Chlorpyrifos toxicity causing delayed myeloneuropathy.

Dear Sir,

Chlorpyrifos is an organophosphate insecticide which can cause delayed neurological toxicity following a high dose exposure. Delayed neuropathy has been often reported; but here we report delayed myeloneuropathy, following chlorpyrifos poisoning.

A 25-year-old man who had consumed about 50 mL of pesticide preparation containing chlorpyrifos 50% was treated with stomach wash, injection atropine, injection pralidoxime, and other supportive medical care. His pseudocholinesterase level was below 1000 U/L (normal being 4650–10440 U/L). By day 7, he started having breathing difficulty and required mechanical ventilation for 2 weeks. By about 6 weeks after poisoning, he started requiring support to stand and to walk and also had urinary urgency and urge incontinence. At 6 month postexposure, he still required support to walk. He improved very gradually in ability to walk. At 5 years postexposure, he was able to walk independently. He was found to have significant spasticity in the lower limbs with brisk deep tendon reflexes. The plantar reflexes showed extensor response bilaterally. There was no sensory loss of any of the modalities. He had weakness of foot dorsiflexion bilaterally which was 4/5 on medical research council grading. The small muscles of the foot were wasted with hammer toes and pes cavus bilaterally. The combination of foot drop, scissoring, and ankle clonus gave his gait a peculiar bobbing character. The upper limbs were essentially normal on neurological examination.

He still had mild bladder symptoms in the form of urgency. His higher mental functions and cranial nerves were normal. He had no history or findings suggestive of autoimmune disorder. His systemic examination revealed no abnormality.

The hemoglobin, complete blood counts, blood sugar, renal function test, liver function tests, and electrolytes were within normal limits. The serum human immunodeficiency virus and VDRL (Venereal disease research laboratory) testing were negative. The serum B12 levels were normal. The magnetic resonance imaging of the whole spine was within normal limits. Nerve conduction study revealed reduced compound muscle action potential amplitudes and reduced conduction velocities in bilateral tibial and peroneal nerves. Upper limb motor nerve conduction study did not reveal any abnormality. The sensory nerve conduction studies were normal. He was managed with physiotherapy and supportive care.

Very few cases like this one have been described in literature following chlorpyrifos exposure.[12] The earlier hypothesis of inhibition of neurotoxicity target esterase as a causative factor is being replaced by implication of aberrant phosphorylation of cytoskeletal proteins leading to axonal instability and degeneration.[3] The combination of upper and lower motor neuron features in our patient bears superficial resemblance to the motor neuron disease. The possible link may be paraoxonase enzyme which is required for chlorpyrifos oxon hydrolysis and its mutation has been linked to the motor neuron disease.[4]

Precise reporting of such neurotoxicities in human may help us in gaining more insight into the mechanism of these toxicities and possibly enhance our understanding of related neurodegenerative diseases.