Invited Review ArticleA comprehensive review on experimental and clinical findings in intermediate syndrome caused by organophosphate poisoning
Introduction
Organophosphate (OP) poisoning is a major global health problem. This poisoning produces various forms of acute, subacute, or delayed neurotoxicity that causes life-threatening acute neurological complications such as seizures, paralysis, neuromuscular and cardiac conduction disorders. The neurotoxic effects of OP in human range from neurobehavioral and electroencephalographic changes to increase in the variability of action potential (AP) latencies in skeletal muscles. Cholinergic crisis, intermediate syndrome (IMS), and OP-induced delayed neuropathy (OPIDN) can be observed in OP intoxication (Dettbern et al., 2006). OPIDN, a sensory-motor distal axonopathy is believed to be a result of inhibition of neuropathy target esterase (Lotti and Moretto, 2005, Vasconcellos et al., 2002). The IMS following OP poisoning has been described in the mid-1980s by Senanayake and Karalliedde (1987). Approximately 20% of patients following exposure to OP pesticides may experience IMS (Karalliedde et al., 2006). The late onset of respiratory failure associated with IMS is a major contributor to the high morbidity, mortality, and cost of OP poisoning treatment. The IMS is clinically characterized by weakness in the cranial nerves, weakness of respiratory, neck and proximal limb muscles, and depressed deep tendon reflexes. These symptoms appear within 24 to 96 h post OP exposure in two types of paralysis. The type 1 paralysis responds to atropine while type 2 does not. Fasciculation that is seen in type 1 is not part of IMS. Delayed polyneuropathy develops within 1 to 3 weeks but duration of the IMS varies from a few days to several weeks (Van den Neucker et al., 1991).
Clinical and experimental electrophysiological studies in the IMS show that subclinical electrophysiological abnormalities are common and progressive. Studies demonstrate a repetitive firing following a single stimulus, gradual reduction in twitch height or compound muscle action potential (CMAP) followed by an increase with repetitive stimulation (decrement–increment phenomenon), and continued reduction in twitch height or CMAP with repetitive simulation (Jayawardane et al., 2009, Karalliedde et al., 2006).
The aim of this study was to gather all data related to IMS and electromyographic changes that may occur after OP poisoning to clarify understanding the involved mechanisms.
Section snippets
Methods
Bibliographic databases including PubMed and Google Scholar were searched between years 1953 to 2011 for the keywords “organophosphate, organophosphorous, intermediate syndrome, myopathy, neuropathy, and electromyography”. In the first step, 599 articles were found, after elimination of duplicates or irrelevant papers, 58 papers were selected and reviewed. Reference lists of published articles were hand-searched to ensure inclusion of all possible studies (Fig. 1).
IMS description
This syndrome was described in patients who develop proximal muscle weakness and cranial nerve lesions after recovery from a cholinergic crisis. It is apparent that all patients who develop such weakness have progressive neuromuscular junction dysfunction since the time of acute exposure. This phenomenon is thought to be due to primary motor endplate dysfunction resulting from prolonged inhibition of AChE. This involves both presynaptic and postsynaptic failures. Patients who develop weakness
Conclusion
Taking collectively, the mechanisms playing the role in induction and progress of IMS in OP poisoning are summarized and drawn in Fig. 2. We can conclude that mechanisms of IMS include prolonged AChE inhibition, muscle necrosis, down regulation or desensitization of postsynaptic ACh receptors, failure of postsynaptic ACh release, and oxidative stress-related myopathy. Toxicokinetic factors, such as a high lipid-solubility, duration of AChE inhibition and metabolite excretion, evolution of
Conflict of interest
The authors declare that there are no conflicts of interest.
Acknowledgment
This paper is an invited review of Prof. Mohammad Abdollahi and the outcome of an in-house non-financially supported study.
References (58)
- et al.
Electrophysiological and biochemical effects of single and multiple doses of the organophosphate diazinon in the mouse
Toxicol. Appl. Pharmacol.
(2000) - et al.
Electroneurophysiological studies in rats of acute dimethoate poisoning
Toxicol. Lett.
