Organophosphorus poisoning induced delayed neurotoxicity: a report of two cases

Abstract

Introduction

Organophosphorus compounds (OPC) are one of the most commonly used pesticides worldwide and are often misused for suicidal poisoning due to their easy availability. Acute manifestations and management of organophosphorus (OP) poisoning have been reported several times. Organophosphorus-induced delayed neurotoxicity (OPIDN) is a rare delayed presentation of OP poisoning that involves central-peripheral distal axonopathy.

Case presentation

In this study, we report two cases of OPIDN developed after a few weeks of OP poisoning. Clinical features, electrodiagnostic study findings, and rehabilitative measures adopted for the patients and their follow-up have been described in the report.

Discussion

Organophosphorus (OP) poisoning may rarely produce features of delayed neurotoxicity, which may gradually appear after acute cholinergic symptoms. This report shows the importance of considering the delayed presentation of possible OPC toxicity in patients with neurological symptoms and a history of OPC exposure.

Introduction

Organophosphorus (OP) is the most widely used pesticide worldwide in agriculture, public health, and households [1]. These are the organic derivatives of phosphorous-containing acids, which act on the neuromuscular junction (NMJ) [2]. Due to the easy availability of OP-based pesticides, it has been misused commonly for suicides. Occupational and accidental exposure to the OP leading to poisoning has also been observed occasionally. According to World Health Organization (WHO) reports, three million OP poisoning cases are reported annually around the globe [3, 4]. Organophosphorus poisoning can present in three clinical forms: acute cholinergic crisis, intermediate syndrome, and delayed neurological manifestations. Organophosphorus-induced delayed neurotoxicity (OPIDN) and organophosphate-induced chronic neurotoxicity (OPICN) have been described as delayed neurological manifestations of OP poisoning in the literature, which are rare presentations [1, 5].

Organophosphorus-induced delayed neurotoxicity (OPIDN) can present as a central-peripheral distal axonopathy and is characterized by cramp-like muscle pain with a tingling sensation followed by paraplegia or tetraplegia and ultimately leading to improvement of peripheral neuropathy and unmasking of central neuropathy manifested by hyperreflexia and spasticity [1, 6]. Even though the rare presentation of delayed neuropathy after OP poisoning has been often reported, presentation as delayed myeloneuropathy has been less reported. We describe two cases with a history of acute cholinergic crisis after exposure to organophosphates and presented as OPIDN with myeloneuropathy. Written informed consent was obtained from both the cases in the study.

Case report

CASE 1

A 20-year-old male from a rural area presented to the outpatient department of our tertiary care hospital with complaints of weakness and tightness in both lower limbs and difficulty in walking. The patient’s medical history revealed suicidal ingestion of organophosphorus pesticides followed by excessive salivation, frothing, and breathlessness. He was admitted to a local hospital where conservative management and supportive care were given. He was hospitalized for 20 days and discharged as his condition improved. After three weeks, he began to experience distal weakness in both lower limbs, but he managed to walk. As the condition progressed, he faced difficulty standing from a sitting position. He also had tightness in the lower limbs. He had no history of any behavioral changes. There was no history of fever, back pain, loss of weight, and appetite.

His higher mental functions were normal on examination, with no evidence of cranial nerve involvement. There was no motor-sensory deficit in the upper limbs. The patient’s physical examination showed a muscle power of 3/5 in the proximal muscle groups and 2/5 in the distal muscle groups of lower limbs, according to the Medical Research Council (MRC) grading with intact sensations. Spasticity of the muscles was observed in the hip adductors (grade 3), knee flexors (grade 3), knee extensors (grade 2), and ankle plantar flexors (grade 3) according to the modified Ashworth scale (MAS). Knee and ankle jerks were exaggerated bilaterally. Ankle clonus was also present bilaterally. Bilateral extensor plantar responses were noted. There was no bladder or bowel involvement. The patient had a spastic scissoring gait.

