Acta Neuropathologica

, Volume 26, Issue 2, pp 157–170 | Cite as

Infantile type of so-called neuronal ceroid-lipofuscinosis

Histological and Electron Microscopic Studies
  • Matti Haltia
  • Juhani Rapola
  • Pirkko Santavuori
Original Investigations

Summary

Autopsy reports are presented of three cases of a rapidly progressive encephalopathy with clinical onset around one year of age, early amaurosis, and microcephaly. Convulsions were few or absent. The disorder led to an extraordinary degree of brain atrophy, due to total loss of neurons from the cerebral and cerebellar cortex, and an advanced degree of neuronal destruction in most subcortical centres. The giant cells of Betz and the primary motor and sensory neurons were notable exceptions. The surviving neurons, other neuroectodermal cells, and a number of extraneural cell types showed accumulation of autofluorescent sudanophilic granules, resistant to lipid solvents, in their cytoplasm. Ultrastructurally, these granules were of the residual body type, consisting of membrane-bound conglomerations of spherical globules 0.2–0.5 μm in diameter, with a homogeneous, finely granular internal structure. These lesions were associated with a pronounced astrocytic and mesenchymal reaction with the presence of large numbers of phagocytic cells in the grey matter of the CNS and, to a lesser extent, in other tissues. In addition, there was almost total loss of myelin from the brain, apparently due to Wallerian degeneration.

The characteristic clinical, histological and ultrastructural features differentiate this condition from other progressive encephalopathies of the age group in question, including the late infantile type of the Batten-Vogt syndrome. Recent ultrastructural and biochemical findings indicate that the disease of our patients is identical with the progressive encephalopathy with disturbed polyunsaturated fat metabolism described by Hagberget al. (1968).

