Delayed myelopathy in a child following organic phosphate poisoning

Abstract

We report a rare manifestation of delayed organophosphate (OP) poisoning in a male patient in his early childhood. After initially presenting with a cholinergic crisis after OP exposure, the patient returned 3 weeks later with paraparesis and difficulty with bladder control. The results of the MRI of the spine and brain as well as the nerve conduction studies were normal. Myelopathy induced by OP poisoning should be considered in any patient with a history of OP exposure and a presentation of paraparesis. At most recent follow-up, the patient had full bladder control and could walk without assistance. However, he demonstrated circumduction while walking with upper motor neuron signs. Furthermore, he had mild Achilles tendon contractures on both sides. To enable early detection, neurologists and paediatricians should be aware of this uncommon complication of OP poisoning which may influence neurological outcome.

Background

Organophosphate (OP) is a potent neurotoxin. Intoxication can occur through ingestion (accidental vs suicidal), dermal absorption or inhalation.¹ The neurological manifestations of OP are categorised into acute cholinergic crises, intermediate syndrome and delayed manifestations.² OP poisoning may have a plethora of delayed manifestations that occur 2–8 weeks post-exposure.^{1 3} Delayed manifestations may include OP-induced delayed neuropathy (OPIND), extrapyramidal manifestations due to toxin accumulation in the basal ganglia,⁴ cerebellar ataxia,² delayed onset encephalopathy or coma, and recently described delayed myelopathy.^5–8 Delayed myelopathy can occur weeks to months following initial exposure, and it can be associated with polyneuropathy, sphincter dysfunction and/or sensory deficit. Furthermore, delayed myelopathy has been reported to predominantly occur in the thoracic spine. We describe a patient with OP-induced delayed myelopathy as a rare neurological complication associated with OP poisoning. The purpose of this report is to enable physicians to recognise it and consider it in the differential diagnosis of any patient presenting with subacute/chronic paraparesis and a history of OP exposure.

Case presentation

A male patient in his early childhood with a history of speech impairment, but otherwise previously healthy, presented to the emergency department after accidental ingestion of chlorpyrifos 50% EC (organic phosphate compound) 30 min earlier. The OP was a pesticide in the house placed in an area accessible to the child. Upon presentation, he demonstrated excessive salivation with drowsiness and apnoea. He was intubated for airway protection due to a low Glasgow Coma Score. He underwent gastric lavage and was given atropine and pralidoxime. Initial blood gas analysis showed metabolic acidosis with high lactate. After a stable 48 hours, pralidoxime and atropine were discontinued, and he was extubated.

He experienced a cholinergic crisis on the day of extubation, which was characterised by miotic pupils with a poor response to light, excessive salivation, bronchorrhoea, temperature instability and bronchospasm. He was restarted on pralidoxime accompanied by symptomatic management of the bronchospasm with nebulised bronchodilators.

Seventy-two hours after ingestion, he was irritable, confused and unable to recognise his father. Furthermore, he was aggressive and attempted to remove all the monitoring cables. In view of these symptoms, a working diagnosis of encephalopathy was made. He underwent CT, which showed no abnormality, and an electroencephalogram, which revealed generalised delta slowing. Serum biochemical test results for electrolytes were normal. The persistence of encephalopathy led to the speculation that his confusion was secondary to OP poisoning.

He was observed to be weak on day 5 post-ingestion, and a detailed neurological assessment was conducted. He was agitated, encephalopathic and had hypotonia in both his lower and upper extremities. He had no fasciculation or muscle group wasting. He was weak, with an upper-limb Medical Research Council scale of muscle strength of 3/5 proximally and 2/5 distally. In the lower extremities, power was 2/5 on both sides. Due to his inability to control his head and axial hypotonia, he was unable to sit without support. A nerve conduction study (NCS) was performed at the time and showed normal results. Because the medical team was looking specifically for evidence of polyneuropathy, repetitive nerve stimulation and needle examination tests were not conducted at that time. Repetitive nerve stimulation testing can provide evidence of neuromuscular junction involvement and needle examination tests provide evidence of neuropathy or myopathy.

On day 9 of his admission, he developed pneumonia which was treated with antibiotics. He then gradually improved 12 days after the ingestion of OP. At the time of discharge, he was fully conscious and had no neurological deficit.

At day 23 post-exposure, he presented to the emergency department with an abnormal gait, weakness in the proximal lower extremities, and an inability to stand up or climb stairs. Over a few days, his weakness worsened. He also suffered urinary incontinence which was not apparent in the initial presentation. He was found to have an extensor plantar reflex, brisk deep tendon reflexes, bilateral clonus, paraparesis and upper motor neuron (UMN) symptoms in the lower limbs. He was weak, with strength of 3/5 in the lower extremities. Neurological examination of the upper limbs and cranial nerves was normal. As per protocol, the Ministry of Social Affairs followed up the patient.

