Acute leucoencephalopathy with restricted diffusion following cobra envenomation

INTRODUCTION

Snakebite envenomation represents a significant neglected tropical disease affecting approximately 2.7 million people globally each year, with children comprising a disproportionate number of victims due to their outdoor activities and inability to avoid snakes effectively.^[1] In India, an estimated 58,000 deaths occur annually from snakebite, with the highest mortality rates observed in rural paediatric populations where healthcare access is limited.^[2] Cobra envenomation primarily causes neurotoxic manifestations, including progressive paralysis, respiratory failure and bulbar palsy. While haematological complications such as coagulopathy and haemolysis are recognised, neurological sequelae beyond peripheral neuromuscular effects remain poorly characterised in the literature.^[3]

Acute leukoencephalopathy with restricted diffusion (ALERD) is an increasingly recognised clinico-radiological syndrome characterised by acute encephalopathy with distinctive bilateral, symmetrical diffusion restriction in cerebral white matter on magnetic resonance imaging (MRI). ALERD has been described following various insults, including toxin exposure, hypoxia and systemic inflammation, but association with envenomation remains exceptionally rare, with limited case reports in the medical literature.

This case addresses a critical knowledge gap by documenting ALERD as a potential neurological complication of cobra envenomation, providing important insights for clinicians managing paediatric snakebite cases and emphasising the need for comprehensive neurological monitoring in severe envenomation.

CASE REPORT

A previously healthy 18-month-old boy presented with a cobra bite. The incident occurred during the night in a rural household in southern India. After awakening with right palm pain, parents noticed puncture marks and identified the offending snake as an Indian cobra (Naja naja). Within 10 min, the child became unresponsive and needed emergency intubation. He was transferred to our tertiary centre 24 h post-envenomation. On admission, the child remained deeply encephalopathic with hypotensive shock requiring inotropic support and mechanical ventilation. The apneustic breathing pattern suggested brainstem involvement. Anthropometric measurements were appropriate for age. Local examination revealed an ecchymotic patch with cellulitis on the right palm [Figure 1]. Neurological examination showed bilateral ptosis, excessive drooling, reduced gag reflex indicating bulbar palsy, generalised hypotonia with significant weakness involving all four limbs and sluggish deep tendon reflexes. On the 4^th-day post-envenomation, three episodes of generalised tonic-clonic seizures occurred, lasting 5 min each, followed by progressive dystonic posturing and increased muscle tone. Deep tendon reflexes, which had initially been sluggish, subsequently returned to normal.

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Figure 1: (a) Photograph of the offending snake, identified as an Indian cobra (Naja naja), brought by caregivers for species confirmation. Note the characteristic hood expansion and brownish colouration typical of this species. (b) Clinical photograph of the bite site on the right palm showing significant swelling, erythema and early skin discolouration suggestive of local tissue necrosis and cellulitis. The puncture marks are visible as dark spots (white arrow). (c) Clinical image showing the child on mechanical ventilation with bilateral ptosis (white arrows) and generalised hypotonia. Note the endotracheal tube in situ and monitoring equipment.

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Laboratory investigations confirmed multisystem involvement: Prolonged whole blood clotting time indicating coagulopathy, haemoglobin 7.6 g/dL suggesting haemolysis, elevated creatine phosphokinase 1284 units/L (normal: 30–200) indicating rhabdomyolysis and marked transaminitis with serum glutamic-oxaloacetic transaminase 3510 units/L (normal: 8–40). Renal function remained normal despite haematuria. Cerebrospinal fluid (CSF) examination was performed and was unremarkable. MRI of the brain [Figure 2] on day 5 revealed bilateral symmetrical diffusion restriction in the subcortical white matter of frontal, parietal and occipital lobes, plus posterior limbs of internal capsules. T2-weighted images showed minimal white matter hyperintensity with mild signal changes in the bilateral putamen and caudate nucleus, consistent with A. Treatment included polyvalent anti-snake venom, intravenous methylprednisolone, intravenous immunoglobulin (2 g/kg), antiseizure medications and comprehensive supportive care, including mechanical ventilation and haemodynamic support. The child improved and was ambulatory at the end of 1 month of follow-up.

