ACMT Toxicology Visual Pearls: “I have a nanging feeling about this”

nitrous oxide

Chronic exposure to which substance can cause this finding on a Cervical Spine MRI?

  1. Arsenic
  2. Carboplatin
  3. Nitrous Oxide
  4. Toluene

nitrous oxide

Chronic exposure to which substance can cause this finding on a Cervical Spine MRI?

  1. Arsenic
  2. Carboplatin
  3. Nitrous Oxide
  4. Toluene

Answer: Nitrous Oxide

Nitrous Oxide Myeloneuropathy

The photo shows demyelination of the posterior dorsal columns (red arrows) resulting from vitamin B12 deficiency from chronic nitrous oxide use. Nitrous oxide is used as an anxiolytic in the medical/dental field, a commercial propellant, and an inhaled recreational drug of abuse. Exposure occurs incidentally through work (dental office workers) or intentionally via recreational use of nitrous oxide purchased online or at “head shops.”  Some recreational users refer to inhalation of nitrous oxide from canisters as “nanging,” representing the sound distortions induced by its use [1].

Clinical Presentation [2-5]

  • Progressive paresthesia, numbness, weakness, and ataxia over months of nitrous oxide exposure
  • Loss of vibratory and proprioceptive sensation, as well as the presence of hyperreflexia, gait abnormalities, and spastic weakness
  • Hematologic effects such as macrocytic anemia

Mechanism of toxicity

  • Vitamin B12 is a cofactor for methionine synthase which is required for DNA synthesis and myelin production.
  • Nitrous oxide irreversibly oxidizes the cobalt within vitamin B12 (cyanocobalamin) converting it into an inactive form.
  • The inactive form of Vitamin B12 irreversibly inactivates methionine synthase leading to bone marrow suppression after short term exposure, and demyelination with chronic exposure.

Diagnosis [2-5]

  • Patients can be found to have a low or normal serum vitamin B12 level possibly due to the measurement of inactive vitamin B12.
  • Folic acid, methylmalonic acid, and homocysteine levels can help with diagnosis.
  • Macrocytic anemia may be seen after chronic use.
  • MRI of the spinal cord may reveal dorsal column pathology as shown in the image.
  • Nerve conduction studies and EMG typically show a distal axonal sensorimotor polyneuropathy.

Treatment [2-5]

  • Removing nitrous oxide exposure is the most important step in management.
  • Vitamin B12 supplementation may help with bone marrow suppression and neurologic dysfunction but are less efficacious in chronic exposure.
  • L-methionine also used in treatment improves outcomes in animal models
  • Patients often have neurologic recovery over months with abstinence from nitrous oxide but can still exhibit lingering deficits

Bedside Pearls

  • Chronic nitrous oxide exposure can cause posterior column demyelination resulting in ataxia, weakness, loss of vibratory and proprioceptive sensation, and macrocytic anemia.
  • Thorough social history including work and recreational drug use history is key to making the diagnosis and differentiating this presentation from pernicious anemia.
  • Treatment involves abstinence and vitamin B12 supplementation.
  • Neurologic recovery can occur over months but may not be complete.

This post has been peer-reviewed on behalf of ACMT by Dr. Louise Kao, Dr. Christine Murphy, and Dr. Laura Tormoehlen


      1. Ng J, Frith R. Nanging. Lancet. 2002;360(9330):384. doi:10.1016/S0140-6736(02)09611-3. PMID: 12241780
      2. Kaufman B, Griffel M. Inhalational Anesthetics. In: Nelson LS, Lewin NA, Howland MA, Hoffman RS, Goldfrank LR, Flomenbaum NE. eds. Goldfrank’s Toxicologic Emergencies, 9e New York, NY: McGraw-Hill; 2011.
      3. Garakani, A., Jaffe, R.J., Savla, D., Welch, A.K., Protin, C.A., Bryson, E.O. and McDowell, D.M. (2016), Neurologic, psychiatric, and other medical manifestations of nitrous oxide abuse: A systematic review of the case literature. Am J Addict, 25: 358-369. doi: 10.1111/ajad.12372 PMID: 27037733
      4. Lan SY, Kuo CY, Chou CC, et al. Recreational nitrous oxide abuse related subacute combined degeneration of the spinal cord in adolescents – A case series and literature review. Brain Dev. 2019;41(5):428-435. doi:10.1016/j.braindev.2018.12.003. PMID: 30611595
      5. Meyers LE, Judge BS. Myeloneuropathy in a dentist. Clin Toxicol (Phila). 2008;46(10):1095-1096. doi:10.1080/15563650802356617. PMID: 18763150

Author information

Brian Lewis, MD

Brian Lewis, MD

Brian Lewis
Resident Physician
Spectrum Health/Michigan State University

The post ACMT Toxicology Visual Pearls: “I have a nanging feeling about this” appeared first on ALiEM.


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