Investigations

The patient underwent MRI of the brain and whole spine, which was normal (figure 1). An NCS was performed twice for the patient during his presentation with paraparesis. During his initial presentation, the NCS included the sensory nerves (both sural nerves, left median and left ulnar nerves), motor nerves (left ulnar and median, both peroneal nerves and both tibial nerves), and F-waves of the left median, left ulnar, both peroneal nerves and both tibial nerves. Repetitive low-frequency nerve stimulation was also performed.

Figure 1.

MRI of the whole spine sagittal T1-weighted (T1W), T2-weighted (T2W) and short tau inversion recovery (STIR) sequences show normal spinal cord morphology and signal intensity. No cord atrophy was seen.

The second NCS was performed 10 days after the first. It included the sensory nerves (right sural, left median and left ulnar nerves), motor nerves (left ulnar and median and right peroneal and tibial), and F-waves of the left median, left ulnar, right peroneal and right tibial nerves. The first and second NCSs were normal with no evidence of neuropathy or neuromuscular junction pathology. The levels of creatine kinase and electrolytes were normal.

Differential diagnosis

Neuroanatomical localisation is crucial for putting together a differential diagnosis. In this case, the patient’s neurological deficit suggested a cord lesion, most likely located above L2 and below C8–T1. The presence of sphincter dysfunction causing urinary incontinence further supported spinal cord involvement. The differential diagnosis for this clinical presentation included hereditary versus acquired causes of spastic paraparesis, and given the history of exposure and the subacute clinical presentation, acquired causes seemed more plausible than hereditary ones. Acquired causes include mass lesions that result in compression or lesions secondary to an infection, toxins or metabolic causes. Normal spine MRI findings excluded the possibility of a compressive mass and transverse myelitis. No information was obtained from the clinical history or imaging that was suggestive of an infectious aetiology. The subacute presentation in the context of a normal brain and spine MRI made OP-induced myelopathy the most likely diagnosis.

Treatment

The patient reported by Gautam et al received intravenous immunoglobulin (IVIG), methylprednisolone and vitamin B₁₂ injections.⁷ However, our patient underwent an early spine MRI (on the second day of presentation with paraplegia and urinary incontinence) and a normal spine MRI scan result rendered the possibility of autoimmune/demyelinating disease unlikely. Furthermore, no evidence was found of a compressive lesion or cytotoxic oedema, which meant that treatment with steroids, IVIG or other immunomodulation therapies was not indicated (as there was no evidence of inflammation or oedema).

Outcome and follow-up

The patient received no intervention at the time of his presentation and was discharged home with physiotherapy. At follow-up 2 months post-exposure, he had no urinary incontinence and had clinically improved. Nevertheless, he exhibited UMN signs and had a scissoring gait (although he was better than when he presented 23 days post-exposure). A further whole spine and brain MRI scan was performed almost 3 months post-exposure; the scan was normal. He was diagnosed with delayed myelopathy secondary to OP intoxication. He was started on baclofen, and his parents were encouraged to continue physiotherapy. On follow-up 6 months post-exposure, the patient had full bladder control and could walk without assistance; however, he showed circumduction during walking with UMN signs. He had mild Achilles tendon contractures on both sides. Treatment with physiotherapy and baclofen was continued. At follow-up 1 year after OP ingestion, he was stable with no further deterioration. He had no bowel or bladder issues. He was able to walk without support, although he had an abnormal gait with tiptoe walking. He continues to be on regular baclofen and receives regular physiotherapy. He received a Botox injection in the calf to assist dorsiflexion on both sides and alleviate Achilles tendon contractures. He has follow-up scheduled with the orthopaedic team to determine whether surgical intervention may be needed. He has been prescribed ankle-foot orthotics.

Discussion

Although our patient developed acute encephalopathy within 72 hours of exposure, he nonetheless had a delayed cholinergic presentation. In addition to other potential causes, such as oxidative damage and downregulation of protein-coupled receptors, this presentation was thought to be caused by overstimulation of the cholinergic synapses.²

Furthermore, our patient presented with a delayed onset of myelopathy, with no evidence of polyneuropathy either clinically or as evidenced on the NCS that was conducted twice.

He had a latent phase for 3 weeks before his presentation, which has been documented in the literature previously.^5–8 He presented in the progressive phase on day 23 post-exposure. This progressive phase extended over weeks and manifested with UMN signs in the lower extremities, including spasticity, circumduction during walking, exaggerated deep tendon reflexes, sustained clonus, extensor plantar reflexes and difficulty with bladder control. He did not report any sensory symptoms that would usually be present in the progressive phase.^5–7 However, due to our patient’s young age, it was difficult for him to communicate with us any sensory symptoms he may have experienced. Although bladder involvement is rare in OP-induced myelopathy,^5–8 it was present in our patient during the progressive and early stationary phases. He underwent two spine MRI scans, both of which showed no evidence of cord atrophy. A normal spine MRI has been previously reported in the literature in a patient with OP-induced myelopathy.⁸ Nevertheless, the timing of the spine MRI scan from the onset of myelopathy symptoms may impact the presence of cord atrophy. A normal NCS result has been reported previously in patients because myelopathy can exist without association with polyneuropathy.^{5–7 9}

This manifestation of OP-induced myelopathy is a rare neurological complication of OP poisoning.^5–8 The risk of developing such complications may be attributed to the type of OP poison, for example, ingestion of chlorpyrifos, compared with other types. Other risk factors may include high-dose exposure necessitating the use of therapeutic agents to reverse the cholinergic crises in the acute phase, the duration and frequency of exposure, and variations in an individual’s metabolism of this toxin.¹ Most of these risk factors were present in our patient, which may explain why he developed myelopathy.

