenhofer,, C. I. Lasmezas,, and S. Weiss. 1997. The human 37-kDa laminin receptor precursor interacts with the prion protein in eukaryotic cells. Nat. Med. 3: 1383– 1388.
101. Rutala, W. A.,, and D. J . Weber. 2001. Creutzfeldt-Jakob disease: recommendations for disinfection and sterilization. Clin. Infect. Dis. 32: 1348– 1356.
102. Salazar, A. M.,, C. L. Masters,, D. C. Gajdusek, and C J. Gibbs. 1983. Syndromes of amyotrophic lateral sclerosis: relation to transmissible Creutzfeldt-Jakob disease. Ann. Neurol. 14: 17— 26.
103. Schatzl, H. M.,, L. Laszlo,, D. M. Holtzman,, J. Tatzelt,, S. J. DeArmond,, R. I. Weiner,, W. C. Mobley,, and S. B. Prusiner. 1997. A hypothalamic neuronal cell line persistently infected with scrapie prions exhibits apoptosis. J. Virol. 71: 8821– 8831.
104. Scott, M. R.,, R. Will,, J . Ironside,, H.-O.B. Nauyen,, P. Tremblay,, S. J. Armond,, and S. B. Prusiner. 1999. Compelling transgenic evidence for transmission of bovine spongiform encephalopathy prions to humans. Proc. Natl. Acad. Sci. USA 96: 15137– 15142.
105. Seipelt, M.,, I. Zerr,, R. Nau,, B . Mollenhauer,, S. Kropp,, B. J. Steinhoff,, C. WilhelnvGossling,, C. Bamberg,, R. W. C. Janzen,, P. Berlit, R Manz, K. Felgienhauer, and S. Poser. 1999. Hashimoto's encephalitis as a differential diagnosis of Creutzfeldt-Jakob disease. J. Neurol. Neurosurg. Psychiatr. 66: 172– 176.
106. Seitelberger, F. 1962. Eigenartige familiar-hereditare Krankheit des Zentralnerven-systems in einer niederosterreichen Sippe. Wien Klin. Wschr. 74: 687– 691.
107. Shaked, G. M.,, R. Englstein,, I. Auraham,, H. Rosenmann,, and R. Bagizon. 2002. Valproic acid treatment results in increased accumulation of prion proteins. Ann. Neurol. 52: 416– 420.
108. Shyng, S. L.,, J. E. Heuser,, and D. A. Harris. 1994. A glycolipidanchored prion protein is endocytosed via clathrin-coated pits. J. Cell Biol. 125: 1239– 1250.
109. Steinhoff, B. J.,, S. Racker,, G. Herrendorf,, S. Poser,, S. Grosche,, I. Zerr,, H. Kretzschmar,, and T. Weber. 1996. Accuracy and reliability of periodic sharp wave complexes in Creutzfeldt-Jakob disease. Arch. Neurol. 53: 162– 166.
110. Tateishi, J.,, Y. Sato,, M. Koga,, H. Doi,, and M. Ohta. 1980. Experimental transmission of human subacute spongiform encephalopathy to small rodents. I. Clinical and histological observations. Acta Neuropathol. 51: 127– 134.
111. Tateishi, J.,, P. Brown,, T. Kitamoto,, Z. M. Hogue,, R. Roos,, R. Wollman,, L. Cerevenakova,, and D. C. Gajdusek. 1995. First experimental transmission of fatal familial insomnia. Nature 376: 434– 435.
112. Thadani, V.,, P. L. Penar,, J . Partington,, R. Kalb,, R. Janssen,, L. B. Schonberger,, C. S. Rabkin,, and J. W. Prichard. 1988. Creutzfeldt-Jakob disease probably acquired from a cadaveric dura mater graft. J . Neurosurg. 53: 1197– 1201.
113. Tobler, I.,, S. E. Gaus,, T. Deboer,, P. Achermann,, M. Fischer,, T. Rulicke,, M. Moser,, B . Oesch,, P. A. McBridge,, and J. C. Manson. 1996. Altered circadian activity rhythms and sleep in mice devoid of prion protein. Nature 380: 639– 642.
114. Ward, H. J. T.,, D. Everington,, E. A. Croes,, A. Alperovitch,, N. Delasnerie-Laupretre,, I. Zerr,, S. Poser,, and, C. M. van Duijn for the European Union (ED) Collaborative Study Group of Creutzfeldt-Jakob Disease . 2002. Sporadic CreutzfeldtJakob disease (CJD)and surgery: a case-control study using community controls. Neurology 59: 543– 548.
115. Weissmann, C.,, A. J. Raeber,, D. Shmerling,, A. Cozzio,, E. Flechsig,, and A. Aguzzi,. 1999. The use of genetically modified mice in prion research, p. 87– 106. In D. A. Harris (ed.), Prions: Molecular and Cellular Biology. Horizon Scientific Press, Norfolk, United Kingdom.
