Medication and Toxin-Induced Peripheral Neuropathy

Abstract

Medication and toxin-induced neuropathies, although uncommon, are important to identify because of potential reversibility. Numerous medications and toxins are implicated with neuropathy, but objective proof is lacking for many. Chemotherapeutic agents, nucleoside analogs, and other medications and toxins have clear causative links with neuropathy, but many agents have only rare temporal associations. Neuropathies are being recognized from new medications approved for use and other medications, which have expanded indications. Some established associations with neuropathy are less widely known while others are overestimated. Peripheral neuropathy from chronic drug exposure is more problematic to determine. Axonal pathology is most common, but some agents cause demyelination and even conduction block, mimicking immune-mediated neuropathies. Multiple and varied toxic mechanisms are implicated. Neuropathy is a dose-limiting complication of some critical treatments and preventative agents are being actively pursued.

Chemotherapy-induced peripheral neuropathy

“…Its neurotoxicity differs in that it affects small fibers, such as thermally sensitive C-fibers, resulting in burning causalgic pain [5,27]. The induction of a neuropathy appears to be idiosyncratic and occurs in 3% to 30% of treated patients.…”

“…Autonomic signs and symptoms can be prominent because the fibers carrying these signals are likely poorly myelinated and thus vulnerable. Dysautonomia may present as dry mouth, constipation, disorders of bladder emptying, and orthostatic intolerance [4,5]. Additionally, patients with pre-existing neuropathies of any kind (eg, diabetic, paraneoplastic, alcoholic, or hereditary) show an increased propensity to develop neuropathy when treated with neurotoxic agents used in cancer treatment [6][7][8].…”

“…Although the neuropathy is frequently reversible, recovery may take up to 2 years and coasting may occur. Pain generally is not a prominent feature at any stage of the neuropathy [5,7,14,22,23].…”

Drug-induced dysimmune demyelinating neuropathies

“…Medications and toxins cause an estimated 2-4% of all neuropathies [1,2]. For the majority of drugs the neurotoxic mechanisms have not been established, but can be inferred from the presumed mechanisms of action of the culprit agent [3].…”

Update on medication-induced peripheral neuropathy

“…Although medication and toxin-induced neuropathies constitute only 2% to 4% of cases [1,2], it is crucial that these causes be identifi ed because-especially if uncovered prior to signifi cant nerve injury-the neuropathy potentially can be reversed and the toxicity limited. Numerous medications and toxins are associated with neuropathy, but objective proof is lacking for many.…”