J Willems

The Intermediate Syndrome in Organophosphate Poisoning: Presentation of a Case and Review of the Literature

A dimethoate-poisoned woman gradually developed a moderately severe cholinergic crisis that was readily treated by atropine. After being symptom-free for nearly two days, she suffered from sudden life-threatening respiratory paresis and weakness of the facial, extraocular, neck flexor and proximal limb muscles. Muscarinic symptoms were absent. Cholinesterase inhibition was severe, and EMG revealed marked decrements at low rates of repetitive nerve stimulation, and increments at a high rate. The clinical course was compatible with the Intermediate Syndrome. This syndrome seems due to persistent cholinesterase inhibition presumably leading to combined pre- and postsynaptic impairment of neuromuscular transmission. Inadequate pralidoxime therapy is proposed but not established as contributory. Prolonged monitoring of respiratory function in patients poisoned by particular organophosphate agents is mandatory.

Prolonged Toxicity with Intermediate Syndrome After Combined Parathion and Methyl Parathion Poisoning

A prolonged type of organophosphate toxicity, previously characterized as the Intermediate Syndrome, has been recognized in 6 out of 7 prospectively studied patients poisoned by insecticide containing parathion and methyl parathion in equal proportions. The clinical characteristics included respiratory paresis, weakness in the territories of several motor cranial nerves, neck flexors and proximal limb muscles, and depressed tendon reflexes, all lasting for several days or weeks. Electromyography in the early stages disclosed diverse types of impaired neuromuscular transmission. EMG normalization preceded clinical recovery. Severe plasma butyrylcholinesterase and erythrocyte acetylcholinesterase inhibition persisted along with the occurrence of Intermediate Syndrome-related symptoms. We conclude that combined parathion and methyl parathion poisoning is more likely to induce Intermediate Syndrome than parathion poisoning alone. The mechanisms underlying this difference remain obscure. The Intermediate Syndrome shows clinical and electromyographic hallmarks of combined postsynaptic impairment of neuromuscular transmission.

Neurological aspects of organophosphate poisoning

Besides their well-known anticholinesterase action resulting in a typical acute cholinergic crisis, organophosphorus (OP) agents are capable of producing several subacute or chronic neurological syndromes. The acute over-stimulation at the neuromuscular junction results in muscle fiber necrosis. The significance of this OP-induced myopathy in human intoxication is unknown. Organophosphate-induced delayed neuropathy (OPIDN) arises 1-3 weeks after exposure to some OP compounds all capable of remarkably inhibiting a distinct esterase called neuropathy target esterase (NTE) during a critical time period. An experimental hen model has been designed to screen new OP compounds as to their delayed neurotoxic effects. The recently described intermediate syndrome emerges 1-4 days after an apparently well-treated cholinergic crisis. It main clinical features are sudden respiratory paralysis, cranial motor nerve palsies, and proximal limb muscle and neck flexor weakness. Whether or not this is a separate entity in OP agent toxicology remains to be seen. Further studies are required to further determine its clinical and paraclinical characteristics and the actual type of underlying neuromuscular dysfunction involved.

Influence of 2,4 dichlorophenoxyacetate and of dantrolene sodium on the target phenomenon in tenotomized rat gastrocnemius muscle

SummaryThe effect of 2,4 dichlorophenoxyacetate and of dantrolene sodium on the occurrence of target fibers in tenotomized rat gastrocnemius muscle was studied. Neither of the drugs influenced the appearance of target fibers or its inhibition by simultaneous neurotomy.