Skip to main content
SpringerLink
Log in

Neuropathologic characteristics of spinal cord lesions in sporadic Creutzfeldt-Jakob disease

  • Regular Paper
  • Published:
Acta Neuropathologica Aims and scope Submit manuscript

Abstract

We investigated the neuropathologic features of spinal cord lesions in 23 patients with sporadic Creutzfeldt-Jakob disease (sCJD), paying particular attention to neuronal loss and gliosis, pyramidal tract degeneration and prion protein (PrP) deposition. The study included 9 cases of subacute spongiform encephalopathy, 13 cases of panencephalopathic-type sCJD and 1 case of sporadic fatal insomnia (sFI). In the spinal gray matter, although gliosis was present in some patients with disease of relatively long duration, the number of neurons, including large motor neurons, was well preserved regardless of disease duration. Pyramidal tract degeneration was observed in some patients with disease lasting more than 14 months but not in the patient with sFI. PrP deposition was present in the spinal cord of all sCJD patients, and was identified predominantly in the posterior horn, particularly in the substantia gelatinosa, regardless of disease duration or disease classification based on cerebral pathology. Relatively prominent PrP deposition was also observed in Clarke’s column. The density of PrP deposition in the sCJD spinal cord was not associated with disease duration or neuronal degeneration. Our results indicate that PrP deposition in the spinal cord is an early pathologic event in sCJD and may remain to the end stage. Although no VV1, VV2 or MV2 cases were included in our study, we suggest that stereotypic accumulation of PrP is a consistent pathologic feature of sCJD and that the spinal cord remains relatively resistant to the pathologic process of sCJD, at least in patients with MM1 sCJD.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Allen IV, Dermott E, Connolly JH, Hurwitz LJ (1971) A study of a patient with the amyotrophic form of Creutzfeldt-Jakob disease. Brain 94:715–724

    PubMed  Google Scholar 

  2. Beck E, Daniel PM (1979) Kuru and Creutzfeldt-Jakob disease: neuropathological lesions and their significance. In: Prusiner SB, Hadlow WJ (eds) Slow transmissible disease of the nervous system, vol 1. Academic Press, New York, pp 253–270

  3. Beekes M, Baldauf E, Cassens S, Diringer H, Keyes P, Scott AC, Wells GA, Brown P, Gibbs CJ Jr, Gajdusek DC (1995) Western blot mapping of disease-specific amyloid in various animal species and humans with transmissible spongiform encephalopathies using a high-yield purification method. J Gen Virol 76:2567–2576

    PubMed  Google Scholar 

  4. Bell JE, Ironside JW (1993) Neuropathology of spongiform encephalopathies in humans. Br Med Bull 49:738–777

    PubMed  Google Scholar 

  5. Brown P (1994) Transmissible human spongiform encephalopathy (infectious cerebral amyloidosis): Creutzfeldt-Jakob disease, Gerstmann-Sträussler-Scheinker syndrome and Kuru. In: Calne DB (ed) Neurodegenerative diseases. Saunders, Philadelphia, pp 839–876

  6. Brown P, Gibbs CJ Jr, Rodgers-Johnson P, Asher DM, Sulima MP, Bacote A, Goldfarb LG, Gajdusek DC (1994) Human spongiform encephalopathy: the National Institutes of Health series of 300 cases of experimentally transmitted disease. Ann Neurol 35:513–529

    PubMed  Google Scholar 

  7. Budka H, Aguzzi A, Brown P, Brucher JM, Bugiani O, Gullotta F, Haltia M, Hauw JJ, Ironside JW, Jellinger K, Kretzschmar HA, Lantos PL, Masullo C, Schlote W, Tateishi J, Waller RO (1995) Neuropathological diagnostic criteria for Creutzfeldt-Jakob disease (CJD) and other human spongiform encephalopathies (prion diseases). Brain Pathol 5:459–466

    PubMed  Google Scholar 

  8. Castellani R, Parchi P, Stahl J, Capellari S, Cohen M, Gambetti P (1996) Early pathologic and biochemical changes in Creutzfeldt-Jakob disease: study of brain biopsies. Neurology 46:1690–1693

    PubMed  Google Scholar 

  9. DeArmond SJ, Prusiner SB (1995) Etiology and pathogenesis of prion diseases. Am J Pathol 146:785–811

    PubMed  Google Scholar 

  10. DeArmond SJ, Dickson DW, DeArmond B (1997) Human prion disease: degenerative disease of the central nervous system. In: Davis RL, Rovertson DM (eds) Textbook of neuropathology, 3rd edn. Williams & Wilkins, Baltimore, pp 1111–1125

  11. DeArmond SJ, Kretzschmar HA, Prusiner SB (2002) Prion disease. In: Greenfield JG, Graham DI, Lantos PL (eds) Greenfield’s neuropathology, vol 2, 7th edn. Arnold, London, pp 273–323

