Acta Neuropathologica

, Volume 43, Issue 1–2, pp 35–42 | Cite as

Chronic relapsing EAE time course of neurological symptoms and pathology

  • H. Lassmann
  • H. M. Wisniewski
Original Investigations


The inflammatory reaction in chronic relapsing EAE was studied with special reference to the alterations found in the early stages of the disease (first attack, first remission, and first relapse). The inflammatory reaction during the early stages of the first attack was dominated by polymorphonuclear leukocytes, together with edema and sometimes hemorrhage, resembling the alterations found in hyperacute or neutrophilic EAE. The tissue reaction consisted of myelin, as well as axonal damage, and involved predominately the root entry zones and the subpial white matter in the lower thoracic and lumbo-sacral spinal cord, with less severe damage in grey and white matter in other regions of the brain. During the first remission, a variable amount of perivascular inflammatory cuffs of lymphocytes and mononuclear cells were found, but cellular infiltration into the neural parenchyma was confined to a few small perivascular areas. In the first relapse, a massive invasion of the neural parenchyma by mononuclear cells was noted, leading to large plaque-like zones of demyelination in the white matter. In this stage of the disease axonal damage was rare. The lesions were predominantly confined to the lower thoracic and lumbo-sacral spinal cord, but with increasing duration of the disease, higher portions of the spinal cord, as well as brain stem, cerebellar white matter, centrum semiovale and fornix were involved, too.

Further relapses showed a similar pattern as described in the second attack, although in these animals lesions of different ages were always found. Parallel with the clinical observations, the inflammatory reaction in the central nervous system also diminished with the duration of the disease.

A comparison between Strain 13 and Hartley guinea pigs revealed a more severe reaction during the first attack in the latter, possibly responsible for the high mortality of these animals during this stage of the disease.