Neurological examination was performed using the American Spinal Injury Association (ASIA)/International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) classification system [7], and a score of AIS-C with a neurological level of T 10 was obtained after the complete neurological examination. All routine blood investigations, liver and renal function tests were normal. Viral serology markers were negative. Magnetic resonance imaging of the spine and brain was unremarkable. CSF examination, autoimmune screening, serum vitamin B12 levels, and other relevant tests to rule out causes of non-compressive myelopathy were done, which were found to be normal. Nerve conduction study revealed motor axonal neuropathy with secondary demyelination in both lower limbs. EMG study showed a neurogenic pattern in both lower limb muscle groups. Somatosensory evoked potential (SSEP) and H reflex were normal. Repetitive nerve stimulation tests showed no decrement. After ruling out all other causes and with the strong positive history of recent OP poisoning, a provisional diagnosis of OPIDN was confirmed after consulting with the neurology department. A neuro-rehabilitation program was planned to improve the patient’s overall functional outcome, prevent complications, and correct deformities.

In-patient rehabilitation consisting of stretching and strengthening exercises was included. Cold packs were applied to spastic muscles, and oral antispastic medication (Baclofen) was started. Botulinum toxin A injection was given to the adductor longus, hamstrings, and gastro-soleus muscle in both lower limbs. At the time of discharge, the patient was able to stand from a sitting position. The patient strictly adhered to the home-based exercise program, and after six months of follow-up, the patient’s condition improved to an ASIA score of D, with a neurological level of T 12. Muscle power improved to 4/5 in the proximal muscle groups and 3/5 in the distal muscle groups. Spasticity decreased to grade 1+ of MAS. The patient can now walk using bilateral ankle-foot orthosis and a cane.

CASE 2

A 34-year-old male was admitted, complaining of weakness in both lower extremities and severe leg tightness. On inquiry of the medical history, it was found that he had ingested pesticides in a suicidal attempt. He was initially managed at a nearby hospital. As his condition gradually deteriorated, he was shifted to a higher medical facility for further management. After two days, the patient developed breathlessness and was moved to an intensive care unit (ICU) due to the need for mechanical ventilation. After five days of ICU admission, he regained consciousness, and mechanical ventilation was continued for two weeks. Later, he began to experience severe weakness and could not move the lower and upper extremities. After four weeks of hospital stay, his condition gradually improved, and he was discharged with residual weakness in the lower extremities. After a few days, he started to experience tightness in both his lower extremities, which gradually progressed, making it difficult for him to walk. He was also experiencing painful spasms in sleep. On examination, his higher mental functions were within normal limits, with no cranial nerve, bowel, or bladder involvement. No behavioral changes were noted in the patient. Muscle power was 2/5 in the proximal muscle groups and 1/5 in the distal muscle groups of the lower limbs, according to the Medical Research Council (MRC) grading.

Hip adductors, knee flexors, and ankle plantar flexors had spasticity of grade 3 according to the modified Ashworth scale (MAS). The patient also had sensory involvement with impaired sensations below T8. Deep tendon reflexes were exaggerated bilaterally in the lower limbs. Bilateral extensor plantar responses were obtained. ASIA scoring of C with a neurological level of T 8 was obtained after the neurological examination. All blood, CSF examination, and radiological investigations similar to the first case were performed to rule out other causes of non-compressive myelopathy. Nerve conduction study showed bilateral symmetrical sensory-motor axonal polyneuropathy in the lower limbs. EMG study revealed a neurogenic pattern similar to the first case. After consulting with the neurology department and ruling out all other causes, a diagnosis of OPIDN was confirmed.

In-patient rehabilitation with stretching and strengthening of the muscles was started. Galvanic intermittent electrical stimulation was given to the distal muscles of the lower limbs. Spasticity was managed with the help of cold packs, oral antispastic medications (Baclofen), and Botulinum toxin A injection. After discharge, the home exercise program was continued. At six months of follow-up, the patient’s condition improved to an AIS of D, with a neurological level of T 11. Muscle power improved to 3/5 in the proximal muscle groups and 2/5 in the distal muscle groups. Spasticity decreased to grade 1 of MAS. The patient can now walk using bilateral knee-ankle-foot orthosis and a pair of elbow crutches.