Key words

Infantile Encephalopathy Granular Osmiophilic Bodies Macrophage Reaction Batten-Vogt Syndrome Neuronal Ceroid-Lipofuscinosis 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Allegranza, A., Strada, G. P., Borri, P. F.: A case of late infantile amaurotic idiocy and a case of an unusual storage disease with visceral involvement. Path. europ.3, 248–258 (1968)Google Scholar
  2. Andrews, J. M., Sorenson, V., Cancilla, P. A., Price, H. M., Menkes, J. H.: Late infantile neurovisceral storage disease with curvilinear bodies. Neurology (Minneap.)21, 207–217 (1971)Google Scholar
  3. Benz, U.-U., Peiffer, J., Schlote, W.: Morphologische und biochemische Untersuchungen über einen Fall von juveniler amaurotischer Idiotie (neuronale Ceroid-Lipofuszinosis). In: H. Bredt u. G. Seifert (ed.): Aktuelle Probleme der Kinderpathologie, S. 427–432. Stuttgart: G. Fischer 1972Google Scholar
  4. Carpenter, S., Karpati, G., Andermann, F.: Specific involvement of muscle, nerve, and skin in late infantile and juvenile amaurotic idiocy. Neurology (Minneap.)22, 170–186 (1972)Google Scholar
  5. Dayan, A. D., Trickey, R. J.: Thyroid involvement in juvenile amaurotic family idiocy (Batten's disease). Lancet1970 II, 296–297Google Scholar
  6. Dolman, C. L., Chang, E.: Visceral lesions in amurotic familial idiocy with curvilinear bodies. Arch. Path.94, 425–430 (1972)Google Scholar
  7. Donahue, S., Zeman, W., Watanabe, I.: Electron microscopic observations in Batten's disease. In: S. M. Aronson and B. W. Volk (eds.): Inborn disorders of sphingolipid metabolism, pp. 3–22. Oxford: Pergamon Press 1967Google Scholar
  8. Duffy, P. E., Kornfeld, M., Suzuki, K.: Neurovisceral storage disease with curvilinear bodies. J. Neuropath. exp. Neurol.27, 351–370 (1968)Google Scholar
  9. Elfenbein, I. B., Cantor, H. E.: Late infantile amaurotic idiocy with multilamellar cytosomes: An electron microscopic study. J. Pediat.75, 253–264 (1969)Google Scholar
  10. Elsner, B., Prensky, A. L.: Ultrastructure of rectal biopsies in juvenile amaurotic idiocy. Neurology (Minneap.)19, 834–840 (1969)Google Scholar
  11. Gambetti, P.: The multilamellar cytosome in late infantile amaurotic idiocy. J. Neuropath. exp. Neurol.29, 138 (1970)Google Scholar
  12. Gonatas, N. K., Gambetti, P., Baird, H.: A second type of late infantile amaurotic idiocy with multilamellar cytosomes. J. Neuropath. exp. Neurol.27, 371–389 (1968)Google Scholar
  13. Haelst, U. J. G. M. van, Gabreëls, F. J. M.: The electron microscopic study of the appendix as early diagnostic means in Batten-Spielmeyer-Vogt disease. Acta neuropath. (Berl.)21, 169–175 (1972)Google Scholar
  14. Hagberg, B., Sourander, P., Svennerholm, L.: Late infantile progressive encephalopathy with disturbed polyunsaturated fat metabolism. Acta paediat. scand.57, 495–499 (1968)Google Scholar
  15. Haltia, M., Rapola, J., Santavuori, P., Keränen, A.: Infantile type of so-called neuronal ceroid-lipofuscinosis. II. Morphological and biochemical studies. J. neurol. Sci.18, 269–285 (1973)Google Scholar
  16. Herman, M. M., Rubinstein, L. J., McKhann, G. M.: Additional electron microscopic observations on two cases of Batten-Spielmeyer-Vogt disease (neuronal ceroid-lipofuscinosis). Acta neuropath. (Berl.)17, 85–102 (1971)Google Scholar
  17. Ishii, T., Gonatas, N. K.: The multilamellar cytosome in late infantile amaurotic idiocy. Acta neuropath. (Berl.)19, 265–270 (1971)Google Scholar
  18. Joosten, E., Gabreëls, F., Stadhouders, A., Bolmers, D., Gabreëls-Festen, A.: Involvement of sural nerve in neuronal ceroid-lipofuscinoses: report of two cases. Neuropädiatrie4, 98–110 (1973)Google Scholar
  19. Kantero, R. L., Tiisala, R.: Growth of head circumference from birth to 10 years. Acta paediat. scand., Suppl. 220 (1971)Google Scholar
  20. Kornfeld, M.: Generalized lipofuscinosis (generalized Kufs disease). J. Neuropath. exp. Neurol.31, 668–682 (1972)Google Scholar
