The Fine Structure of Spheromembranous Degeneration of Skeletal Muscle Induced by Vincristine*†‡

Abstract

The development of a syndrome resembling peripheral neuropathy has been repeatedly observed in patients treated with vincristine sulfate (17, 20, 32) and has been reproduced experimentally in rats (34). Histopathologic and histochemical study of the effects of vincristine on nerve and muscle of rat disclosed extensive non-inflammatory degeneration of skeletal muscle but no detectable abnormality of peripheral nerve (34). Myofibrillar and sarcoplasmic degeneration was preceded by the elaboration of interfibrillary spheromembranous bodies up to 3μ in diameter. Their appearance was followed by loss of myofibrillar profile, homogenization of myofibrils, and progressive dissolution of the sarcoplasm. Four points of evidence suggested that the spheromembranous bodies developed from remnants of mitochondria and sarcoplasmic reticulum: 1. their morphology was membranous, 2. their histochemical reactions were compatible with a complex lipid composition (e.g. phospholipid), 3. their location between myofibrils and opposite I-bands corresponded to the arrangement of the triads of sarcoplasmic reticulum, and 4. the absence of oxidative enzyme reactions implied a loss or degeneration of mitochondria in their vicinity. The purposes of the present study are to define the ultrastructure of the spheromembranous bodies and to re-examine the peripheral nerve and motor end-plates at the submicroscopic level.