Summary
Electron microscopic findings of a cortical biopsy from a four-year-old child suffering from muscular weakness and psychomotor retardation are presented. Morphological evidence obtained in this study suggests a unique pathogenetic mechanism underlying INAD. The spheroids appear to be caused by an accumulation of a macromolecular substance synthesized in the neuron and transported to the nerve endings. The abnormal substance initially takes the form of an amorphous material, it eventually aggregates into highly characteristic angulated membranous profiles. The selective involvement of the nerve endings, synapses and motor end plates in this disease suggests a derangement of the metabolic pathway in the synthesis or packaging of the neurotransmitters or their receptors.
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Austin, L., Chubt, I. W., Livett, B. G.: The subcellular localization of catecholamines in nerve terminals in smooth muscle tissue. J. Neurochem.14, 473–478 (1967)
Barondes, S. H.: On the site of synthesis of the mitochondrial protein of nerve endings. J. Neurochem.13, 721–727 (1966)
Borondes, S. H.: Further studies on the transport of protein to nerve endings. J. Neurochem.15, 343–350 (1968)
Bérard-Badier, M., Gambarelli, D., Pinsard, N., Hassoum, J., Toga, M.: Infantile neuroaxonal dystrophy or Seitelberger's disease. II. peripheral nerve involvement: electron microscopic study in one case. Acta neuropath. (Berl.), Suppl.5, 30–39 (1971)
Carlton, W. W., Kreutzberg, G.: Isonicotinic acid hydrazid induced sponge degeneration of the white matter in the brains of Peking ducks. Amer. J. Path.48, 91–105 (1966)
Chou, S. M., Hartman, H. A.: Axonal lesions and waltzing syndrome after IDPN administration in rats with a concept “axostasis”. Acta neuropath. (Berl.)3, 428–450 (1964)
Coster, W. de, Roels, H., Eecken, H. vander: Electron microscopic study of neuroaxonal dystrophy. Europ. Neurol.5, 65–83 (1971)
Cowen, D., Olmstead, E. V.: Infantile neuroaxonal dystrophy. J. Neuropath. exp. Neurol.22, 175–236 (1963)
Crome, L., Weller, S. D. V.: Infantile neuroaxonal dystrophy. Arch. Childh.40, 502–507 (1965)
De Robertis, E.: Molecular biology of synaptic receptors. Science171, 963–971 (1971)
Droz, B., Leblond, C. P.: Axonal migration of proteins in central nervous system and peripheral nerves as shown by autoradiography. J. comp. Neurol.121, 325–345 (1963)
Duffy, P. E., Tennyson, V. M.: Phase and electron microscopic observations of Lewy bodies and melanin granules in the substantia nigra and locus ceruleus in Parkinson's disease. J. Neuropath. exp. Neurol.24, 398–414 (1965)
Ellis, W. G., McCulloch, J. R., Yatsu, F.: Infantile neuroaxonal dystrophy. An ultrastructural and biochemical studies. Abst. Neurology (Minneap.)19, 304 (1969)
Gonatas, N. K., Goldensohn, E. S.: Unusual neocortical presynaptic terminals in a patient with convulsion, mental retardartion and cortical blindness. An electron microscopy study. J. Neuropath. exp. Neurol.24, 539–562 (1965)
Grillo, M. A.: Electron microscopy of sympathetic tissue. Pharmacol. Rev.18, 387–399 (1966)
Haberland, C., Brunngraber, E., Witting, L. A.: Infantile neuroaxonal dystrophy. Neuropathological and biochemical study of a case. Arch. Neurol. (Chic.)26, 391–402 (1972)
Häggendal, J., Dahlstrom: The importance of axoplasmic transport of amine granules for the function of adrenergic neurons. Acta neuropath. (Berl.) Suppl.5, 238–248 (1971)
Hedley-Whyte, E. T., Gilles, F. H., Uzman, B. G.: Infantile neuroaxonal dystrophy, a disease characterized by altered terminal axons and synaptic endings. Neurology (Minneap.)18, 891–906 (1968)
Herman, M. M., Huttenlocker, P. R., Bensch, F.: Electron microscopy observation in infantile neuronaxonal dystrophy. Arch. Neurol. (Chic.)20, 19–34 (1969)
Hökfelt, T.: Distribution of noradrenaline storage particles in peripheral adrenergic neurons as revealed by electron microscopy. Acta physiol. scand.76, 427–440 (1969)
