Organophosphates intermediate syndrome

Senanayake N, Karalliedde E. 1992. Intermediate syndrome in anticholinesterase neurotoxicity. In Ballantyne B, Marrs TC, ed. Clinical and experimental toxicology of organophosphates and carbamates. Jordan Hill, Oxford, England Butterworth-Heinemann Etd., 57-62. 

De Bleecker, J. (1992). The intermediate syndrome in organophosphate poisoning presentation of a case and review of the literature. Clin. Toxicol. 30 321-9. 

Karalliedde, L., Baker, D., Marrs, T.C. (2006). Organophosphate-induced intermediate syndrome aetiology and relationships with myopathy. Toxicol. Rev. 25 1-14. 

The organophosphate (OP) insecticide-induced intermediate syndrome (IMS) was reported for the first time in human patients in Sri Lanka in 1987 (Senanayake and Karalliede, 1987 Karalliede and Henry, 1993). Thereafter, this syndrome has been reported in South Africa (1989), Turkey (1990), Belgium (1992), India (2003), and many other countries. IMS is clearly a separate entity from acute... 

DeBleecker, J.L. (2006). Intermediate syndrome in organ-phosphate poisoning. In Toxicology of Organophosphate and Carbamate Compounds (R.C. Gupta, ed.), pp. 371-80. Academic Press, Amsterdam. 

Quite frequently, and typically 1-4 days after resolution of symptoms of acute exposure, the intermediate syndrome may develop, characterised by a proximal flaccid limb paralysis which may reflect muscle necrosis. Even later, after a gap of 2-4 weeks, some exposed persons exhibit the delayed polyneuropathy, with sensory and motor impairment usually of the lower limbs. Claims of chronic effects (subtle cognitive defects, peripheral neuropathy) following recurrent, low-dose exposure, as with organophosphate used as sheep dip, continues to be the subject of investigation but, as yet, no conclusive proof. 

See also Cholinesterase Inhibition Neurotoxicity Organophosphate Poisoning, Delayed Neurotoxicity Organophosphate Poisoning, Intermediate Syndrome Organophosphates. 

Table 1 Organophosphates known to cause intermediate syndrome in humans...

Karademir M, Erturk E, and Kocak R (1990) Two cases of organophosphate poisoning with development of intermediate syndrome. Human Experimental Toxicology 9 187-189. 

Organophosphate Poisoning, intermediate Syndrome, Pages 306-308, Ramesh C. Gupta SummaryPlus Full Text + Links PDF (57 K) ARTICLE INDEX... 

Separate from the acute effects of anticholinesterases upon the neuromuscular junction (discussed previously), two further syndromes involving the neuromuscular system have been associated with OP poisoning. These are (1) the intermediate syndrome (IMS), and (2) organophosphate-induced delayed polyneuropathy (OPIDP). 

Senanayake N and Karalliedde L 1992). The intermediate syndrome in anticholinesterase neurotoxicity. In Clinical and Experimental Toxicology of Organophosphates and Carbamates (B Ballantyne and TC Marrs, eds), pp. 126-134. Oxford, UK Butterworth-Heinemann. 

Neurological Headache, coma, loss of reflexes, Cheyne-Stokes respiration, seizures, electroencephalogram abnormalities Organophosphate-induced delayed polyneuropathy manifested by flaccidity or paralysis of extremities, paresthesias, footdrop, gait ataxia, spasticity develops 1-2 weeks after exposure Intermediate syndrome 1-4 days after exposure manifested by weakness of proximal limb and respirator muscles, loss of knee reflexes, cranial nerve palsy, death... 

After acute effects subside, OPs produce a condition called the intermediate syndrome mediated through the enzyme neurotoxic esterase (Annau 1992). Symptoms consist of muscle weakness developing days after initial symptoms. Organophosphate-induced delayed neurotoxicity, a second delayed OP effect, develops weeks after exposure (Davis and Richardson 1980 Ecobichon 1996 Willems et al. 1984). Another condition described as wasting away results from toxic by-products generated during synthesis of OP insecticides, especially malathion (Chambers 1992). 

A second type of delayed neurological manifestation of organophosphate insecticide poisoning is the intermediate syndrome. In a series of 200 consecutive cases of organophosphate insecti-... 

Two additional cases of this syndrome were reported several years later both patients required ventilatory support during the paralytic phase.47 In another series, 29 of 90 patients with organophosphate poisoning had the intermediate syndrome.48 Tetanic fade with no posttetanic facilitation was maximal between days 4 and 6, and the response to electrical stimulation had returned to normal by 8 to 10 days. The author suggested that a neuromuscular junction defect was responsible for the lesion. 

Benson B. Is the intermediate syndrome in organophosphate poisoning the result of insufficient oxime therapy Clin Toxicol. 1992 30 347-349. 

Haddad LM. Organophosphate poisoning—intermediate syndrome Clin Toxicol. 1992 30 331-332. 

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