(1999) - et al.
Changes in mRNA expression levels of synaptic- and target tissue-specific proteins after organophosphate exposure
Leg. Med.
(2000) - et al.
The importance of electrodiagnostic studies in acute organophosphate poisoning
J. Neurol. Sci.
(1998) - et al.
Lipid peroxidation and changes in cytochrome c oxidase and xanthine oxidase activity in organophosphorus anticholinesterase induced myopathy
J. Physiol. Paris
(1998) - et al.
Repetitive nerve stimulation and stimulation single fiber electromyography studies in rats intoxicated with single or mixed insecticides
Toxicology
(2001) - et al.
Biochemical changes in primary culture of skeletal muscle cells following dimethoate exposure
Toxicology
(2002) Organophosphate poisoning-induced intermediate syndrome: can electrophysiological changes help predict outcome?
PLoS Med.
(2008)- et al.
Pesticides and oxidative stress: a review
Med. Sci. Monit.
(2004) - et al.
Protection by pentoxifylline of diazinon-induced toxic stress in rat liver and muscle
Toxicol. Mech. Methods
(2007)
Reversible necrosis at the end plate region in striated muscle of rat poisoned with cholinesterase inhibitors
Experentia
Serial neuro-electrophysiological studies in acute organophosphate poisoning—correlation with clinical findings, serum cholinesterase levels and atropine dosages
J. Assoc. Physicians India
The clinical and electrophysiological features of a delayed polyneuropathy developing subsequently after acute organophosphate poisoning and it's correlation with the serum acetylcholinesterase
Electromyogr. Clin. Neurophysiol.
Single fibre electromyographic changes in man after organophosphate exposure
Hum. Exp. Toxicol.
End-plate dysfunction in acute organophosphate intoxication
Neurology
Methamidophos: an anticholinesterase without significant effects on postsynaptic receptors or transmitter release
Neurotoxicology
Nature of the anticholinesterase-induced repetitive response of rat and mouse striated muscle to single nerve stimuli
J. Physiol.
Oxidative damage in intermediate syndrome of acute organophosphorous poisoning
Indian J. Med. Res.
Human pesticide poisonings by a fat-soluble organophosphate insecticide
Arch. Environ. Health
The intermediate syndrome in organophosphate poisoning: an overview of experimental and clinical observations
Clin. Toxicol.
Histological and histochemical study of paraoxon myopathy in the rat
Acta Neurol. Belg.
The intermediate syndrome in organophosphate poisoning: presentation of a case and review of the literature
J. Toxicol. Clin. Toxicol.
Intermediate syndrome in organophosphorus poisoning: a prospective study
Crit. Care Med.
Electromyography in relation to end-plate acetylcholinesterase in rats poisoned by different organophosphates
Neurotoxicology
Postsynaptic neuromuscular dysfunction in organophosphate induced intermediate syndrome
Klin. Wochenschr.
Pesticide induced muscle necrosis: mechanisms and prevention
Fundam. Appl. Toxicol.
Toxicology of Organophosphate and Carbamate Compounds
Biotransformation enzyme polymorphism and pesticide susceptibility
Neurotoxicology
Mechanism of action of organophosphorus and carbamate insecticides
Environ. Health Perspect.
Cited by (110)
Assessment of the serum glucose/potassium GLU/K ratio as a predictor of intermediate syndrome following acute anticholinesterase exposure
2022, NeuroToxicologyCitation Excerpt :Chlorpyrifos and its active metabolites cause significant disruption of DNA-synthesis as well as neuronal development and activation (Uchendu, 2012). OPCs with high lipid solubility, such as Chlorpyrifos, can pass through the blood–brain barrier and are believed to be associated with IMS (Abdollahi and Karami-Mohajeri, 2012). In disparity, Parathion and Omethoate have been reported as the most common IMS-inducing substances (He et al., 1998).
Patterns of cardio-respiratory motor outputs during acute and subacute exposure to chlorpyrifos in an ex-vivo in situ preparation in rats
2022, Toxicology and Applied Pharmacology