Muscle and nerve changes induced by perhexiline maleate in man and mice

Perhexiline maleate therapy may produce a polyneuropathy as well as other side effects in man. The Schwann-cell origin of the neuropathy is demonstrated by morphologic studies. Ultrastructural studies of muscle and nerve biopsies showed the presence of intracytoplasmic inclusions, primarily in Schwann cells, muscle fibers, and endothelial cells. These inclusions were polymorphic and varied from one cell type to another. They were frequently associated with calcium deposits, and their structure suggested a lysosomal origin. It was possible experimentally to reproduce similar inclusions in mice. Furthermore, numerous tubular aggregates were observed in intoxicated mouse muscle fibers.