  12. Favereaux A, Quadrio I, Perret-Liaudet A, Vital C, Ouallet JC, Brochet B, Biacabe AG, Petry KG, Kopp N, Vital A (2003) Prion protein accumulation involving the peripheral nervous system in a sporadic case of Creutzfeldt-Jakob disease. Neuropathol Appl Neurobiol 29:602–605

    Article  PubMed  Google Scholar 

  13. Favereaux A, Quadrio I, Vital C, Perret-Liaudet A, Anne O, Laplanche JL, Petry KG, Vital A (2004) Pathologic prion protein spreading in the peripheral nervous system of a patient with sporadic Creutzfeldt-Jakob disease. Arch Neurol 61:747–750

    Article  PubMed  Google Scholar 

  14. Goodbrand IA, Ironside JW, Nicolson D, Bell JE (1995) Prion protein accumulation in the spinal cords of patients with sporadic and growth hormone associated Creutzfeldt-Jakob disease. Neurosci Lett 183:127–130

    Article  PubMed  Google Scholar 

  15. Hainfellner JA, Budka H (1999) Disease associated prion protein may deposit in the peripheral nervous system in human transmissible spongiform encephalopathies. Acta Neuropathol 98:458–460

    PubMed  Google Scholar 

  16. Ironside JW (1996) Review: Creutzfeldt-Jakob disease. Brain Pathol 6:379–388

    PubMed  Google Scholar 

  17. Ironside JW, Head MW, Bell JE, McCardle L, Will RG (2000) Laboratory diagnosis of variant Creutzfeldt-Jakob disease. Histopathology 37:1–9

    PubMed  Google Scholar 

  18. Ishida C, Okino S, Kitamoto T, Yamada M (2005) Involvement of the peripheral nervous system in human prion diseases including dural graft associated Creutzfeldt-Jakob disease. J Neurol Neurosurg Psychiatry 76:325–329

    Article  PubMed  Google Scholar 

  19. Iwasaki Y, Hashizume Y, Yoshida M, Kitamoto T, Sobue G (2005) Neuropathologic characteristics of brainstem lesions in sporadic Creutzfeldt-Jakob disease. Acta Neuropathol 109:557–566

    Article  PubMed  Google Scholar 

  20. Kandel ER, Schwartz JH, Jessell TM (1991) Principles of neural science, 3rd edn. Elsevier, Amsterdam

  21. Kascsak RJ, Rubenstein R, Merz PA, Tonna-Demasi M, Fersko R, Carp RI, Wisniewski HM, Diringer H (1987) Mouse polyclonal and monoclonal antibody to scrapie-associated fibril proteins. J Virol 61:3688–3693

    PubMed  Google Scholar 

  22. Kirschbaum WR (1968) Jakob-Creutzfeldt Disease. American Elsevier, New York

  23. Kitamoto T, Tateishi J (1994) Human prion diseases with variant prion protein. Philos Trans R Soc Lond B Biol Sci 343:391–398

    PubMed  Google Scholar 

  24. Kitamoto T, Shin RW, Doh-ura K, Tomokane N, Miyazono M, Muramoto T, Tateishi J (1992) Abnormal isoform of prion proteins accumulates in the synaptic structures of the central nervous system in patients with Creutzfeldt-Jakob disease. Am J Pathol 140:1285-1294

    PubMed  Google Scholar 

  25. MacDonald ST, Sutherland K, Ironside JW (1996) Prion protein genotype and pathological phenotype studies in sporadic Creutzfeldt-Jakob disease. Neuropathol Appl Neurobiol 22:285–292

    PubMed  Google Scholar 

  26. Mahadevan A, Shankar SK, Yasha TC, Santosh V, Sarkar C, Desai AP, Satishchandra P (2002) Brain biopsy in Creutzfeldt-Jakob disease: evolution of pathological changes by prion protein immunohistochemistry. Neuropathol Appl Neurobiol 28:314–324

    Article  PubMed  Google Scholar 

  27. Malamud N (1979) Creutzfeldt-Jakob’s disease: a clinicopathologic study. In: Prusiner SB, Hadlow WJ (eds) Slow transmissible disease of the nervous system, vol 1. Academic Press, New York, pp 271–285

  28. Masters CL, Richardson EP Jr (1978) Subacute spongiform encephalopathy (Creutzfeldt-Jakob disease). The nature and progression of spongiform change. Brain 101:333–344

    PubMed  Google Scholar 

  29. Mizutani T (1985) Panencephalopathic type of Creutzfeldt-Jakob Disease. In: Mizutani T, Shiraki H (eds) Clinicopathological aspects of Creutzfeldt-Jakob disease. Elsevier, Amsterdam, pp 123–162