Discussion

Organophosphate (OP) poisoning causes three major toxic effects [2, 8, 9]. Within minutes to hours of exposure, cholinergic symptoms (Type 1) arise, manifested by miosis, sweating, rhinorrhoea, involuntary urination, and defecation, and are accompanied by central effects like dizziness, confusion, seizures, coma, and respiratory failure, ultimately leading to death. In patients who survived Type 1, intermediate syndrome (Type 2) develops within 24–96 h of OPC exposure in up to 20–50% of cases [10], characterized by acute ventilatory insufficiency due to paralysis of respiratory muscles due to downregulation of both presynaptic and postsynaptic receptors [2, 6, 8]. Rarely, some OP compounds may produce ester-related delayed neurotoxicity (Type3) after one week to 6 months of exposure. Organophosphate-induced chronic neurotoxicity (OPICN) entails neurobehavioral alterations with memory and cognitive deficits that were not observed in our cases. Patatin-like phospholipase domain-containing protein 6 (PNPLA6), earlier called Neuropathy target esterase enzyme (NTE) inhibition, has been linked to OPIDN [11], but no such relation was found for OPICN. OPIDN involves central-peripheral distal axonopathy and is related to Wallerian degeneration of long axons followed by myelin degeneration of long and large diameter tracts of the peripheral and central nervous systems, leading to paralysis and later spasticity [8, 12–14].

We reported two cases of OPIDN, which occurred gradually after the acute cholinergic features of OP poisoning. The first case developed OPIDN without the intermediate syndrome, but the second case had features of the intermediate syndrome, which developed after two days of recovery from the cholinergic crisis, followed by OPIDN. Different mechanisms in the literature have explained the pathogenesis of OPIDN. The first mechanism is the phosphorylation and inhibition of the PNPLA 6/NTE enzyme, which plays a role in membrane lipid hydrolysis [11, 15]. The second mechanism involves the interaction of OPC with Ca2+/calmodulin kinase II (CaM kinase II), leading to increased cytoskeletal protein phosphorylation and later dissociation of these proteins [16]. A newer mechanism involves the transient receptor potential cation channel, member A1 (TRPA1), a channel for calcium ions. The agonism of TRPA1 with OPC increases the influx of calcium ions and has a role in myelin damage [17].

Organophosphorus-induced delayed neurotoxicity (OPIDN) can occur in four phases: latent, progressive, stationary, and improvement [6]. Usually, the latent period occurs about two to three weeks after OP poisoning, as seen in both cases. The progressive phase has features of sensory and motor polyneuropathy affecting the lower extremities more commonly. Stabilization of the symptoms is characteristic of the stabilization phase. Sensory symptoms disappear gradually, and motor symptoms improve during the improvement phase. As the peripheral nervous system recovers, the unmasking of central nervous system damage occurs, spasticity appears, and reflexes become exaggerated, as seen in the cases reported here. Some studies showed OPIDN presenting as flaccid paralysis with predominant polyneuropathy [4, 18–21]. Similar to the present cases, OPIDN presenting as spastic paralysis of the extremities had been reported previously [22–26]. Guillain Barré syndrome, acute disseminated encephalomyelitis, transverse myelitis, infectious/inflammatory myelopathy, Vitamin B12 and copper deficiency myelopathy are a few of the differential diagnoses of OPIDN. The clinical presentation, management and treatment outcome of some of the OPIDN cases reported in the literature from 2002 to 2022 have been included in Table 1 for comparison of the cases reported here. These reports elucidate the different manifestations of OPIDN, which help clinicians establish early diagnosis and management.

Table 1.

The clinical presentation, management and treatment outcome of some of the OPIDN cases reported in the literature from 2002 to 2022.

