Organophosphate-Induced Delayed Polyneuropathy

Abstract

Organophosphate-induced delayed polyneuropathy (OPIDP) is a rare toxicity resulting from exposure to certain organophosphorus (OP) esters. It is characterised by distal degeneration of some axons of both the peripheral and central nervous systems occurring 1-4 weeks after single or short-term exposures. Cramping muscle pain in the lower limbs, distal numbness and paraesthesiae occur, followed by progressive weakness, depression of deep tendon reflexes in the lower limbs and, in severe cases, in the upper limbs. Signs include high-stepping gait associated with bilateral foot drop and, in severe cases, quadriplegia with foot and wrist drop as well as pyramidal signs. In time, there might be significant recovery of the peripheral nerve function but, depending on the degree of pyramidal involvement, spastic ataxia may be a permanent outcome of severe OPIDP. Human and experimental data indicate that recovery is usually complete in the young. At onset, the electrophysiological changes include reduced amplitude of the compound muscle potential, increased distal latencies and normal or slightly reduced nerve conduction velocities. The progression of the disease, usually over a few days, may lead to non-excitability of the nerve with electromyographical signs of denervation. Nerve biopsies have been performed in a few cases and showed axonal degeneration with secondary demyelination. Neuropathy target esterase (NTE) is thought to be the target of OPIDP initiation. The ratio of inhibitory powers for acetylcholinesterase and NTE represents the crucial guideline for the aetiological attribution of OP-induced peripheral neuropathy. In fact, pre-marketing toxicity testing in animals selects OP insecticides with cholinergic toxicity potential much higher than that to result in OPIDP. Therefore, OPIDP may develop only after very large exposures to insecticides, causing severe cholinergic toxicity. However, this was not the case with certain triaryl phosphates that were not used as insecticides but as hydraulic fluids, lubricants and plasticisers and do not result in cholinergic toxicity. Several thousand cases of OPIDP as a result of exposure to tri-ortho-cresyl phosphate have been reported, whereas the number of cases of OPIDP as a result of OP insecticide poisoning is much lower. In this article, we mainly discuss OP pesticide poisoning, particularly when caused by chlorpyrifos, dichlorvos, isofenphos, methamidophos, mipafox, trichlorfon, trichlornat, phosphamidon/mevinphos and by certain carbamates. We also discuss case reports where neuropathies were not convincingly attributed to fenthion, malathion, omethoate/dimethoate, parathion and merphos. Finally, several observational studies on long-term, low-level exposures to OPs that sometimes reported mild, inconsistent and unexplained changes of unclear significance in peripheral nerves are briefly discussed.

Intermediate Syndrome Following Organophosphate Insecticide Poisoning in Emergency Department of Eastern Nepal

“…The disease entity is believed to be due to the inhibition of a poorly characterized esterase called the neuropathy target esterase. [2][3][4][5] In between the interval of acute cholinergic crisis and OPIDN, organophosphate compound can cause IMS which was first described by Senanayake et.al.1987. It is mainly characterized by weakness of proximal limb muscles, neck flexors, respiratory muscles, and motor cranial nerves, and was attributed to muscle fiber necrosis following acute cholinergic crisis.…”

Chlorpyrifos- and chlorpyrifos oxon-induced neurite retraction in pre-differentiated N2a cells is associated with transient hyperphosphorylation of neurofilament heavy chain and ERK 1/2

“…Furthermore, CPF poisoning can have a neurodegenerative effect on CNS neurons, especially in the spinal cord, resulting in a condition known as OP-induced delayed neuropathy (OPIDN). In such cases, the primary target of this compound is the enzyme neuropathy target esterase (NTE), which has a crucial role in embryonic development and maintenance of peripheral axons (Lotti and Moretto 2005).…”

Dichlorvos Exposure Aggravates Complications Associated with Diabetes in Wistar Rats

“…Their extensive use in agriculture and public health has resulted in large scale environmental pollution [2]. Their uncontrolled use in many developing and some developed countries has led to serious health issues among the population [3,4]. The potential adverse impact of pesticides on human health may be higher in developing countries due to easy accessibility to these chemicals and reduced risk awareness among the populace.…”