  30. Mizutani T, Okumura A, Oda M, Shiraki H (1981) Panencephalopathic type of Creutzfeldt-Jakob disease: primary involvement of the cerebral white matter. J Neurol Neurosurg Psychiatry 44:103–115

    PubMed  Google Scholar 

  31. Parchi P, Castellani R, Cortelli P, Montagna P, Chen SG, Petersen RB, Manetto V, Vnencak-Jones CL, McLean MJ, Sheller JR, Lugaresi E, Autilio-Gambetti L, Gambetti P (1995) Regional distribution of protease-resistant prion protein in fatal familial insomnia. Ann Neurol 38:21–29

    PubMed  Google Scholar 

  32. Parchi P, Castellani R, Capellari S, Ghetti B, Young K, Chen SG, Farlow M, Dickson DW, Sima AA, Trojanowski JQ, Petersen RB, Gambetti P (1996) Molecular basis of phenotypic variability in sporadic Creutzfeldt-Jakob disease. Ann Neurol 39:767–778

    Article  PubMed  Google Scholar 

  33. 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 46:224–233

    Article  PubMed  Google Scholar 

  34. Parchi P, Capellari S, Chin S, Schwarz HB, Schecter NP, Butts JD, Hudkins P, Burns DK, Powers JM, Gambetti P (1999) A subtype of sporadic prion disease mimicking fatal familial insomnia. Neurology 52:1757–1763

    PubMed  Google Scholar 

  35. Safar J, Ceroni M, Piccardo P, Gajdusek DC, Gibbs CJ Jr (1990) Scrapie-associated precursor proteins: antigenic relationship between species and immunocytochemical localization in normal, scrapie, and Creutzfeldt-Jakob disease brains. Neurology 40:513–517

    PubMed  Google Scholar 

  36. Satoh K, Muramoto T, Tanaka T, Kitamoto N, Ironside JW, Nagashima K, Yamada M, Sato T, Mohri S, Kitamoto T (2003) Association of an 11–12 kDa protease-resistant prion protein fragment with subtypes of dura graft-associated Creutzfeldt-Jakob disease and other prion diseases. J Gen Virol 84:2885–2893

    Article  PubMed  Google Scholar 

  37. Shimizu S, Hoshi K, Muramoto T, Homma M, Ironside JW, Kuzuhara S, Sato T, Yamamoto T, Kitamoto T (1999) Creutzfeldt-Jakob disease with florid-type plaques after cadaveric dura mater grafting. Arch Neurol 56:357–362

    Article  PubMed  Google Scholar 

  38. Taguchi Y, Mohri S, Ironside JW, Muramoto T, Kitamoto T (2003) Humanized knock-in mice expressing chimeric prion protein showed varied susceptibility to different human prions. Am J Pathol 163:2585–2593

    PubMed  Google Scholar 

  39. Tateishi J, Kitamoto T (1993) Developments in diagnosis for prion diseases. Br Med Bull 49:971–979

    PubMed  Google Scholar 

  40. Watanabe H, Hamada K, Hishikawa N, Iwasaki Y, Ito H, Hirayama M, Sobue G, Ito H, Yoshida M, Hashizume Y (2003) An autopsy case of severe autonomic failure with Parkinson’s disease associated with Creutzfeldt-Jakob disease. Neuropathology 23: A42

    Google Scholar 

  41. Worrall BB, Rowland LP, Chin SS, Mastrianni JA (2000) Amyotrophy in prion diseases. Arch Neurol 57:33–38

    Article  PubMed  Google Scholar 

  42. Yamada M, Tomimitsu H, Yokota T, Tomi H, Sunohara N, Mukoyama M, Itoh Y, Suematsu N, Otomo E, Okeda R, Matsushita M, Mizusawa H (1999) Involvement of the spinal posterior horn in Gerstmann-Sträussler-Scheinker disease (PrP P102L). Neurology 52:260–265

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neurology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, 466-8550, Nagoya, Japan

    Yasushi Iwasaki & Gen Sobue

  2. Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University, Aichi, Japan

    Mari Yoshida & Yoshio Hashizume

  3. Department of Neurological Science, Tohoku University Graduate School of Medicine, Sendai, Japan

    Tetsuyuki Kitamoto

Authors
  1. Yasushi Iwasaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mari Yoshida
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yoshio Hashizume
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Tetsuyuki Kitamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Gen Sobue
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yasushi Iwasaki.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Iwasaki, Y., Yoshida, M., Hashizume, Y. et al. Neuropathologic characteristics of spinal cord lesions in sporadic Creutzfeldt-Jakob disease. Acta Neuropathol 110, 490–500 (2005). https://doi.org/10.1007/s00401-005-1076-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00401-005-1076-7

Keywords

Search

Navigation