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.