No laughing matter: subacute degeneration of the spinal cord due to nitrous oxide inhalation

Abstract

Background: Whilst the dangers of 'legal highs' have been widely publicised in the media, very few cases of the neurological syndrome associated with the inhalation of nitrous oxide (N₂O) have been reported. Here we set out to raise awareness of subacute degeneration of the spinal cord arising from recreational N₂O use so that formal surveillance programs and public health interventions can be designed.

Methods: Case series documenting the clinical and investigational features of ten consecutive cases of subacute degeneration of the spinal cord presenting to a hospital with a tertiary neurosciences service in East London.

Results: Sensory disturbance in the lower (± upper) limbs was the commonest presenting feature, along with gait abnormalities and sensory ataxia. MRI imaging of the spine showed the characteristic features of dorsal column hyperintensity on T₂ weighted sequences. Serum B₁₂ levels may be normal because subacute degeneration of the spinal cord in this situation is triggered by functional rather than absolute B₁₂ deficiency.

Discussion: A high index of suspicion is required to prompt appropriate investigation, make the diagnosis and commence treatment early. This is the largest reported series of patients with subacute degeneration of the spinal cord induced by recreational use of N₂O. However, the number of patients admitted to hospital likely represents the 'tip of the iceberg', with many less severe presentations remaining undetected. After raising awareness, attention should focus on measuring the extent of the problem, the groups affected, and devising ways to prevent potentially long-term neurological damage.

Keywords: Hydroxocobalamin; Myelopathy; Subacute degeneration of the spinal cord; Vitamin B12.

Fig. 1

Pre- and post-treatment sagittal and axial T2 weighted MRI imaging of the cervical cord in N₂O-induced subacute degeneration of the spinal cord. a-1: Sagittal T2 weighted sequence demonstrating extensive cord signal change from the C2 to the C7 level within the dorsal aspect of the cord confirmed on the axial sequences, with enhancement (not shown). a-2: Taken 5 months following showing persistent abnormal T2 signal change within the dorsal columns on this sagittal T2 weighted sequence; however, the abnormal enhancement had resolved (not shown). b-1: Sagittal T2 weighted sequence demonstrating cord signal change from C3 to C5 within the dorsal aspect of the cord confirmed on the axial sequences, without enhancement, and resolution over time (b-2)

Fig. 2

a Discarded nitrous oxide canisters and balloons in East London. b Metabolic pathway of vitamin B₁₂ involved in pathogenesis of N₂O-induced subacute degeneration of the spinal cord. Vitamin B12 is a cofactor in the conversion of methylmalonyl-CoA to succinyl-CoA and homocystine to methionine. Non-functioning B₁₂ leads to accumulation of methylmalonic acid and homocystine, which can be tested in the patient sera when B₁₂ levels appear normal, suggesting a ‘functional; B₁₂ disorder. Figure created using Microsoft Word