**5.3 Organophosphates**

Organophosphates (OP) are chemical substances involved in the main components of herbicides, pesticides, and insecticides. Acute or chronic exposure to organophosphates causes several toxic effects in humans and animals. The exposure to organophosphates might be accidental or intentional. The organophosphate intoxication may occur after exposure to pesticides, either through occupational contact or suicide attempts. Acute toxic effects and delayed toxic neuropathy are related to central and peripheral nervous system involvement. The main effect of OP exposure is poisoning; however, peripheral neuropathy has been linked to chronic exposure. Several recent cases were reported associated with organophosphate-induced delayed neuropathy (OPIDN) after ingestion of organophosphate insecticides. The peripheral neuropathy associated with organophosphate intoxication may be seen with mild exposure. The mechanism of OPIDN is explained by loss of function of both motor and sensory axons located distally and ascending and descending tracts of the spinal cord [120, 121]. Organophosphate-induced delayed neuropathy is an uncommon clinical condition characterized by a distal paresis in the lower limbs and sensory symptoms. Electrophysiological findings show motor axonal neuropathy. The delayed onset of peripheral neuropathy and axonal motor involvement without a progressive course is needed for the diagnosis. Organophosphates can irreversibly bind to acetylcholine esterase (AChE) and prevent the breakdown of acetylcholine (ACh). The liberation of ACh overstimulates the muscarinic and nicotinic receptors. The main mechanism of OPIDN development is related to the inhibition of neuropathy target esterase (NTE) via phosphorylation. Neuropathy target esterase is an essential integrated membrane protein in neurons that takes part in axonal maintenance [122]. Its activity plays a crucial role in axonal maintenance since it facilitates the transport of macromolecules to the end of axons [120].

The symptoms are attributed to the effects on sensory and motor nerves with a typical axonal length-associated pattern. Lower extremities are predominantly affected. However, upper extremities are affected at higher OP exposure. The prognosis of peripheral neuropathy varies due to clinical involvement. It is primarily associated with the age of the individual (a younger age is associated with mild neuropathy), type of organophosphate, the persistence of myelopathic features, pyramidal involvement, degree of CNS involvement to peripheral nerve dysfunction [120, 123, 124]. There is no treatment approved for OPIDN, and the recovery is slow and partial. Thivakaran et al. reported a 15-year-old female who developed OPIDN with a smaller dose of chlorpyrifos [124]. Akçay et al. reported a similar

case diagnosed with organophosphate-induced delayed neuropathy (OPIDN) complicated with central nervous system findings. They observed partial improvement in muscle strength despite motor axonal polyneuropathy [125]. In addition, Moretto et al. reported electrophysiological findings in 11 patients with acute OP poisoning [126]. Three of these patients developed OPIDN, mainly sensory-motor polyneuropathy. The diagnostic approach should be made carefully in peripheral neuropathy patients, excluding other possible causes, especially those who did not display cholinergic toxicity before the onset of neuropathy. Early recognition of OP poisoning and a professional approach to intoxication can be life-saving.
