"dying-back" degeneration of large distal axons

Q: The "dying-back" degeneration of large distal axons is characteristic of which chemical toxicity? 

Answer: Organophosphate (OP) 

Although most critical care medicine curricula emphasize acute management of OP poisoning, one vital and delayed aspect of OP often goes unnoticed. =

OPIDN (OP-induced delayed neuropathy) is characterized by a painful "stocking-glove" paresthesias followed by a symmetrical motor polyneuropathy with flaccid weakness of the lower extremities that ascends to involve the upper extremities, primarily affecting distal muscles; in severe neurotoxicity, proximal muscle groups may also be affected. Sensory disturbances are usually mild. 

It occurs one to three weeks after OP exposure (delayed). Usually transient, but in severe cases, an upper motor neuron syndrome with spasticity of the lower extremities usually causes permanent disability. Electromyograms and nerve conduction studies reveal decreased firing of motor conduction units, and histopathologic sections of peripheral nerves show Wallerian degeneration, commonly known as "dying-back" degeneration, of large distal axons. The underlying mechanism involves inhibition of neuropathy target esterase (NTE), which is found in the brain, peripheral nerves, and lymphocytes, and is basically responsible for the metabolism of various esters in the cytoplasm. 

Other reported long-term effects of OP toxicity are either transient or permanent decreased memory, abstraction, attention, and Parkinsonism. Severity may differ with different brands of OP pesticides. 

#toxicity 

#neurology 

 References: 

 1. Aygun D, Onar MK, Altintop BL. 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 2003; 43:421. 

 2. Johnson MK. Organophosphorus esters causing delayed neurotoxic effects: mechanism of action and structure activity studies. Arch Toxicol 1975; 34:259. 

 3. Arima H, Sobue K, So M, et al. Transient and reversible parkinsonism after acute organophosphate poisoning. J Toxicol Clin Toxicol 2003; 41:67.