Sl No	Study	Published year	Type of study	Case details
				Age/Sex	Mode of poisoning	Latency period (Time since onset of OPIDN symptoms)	Clinical features	Laboratory findings			Radiological findings	Treatment received for OPIDN	Treatment outcome
											MRI spine
							At the time of diagnosis	Blood investigations	CSF analysis	Electrodiagnostic test
1.	Vasconcellos LF et al. [10]	2002	Case report	39/F	Suicidal	3 weeks	Sensory: cramping calf pain and hyperesthesia in the plantar area; loss of temperature discrimination and nociception in distal lower limbs. Touch pressure, vibratory and joint position senses- normal Motor: hands amyotrophy, equine gait, distal motor deficit in lower limbs & increased reflex response in the upper limbs with Hoffman sign. (B/L); Achilles tendon reflex absent; No Babinski sign. Bladder/bowel: NR	NR	NR	NCS findings: Reduced amplitudes of the compound muscle action potentials (CMAP) with mildly reduced motor nerve conduction velocity (MNCV) of ulnar nerve in the upper limbs. Sensory nerve action potentials (SNAP) were normal in the upper and mildly reduced in the lower limbs. CMAPs were not elicited in the lower limbs. EMG findings: Positive sharp waves and fibrillation in the four limbs.	NR	Pharmacological: Amitriptyline (50 mg/d), carbamazepine (600 mg/d), capsaicin, thiamine (300 mg/d) Non-pharmacological: Physiotherapy	Sensory changes: Hyperaesthetic pain relieved with medical management Motor changes: NR Bladder/bowel changes: NR
2.	Azazh A et al. [2]	2011	Case report	19/M	Suicidal	3 weeks	Sensory: Numbness of (B/L) feet. Motor: flaccid tetra paresis, muscle power: (B/L) UL- 3/5, (B/L) LL- 0/5(MRC Grade) Bladder/bowel: Urinary and faecal incontinence.	Routine blood investigations were normal	NR	NCS findings: No motor response from Tibial and Peroneal nerves, severe reduction in amplitude of right Median motor nerve. Sural and plantar sensory nerves were normal. Suggestive of severe motor axonal neuropathy sparing sensory nerves. EMG findings: NR	NR.	Pharmacological: NR Non-pharmacological: Physiotherapy	Sensory changes: NR Motor changes: Wheelchair dependent, Functional improvement in UL Bladder/bowel changes: Sphincter function recovered
3.	Thivakaran T et al. [13]	2012	Case report	15/F	NR	6 weeks	Sensory: NR Motor: spastic tetra paresis, muscle power: (B/L) UL- 4/5, (B/L) LL-proximal 2/5, distal 1/5 (MRC Grade); Knee jerks- (B/L) extensor, Ankle jerks- (B/L) absent; Plantar- (B/L) extensor Bladder/bowel: Urinary incontinence	Electrolytes, erythrocyte sedimentation rate, C-reactive protein, full blood count, serum vitamin B12 levels, VDRL test, autoimmune screening- normal	Normal	NCS findings: Markedly reduced amplitude of CMAP with reduced MNCV in tibial and peroneal nerves of both lower limbs. CMAP and MNCV were mildly reduced in median and ulnar nerves. SNAP was normal in all limbs. EMG findings: Compatible (distal > proximal) symmetrical limb denervation changes with sparing of thoracic paraspinals	Normal	Pharmacological: NR Non-pharmacological: Physiotherapy	Sensory changes: NR Motor changes: Upper limbs muscle power improved, increased spasticity in lower limbs Bladder/bowel changes: NR
4.	Mundu PA et al. [26]	2016	Case report	22/M	Suicidal	3 weeks	Sensory: Tingling sensation and numbness in (B/L) LL Motor: spastic paraparesis; Ankle jerk & knee jerk- exaggerated; Babinski sign (+) Bladder/bowel: NR	Routine blood investigations were normal	Normal	NCS findings: Suggestive of Motor Axonal Polyneuropathy. Sensory Nerve studies were within normal range. EMG findings: NR	Loss of lumbar lordosis	Pharmacological: NR Non-pharmacological: NR	Sensory changes: NR Motor changes: NR Bladder/bowel changes: NR
