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

J Neurol. 2018 May;265(5):1089-1095. doi: 10.1007/s00415-018-8801-3. Epub 2018 Mar 3.


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.

MeSH terms

  • Adolescent
  • Adult
  • Ataxia / chemically induced
  • Ataxia / diagnostic imaging
  • Ataxia / physiopathology
  • Ataxia / therapy
  • Diagnosis, Differential
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Neurodegenerative Diseases / chemically induced*
  • Neurodegenerative Diseases / diagnostic imaging
  • Neurodegenerative Diseases / physiopathology
  • Neurodegenerative Diseases / therapy
  • Nitrous Oxide / toxicity*
  • Retrospective Studies
  • Spinal Cord / diagnostic imaging
  • Spinal Cord Diseases / chemically induced*
  • Spinal Cord Diseases / diagnostic imaging
  • Spinal Cord Diseases / physiopathology
  • Spinal Cord Diseases / therapy
  • Substance-Related Disorders / diagnostic imaging
  • Substance-Related Disorders / etiology*
  • Substance-Related Disorders / physiopathology
  • Substance-Related Disorders / therapy
  • Vitamin B 12 / blood
  • Young Adult


  • Nitrous Oxide
  • Vitamin B 12