Summary
The pathological findings in four nerves and muscles and in one skin biopsies from four patients treated with perhexiline maleate for angina pectoris are reported. In every case, a muscular denervation atrophy and a decrease in the large diameter myelinated fibers were observed. Only one case showed a decrease of the total number of myelinated fibers, on quantitative studies. The electron microscopic study of each nerve displayed findings consistent with a predominant schwannian degeneration, associated with a few onion bulbs formations and, in two cases, with a mild wallerian degeneration. The most striking finding consisted in the presence of polymorphous membrane-bound inclusions reminding the morphology of lysosomal complex lipids. These structures were very abundant in Schwann cells, but they were seen also in fibrocytes, endothelial and pericytic cells. Similar inclusions were present in the single muscle and skin biopsies studied by electron microscopy. In the muscle, they were seen in muscular cells as well as in endothelial and pericytic cells.
In the skin, similar inclusions were observed in endothelial, smooth muscle and sweat gland cells.
These inclusions were difficult to identifiy in one micron thick sections, emphazing the need of ultrastructural study for diagnostic purposes.
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Abaza, A., Cattan, D., Aziza, C., Pappo, E.: Effets secondaires mais réversibles à la prise de perhexiline. Nouv. Presse méd.2, 2820 (1973)
Bourrat, C., Viala, J.-J., Guastala, J.-P.: Neuropathie périphérique arrès absorption prolongée de maléate de perhexiline. Deux cas. Nouv. Presse méd4, 2528 (1975)
Bousser, M.-G., Bouche, P., Brochard, C., Herreman, G.: Sept neuropathies périphériques après traitement par maléate de perhexiline. Nouv. Presse méd.5, 652–653 (1976)
Bousser, M.-G., Bouche, P., Brochard, C., Herreman, G.: Neuropathies périphériques au maléate de perhexiline. A propos de 7 observations. Coeur Méd., Int.15, 181–188 (1976)
Castaigne, P., Laplane, D., Escourolle, R., Hauw, J. J., Mussini, J. M.: Etude des lésions nerveuses périphériques observées au cours de traitements prolongés par le maléate de perhexiline. Rev. neurol.132, 431 (1976)
Del Cerro, M. D., Snyder, R. S.: Studies on dilantin intoxication Ultrastructural analogies with lipidosis. Neurology (Minneap.)17, 452–466 (1967)
Dietert, S. E., Scallen, T. J.: An ultrastructural and biochemical study of the effects of three inhibitors of cholesterol biosynthesis upon murine adrenal gland and testis. Histochemical evidence for a lysosome response. J. Cell Biol.40, 44–60 (1969)
Fedorko, M. E., Hirsch, J. G., Cohn, Z. A.: Autophagic vacuoles produced in vitro I studies on cultured macrophages exposed to chloroquine. J. Cell Biol.38, 377–391 (1968)
Fedorko, M. E., Hirsch, J. G., Cohn, Z. A.: Autophagic vacuoles produced in vitro II studies on the mechanism of formation of autophagic vacuoles produced by chloroquine. J. Cell Biol.38, 392–402 (1968)
Fildes-Brosnan, F. C., Bunge, M. B., Murray, M. R.: The response of lysosomes in cultured neurons to chlorpromazine. J. Neuropath. exp. Neurol.29, 337–353 (1970)
Garcin, R., Rondot, P., Fardeau, M.: Neuromyopathie au cours des traitements prolongés par la chloroquine. Thérapeutique Bichat 1–3 (1966)
Hendelman, W. J.: A morphologic study of the effects of LSD on neurons in cultures of cerebellum. J. Neuropath. exp. Neurol.31, 411–432 (1972)