5.	Kataria V et al. [24]	2016	Case report	18/F	Suicidal	8 weeks	Sensory: Normal Motor: spastic paraparesis; DTR- exaggerated (B/L) LL; Plantar- (B/L) extensor Bladder/bowel : Normal	Routine blood investigations were normal S. Vit B12, folate levels- normal	Normal	NCS findings: Motor axonal neuropathy with evidence of chronic reinnervation in lumbosacral myotomes (L4, L5 and S1 myotomes). EMG findings: NR	Diffuse thinning of the dorsal cord without signal changes	Pharmacological: NR Non-pharmacological: Physiotherapy	Sensory changes: NR Motor changes: NR Bladder/bowel changes: NR
6.	Kobayashi S et al. [19]	2017	Case report	89/M	Suicidal	4 weeks	Sensory: Total analgesia below (B/L) knees JPS & Vibration sensation- impaired Motor: flaccid tetra paresis, Muscle power: (B/L) UL- proximal 2–3/5, distal 0/5; Iliopsoas (B/L)-3/5, Quadriceps (B/L)-1/5; Rest of the lower limb muscles-0/5 (MRC Grade); DTR of (B/L)UL-diminished ; Areflexia in (B/L) LL; Plantar reflex (B/L) absent Bladder/bowel: NR	Screening for serum anti-ganglioside antibodies- negative Serum levels of vitamin B1, folate and copper: Normal	No pleocytosis; protein level was elevated.	NCS findings: suggested severe sensory motor axonal polyneuropathy EMG findings: Denervation potentials in the anterior tibialis, quadriceps femoris and biceps brachii	NR	Pharmacological: NR Non-pharmacological: NR	Sensory changes: NR Motor changes: NR Bladder/bowel changes: NR
7.	Yalbuzdag S et al. [9]	2017	Case report	27/M	Suicidal	4 weeks	Sensory: Normal Motor: Atrophy of left hand intrinsic muscles, Right Hoffman’s sign (+); muscle power – proximal 3/5, distal 0/5 (MRC Grade), Spasticity (+); Plantar- absent (B/L) Bladder/bowel: Normal	NR	NR	NCS findings: Absence of CMAP in distal muscles of lower limbs and diminished CMAPs in the upper limbs. Sensory nerve action potentials (SNAP) were normal in all limbs. Suggestive of pure motor axonal neuropathy involving long axons of peripheral nervous system. EMG findings: Fibrillation potentials and positive sharp waves were observed in affected distal muscles of lower limbs.	Normal	Pharmacological: Oral antispastic medication (Baclofen), Botulinum toxin injection for management of spasticity. Non-pharmacological: Neurological rehabilitation program	Sensory changes: NR Motor changes: muscle power improved to proximal 4/5, distal 2/5 (MRC Grade) in the LL Able to walk with a custom made plastic ankle-foot orthosis (AFO) and a walker Bladder/bowel changes: NR
8.	Thapa B et al. [20]	2018	Case report	22/F	Suicidal	4 weeks	Sensory: Tingling sensation and numbness in (B/L) lower limbs Motor: Flaccid paraparesis, Unable to walk, Muscle power: (B/L) ankle 1/5, (B/L) knee- 2/5 (MRC Grade) Plantar reflex (B/L) absent Bladder/bowel: NR	Routine blood investigations were normal Serum Vitamin B12- Normal	Normal	NCS findings: Moderately delayed distal motor latency with markedly decreased amplitudes and MNCV of bilateral peroneal and tibial nerves. Suggestive of motor polyneuropathies of bilateral peroneal and tibial nerves(predominantly axonal). EMG findings: NR	Normal	Pharmacological: NR Non-pharmacological: NR	Sensory changes: NR Motor changes: NR Bladder/bowel changes: NR
9.	Mahesh M et al. [4]	2019	Case report	42/M	Suicidal	NR	Sensory: Normal Motor: Flaccid paraparesis, muscle power: 2/5 proximally and 4/5 distally (MRC Grade); (B/L) ankle jerks- absent; Plantar- (B/L) flexor Bladder/bowel: Normal	NR	Normal	NCS findings: Motor axonopathy of bilateral tibial nerves with sensory axonopathy of left ulnar, superficial peroneal, and right sural nerves, and radiculopathy of bilateral common peroneal nerve. EMG findings: NR	NR	Pharmacological: NR Non-pharmacological: Physiotherapy	Sensory changes: NR Motor changes: Able to walk without support, able to stand from sitting position Bladder/bowel changes: NR