Jellinger, K., Jirasek, A.: Neuroaxonal dystrophy in man: character and natural history. Acta neuropath. (Berl.) Suppl.5, 3–16 (1971)
Kamoshita, S., Neustein, H. B., Landing, B. H.: Infantile neuroaxonal dystrophy with neonatal onset. Neuropathological and electron microscopic observations. J. Neuropath. exp. Neurol.27, 300–323 (1968)
Kent, G., Minick, O. T., Volini, F. I., Orfei, E., de la Huerga, J.: Iron storage in N-2 Fluorenylacetamide induced hepatic injury. Electron microscopic observation following the injection if iron dextran complex. J. Path. Bact.82, 453–470 (1961)
Koenig, H.: Some observations on the experimental production of acute neuroaxonal and synaptosomal dystrophy. Acta neuropath. (Berl.) Suppl.5, 121–131 (1971)
Koenig, E.: Synthetic mechanisms in the axon. 1. Local axonal synthesis of acetylcholinesterase. J. Neurochem.12, 343–355 (1965)
Lampert, P., Blumberg, J. M., Pentschew, A.: An electron microscopic study of dystrophic axons in the gracile and cuneate nuclei of vitamin E deficient rats. Axonal dystrophy in vitamin E deficiency. J. Neuropath. exp. Neurol.23, 60–77 (1964)
Leninger, A.: Biochemistry. Molecular basis of cell structure and function, p. 756. New York: Worth 1972
Liu, H. M.: Schwann cell properties: 1. Origin of Schwann cell during peripheral nerve regeneration. J. Neuropath. exp. Neurol. (in press).
Liu, H. M.: Schwann cell properties: II. Identity of phagocytes in the degenerated nerve (in preparation)
Livett, B. G., Greffen, L. B., Austin, L.: Proximo-distal transport of14C nordrenaline and protein in sympathetic nerves. J. Neurochem.15, 731–939 (1968)
Lubinska, L.: Axoplasmic streaming in regenerating and in normal nerve fibers. Progr. Brain Res.12, 1–16 (1964)
Martin, J. J., Martin, L.: Infantile neuroaxonal dystrophy, ultrastructural study of the peripheral nerves and of the motor end plates. Europ. Neurol.8, 239–250 (1972)
Pentschew, A., Schwarz, K.: Systemic axonal dystrophy in vitamin E deficient adult rats. Acta neuropyth. (Berl.)1, 313–334 (1962)
Sandbank, U., Lerman, P., Geiman: Infantile neuroaxonal dystrophy, cortical, axonic and presynaptic changes. Acta neuropath. (Berl.)16, 342–352 (1970)
Seitelberger, F.: Eine unbekannte Form von infantiler Lipoidspeicher-Krankheit des Gehirns. Proc. 1st. Internat. Congr. Neuropath. Rome, vol. 3, pp. 323–333. Torino: Rosenberg & Seller 1952
Seitelberger, F.: Eine eigenartige Stoffwechselerkrankung der Ganglienzellen im Zentralnervensystem. In: Proc. 5th Internat. Congr. Neurol. Lisbon, vol. 3, p. 484 (1954)
Seitelberger, F.: Neuropathological conditions related to neuroaxonal dystrophy. Acta neuropath. (Berl.) Suppl.5, 17–29 (1971)
Taylor, A. C., Weiss, P.: Demonstration of axonal flow by the movement of tritium labeled protein in mature optic nerve fibers. Proc. nat. Acad. Sci. (Wash.)54, 1521–1527 (1965)
Terry, R. D., Gonatas, N. K., Weiss, M.: Alzheimer's presenile dementia. Amer. J. Path.44, 269–298 (1965)
Toga, M., Dubois, D., Hassoum, J.: Ultra-structure des corps de Lafora. Acta neuropath. (Berl.)10, 132–142 (1968)
Toga, M., Bérard-Bodier, M., Gambarelli, D.: La dystrophie neuroaxonale infantile ou Maladie de Seitelberger. Acta neuropath. (Berl.)15, 327–350 (1970)
Weiss, P.: Neuronal organelles in neuroplasmic “axonal” flow. Mitochondria. Acta. neuropath. (Berl.) Suppl.5, 187–197 (1971)
Zeman, W., Scapelli, D. G.: The non specific lesions of Hallervorden-Spatz disease. A histochemical study. J. Neuropath. exp. Neurol.17, 622–639 (1958)
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Mei Liu, H., Larson, M. & Mizuno, Y. An analysis of the ultrastructural findings in infantile neuroaxonal dystrophy (Seitelberger's disease). Acta Neuropathol 27, 201–213 (1974). https://doi.org/10.1007/BF00687630
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DOI: https://doi.org/10.1007/BF00687630