Hendy, R. J., Abrahan, R., Grasso, P.: The effect of chloroquine on rat heart lysosomes. J. Ultrastruct. Res.29, 485–495 (1969)
Kim, S. U.: Effects of the cholesterol biosynthesis inhibitor AY 9944 on organotypic cultures of mouse spinal cord. Retarded myelinogenesis and induction of cytoplasmic inclusions. Lab. Invest.32, 720–728 (1975)
Lhermitte, F., Fardeau, M., Chedru, F., Mallecourt, J.: Polyneuropathy after perhexiline maleate therapy. Brit. med. J.1976 I, 1256
MacDonald, R. D., Engel, A. G.: Experimental chloroquine myopathy. J. Neuropath. exp. Neurol.29, 479–499 (1970)
Mussini, J.-M., Vanderkelen, B., Hauw, J.-J., Escourolle, R.: Etude quantitative du nerf périphérique sur coupes semifines par la technique du contraste interférentiel de Nomarki. Rev. neurol. (sous presse)
Pelletier, M., Lambert, R., Paliard, P., Bory, R.: Hépatite toxique subaigue après traitement par maléate de perhexiline. Nouv. Presse méd.5, 1070 (1976)
Pilcher, S., Chandrasekhar, K. P., Russel-Rees, J., Boyce, M. J., Peirce, T. H., Idram, H.: Long term assessment of perhexiline maleate in angina pectoris. Postgrad. med. J.49, (Suppl. 3), 115–118 (1973)
Rawlins, F. A., Uzman, B. G.: Retardation of peripheral nerves myelination in mice treated with inhibitors of cholesterol biosynthesis: a quantitative electron microscopic study. J. Cell Biol.46, 505–517 (1970)
Roizin, L., Schneider, J., Wilson, N., Liu, J. C., Mulen, C.: Effects of prolonged LSD 25 administration upon neurons of spinal cord ganglia tissue cultures. J. Neuropath. exp. Neurol.23, 212–225 (1974)
Stern, J.: The induction of ganglioside storage in nervous system cultures. Lab. Invest.26, 509–514 (1972)
Stern, J., Novikoff, A. B., Terry, R. D.: The induction of sulfatide, ganglioside and cerebroside storage in organised nervous system cultures. In: Sphingolipides, sphingolipidosis and allied disorders (eds. B. W. Volk et S. M. Aronson), pp. 651–660. Plenum Publishing Corporation 1972
Suzuki, K., Zagoren, J. C., Gonatas, J., Suzuki, K.: Ultrastructural study of neuronal cytoplasmic inclusions produced by hypocholesterolemic drug AY 9944. Acta neuropath. (Berl.)26, 185–197 (1973)
Tischner, K. H.: Chloroquine induced alterations in rat sensory ganglia cultivated in vitro. A light and electron microscope study. Acta neuropath. (Berl.)22, 208–221 (1972)
Toga, M., Berard Badier, M., Pinsard, N., Gambarelli, D., Hassoun, J., Tripier, M.-F.: Etude clinique, histologique et ultrastructurale de quatre cas de leucodystrophie métachromatique infantile et juvénile. Acta neuropath. (Berl.)21, 23–38 (1972)
Wisnant, J. P., Espinosa, R. E., Kierland, R. R., Lambert, E. H.: Chloroquine myopathy. Proc. Mayo Clin.38, 501–513 (1963)
Wright, G. J., Zeiger, A. F., Leeson, G. A., Lang, J. F.: The absorption excretion and metabolism of perhexiline maleate by the human. Postgrad. med. J.49, (Suppl. 3), 8–15 (1973)
Zagoren, J. C., Suzuki, K., Bornstein, M. B., Chen, S. C., Suzuki, K.: Effects of hypocholesterolemic drug AY 9944 on cultured nervous tissue. Morphologic and biochemical studies. J. Neuropath. exp. Neurol.34, 375–387 (1975)
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Mussini, J.M., Hauw, J.J. & Escourolle, R. Etude en microscopie électronique des lésions nerveuses, musculaires et cutanées déterminées par le maléate de perhexiline. Acta Neuropathol 38, 53–59 (1977). https://doi.org/10.1007/BF00691277
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DOI: https://doi.org/10.1007/BF00691277