10.	Nayak P et al. [6]	2019	Case report	Case 1: 18/M Case 2: 15/F Case 3 : 14/F	NR	Case 1: 8 weeks Case 2: 6 weeks Case 3: 3 weeks	Case 1: Sensory: Pain, temperature loss below T6 by 60%; Vibration lost below ASIS Motor: Spastic paraparesis, muscle power in (B/L) LL: 4/5 (MRC Grade); DTR: brisk in (B/L) knee, Diminished in (B/L) ankle; Plantar reflex: extensor (B/L) Bladder/bowel: NR Case 2: Sensory: Pain, temperature loss below T10 by 40% – Vibration lost below ASIS Motor: Spastic paraparesis; muscle power in (B/L) LL: 4/5 (MRC Grade); Plantar reflex: extensor (B/L) Bladder/bowel: NR Case 3: Sensory: Pain, temperature, vibration loss in glove and-stocking pattern Motor: Spastic paraparesis, muscle power in (B/L) LL -4+/5; DTR brisk in (B/L) LL; Plantar -extensor (B/L) Bladder/bowel: NR	Routine blood investigations normal in all three cases	NR	NCS findings: Case 1: markedly reduced amplitude of CMAP with reduced MNCV in both tibial and peroneal nerves of both lower limbs. – SNAP was normal in all peripheral nerves Case 2: markedly reduced amplitude of CMAP with reduced MNCV in peroneal nerves of both lower limbs – SNAP was normal in all peripheral nerves Case 3: markedly reduced amplitude of CMAP with reduced MNCV in tibial and peroneal nerves of both lower limbs–CMAP and MNCV were mildly reduced in median and ulnar nerves–SNAP was decreased in all peripheral nerves. EMG findings: NR	Case 1: Cord atrophy involving T3 and T4 spinal segments. No spinal canal stenosis Case 2: Normal Case 3: Cord atrophy involving T9 and T10 spinal segments. No spinal canal stenosis	Pharmacological: Case 1: Inj Methylcobalamin, Case 2: Inj Methylprednisolone, Inj Methylcobalamin, Case 3: Inj Methylprednisolone, Inj Methylcobalamin, Non-pharmacological: Physiotherapy Occupational therapy	Case 1: Mild improvement after 2 months Sensory changes: NR Motor changes: NR Bladder/bowel changes: NR Case 2: Subjective improvement seen after 2 months Sensory changes: NR Motor changes: NR Bladder/bowel changes: NR Case 3: Mild improvement after 2 months Sensory changes: NR Motor changes: NR Bladder/bowel changes: NR
11.	Agarwal A et al. [25]	2020	Case report	21/M	Suicidal	8 weeks	Sensory: Normal Motor: Spastic paraparesis; Weakness in B/L lower limbs [Muscle power: 4/5 (MRC Grade) in (B/L) LL]; DTR: brisk (B/L) LL; Plantar reflex: extensor (B/L) Bladder/bowel: NR	Routine blood investigations were normal	NR	Normal	Dorsal cord atrophy	Pharmacological: NR Non-pharmacological: NR	Sensory changes: NR Motor changes: NR Bladder/bowel changes: NR
12.	Pannu A K et al. [21]	2021	Prospective observational study; Sample size- 23	Mean age- 24.4 ± 7, Males- 14 Females-9	NR	2 weeks (n = 1) 3-12 weeks (n = 7)	Sensory: Paraesthesia (n = 2) Motor: No motor deficits/ asymptomatic (n = 5); Left foot drop (n = 1); (B/L) foot drop (n = 1), Gait ataxia (n = 2), Abnormal reflexes (superficial and deep reflexes) (n = 2) Bladder/bowel: NR	Routine blood investigations were normal	NR	NCS findings: Axonal sensory motor type neuropathy (n = 1); Axonal predominant motor type neuropathy (n = 2); Axonal pure motor type (n = 4); Axonal sensory type (n = 1) EMG findings: NR	NR	Pharmacological: NR Non-pharmacological: NR	Fully recovered (n = 1) Sensory: Paraesthesia (n = 1) Motor: Left foot drop (n = 1); (B/L) foot drop (=1), Gait ataxia (n = 2), Abnormal reflexes (superficial and deep reflexes) (n = 2) Bladder/bowel: NR