116. Wells, G. A. H.,, A. C. Scott,, C. T. Johnson,, R. E. Gunning,, R. D. Hancock,, M. Jeffrey,, M. Dawson,, and R. Bradley. 1987. A novel progressive spongiform encephalopathy in cattle. Vet. Rec. 121: 419– 420.
117. White, A. R.,, S. J . Collins,, F. Maher,, M. F. Jobling,, L. R. Stewart,, J. M. Thyer,, K. Beyreuther,, C. L. Masters,, and R. Cappai. 1999. Prion protein-deficient neurons reveal lower glutathione reductase activity and increased susceptibility to hydrogen peroxide toxicity. Am. J . Pathol. 155: 1723– 1730.
118. Wilesmith, J . W.,, G. A. H. Wells,, M. P. Cranwell,, and J. B. M. Ryan. 1988. Bovine spongiform encephalopathy: epidemiological studies. Vet. Rec. 123: 638– 644.
119. Will, R. G.,, and W. B. Matthews. 1984. A retrospective study of Creutzfeldt-Jakob disease in England and Wales 1970-79. I. Clinical features. J. Neurol. Neurosurg. Psychiatr. 47: 134– 140.
120. Will, R. G.,, J . W. Ironside,, M. Zeidler,, S. N. Cousens,, K. Estibeiro,, A. Alperovitch,, S. Poser,, M. Pocchiari,, A. Hofman,, and P. G. Smith. 1996a. A new variant of Creutzfeldt- Jakob disease in the UK. Lancet 347: 921– 925.
121. Will, R. G.,, M. Zeidler,, P. Brown,, M. Harrington,, K. H. Lee,, and K. L. Kenney. 1996b. Cerebrospinal-fluid test for new-variant Creutzfeldt-Jakob disease. Lancet 348: 955.
122. Will, R. G.,, M. Zeidler,, G. E. Stewart,, M. A. Macleod,, J . W. Ironside,, S. N. Cousens,, D. M. Stat,, J. Mackenzie,, K. Estibeiro,, A. J. E . Green,, and R. S. G. Knight. 2000. Diagnosis of new variant Creutzfeldt-Jakob disease. Ann. Neurol. 47: 575– 582.
123. Williams, E. S.,, and S. Young. 1980. Chronic wasting disease of captive mule deer: a spongiform encephalopathy. J. Wildlife Dis. 16: 89– 98.
124. World Health Organization. 1998. Human transmissible spongiform encephalopathies. Weekly Epidemiol. Rec. 73: 361– 365.
126. World Health Organization. 2002. The revision of the surveillance case definition for variant Creutzfeldt-Jakob disease (vCJD). Report of a WHO consultation. World Health Organization, Edinburgh, United Kingdom.
127. Zanusso, G.,, S. Ferrari,, F. Cardone,, P. Zampieri,, M. Gelati,, M. Fiorini,, A. Farinazzo,, M. Gardiman,, T. Cavallaro,, M. Bentivoglio,, P. G. Righetti,, M. Pocchiari,, N. Rizzuto,, and S. Monaco. 2003. Detection of pathologic prion protein in the olfactory epithelium in sporadic Creutzfeldt-Jakob disease. N. Engl. J. Med. 348: 711– 719.
128. Zeidler, M.,, R. J. Sehlar,, D. A. Collie,, R. Knight,, G. Stewart,, M. A. Macleod,, J. W. Ironside,, S. Cousens,, A. E. C. Colchester,, D. M. Hadley, and, R. G. Will. 2000. The pulvinar sign on magnetic resonance imaging in variant Creutzfeldt-Jakob disease. Lancet 355: 1412– 1418.
129. Zerr, I.,, M. Pocchiari,, S. Collins,, J. P. Brandel,, J . dePedro Cuesta,, R. S. G. Knight,, H. Bernheimer,, F. Cardone,, N. Delasnerie-Laupretre,, N. C Corrales,, A. Ladogana,, M. Bodemer,, A. Fletcher,, T. Awan,, A. R. Bremon,, H. Dubka,, J. L. Laplanche,, R. G. Will,, and S. Poser. 2000a. Analysis of EEG and CSF 14-3-3 proteins as aids to the diagnosis of Creutzfeldt-Jakob disease. Neurology 55: 811– 815.
130. Zerr, I.,, W. J. SchulzSchaeffer,, A. Giese,, M. Bodemer,, A. Schroter,, K. Henke,, H. J. Tschampa,, O. Windl,, A. Pfahlberg,, B. J. Steinhoff,, O. Gefeller,, H. A. Kretzschmar,, and S. Poser. 2000b. Current clinical diagnosis in Creutzfeldt-Jakob disease: identification of uncommon variants. Ann. Neurol. 48: 323– 329.

References: V. 
 V. 
 V. 
 V. 
 V. 
 V. 
 V.