OP-induced myeloneuropathy has been previously reported in six patients (table 1), and our patient is the youngest patient to be reported in the literature, which is most likely due to the high rate of incidental OP ingestion among children in Oman.

Table 1.

Reported patients with organophosphate-induced delayed myelopathy

Author	Age/gender	Chemical	Onset from exposure	Examination findings	Spine MRI	Bowel/bladder involvement	NCS	Treatment
The patient in case report	Early childhood/M	Chlorpyriphos/50% EC	23 days	Diminished power in B/L LE Spasticity Brisk DTRs in LE B/L extensor plantars B/L sustained clonus	Normal	+	–	Baclofen
Gautam et al7	Early adolescence/M	50% chlorpyrifos and 5% cypermethrin/100 mL	6 weeks	LE weakness (proximal 4 and distal 3) Spasticity B/L clonus B/L extensor plantars	Cord atrophy	–	–	IVIG Methylprednisolone Vitamin B1 injections
Nayak et al8 Patient 1	Early adolescence/M	–	4 weeks	Spasticity of the LE Brisk DTRs (↓ B/L ankle reflexes) ↓ B/L pain & temp below T6 ↓ vibration below ASIS	Cord atrophy involving T3 and T4 spinal segments	–	–	–
Nayak et al8 Patient 2	Early adolescence/F	Chlorpyrifos	15 days	Spasticity of the LE B/L foot drop Brisk DTRs ↓ pain and temp below T10 Loss of vibration sense	Normal	–	–	–
Nayak et al8 Patient 3	Early adolescence/F	Chlorpyrifos	10 days	Diminished power in B/L LE Spasticity Brisk DTRs in LE B/L extensor plantars Loss of temp and vibration in stock and gloves pattern	Cord atrophy involving T9 and T10 spinal segments	–	–	–
Agarwal et al5	20s/M	Chlorpyrifos (50%)/100 mL	8 weeks	Motor weakness (proximal followed by distal) Spasticity Difficulty in ambulation Brisk DTRs B/L extensor plantars	Dorsal cord atrophy	–	–	–
Thivakaran et al6	Early adolescence/F	Chlorpyrifos/large dose	6 weeks	LMN and UMN signs in the LE without sensory loss Spasticity	Early signs of thoracic cord atrophy	+	Pure motor neuropathy	–

ASIS, Anterior superior iliac spine; B/L, bilateral; DTRs, deep tendon reflexes; F, female; IVIG, intravenous immunoglobulin; LE, lower extremities; LMN, lower motor neuron; M, male; NCS, nerve conduction study; temp, temperature; UMN, upper motor neuron.

When the patient was assessed 5 months post-exposure, he was found to have paraparesis with clear UMN signs in the lower extremities, including a scissoring gait, contractures at the ankles and knees, brisk deep tendon reflexes, extensor plantar reflexes and sustained bilateral clonus. His parents reported improvement in his bladder control (he regained full control), gait and lower extremity weakness.

Chlorpyrifos is known to cause OPIND.¹ The mechanism by which OP can induce such damage in the central nervous system is attributed to OP neurotoxicity. Three mechanisms are thought to underlie neurotoxicity: cholinergic neurotoxicity during the acute phase, ester-induced delayed neurotoxicity or ester-induced chronic neurotoxicity.¹ OPIND has been described as a neurodegenerative disorder manifesting with UMN signs secondary to single or repeated exposure to OP.⁹ Such an exposure results in central–peripheral distal axonal Wallerian degeneration. This process will be followed by myelin degeneration of the large diameter and long tracts of the central and peripheral nervous systems.^{1 10} This explanation may reveal why OPIND predominantly affects the pyramidal tracts in the caudal spine, resulting in paraplegia, and relative sparing of the cranial portion and subcortical pyramidal tracts.

In conclusion, as demonstrated in our case of a child with OPIND manifesting as isolated myelopathy, neurologists and paediatricians should be aware of this uncommon complication of OP poisoning to facilitate early detection. Early detection may influence the outcome. Counselling should be provided to patients and their families.

Learning points.

• Organophosphate (OP) is a potent neurotoxin that can cause various neurological complications when ingested, including acute cholinergic crises, intermediate syndromes and delayed manifestations.

• Since isolated myelopathy can be one of the delayed manifestations of OP, it should be considered in the differential diagnoses of patients with paraparesis with a history of OP poisoning.

• All patients with a history of OP poisoning should be monitored for the possibility of developing delayed neurological complications that were not present during the acute phase.

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