13.	Arshad Z et al. [23]	2022	Case report	28/ F	Accidental	4 weeks	Sensory: Numbness in (B/L) UL & LL Motor: Weakness (B/L) lower limbs [muscle power: 3/5 (MRC grade)]; DTR: exaggerated in (B/L) LL; Plantar reflex: extensor (B/L) Bladder/bowel: NR	Routine blood investigations were normal Vitamin B12, homocysteine, CPK levels: Normal	NR	NCS findings: Sensory NCS- Right and left median and ulnar SNAP are of prolonged peak latency, normal amplitude and conduction velocity. Right and left Sural SNAP are of normal peak latency amplitude and conduction velocity. Motor NCS- Right and left medial & ulnar CMAPs are of normal distal latency reduced amplitude and conduction velocity. Right and Left Common Peroneal Nerve and Posterior Tibial Nerve CMAP are of normal latency, amplitude and conduction velocity EMG findings: NR	Long segment linear area of signal intensity alterations within the cord in ventral aspects extending from C3 to D5 levels	Pharmacological: NR Non-pharmacological: NR	Sensory changes: NR Motor changes: NR Bladder/bowel changes: NR
14.	Gautam et al. [22]	2022	Case report	16/M	Suicidal	5 weeks	Sensory: Normal Motor: Spastic paraparesis; Weakness in B/L lower limbs [Muscle power in (B/L) hip muscles: 4/5 in MRC (grade)]; Muscle power in (B/L) knees and ankles: 3/5 in MRC Grade; Plantar reflex: extensor (B/L) Bladder/Bowel: Normal	Routine blood investigations were normal	Normal	NCS findings: Normal motor and sensory amplitudes, latencies and conduction velocities EMG findings: NR	Mildly roomy CSF space around the dorsal cord without any signal changes in the cord suggestive of cord atrophy	Pharmacological: Intravenous Methylprednisolone (1 g/day) for 5 days, calcium and vitamin B1 supplements. Followed by oral dose of 50 mg of prednisolone for 10days Non-pharmacological: Physiotherapy	Sensory changes: NR Motor changes: The patient improved with a power of 4/5 in ankles and 5/5 in knee and hip joints bilaterally. Able to walk without support on a plain surface but had a spastic gait. Difficulty while standing from supine and sitting position, and needed support on walking upstairs and downstairs. Bladder/bowel changes: NR

M Male, F Female, NR Not reported, B/L Bilateral, UL Upper limbs, LL Lower limbs, DTR Deep tendon reflex, MRC Medical research council, NCS Nerve conduction study, EMG Electromyography, CMAP Compound muscle action potential, SNAP Sensory nerve action potential, MNCV Motor nerve conduction velocity, CSF Cerebrospinal fluid, MRI Magnetic Resonance Imaging, VDRL Venereal disease research laboratory, JPS Joint Position Sense, AFO Ankle foot orthosis

Conclusion

Even though organophosphate-induced delayed neurotoxicity (OPIDN) is a rare cause of neurological involvement, a history of accidental, occupational, or suicidal exposure to organophosphates should be considered while investigating the cause and included as one of the differential diagnoses. These two cases also emphasize the need for follow-up of OP poisoning patients for the development of OPIDN, and proper management should be initiated at the earliest to prevent further complications and morbidity in the patient.

Author contributions

All authors participated in drafting of the paper, and critical revision of the article. All authors approved the final version of the article.

Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Competing interests

The authors declare no competing interests.

Supplementary information

The online version contains supplementary material available at 10.1038/s41394-023-00611-4.