Acta Neuropathologica

, Volume 56, Issue 1, pp 1–8 | Cite as

Immunological and pathological findings in demyelinating encephalitis associated with canine distemper virus infection

  • M. Vandevelde
  • F. Kristensen
  • B. Kristensen
  • A. J. Steck
  • U. Kihm
Original Works


Nine dogs with canine distemper encephalitis (CDE) were examined with immunological techniques including demonstration of antibodies against canine distemper virus (CDV) in the serum and against myelin basic protein (MBP) in serum and in CSF. Mitogen stimulation tests of lymphocytes were also done. The brains were examined pathologically and immunoglobulin and C3 were demonstrated in lesions by means of immunohistological techniques.

Six dogs with acute CDE had none or low antibody levels against CDV or MBP, and there was no immunoglobulin in demyelinating lesions. Some of these dogs had depressed lymphocyte mitogen responses. Two dogs with chronic CDE showed recovery of lymphocyte mitogen responses. One of these had a significant antibody response against CDV and MBP in the serum. Both dogs with chronic CDE had very high antibody titers against MBP in the CSF and demyelinating lesions contained immunoglobulin. These results suggest that acute demyelination in CDE is probably due to some direct viral activity and that the progression of demyelination in chronic CDE is associated with a local immune response.

Key words

Canine distemper encephalitis (CDE) Immunopathology Demyelination Immunoglobulin Local immune response 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Appel MJG, Gillespie JH (1972) Canine distemper virus. Virology monographs. Springer, Wien New YorkGoogle Scholar
  2. Appel MJG, Robson DS (1973) A microneutralization test for canine distemper virus. Am J Vet Res 34:1459–1463Google Scholar
  3. Brosnan CF, Stoner GL, Bloom BR, Wisniewski HM (1977) Studies on demyelination by activated lymphocytes in the rabbit eye. II. Antibody-dependent cell-mediated demyelination. J Immunol 118:2103–2110Google Scholar
  4. Fankhauser R (1962) The cerebrospinal fluid. In: Innes JRM, Saunders LZ (eds) Comparative neuropathology. Academic Press. New York LondonGoogle Scholar
  5. Golds EE, Braun P (1978): Cross-linking studies on the conformation and dimerisation of myelin basic protein in solution. J Biol Chem 253:8171–8177Google Scholar
  6. Grundke-Iqbal I, Lassmann H, Wisniewski HM (1980) Chronic relapsing experimental allergic encephalomyelitis. Arch Neurol 37:651–656Google Scholar
  7. Higgins RJ, Krakowka S, Koestner A (1982a) Acute canine distemper virus induced encephalomyelitis in gnotobiotic dogs—A sequential ultrastructural study. (Submitted) Acta neuropathol (Berl)Google Scholar
  8. Higgins RJ, Krakowka S, Metzler AK, Koestner A (1982b) Primary demyelination in CDV-induced encephalomyelitis in gnotobiotic dogs. (Submitted) Acta Neuropathol (Berl)Google Scholar
  9. Ho CK, Babiuk LA (1979) Immune mechanisms against canine distemper. I. Identification of K cell against canine distemper virus-infected target cells in vitro. Immunology 37:231–239Google Scholar
  10. Itoyama Y, Sternberger NH, Kies MW, Cohen SR, Richardson EP Jr, Webster H de F (1980a) Immunocytochemical, method to identify myelin basic protein in oligodendroglia and myelin sheaths of the human nervous system. Ann Neurol 7:157–166Google Scholar
  11. Itoyama Y, Sternberger NH, Webster H de F, Quarles RH, Cohen SR, Richardson EP, Jr (1980b) Immunocytochemical observations on the distribution of myelin-associated glycoprotein and myelin basic protein in multiple selerosis lesions. Ann Neurol 7:167–177Google Scholar
  12. Imagawa DT (1968) Relationship among measles, canine distemper, and Rinderpest viruses. Prog Med Virol 10:160–193Google Scholar
  13. Koestner A, McCullough B, Krakowka GS, Long JF, Olsen RG (1974) Canine distemper, a virus-induced demyelinating encephalomyelitis. In: Zeman W, Lenette EH (eds) Slow virus diseases. Williams and Wilkins, Baltimore, pp 86–101Google Scholar
  14. Koestner A (1975) Animal model of human disease. Subacute sclerosing panencephalitis, multiple sclerosis. Am J Pathol 78:361–364Google Scholar