  21. Kristensson, K., Rayner, S., Sourander, P.: Visceral involvement in juvenile amaurotic idiocy. Acta neuropath. (Berl.)4, 421–424 (1965)Google Scholar
  22. Peiffer, J.: Miorphologische Aspekte der Epilepsien. Berlin-Göttingen-Heidelberg: Springer 1963Google Scholar
  23. Richardson, M. E., Bornhofen, J. H.: Early childhood cerebral lipidosis with prominent myoclonus. Ultrastructural and histochemical studies of a cerebral biopsy. Arch. Neurol. (Chic.)18, 34–43 (1968)Google Scholar
  24. Richter, R., Parmelee, A. H.: Late infantile amaurotic idiocy with marked cerebral atrophy. Clinical and anatomic report of a case. Amer. J. Dis. Child.50, 111–131 (1935)Google Scholar
  25. Ryan, G. B., Anderson, R. McD., Menkes, J. H., Dennett, X.: Lipofuscin (ceroid) storage disease of the brain. Neuropathological and neurochemical studies. Brain93, 617–628 (1970)Google Scholar
  26. Santavuori, P.: Batten-Spielmeyer-Vogt in tauti. Duodecim88, 35–39 (1972)Google Scholar
  27. Santavuori, P., Haltia, M., Rapola, J., Raitta, C.: Infantile type of so-called neuronal ceroid-lipofuscinosis. I. A clinical study of 15 cases. J. neurol. Sci.18, 257–267 (1973)Google Scholar
  28. Schröder, J. M., Thomas, E., Kollmann, F.: Formvarianten kurvilinearer Zytosomen in Gehirn-, Leber- und Knochenmarksbiopsien bei neuroviszeralen Lipidosen. In: H. Bredt u. G. Seifert (eds.): Aktuelle Probleme der Kinderpathologie, S. 432–437. Stuttgart: G. Fischer 1972Google Scholar
  29. Seitelberger, F.: Sonderformen zerebraler Lipidosen. Histochemische und histologische Befunde. In: Proc. IVth Internat. Congr. Neuropath., Vol. I, pp. 3–13. Stuttgart: G. Thieme 1962Google Scholar
  30. Seitelberger, F., Jacob, H., Schnabel, R.: The myoclonic variant of cerebral lipidosis. In: S. M. Aronson, and B. W. Volk (eds.): Inborn disorders of sphingolipid metabolism, pp. 43–74. Oxford: Pergamon Press 1967Google Scholar
  31. Seitelberger, F., Sluga, E., Bernheimer, H.: Studies on neuronal lipid dystrophies. Path. europ.3, 230–247 (1968)Google Scholar
  32. Sjövall, E., Ericsson, E.: The anatomical type in the Swedish cases of juvenile amaurotic idiocy. Acta path. microbiol. scand., Suppl.16, 460–471 (1932)Google Scholar
  33. Sluga, E., Majdetzki, Th.: Zur Ultrastruktur des Speichermaterials von spätinfantiler amaurotischer Idiotie. Acta neuropath. (Berl.)9, 254–272 (1967)Google Scholar
  34. Suzuki, K., Johnson, A. B., Marquet, E., Suzuki, K.: A case of juvenile lipidosis: electron microscopic, histochemical and biochemical studies. Acta neuropath. (Berl.)11, 122–139 (1968)Google Scholar
  35. Tingey, A. H., Norman, R. M., Urich, H., Beasley, W. H.: Chemical and pathological findings in a case of late infantile amaurotic family idiocy of the Batten type. J. ment. Sci.104, 91–102 (1958)Google Scholar
  36. Towfighi, J., Baird, H. W., Gambetti, P., Gonatas, N. K.: The significance of cytoplasmic inclusions in late infantile and juvenile amaurotic idiocy. An ultrastructural study. Acta neuropath. (Berl.)23, 32–42 (1973)Google Scholar
  37. Ulrich, J.: Die cerebralen Entmarkungskrankheiten im Kindesalter. Diffuse Hirnsklerosen. Berlin-Heidelberg-New York: Springer 1971Google Scholar
  38. Zeman, W., Donahue, S.: Fine structure of the lipid bodies in juvenile amaurotic idiocy. Acta neuropath. (Berl.)3, 144–149 (1963)Google Scholar
  39. Zeman, W., Donahue, S., Dyken, P., Green, J.: The neuronal ceroid-lipofuscinoses (Batten-Vogt syndrome). In: P. J. Vinken, and G. W. Bruyn (eds.): Handbook of clinical neurology, vol. 10, pp. 588–679. Amsterdam: North-Holland Publishing Co. 1970Google Scholar
  40. Zeman, W., Dyken, P.: Neuronal ceroid-lipofuscinosis (Batten's disease): relationship to amaurotic family idiocy? Pedriatrics44, 570–583 (1969)Google Scholar

Copyright information

© Springer-Verlag 1973

Authors and Affiliations

  • Matti Haltia
    • 1
  • Juhani Rapola
    • 1
  • Pirkko Santavuori
    • 1
  1. 1.II. Department of Pathology and Children's HospitalUniversity of HelsinkiHelsinki 29Finland

Personalised recommendations