Key words

Chronic relapsing EAE Demylination Guinea pigs 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Adams, R. D., Kubik, C. S.: The morbid anatomy of the demyelinative diseases. Amer. J. Med.12, 510–546 (1952)Google Scholar
  2. Barnhart, M. I., Sulisz, L., Bluhm, G. B.: Role of blood coagulation in acute inflammation. In: Immunopathology of Inflammation, pp. 59–65. Ed. B. K. Forscher, Amsterdam: Excerpta Medica 1971Google Scholar
  3. Cohen, S., Ward, P., Bigazzi, P. E.: Cell cooperation in cell mediated immunity. In: Mechanisms of cell mediated immunity, pp. 331–358. Ed. R. T. McCluskey and S. Chohen. New York, London, Sidney, Toronto: Wiley 1974Google Scholar
  4. Ferraro, A., Cazzullo, C. L.: Chronic experimental allergic encephalomyelitis in monkeys. J. Neuropath. exp. Neurol.7, 235–260 (1948)Google Scholar
  5. Field, E. J., Raine, C. S.: Experimental allergic encephalomyelitis in the Rhesus monkey. An electron microscopic study. J. Neurol. Sci.8, 397–411 (1969)Google Scholar
  6. Freund, J., Lipton, M. M., Morrison, C. R.: Demyelination in the guinea pig in chronic allergic encephalomyelitis. Arch. Path.50, 108 (1950)Google Scholar
  7. Jervis, G. A., Koprowski, H.: Experimental allergic encephalomyelitis. J. Neuropath. exp. Neurol7, 309–320 (1948)Google Scholar
  8. Lampert, P.: Electron microscopic studies on ordinary and hyperacute experimental allergic encephalomyelitis. Acta neuropath. (Berl.)9, 99–126 (1967)Google Scholar
  9. Levine, S.: Hyperacute, neutrophilic, and localized forms of experimental allergic encephalomyelitis: A review. Acta neuropath. (Berl.)28, 179–189 (1974)Google Scholar
  10. Levine, S., Hoenig, E. M.: A new form of localized allergic encephalomyelitis featuring polymorphonuclear neutrophilic leukocytes. Amer. J. Path.64, 13–27 (1971)Google Scholar
  11. Levine, S., Wenk, M. A.: A hyperacute form of allergic encephalomyelitis. Amer. J. Path.47, 61–88 (1965)Google Scholar
  12. Levine, S., Hoenig, E. M., Wenk, M. A.: Altered distribution of lesions after repeated passive transfers of allergic encephalomyelitis. Proc. Soc. Exp. Biol. (N.Y.)126, 454–458 (1967)Google Scholar
  13. Levine, S., Cochrane, C. G., Carpenter, C. B., Behan, P. O.: Allergic encephalomyelitis: Effect of complement depletion with cobra venom. Proc. Soc. exp. Biol. (N.Y.)138, 285–289 (1971)Google Scholar
  14. Levine, S., Sowinski, R., Shaw, C. M., Alvord, E. C.: Do neurological signs occur in experimental allergic encephalomyelitis in the absence of inflammatory lesions of the central nervous system? J. Neuropath. exp. Neurol.34, 501–507 (1975)Google Scholar
  15. Paterson, P.Y.: The demyelinating diseases: Clinical and experimental correlates. In: Immunological Diseases, pp. 1269–1299. Boston: Little, Brown & Co. 1971Google Scholar
  16. Paterson, P. Y.: Experimental allergic encephalomyelitis: role of fibrin deposition in immunopathogenesis of inflammation in rats. Fed. Proc.35, 2428–2434 (1976)Google Scholar
  17. Prineas, J. W.: The etiology and pathogenesis of multiple sclerosis. In: Handbook of Clin. Neurol. Vol 9, pp. 107–161, Eds. P. J. Vinken, G. W. Bruyn, New York: Elsevier 1970Google Scholar
  18. Remold, H. G., David, J. R.: Migration inhibition factor and other mediators in cell mediated immunity. In: Mechanisms of cell mediated immunity, pp. 25–43. Ed. R. T. McCluskey and S. Cohen. New York, London, Sidney, Toronto: Wiley 1974Google Scholar
  19. Snyder, D. H., Valsamis, M. P., Stone S. H., Raine, C. S.: Progressive and reparatory events in chronic experimental allergic encephalomyelitis. J. Neuropath. Exp.34, 209–221 (1975)Google Scholar
  20. Smith, S. B., Waksman, B. H.: Passive transfer and labelling studies on the cell infiltrate in experimental allergic encephalomyelitis. J. Path.99, 237–244 (1969)Google Scholar
  21. Stone, S. H., Lerner, E. M.: Chronic disseminated allergic encephalomyelitis in guinea pigs. Ann. N. Y. Acad. Sci.122, 227–241 (1965)Google Scholar
  22. Stone, S. H., Lerner, E. M., Goode, J. H.: Acute and chronic autoimmune encephalomyelitis: Age, strain and sex dependency. The importance of the source of antigen. Proc. Soc. exp. Biol. (N.Y.)132, 341–344 (1969)Google Scholar
  23. Stone, S. H., Lerner, E. M., Myers, R. E., Niemann, W. H.: Autoimmune encephalomyelitis and ocular lesions in monkeys sensitized during the neonatal period. Science151, 473–475 (1966)Google Scholar
  24. Stossel, T. P.: Phagocytosis (first of the three parts). Med. Progr.290, 717–723 (1974)Google Scholar
  25. Waksman, B. H., Adams, R. D.: A histologic study of the early lesions in experimental allergic encephalomyelitis in the guinea pig and rabbit. Amer. J. Path.41, 135–153 (1962)Google Scholar
  26. Ward, P. A., Hill, J. F.: Role of complement in the generation of leucotactic mediators and nonspecific tissue injuries. In: Immunopathology of Inflammation, pp. 52–58. Ed. B. K. Forscher and J. C. Houck. Amsterdam: Excerpta Medica 1971Google Scholar
  27. Willoughby, D. A., DiRosa, M.: A unifying concept for inflammation: A new appraisal of some old mediators. In: Immunopathology of inflammation, pp. 1–38, Amsterdam: Excerpta Medica 1971Google Scholar
  28. Wisniewski, H. M., Keith, A. B.: Chronic relapsing experimental allergic encephalomyelitis: An experimental model of multiple sclerosis. Ann. Neurol.1, 144–148 (1976)Google Scholar

Copyright information

© Springer-Verlag 1978

Authors and Affiliations

  • H. Lassmann
    • 1
  • H. M. Wisniewski
    • 1
  1. 1.New York State Institute for Basic Research in Mental RetardationNew YorkUSA

Personalised recommendations