Organophosphate (OP) exposure can trigger seizures within minutes and can rapidly evolve into status epilepticus (SE). Early seizure generation is plausibly driven by acetylcholinesterase inhibition, leading to central cholinergic overstimulation. With increasing seizure duration, experimental data are consistent with a time-dependent shift toward glutamatergic maintenance (NMDA/AMPA), oxidative stress, neuroinflammation, and progressive failure of GABAergic inhibition. This framework predicts a narrow window in which benzodiazepine (BDZ) monotherapy is most effective and a rising probability of BDZ non-response when seizures are prolonged, while anti-glutamatergic strategies may retain relative efficacy later in the course. This narrative review integrates clinical phenomenology, diagnostic limitations, and mechanistic evidence to propose an operational approach for OP-related seizures and SE in emergency settings. We discuss a pragmatic “Stage 1 Plus” framing for patients presenting after prolonged seizures or in non-convulsive SE with coma. Human evidence remains limited and heterogeneous, and inference is constrained by confounding due to delayed recognition, variable decontamination/resuscitation pathways, sparse EEG confirmation, and selection bias in mass-casualty reporting.

Seizure and Status Epilepticus in Human Organophosphate Poisoning: A Narrative Review

Giuseppe Magro;Oreste Marsico;Federico Tosto;Concetta Lobianco;Laura Rapisarda;Giovanni Mastroianni;Angelo Pascarella
2026-01-01

Abstract

Organophosphate (OP) exposure can trigger seizures within minutes and can rapidly evolve into status epilepticus (SE). Early seizure generation is plausibly driven by acetylcholinesterase inhibition, leading to central cholinergic overstimulation. With increasing seizure duration, experimental data are consistent with a time-dependent shift toward glutamatergic maintenance (NMDA/AMPA), oxidative stress, neuroinflammation, and progressive failure of GABAergic inhibition. This framework predicts a narrow window in which benzodiazepine (BDZ) monotherapy is most effective and a rising probability of BDZ non-response when seizures are prolonged, while anti-glutamatergic strategies may retain relative efficacy later in the course. This narrative review integrates clinical phenomenology, diagnostic limitations, and mechanistic evidence to propose an operational approach for OP-related seizures and SE in emergency settings. We discuss a pragmatic “Stage 1 Plus” framing for patients presenting after prolonged seizures or in non-convulsive SE with coma. Human evidence remains limited and heterogeneous, and inference is constrained by confounding due to delayed recognition, variable decontamination/resuscitation pathways, sparse EEG confirmation, and selection bias in mass-casualty reporting.
2026
acetylcholinesterase inhibition
benzodiazepine resistance
benzodiazepines
nerve agents
nonconvulsive status epilepticus
organophosphate
receptor trafficking
seizures
status epilepticus
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.12317/117700
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus ND
  • ???jsp.display-item.citation.isi??? ND
social impact