Which histologic findings are characteristic of toxic neuropathy?

Updated: Dec 06, 2017
  • Author: Jonathan S Rutchik, MD, MPH, FACOEM; Chief Editor: Tarakad S Ramachandran, MBBS, MBA, MPH, FAAN, FACP, FAHA, FRCP, FRCPC, FRS, LRCP, MRCP, MRCS  more...
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Answer

Muscle and nerve pathology findings associated with ethylene oxide or mercury exposure include the following:

  • Muscle and nerve biopsies were carried out by Kuzuhara et al on 2 patients who developed distal symmetrical polyneuropathies after being exposed to EtO while working as employees of a factory that produced medical supplies. The nerve biopsies of both patients implied axonal degeneration and regeneration. Swollen Schwann cell processes with numerous filaments, myelin figures, debris, and vacuoles with and without granules were seen on the electromicrogram of the sural nerve of patient 1. Growth cones of damaged axons were seen on the sural nerve of patient 2. [24]

  • Muscle biopsies revealed smearing and distortion of the Z bands. Some revealed absence of mitochondria and target or targetoid structures. Transverse sections showed atrophic fibers, scattered or grouped with many target fibers. Enzyme histochemistry of muscle from patient 2 revealed atrophy of both type 1 and type 2 fibers in the myosin adenosine triphosphatase (ATPase) reaction and dark angulated fibers, target, targetoid, and moth-eaten fibers on nicotinamide adenine dinucleotide-tetrazolium reductase (NADH-TR) reaction.

  • In 1993, Ohnishi and Murai reported that histologic studies of the sural nerves biopsied in 3 patients revealed decreased density of large myelinated fibers, reduction of the cross-sectional area of axons, reduction of axonal circularity, and presence of myelin ovoid and Bunger bands, which are compatible with a mild degree of axonal degeneration. [50]

  • Experimental EtO neuropathy was produced by Ohnishi in rats exposed to a one-time dose of 500 ppm for 6 hours or 5 doses of 250 ppm for 6 hours at a time over a week. In both experiments, distal axonal degeneration was found both in peripheral and central myelinated axons of lumbar primary sensory neurons of rats. In hind leg nerves and in the fasciculus gracilis, myelinated fibers showed axonal degeneration sparing the nerve cell body of the lumbar dorsal root ganglion and myelinated fibers of lumbar dorsal and ventral roots. The rats exposed to 250 ppm also showed a retardation of growth and maturation of myelinated fibers in the presence of mild axonal degeneration.

  • In a patient with EtO polyneuropathy after 5 months of exposure, Schroder et al performed a sural nerve biopsy that revealed nerve fiber degeneration of the wallerian type associated with reduction of axonal cross-sectional areas and some degree of nerve fiber regeneration. Conspicuous paranodal vesicular disintegration of individual myelin lamella also was present. Unusual cisternae with introverted hemidesmosomes were noted in endoneural fibroblasts. [23]

  • Nerve pathology was investigated in those exposed to organic mercury. Miyakawa et al reported selective swelling and degeneration of the Schwann cells, noticeable changes of both myelin sheaths and the axon. Pathologic changes began at the nodes of Ranvier. Primary site of damage was noted to be in the cell bodies of the sensory ganglion cells, with axonal degeneration occurring later in rats poisoned by methylmercury hydroxide. The largest myelinated fibers were affected to a greater extent than the smaller caliber fibers in the dorsal root. [55]

  • An autopsy performed on a descendant of a woman exposed to mercury at Minimata Bay demonstrated segmental demyelination of the PNS. In both humans and animals, the major pathologic effect of methylmercury appears to be on the dorsal root ganglion cells. Similar data are not available for inorganic or metallic mercury poisoning.


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