  15. Krakowka S, McCullough B, Koestner A, Olsen RG (1973) Myelinspecific autoantibodies associated with central nervous system demyelination in canine distemper, virus infection. Infect Immun 8:819–827Google Scholar
  16. Krakowka S, Higgins RJ, Koestner A (1980) Canine distemper virus: Review of structural and functional modulations in lymphoid tissues. Am J Vet Res 41:284–292Google Scholar
  17. Krakowka S, Wallace AL, Koestner A (1981) Shared antigenic determinants between brain and thymus-derived lymphocytes in dogs. Implications regarding the significance of antimyelin antibodies in demyelination. Acta Neuropathol (Berl) 54:75–82Google Scholar
  18. Kristensen B, Kristensen F, Vandevelde M, Higgins RJ, de Weck AL (1982a): Canine lymphocyte cultures in vitro: Evaluation of peripheral blood lymphocyte response to mitogens (Submitted) Vet Immunol ImmunopatholGoogle Scholar
  19. Kristensen F, Kristensen B, Vandevelde M, Higgins RJ, de Weck AL (1982b): Analysis of the in vitro activation and proliferation process in lymphocytes deriving from canine thymus and mesenteric lymph node. (Submitted) Vet Immunol ImmunopatholGoogle Scholar
  20. Kristensson K, Thormar H, Wisniwski HM (1979) Myelin lesions in the rabbit eye model as a bystander effect of herpes simplex and visna virus sensitization. Acta Neuropathol (Berl) 48:215–217Google Scholar
  21. Lassmann H, Wisniewski HM (1978) Chronic relapsing EAE. Time course of neurological symptoms and pathology. Acta Neuropathol (Berl) 43:35–42Google Scholar
  22. Martin JR, Nathanson N (1979) Animal models of virus-induced demyelination. In: Zimmerman HM (ed) Progress in neuropathology, vol 4. Raven Press, New York, pp 27–50Google Scholar
  23. McCullough B, Krakowska S, Koestner A (1974) Experimental canine distemper virus-induced lymphoid depletion. Am J Pathol 74:155–165Google Scholar
  24. Moulton JE (1956) Fluorescent antibody studies of demyelination in canine distemper. Proc Soc Exp Biol 91:460–464Google Scholar
  25. Raine CS (1976) On the development of CNS lesions in natural canine distemper encephalomyelitis. J Neurol Sci 30:13–28Google Scholar
  26. Shek WR, Schultz RD, Appel MJ (1980): Natural and immune cytolysis of canine distemper virus-infected target cells. Infect Immun 28:724–734Google Scholar
  27. Steck AJ, Tschannen R, Schaefer R (1981) Induction of antimyelin and antioligodendrocyte antibodies by vaccinia virus: experimental study in the mouse. J Neuroimmun 1:117–124Google Scholar
  28. Sternberger LA (1979) Immunocytochemistry, 2nd edn. Wiley & Sons, New York Chichester Brisbane Toronto, pp 122–129Google Scholar
  29. Summers BA, Greisen HA, Appel MJG (1979) Early events in canine distemper demyelinating encephalomyelitis. Acta Neuropathol (Berl) 46:1–10Google Scholar
  30. Traugott U, Raine CS (1979) Acute experimental allergic encephalomyelitis. Myelin basic protein-reactive T cells in the circulation and in meningeal infiltrates. J Neurol Sci 42:331–336Google Scholar
  31. Vandevelde M, Kristensen B (1977) Observations on the distribution of canine distemper virus in the central nervous system of dogs with demyelinating encephalitis. Acta Neuropathol (Berl) 40:233–236Google Scholar
  32. Vandevelde M, Spano JS (1977) Cerebrospinal fluid cytology in canine neurologic disease. Am J Vet Res 38:1827–1832Google Scholar
  33. Vandevelde M, Fankhauser R, Kristensen F, Kristensen B (1981) Immunoglobulins in demyelinating lesions in canine distemper encephalitis. Acta Neuropathol (Berl) 54:31–41Google Scholar
  34. Wisniewski HM, Brosnan CF, Bloom BR (1980) Bystander and antibody-dependent cell-mediated demyelination. In: Davison AN, Cuzner ML (eds) The suppression of experimental allergic encephalomyelitis and multiple sclerosis. Academic Press, London New York Toronto Sydney San Francisco, pp 45–57Google Scholar

Copyright information

© Springer-Verlag 1982

Authors and Affiliations

  • M. Vandevelde
    • 1
  • F. Kristensen
    • 2
  • B. Kristensen
    • 2
  • A. J. Steck
    • 3
  • U. Kihm
    • 4
  1. 1.Institute of Comparative NeurologyUniversity of BerneBerneSwitzerland
  2. 2.Institute of Clinical Immunology, InselspitalUniversity of BerneBerneSwitzerland
  3. 3.Department of NeurologyUniversity of LausanneLausanneSwitzerland
  4. 4.National Vaccine InstituteBasleSwitzerland

Personalised recommendations