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.

No abstract

No abstract

No abstract

Objectives-Poisoning by organophosphate insecticides causes cholinergic toxicity. Organophosphate induced delayed polyneuropathy (OPIDP) is a sensorymotor distal axonopathy which usually occurs after ingestion of large doses of certain organophosphate insecticides and has so far only been reported in patients with preceding cholinergic toxicity. Surprisingly, it was recently reported by other authors that an exclusively sensory neuropathy developed in eight patients after repeated unquantified exposures to chlorpyrifos, which did not cause clear-cut cholinergic toxicity. The objective was to assess whether an exclusively sensory neuropathy develops in patients severely poisoned by various OPs. Methods-Toxicological studies and electrophysiological measurements were performed in peripheral motor and sensory nerves in 11 patients after acute organophosphate poisoning among which two subjects were poisoned with chlorpyrifos. Results-Three patients developed OPIDP, including one poisoned by chlorpyrifos. Exclusively sensory neuropathy was never seen after either single or repeated acute organophosphate poisoning. A mild sensory component was associated with a severe motor component in two of the three cases of OPIDP, the other was an exclusively motor polyneuropathy. Conclusion-A sensory-motor polyneuropathy caused by organophosphate insecticides might occur after a severe poisoning and the sensory component, if present, is milder than the motor one. Bearing in mind the toxicological characteristics of these organophosphate insecticides, other causes should be sought for sensory peripheral neuropathies in patients who did not display severe cholinergic toxicity a few weeks before the onset of symptoms and signs.

No abstract

The comparative inhibitory power of organophosphorus esters in vitro against hen brain acetylcholinesterase and neurotoxic esterase correlates with their comparative effects (death or delayed neuropathy) in vivo. Further comparisons of the in vitro effects seen with hen and human enzymes facilitates extrapolations to the human in vivo situation.

Cholinesterases are measured to assess exposures to or effects of organophosphorus esters and carbamates. Plasma butyrylcholinesterase is usually most sensitive to inhibitors, but it has no known physiological function(s); its inhibition reflects exposure. The physiological function of erythrocyte acetylcholinesterase (AChE) also is not known, but the enzyme is the same as that involved in synaptic transmission and its measurement is used to mirror effects on the nervous system. Erythrocyte AChE has large inter- and intraindividual variation, and small changes are detectable by comparison with preexposure values. The relation between inhibition of erythrocytes and nervous tissue AChE depends on the pharmacokinetics of inhibitors. Usually, erythrocyte AChE inhibition overestimates that in the nervous system. Pharmacodynamic factors such as spontaneous reactivation and aging of inhibited enzyme should also be considered in assessing AChE inhibition. Other factors, such as timing of measurement, add complexity because erythrocyte AChE inhibition persists longer than that in the nervous tissues. Cholinergic transmission might also be impaired because of direct effects of organophosphorus esters and carbamates on receptors.