Nitrous oxide (N2O) toxicity has serious medical sequelae including encephalopathy, myelopathy, neuropathy and endovascular effects 1. This results from demyelination and gliosis due to selective inhibition of vitamin B12.
N2O is an established and widely used anaesthetic gas though also misused quite commonly for recreational purposes. Canisters of nitrous oxide, colloquially known as “whippets”, "nangs", or "bulbs" 5, used commercially as a propellant for whipped cream is commonly abused.
The classic neurological appearance of vitamin B12 deficiency is the so-called subacute combined degeneration of the cord manifested as damage to the dorsal columns of the spinal cord, responsible for the transmission of vibratory and proprioceptive input. Peripheral neuropathy, optic atrophy, and dementia can also occur.
Neurotoxicity is secondary to the selective inhibition of vitamin B12 (hydroxocobalamin), which serves as a cofactor for methionine synthase, which is an enzyme active in folate metabolism and the formation of myelin sheath phospholipids 2,4.
Radiographic features are identical to those of subacute combined degeneration of the cord.
- T2: thoracic hyperintense signal involving the dorsal columns (inverted "V" sign), although less commonly lateral tracts of the spinal cord may also be affected; very rarely is there involvement of the anterior spinal cord
Treatment and prognosis
Treatment options include:
- halting exposure to nitrous oxide
- high dose of intramuscular vitamin B12, followed by oral supplementation
- methionine supplementation has also been used 2
On imaging, the differential diagnosis includes:
- other aetiologies of subacute combined degeneration of the cord
- copper deficiency myeloneuropathy: can look identical
- vitamin E deficiency: can look identical
- infectious causes
- inflammatory processes
- hereditary syndromes
- leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation: characteristically also involves the cerebral white matter and the brainstem
- Friedreich ataxia: also causes cervical cord atrophy ('thinning')
- 1. Shulman RM, Geraghty TJ, Tadros M. A case of unusual substance abuse causing myeloneuropathy. (2007) Spinal cord. 45 (4): 314-7. doi:10.1038/sj.sc.3101962 - Pubmed
- 2. Stacy CB, Di Rocco A, Gould RJ. Methionine in the treatment of nitrous-oxide-induced neuropathy and myeloneuropathy. (1992) Journal of neurology. 239 (7): 401-3. Pubmed
- 3. Healton EB, Savage DG, Brust JC, Garrett TJ, Lindenbaum J. Neurologic aspects of cobalamin deficiency. (1991) Medicine. 70 (4): 229-45. Pubmed
- 4. Weimann J. Toxicity of nitrous oxide. (2003) Best practice & research. Clinical anaesthesiology. 17 (1): 47-61. Pubmed
- 5. Begley P, Sier J. 'Nanging' out: the rise of nitrous oxide as a Sydney party drug. The Sydney Morning Herald. http://www.smh.com.au/nsw/nanging-out-the-rise-of-nitrous-oxide-as-a-sydney-party-drug-20150820-gj4ai4.html. Accessed September 2017.
Toxic and metabolic encephalopathies
- overview by region
- white matter
- grey matter
- by agent/substance
- inhaled toxins
- oral toxins
- drugs (oral or IV)
- by systemic illness
- overview by region
- by substance
- Wernicke encephalopathy (vitamin B1)
- by substance
- Kearns-Sayre syndrome
- Leigh syndrome
- mitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS)
- myoclonus epilepsy with ragged red fibres (MERRF)
- mitochondrial deletion syndromes
- progressive cerebral poliodystrophy (also known as Alpers syndrome)
- trichopoliodystrophy (also known as Menkes disease)