Etude en microscopie �lectronique des l�sions nerveuses, musculaires et cutan�es d�termin�es par le mal�ate de perhexiline

Abstract

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 identify in one micron thick sections, emphazing the need of ultrastructural study for diagnostic purposes.

Interactions of acid sphingomyelinase and lipid bilayers in the presence of the tricyclic antidepressant desipramine

“…Our results suggest that desipramine possibly induces intracellular proteolysis of A‐SMase by displacing the enzyme from its membrane‐bound lipid substrate and thereby making it sensitive to proteolysis. The resulting loss of lysosomal A‐SMase activity may well trigger the lysosomal lipid accumulation described before [10–14].…”

“…Lysosomal inclusions similar to those known from patients with lipid storage diseases were observed in various organs of rats upon treatment with amphiphilic cationic drugs, including lung and liver as well as the central nervous system. Retinal alterations, corneal opacities, hepatosplenomegaly, abnormalities of liver function and neuro‐myopathies accompanied by inclusions especially abundant in Schwann cells were observed in humans [11–14].…”

Amiodaron Neuropathy: Further Arguments for Human Drug-Induced Neurolipidosis

“…1976], Peripheral neuropathy associated with similar inclusions has been observed after perexiline maleate treatment [Lhermille et al, 1976;Mussini et al, 1977;Nick et al. 1978].…”