|Year : 2019 | Volume
| Issue : 1 | Page : 42-45
Organophosphorus-induced toxic myeloneuropathy: Series of three adolescent patients with short review
Priyabrata Nayak, Ashok K Mallick, Shubhankar Mishra, Debasish Panigrahy
Department of Neurology, Sriram Chandra Bhanja (S.C.B.) Medical College, Cuttack, Odisha, India
|Date of Web Publication||18-Jun-2019|
Dr. Shubhankar Mishra
Department of Neurology, Sriram Chandra Bhanja (S.C.B.) Medical College, Cuttack, Odisha
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Organophosphate (OP) poisoning is the most common poisoning in India, accounting for almost half of the hospital admissions due to poisoning. Delayed neuropathy is initiated by an attack on a nervous tissue esterase. Although uncommon, delayed neurotoxicity has been consistently reported in literature. This mechanism is implicated not only in damaging peripheral nervous system but also in causing central processes leading to myelopathy. We report a series of three adolescent patients who came to our hospital with delayed neurological manifestations of organophosphorus poisoning, which came out to be OP-induced myeloneuropathy after detailed analysis and evaluation.
Keywords: Myeloneuropathy, nerve conduction velocity, OPIDN, organophosphorus
|How to cite this article:|
Nayak P, Mallick AK, Mishra S, Panigrahy D. Organophosphorus-induced toxic myeloneuropathy: Series of three adolescent patients with short review. J Pediatr Neurosci 2019;14:42-5
| Introduction|| |
Organophosphate (OP) poisoning is known to cause varied neurological presentations in the form of acute, intermediate, and delayed neuropathy. Many organophosphorus esters cause acute cholinergic neurotoxicity. Some of these compounds are capable of producing organophosphorus ester–induced delayed neurotoxicity. Chlorpyrifos (O,O-diethyl O-3, 5, 6-trichloro-2-pyridylphosphorothioate) is known to cause a delayed syndrome or type III syndrome also called Organophosphorus-induced delayed neuropathy (OPIDN). It occurs especially in instances of high-dose exposure and in instances in which therapeutic agents were used to resolve acute cholinergic toxicity. The pathology involves a central-peripheral distal axonopathy. This is caused by a Wallerian-type degeneration of the axon, followed by myelin degeneration of long and large-diameter tracts of the peripheral and central nervous systems. The prevalence of OPIDN is variable; however, it occurred in 22% of patients with OP poisoning in a recent study. OPIDN occurs within a period of 1 week to 5–6 months of the ingestion of an OP compound, almost exclusively in patients with preceding acute cholinergic toxicity related to severe acute exposure (to an OP compound). But as the incidence of myeloneuropathy is very rare in OP poisoning, exact incidence is not known.
| Case analysis|| |
Details about case analysis are given in [Table 1].
| Discussion|| |
OP and carbamates compounds are used for pest control. Adolescent age group is highly vulnerable for suicidal attempts due to increasing adaptation problems and emotional situations. Easy accessibility and cheap economical value make the OP and carbamates primary substance as suicidal agents. Three different types of neurological presentations have been recognized following OP poisoning.
Type I paralysis or cholinergic crisis occurs due to excessive stimulation of muscarinic receptors by Ach due to blockade of acetylcholinesterase by an OP agent.
Type II paralysis or intermediate syndrome is a distinct clinical entity having incidence of 8%–49% and it usually appears 24–96h after poisoning. The pathogenesis is hypothesized to be the dysfunction of neuromuscular junction due to downregulation of both presynaptic and postsynaptic nicotinic receptors due to release of excessive Ach and Ca2+, respectively. The cardinal clinical features comprise muscular weakness affecting predominantly the proximal muscles and neck flexors.
Type III paralysis or OPIDN is a pure motor or predominantly motor axonal neuropathy characterized by wrist drop and foot drop with minimal or no sensory loss, which occurs 7–20 days after exposure to an OP agent.
Delayed organophosphorus ester-induced neurotoxicity (OPIDN) is further classified into four stages that consist of the latent period, progressive phase, stationary phase, and improvement phase.
Latent period: It is characterized by a delay in the onset of neurological deficits after exposure to OPs. The length of this latent period varies from 10 days to 3 weeks after exposure and depends on several factors such as nature of the chemical, the route of exposure, the dose size, duration and frequency of exposure, and individual variation in metabolism. This phase was widely variable in our study. In the first case, it was 8 weeks. This is quite long according to reported literature. A lengthy “latent period” as in this case has been documented previously., In the other two cases, latent period was 6 and 3 weeks, respectively.