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Figure 2: Magnetic resonance imaging findings. (a and b) Axial diffusion-weighted imaging at two different levels showing bilateral, symmetrical hyperintensity (black arrows) in the subcortical white matter of frontal, parietal and occipital lobes. (c and d) Corresponding apparent diffusion coefficient maps demonstrate true diffusion restrictions appearing as hypointense areas (black arrows) in the same regions, confirming acute leukoencephalopathy with restricted diffusion (ALERD). (e) Axial T2-weighted image showing minimal hyperintensity in subcortical white matter regions but demonstrating mild increased signal intensity in bilateral putamen (black arrows) and caudate nucleus (black arrows). (f) Higher axial T2-weighted image showing absence of significant T2 hyperintensity in the affected subcortical white matter, distinguishing this pattern from typical vasogenic oedema. Symmetrical involvement and subcortical predominance are characteristic features of ALERD (black arrows).

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DISCUSSION

The combination of acute encephalopathy with seizures following cobra envenomation initially raised several diagnostic possibilities that required systematic evaluation.^[4,5] Hypoxic-ischaemic encephalopathy was the primary initial consideration, but no documented cardiorespiratory arrest or resuscitation. However, the MRI pattern argued against this diagnosis. Hypoxic-ischaemic injury typically demonstrates cortical involvement with preferential damage to watershed territories and deep gray matter structures.^[6,7] The predominantly subcortical white matter pattern with cortical sparing observed in this case was inconsistent with typical hypoxic-ischaemic injury. Direct neurotoxic effects of cobra venom could explain the encephalopathy, but established literature describes cobra neurotoxicity as primarily affecting peripheral neuromuscular function rather than causing central white matter injury.^[8,9] The bilateral symmetrical diffusion restriction pattern had not been previously described with cobra envenomation alone.

Infectious encephalitis was considered, given the fever and encephalopathy. However, CSF examination was unremarkable, and the close temporal relationship with envenomation, together with the characteristic bilateral symmetrical diffusion restriction pattern, was atypical for viral or bacterial encephalitis, making an infectious aetiology less likely. Metabolic leukoencephalopathy from inherited disorders was entertained, given the white matter involvement. The acute onset following a clear precipitating event, normal development before envenomation and absence of metabolic acidosis effectively excluded this possibility. Posterior reversible encephalopathy syndrome can present with acute neurological symptoms and white matter changes. However, the typical parieto-occipital predominance with cortical and subcortical involvement was not observed. In addition, the diffusion restriction pattern was inconsistent with the vasogenic oedema characteristic of this syndrome. The final diagnosis of ALERD was established based on the characteristic bilateral, symmetrical diffusion restriction predominantly affecting subcortical white matter, the temporal relationship with systemic insult (envenomation with hypoxia) and the clinical presentation of acute encephalopathy with seizures.^[10] This pattern has been increasingly recognised following various toxic and hypoxic insults, though association with envenomation represents a novel trigger for this syndrome.

This case demonstrates ALERD as a rare neurological sequela of cobra envenomation. The pathophysiology involves multiple mechanisms: Direct neurotoxic effects, prolonged hypoxia from respiratory arrest and systemic inflammation triggering white matter injury. Cobra venom contains α-neurotoxins blocking acetylcholine receptors and phospholipase A2 plus hyaluronidase that disrupts blood–brain barrier integrity, potentially facilitating central nervous system penetration. Combined toxicity, hypoxic injury and inflammatory cascade likely contributed to the observed white matter pathology. ALERD following snake envenomation appears to be exceedingly rare, with only a few cases described in the literature. One case described similar MRI findings following snake envenomation in an adult, though with motor weakness rather than encephalopathy.^[11] This appears to be the first documented ALERD with restricted diffusion following cobra envenomation in a child, representing a unique literature contribution.

CONCLUSION

ALERD can occur as a rare but serious neurological complication following cobra envenomation in children, resulting from combined neurotoxic effects, hypoxic injury and systemic inflammation. Post-envenomation encephalopathy or seizures warrant urgent brain MRI of the brain with diffusion-weighted sequences to identify treatable white matter complications beyond typical peripheral neurotoxicity.