Delayed-onset status epilepticus without cholinergic features in organophosphate poisoning: a case report

Abstract

Background: Organophosphates (OPs) exert their toxic effects by inhibiting acetylcholinesterase in both central (CNS) and peripheral nervous systems (PNS), resulting in accumulation of acetylcholine and overstimulation of cholinergic synapses. Seizures associated with OP poisoning typically occur in the context of overt systemic cholinergic manifestations. We report a patient with OP poisoning who developed status epilepticus without developing peripheral cholinergic features.

Case presentation: A 40-year-old Sri Lankan man presented six hours after deliberate ingestion of 50 mL of profenofos (500 g/L emulsifiable concentrate). His past medical history was unremarkable. There was no history of substance misuse. On admission, he was conscious, haemodynamically stable, and did not have signs of cholinergic excess. Thirty-six hours post-ingestion, he developed generalized tonic-clonic seizures, which were refractory to intravenous (IV) midazolam boluses and IV levetiracetam. He was intubated and mechanically ventilated. Continuous electroencephalographic monitoring confirmed termination of seizure activity with an intravenous midazolam infusion. Atropine was administered empirically for possible central cholinergic toxicity. The patient made a full neurological recovery and was successfully extubated 72 h after ingestion. The patient remained asymptomatic in a six month follow up.

Conclusion: This case illustrates an uncommon presentation of OP poisoning: delayed-onset status epilepticus in the absence of peripheral cholinergic features. The high lipophilicity of profenofos may facilitate preferential accumulation in the CNS, leading to a predominantly central cholinergic syndrome. This underscores the importance of recognising atypical neurotoxic presentations of OP poisoning and the potential need for CNS-directed therapy even in the absence of classic peripheral signs.

Keywords: Cholinergic toxidrome; Organophosphate; Profenofos; Status epilepticus.

Graphical abstract

Fig. 1

The majority of organophosphate (OP) insecticides can be grouped according to their chemical structure as a diethoxy OP [with two O–C₂H₅ groups attached to the phosphorus that binds to and inhibits acetylcholinesterase (AChE)] or a dimethoxy OP (with two O–CH₃ groups). The identity of these alkyl groups has fundamental effects on the pharmacodynamics of poisoning and treatment. Profenofos does not confer to these categories of organophosphates. Profenofos has an S-alkyl (S–C₃H₇) group attached to the phosphorus, in addition to the more typical O–C₂H₅ group. The chemical structure of prosfenofos makes it more lipid soluble than the other organophosphates. The chemical structure of the commonly used organophosphates, logP values and molecular weights are given in the Figure , , , , , , . The background colour (ranging from white to dark grey) indicate the estimated degree of CNS penetrance. CNS penetrance was inferred using a combination of log P values (PubChem), molecular weight, and evidence from in vivo studies and case reports. Log P values between 2–5 and molecular weight < 400 Da are well-established predictors of blood brain barrier permeability. Compounds with documented CNS effects were classified as having high or moderate CSF penetrance. Note that methamidophos has a moderate CSF penetrance despite the very low logP value, due to its small molecular weight.