ABSTRACT:
Organophosphorus induced delayed neuropathy (OPIDN) is a delayed sequel of organophosphorus poisoning, occurs rarely1,2,6 after an acute cholinergic crisis and is confused with Guillain Barre’ Syndrome (GBS) or other causes of polyneuropathy. We report one case of OPIDN which we managed conservatively with steroids & we found improvement of CMAP (Compound Muscle Action Potential) within one month.

KEYWORDS:
Organophosphorus (OP), OPIDN, Axonal degeneration, neuropathic target esterase (NTE), Pralidoxim (PAM).

INTRODUCTION:
OPIDN refers to delayed effects of organophosphorus poisoning (OP poisoning), occurs due to binding of esterase enzyme called neuropathic target esterase (NTE)2,3 and cause predominant axonal degeneration (dying back axonopathy5) and minor demylenation7. Typically patient presents 3-5 weeks after OP poisoning with lower extremity weakness, bilateral foot drop, glove and stocking type of sensory loss5. Present case study documents one case of OPIDN due to tri Ortho cresyl phosphate poisoning after one month of cholinergic crisis and prevention of OPIDN is by early treatment of cholinergic crisis with PAM (before organophosphorus compound ages), steroids and other supportive measures (e.g splintage, physiotherapy and carbamazepine for neuropathic pain).

CASE REPORT:
A 19 year male presented to the hospital with complains of tingling sensation and weakness of lower limbs and hands 15 days back. He was apparently alright 15 days back, had 4 episodes of loose motion which subsided with medication. Then he had tingling sensation over lower limbs and hands and weakness of lower limbs followed by weakness and clumsiness of both hands. Weakness was progressive and in one week the patient was not able to walk. No history of fever, dog bite, vaccination, previous similar episode, contact, diabetes, leprosy was elicited.

Allegedly he took insecticides and suffered from acute cholincrgic crisis one and half month ago for which he was hospitalized for 11 days and recovered. On general examination the patient was conscious, afebrile with pulse rate 80/min, BP 126/80mm Hg without any other positive findings. CNS examination revealed intact cranial nerves, wasting of hypothenar, thenar (Fig. 1), calf and peroneal muscles of limbs (Fig. 2). Hypotonia involving flexor and extensor of ankle, weakness of abductor pollicis berevis, adductor pollicis and oppones pollicis seen. Long flexors and extensors of digits were normal. Lower limbs evertor, invertor, flexor and extensor of ankle were 0/5 power on both sides. Extensor and flexor of knee and hip were normal. Supinator jerk was diminished, ankle jerk was absent on both sides. Rest deep tendon jerks were normal. Plantar was nonresponsive both sides. There was in-coordinated movement, Rhomberg's test was positive and gait was high stepping. Sensory examination revealed all modalities diminished below ankle and wrist bilaterally. Peripheral nerves were normal.

Laboratory investigation revealed:
o Hb 12.7 gm%, TLC 10,700/mm3, DC N-69 L-30 E-l, ESR 8mm/lst hr, FBS 85 mg% .
o Serum Na'-132meq/lt, Serum K-4.8meq/lt, Serum urea -28mg%, Serum creatinine -1.18 mg%.
o HIV ELISA - Negative, CSF study showed TLC 3/mm3 (all lymphocytes) RBC absent, Glucose 61mg%, Protein 27 mg%, TB ELlSA- Negative.

NERVE CONDUCTION STUDY:
Initial Nerve Conduction Study:
Motor - Compound muscle action potential (CMAP) was absent in bilateral Median, Common peroneal nerve (CPN) , bilateral posterior tibial nerve (PTN).
CMAP in bilateral ULNAR - Amplitude less than normal, velocity in right ulnar less than normal , Left ulnar velocity within the normal limits.
Sensory - In bilateral Median Velocity was reduced, Right ulnar velocity was reduced no potential in Right sural, left Sural velocity and amplitude within normal limit.

Repeat Nerve conduction Study: (After one month)
CMAP- left median no potential, Right median small amplitude potential
Velocity in the above is reduced
Conduction in bilateral ulnar as before
No CMAP in bilateral CPN and bilateral PTN
Sensory as before

DISCUSSION:
Chronic complication of OP poisoning are neurobehavioral and poly-neuropathy1. Sensory motor polyneuropathy or OPIDN typically ocours after 3 to 5 weeks of exposure where motor deficit dominates the clinical picture5. Patient initially complains of tingling sensation over extremities, symmetric lower extremity weakness, and leg cramping and calf pain. Atrophy of calf muscles, ataxia and bilateral foot drop gradually ensues. It may progress to cause truncal weakness. Cranial nerves and autonomic system are not involved3. Sensory symptoms resolve over months. In mild cases motor symptoms may resolve over 15 months or may not resolve at all3. Severe cases may develop spasticity due to spinal cord involvement in the form of diffused spinal cord atrophy predominantly of thoracic spine2,5. Neuropathology of OPIDN demonstrates that large distal neurons tend to be affected first. There is slowing and stoppage of axonal flow, blockage transport of protein and other substances as well as demyelination7. Axonal degeneration precedes demyelination and there is "dying back" axonopathy5. Site of OP attack is a membrane bound target esterase called neuropathic target esterase (NTE)2,3. Function of NTE is not known. It is present in brain, spinal cord and peripheral nerve6, lymphocytes4 where specific OP binds and ages1 by losing 1 carbon and forming P-O carbon linkage. Critical mass of 70% of NTE must be inhibited to cause clinical symptom6. The delay in symptoms is due to the fact that not all axons will degenerate at the same time and nerve may continue to function until significant number of axons is degenerated.

OPIDN diagnosis is made by clinical and neurophysiologic examination and ruling out other possibilities. Currently platelet, RBC and lymphocyte NTE inhibition for confirming neuropathic potential of organophosphorus is under study . Use of hen test as screening test of neurotoxicity is flawed1.

Treatment of OPIDN is conservative and can be prevented by early and prolonged use of PAM. Tingling sensation over palm and sole responds to carbamazepine5.

REFRENCE:
1. Angelo Moretto et al: Poisoning by organophosphorus insecticides and sensory neuropathy; J. Neurol. Neurosurg. Psychiatry: 1998;64;463-468.
2. Cnia-Chang Chuang et al: Delayed Neuropathy and Myelopathy after Organophosphate Intoxication: NEJM, Volume 347:1119-1121 October 3, 2002 Number 14.
3. J. Mirandal et al : Muscular Strength and vibration thresholds during two years after acute poisoning with organophosphate insecticides. Occupational and Environmental Medicine BMJ 2004; 61: e4.
4. M. Lotti et al: Inhibition of lymphocyte neuropathy target esterase predicts the development organophosphate induced delayed polyneuropathy:J. Arch of Toxicology, Vol 59/3 Oct 1986, Pg 176-179.
5. R. Hierons and M.K. Johnson : Clinical and Toxicological investigations of a case of delayed neuropathy in man after acute poisoning by an organophosphorus pesticide: J Arch of Toxicology, Issue Volume 40, Number 4/Deceber , 1978.
6. Singh H, Sharma N: Neurological Syndromes Following organo-phosphate poisoning, Year 2000 , Neurology India, Volume 48, issue 4, Page 308-13.
7. Versik P et al: Chronic Toxic Neurophaty in Qualis: British Lek Letsy 106 (10), 293 – 296, 2005.