Toxicity in Peripheral Nerves: An Overview

Abstract

Introduction to a collection. This article is intended to introduce a collection of papers on toxic neuropathies. Toxic neuropathies can be caused by a variety of substances and by different mechanisms. Toxic agents are numerous and can be distinguished between drugs, recreational agents, heavy metals, industrial agents, pesticides, warfare agents, biologic substances and venoms. Toxic agents reach the nervous system by ingestion, transcutaneously, via the mucous membranes, parenterally and by aerosols. The most frequent types are cumulative toxicities. Other types are acute or delayed toxicities. Pathogenetic mechanisms range from a specific toxic substance profile causing axonal or demyelinating lesions, towards ion channel interferences, immune-mediated mechanisms and a number of different molecular pathways. In addition, demyelination, focal lesions and small fiber damage may occur. Clinically, neurotoxicity presents most frequently as axonal symmetric neuropathies. In this work, we present a panoramic view of toxic neuropathy, in terms of symptoms, causes, mechanisms and classification.

Keywords: dorsal root ganglia; pathogenetic mechanisms; peripheral nerve; peripheral neuropathy; toxic agents.

Figure 1

A schematic representation of the time course of toxic neuropathy caused by chemotherapy from exposure and onset of the toxicity on the PNS to the late effects and coasting phenomenon. Variable time course in patients receiving cancer treatment. The figure contains 3 critical time aspects (zones) for the development of chemotherapy-induced neurotoxicity (CIPN): (A): Acute toxicity is less frequent, and can be demonstrated in oxaliplatin toxicity. The acute toxic effects typically occur at the first intervention. (B): Cumulative toxicity, which usually follows the cumulation of the toxic agents’ chemotherapy cycle. Toxicity is usually incrementally increasing (symbolized by the black line). “Late and delayed” as well as intermediate toxicity stand for other patterns, such as immune-induced effects in ICI or intermediate effects caused by OPS. (C): Other late effects. After termination of chemotherapy, symptoms can progress for a variable time and then remit (“Coasting”). The extent of late effects in chemotherapy-induced neuropathies is an important question, as the number of cured patients and long-term survivors increases. In a few instances, such as TCE intoxication and also some OPS, progression after the termination of the exposure has also been described (self-perpetuation).