Mechanisms of toxic injury in the peripheral nervous system: neuropathologic considerations

The anatomical distribution and organization of the peripheral nervous system as well as its frequent ability to reflect neurotoxic injury make it useful for the study of nerve fiber and ganglionic lesions. Contemporary neuropathologic techniques provide sections with excellent light-microscopic resolution for use in making such assessments. The histopathologist examining such peripheral nerve samples may see several patterns of neurotoxic injury. Most common are axonopathies, conditions in which axonal alterations are noted; these axonopathies often progress toward the Wallerian-like degeneration of affected fibers. These are usually more severe in distal regions of the neurite, and they affect both peripheral and central fibers. Examples of such distal axonopathies are organophosphorous ester-induced delayed neuropathy, hexacarbon neuropathy, and p-bromophenylacetylurea intoxication. These axonopathies may have varying pathologic features and sometimes have incompletely understood toxic mechanisms. In such neuropathies with fiber degeneration, peripheral nerve axons may regenerate, which can complicate pathologic interpretation of neurotoxicity. On occasion neurotoxins elicit more severe injury in proximal regions of the fiber (not included in this review). Axonal pathology is also a feature of the neuronopathies, toxic states in which the primary injuries are found in neuronal cell bodies. This is exemplified by pyridoxine neurotoxicity, where there is sublethal or lethal damage to larger cytons in the sensory ganglia, with failure of such neurons to maintain their axons. Lastly, one may encounter myelinopathies, conditions in which the toxic effect is on the myelin-forming cell or sheath. An example of this is tellurium intoxication, where demyelination noted in young animals is coincident with toxin-induced interference of cholesterol synthesis by Schwann cells. In this paper, the above-noted examples of toxic neuropathy are discussed, with emphasis on mechanistic and morphologic considerations.