Analysis of clinical characteristics and prognostic factors in 110 patients with nitrous oxide abuse

Brain Behav. 2022 Apr;12(4):e2533. doi: 10.1002/brb3.2533. Epub 2022 Mar 20.


Purpose: To review the clinical symptoms, auxiliary examination findings, and outcomes of patients with nitrous oxide (N2 O) abuse, and analyze the factors that affect outcomes.

Methods: Patients with N2 O abuse treated in the Department of Neurology between January 2018 and December 2020 were included. The clinical data of these patients were collected, and follow-up was conducted to determine the outcomes.

Results: The average age of the 110 patients with N2 O abuse was 21.4 ± 4.2 years (range: 14-33 years). Clinical presentation primarily included neurological symptoms, such as limb numbness and/or weakness (97%), psychiatric symptoms, changes in appetite, and skin hyperpigmentation. Laboratory test results were characterized by vitamin B12 deficiency (60%, 34 out of 57 cases) and high homocysteine level (69%, 31 out of 45 cases). Electromyography indicated mixed axonal and demyelination injury (92%, 80 out of 87 cases). Motor and sensory nerves were simultaneously involved, and injury primarily involved the lower limbs. One hundred and seven (97%) patients were clinically diagnosed with peripheral neuropathy, of whom 26 (24%) exhibited spinal abnormalities on magnetic resonance imaging, supporting a diagnosis of subacute combined degeneration. Treatment included N2 O withdrawal and vitamin B12 supplementation. Reexamination of six patients indicated that treatment was effective. Follow-up was completed for 51 patients. Thirty-four patients (67%) recovered completely, 17 patients (33%) had residual limb numbness, and only one patient experienced relapse. Sex was an independent prognostic factor; the outcomes of female patients were better than that of male patients.

Conclusion: The recreational use of N2 O has largely expanded among youth in recent decades, which has become a growing public health concern in China. It highlights the importance of the recognition of various clinical symptoms, particularly limb numbness and/or weakness related to the cases of N2 O abuse. The therapeutic administration of vitamin B12 supplementation and N2 O withdrawal can make the overall prognosis good, especially for female patients.

Keywords: clinical characteristics; nitrous oxide; outcomes; peripheral neuropathy; vitamin B12 deficiency.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Female
  • Humans
  • Hypesthesia / chemically induced
  • Hypesthesia / drug therapy
  • Male
  • Nitrous Oxide* / adverse effects
  • Prognosis
  • Vitamin B 12 / therapeutic use
  • Vitamin B 12 Deficiency* / chemically induced
  • Vitamin B 12 Deficiency* / diagnosis
  • Vitamin B 12 Deficiency* / drug therapy
  • Vitamins
  • Young Adult


  • Vitamins
  • Nitrous Oxide
  • Vitamin B 12