Progressive phase: In this phase, symptoms and signs progress rapidly and present with motor sensory polyneuropathy predominantly affecting the lower limbs. Sensory symptoms include both positive and negative sensory symptoms such as cramping, burning pain in the calves, numbness, and tingling in the extremities and limbs. Sensory symptoms include “glove-and-stocking” sensory loss and involvement of posterior column. Motor signs are predominant and consist of bilateral foot drop, which may progress to flaccid paralysis involving all four limbs. Bladder and bowel involvement is though rare but evident in many cases. In our series, all the cases were having both motor and sensory involvements.
Stationary phase: During this phase, bilateral paraplegia or quadriplegia persists. Case 1 patient in our study was in this phase. Other two cases were in late progressive and early stationary phase. That insisted us to treat by injection methylprednisolone.
Improvement phase: During this phase, sensory symptoms disappear first followed by improvement in motor function in cranio-caudal manner. As improvement resulting from regeneration of the peripheral nervous system occurs, cord damage is unmasked, which manifests as spasticity with exaggerated reflexes. On follow-up, all our patients are in improvement phase with sequential improvement of sensory symptoms followed by motor symptoms. During follow-up, spasticity with the absence of lower motor signs was in keeping with the improvement phase, signifying rapid regeneration of the peripheral nerves.
Myeloneuropathy in delayed OP poisoning is a predominant feature in chlorpyrifos poisoning like our two cases. One hypothesis involves neuropathy target esterase (NTE), an enzyme with unclear function in the brain, spinal cord, and the peripheral nervous system and is thought to be implicated in the pathophysiology of OPIDN. The axonopathy is thought to be attributed to the inhibition of NTE by phosphorylation and subsequent aging of NTE that involves cleavage of the lateral side chain from the phosphorylated NTE. Chlorpyrifos is classified as “Moderately Hazardous (Class II)” as per the World Health Organization Organophosphorus Compound Classification. For OPIDN to occur, phosphorylated and cleaved NTE is necessary in significant amounts. In chlorpyrifos, the active metabolite has an anticholinesterase to anti-NTE ratio of 0.07. Carbamates are only rarely associated with the development of OPIDN.
In all the three cases, myelopathy was the predominant picture than neuropathy. It is very rare but reported in some studies. A Sri Lankan study reported more than half of the 20 young girls who consumed OP compound presented with pyramidal signs during the latter part of the illness. Some case reports were surfaced with this rare manifestation of OPIDN., Prognosis of OP-induced neurotoxicity depends on the degree of axonal degeneration.
| Conclusion|| |
OP poisoning is one of the most common hazards seen in Indian households. Delayed myeloneuropathy is one of the complications seen after stabilization in the acute phase. Early diagnosis and adequate therapy can help many young people to fight this irreversible morbidity. Precise reporting of such neurotoxicities of common household toxins may help us in gaining more insight into the mechanism to provide a better therapy in future. All neurophysicians must be aware of this rare complication for further studies to delineate better dimensions in neurotoxicology.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Singh S, Sharma N. Neurological syndromes following organophosphate poisoning. Neurol India 2000;48:308-13.
] [Full text]
Abou-Donia MB. Organophosphorus ester-induced chronic neurotoxicity. Arch Environ Health 2003;58:484-97.
Moretto A, Lotti M. Poisoning by organophosphorus insecticides and sensory neuropathy. J Neurol Neurosurg Psychiatry 1998;64:463-8.
Aygun D, Doganay Z, Altintop L, Guven H, Onar M, Deniz T, et al
. Serum acetylcholinesterase and prognosis of acute organophosphate poisoning. J Toxicol Clin Toxicol 2002;40:903-10.
Samuel J, Thomas K, Jeyaseelan L, Peter JV, Cherian AM. Incidence of intermediate syndrome in organophosphorous poisoning. J Assoc Physicians India 1995;43:321-3.
Chatterjee M, Sarma PS. Unusual neurological complications in a case of organophosphate poisoning. Neurol India 2003;51:290-1.
] [Full text]
Sevim S, Aktekin M, Dogu O, Ozturk H, Ertas M. Late onset polyneuropathy due to organophosphate (DDVP) intoxication. Can J Neurol Sci 2003;30:75-8.
Lotti M, Moretto A. Organophosphate-induced delayed polyneuropathy. Toxicol Rev 2005;24:37-49.
Dickoff DJ, Gerber O, Turovsky Z. Delayed neurotoxicity after ingestion of carbamate pesticide. Neurology 1987;37:1229-31.
Senanayake N. Tri-cresyl phosphate neuropathy in Sri Lanka: A clinical and neurophysiological study with a three year follow up. J Neurol Neurosurg Psychiatry 1981;44:775-80.
Nand N, Aggarwal HK, Bharti K, Chakrabarti D. Organophosphate induced delayed neuropathy. J Assoc Physicians India 2007;55:72-3.
Ostwal P, Dabadghao VS, Sharma SK, Dhakane AB. Chlorpyrifos toxicity causing delayed myeloneuropathy. Ann Indian Acad Neurol 2013;16:736