Chemical-Induced Seizures: Mechanisms,Consequences and Treatment

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Since the Tokyo Sarin Subway Attack, the threat of chemical warfare agents has migrated from the battlefield to become a major concern for homeland security in the 21th century. While current fielded ...
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Organophosphate Toxicity Relating to Exposure Route and Type of Agent

Pp. 39-48 (10)

Marloes J.A. Joosen, Marcel J. van der Schans, August B. Smit and Herman P.M. van Helden

Abstract

The current medical countermeasures for organophosphate (OP) poisoning are effective to a reasonable extent, yet, there is room for improvement. In this review, suspected causes of acute and long term-effects of OPexposure and possible interventions will be discussed, in relation to the type of nerve agent and different exposure routes. Inhibition of AChE by organophosphates leads to excessive buildup of released acetylcholine (ACh) at cholinergic synapses resulting in a failure of neuromuscular transmission and leads to seizures followed by status epilepticus. Eventually, poisoning with OPs is likely to result in death or long-term neuronal deficits.

Although, the OP nerve agents soman and VX act via a similar mechanism, that is inhibition of AChE, the toxicological impact following exposure shows to be quite different. Whereas, toxic signs upon sc exposure to soman in general develop very rapidly with the presence of seizures, pc exposure to VX animals shows delayed development of clinical signs compared to sc soman exposure. Such differences in agent behavior put special demands on treatment.

Another important conclusion of the present study is that an effective life-saving treatment at short term, may not be sufficient to prevent long term cognition deficits. This implies that a more thorough understanding of the cause of such deficits is needed to design improved treatment strategies. Suppression of the inflammatory processes in seizure initiation and continuation and restoring impaired neurogenesis, the latter proposed as a cause of cognition deficits following soman exposure, could be starting points for improved treatment.

Affiliation:

TNO Defence, Security and Safety, Department of Chemical Toxicology, Lange Kleiweg 137, 2288GJ, Rijswijk, The Netherlands.