The Literature → Nitrous Oxide (N₂O)

Nitrous oxide inhalant abuse: 15+ papers with practical takeaways

Functional B12 inactivation → myeloneuropathy & neuropathy, dose–injury signals, ED presentations, imaging patterns, biomarkers (MMA/homocysteine), and treatment pathways. All items link to PubMed/PMC.

Updated: Oct 18, 2025 Audience: Clinicians & Parents Format: Short summaries + citations

Curated Articles

Case Series • n=119

N₂O-induced myeloneuropathy: exposure–injury relationship

Dorsal column T2 signal, paresthesias/ataxia; weekly canister count correlated with ↑ methylmalonic acid (functional B12 deficiency).

Summary

Largest modern cohort; links consumption intensity to biomarker abnormality and severity. Recovery better with early abstinence + hydroxocobalamin.

Mair D, Paris A, Zaloum SA, et al. Nitrous oxide-induced myeloneuropathy: a case series. J Neurol Neurosurg Psychiatry. 2023;94(9):681-688. PubMed

Epidemiology • Paris

Marked increase in severe N₂O neurological disorders

Retrospective multicenter analysis shows rising severe neuro cases—policy and awareness implications.

Summary

Greater Paris hospitals report sharp increases over a few years; common features include gait ataxia, sensory loss, and dorsal column lesions.

Dawudi Y, Azoyan L, De Broucker T, et al. Marked increase in severe neurological disorders after nitrous oxide abuse: a retrospective study in the Greater Paris area. J Neurol. 2024;271(6):3340-3346. PubMedPMC

Clinical Primer • Diagnosis

How to diagnose N₂O myeloneuropathy (even with normal B12)

Homocysteine/MMA and dorsal column MRI changes clinch the diagnosis; treat with parenteral B12 and abstinence.

Summary

Explains functional B12 inactivation and outlines a pragmatic diagnostic algorithm; includes recovery timelines and pitfalls.

Swart G, Blair C, Lu Z, et al. Nitrous oxide–induced myeloneuropathy. Eur J Neurol. 2021;28(12):3938-3944. PubMed

Biomarkers • Diagnostics

What to measure: MMA & homocysteine outperform serum B12

Reviews limits of direct N₂O measurement and highlights best-effect biomarkers to diagnose and follow patients.

Summary

Explains kinetics, lab selection, and interpretation; integrates pathophysiology of methionine synthase inhibition and folate interactions.

Lucas A, Noyce AJ, Gernez E, et al. Nitrous oxide abuse direct measurement for diagnosis and follow-up: update on kinetics and impact on metabolic pathways. Clin Chem Lab Med. 2024;62(12):2356-2372. PubMed

Mechanisms • Review

Mechanisms & recent advances in N₂O-related neuro disorders

Up-to-date review of functional B12 inactivation, myelopathy/neuropathy phenotypes, differential diagnosis, and treatment principles.

Summary

Consolidates imaging, lab, and clinical pearls; emphasizes early recognition and parenteral B12 to improve neurologic outcomes.

Zou X, Yin X, Sun J, et al. Mechanisms and recent advances in the diagnosis and treatment of nitrous oxide-related neurological disorders. Front Neurol. 2024;15: [article]. PMC

Emergency Dept • Presentations

How nitrous users present to the ED

Limb numbness/weakness, gait issues, and frequent co-use; sets expectations for triage and screening.

Summary

ED cohort describes typical neurologic complaints, labs, imaging, and dispositions; underscores need to ask explicitly about N₂O and “whippets.”

Lin JP, Zhao YL, Chen YJ, et al. The clinical presentations of nitrous oxide users in an emergency department. Toxics. 2022;10(3):112. PubMedPMC

Cohort • Time-to-Symptoms

When do neurologic symptoms start after N₂O use?

Characterizes exposure levels and latency to myeloneuropathy; useful for counseling and risk stratification.

Summary

Recreational users developed paresthesias and gait ataxia after sustained use; MRI and functional B12 markers supported diagnosis.

Largeau B, Segouin C, Aufauvre M, et al. Myeloneuropathy induced by recreational nitrous oxide: a cohort study. Rev Neurol (Paris). 2022;178(8–9):877–885. PubMed

Phenotype • Dose vs Duration

What drives myelopathy vs neuropathy?

Higher dose → more myelopathy; longer duration → more neuropathy — helpful for prognosis and rehab planning.

Summary

Case-series analysis proposes a dose–topography relationship of spinal-cord vs peripheral-nerve injury in N₂O users.

Cruz E S, Rivera-Ortega P, Singh M, et al. Factors affecting the topography of nitrous oxide-induced myeloneuropathy. Clin Case Rep. 2024;12(5):e8757. PubMedPMC

Case • Functional B12 Deficiency

Classic N₂O myelopathy with abnormal MMA/homocysteine

Posterior-column MRI changes with elevated MMA/homocysteine despite “normal” B12; improved with abstinence + B12.

Summary

Walks through labs, imaging, and management steps (parenteral hydroxocobalamin, folate support, rehab) with good clinical photos.

Campdesuner V, Meadows R, Halalau A. Nitrous oxide-induced vitamin B12 deficiency resulting in myelopathy. Cureus. 2020;12(6):e8464. PubMed

Adolescent • Severe Myelopathy

Teen with N₂O myelopathy and “normal” B12

17-year-old with profound gait disturbance; highlights pediatric/young-adult vulnerability and the need for functional B12 testing.

Summary

Illustrates dorsal-column signal on MRI, high MMA, and recovery trajectory after cessation and parenteral B12.

Williamson J, Melrose J, Porter L, et al. Nitrous oxide myelopathy with functional vitamin B12 deficiency in an adolescent. BMJ Case Rep. 2019;12(2):e227109. PubMed

Peripheral Neuropathy • Case

Peripheral neuropathy from heavy “whippet” use

Progressive peripheral weakness after months of daily use—reminds clinicians to check for distal as well as cord findings.

Summary

Describes stocking–glove sensory loss and distal weakness resolving only partially after abstinence; supports combined cord and peripheral toxicity.

Dong M X, Teo J T H, Goh J P Y. Recreational nitrous oxide abuse triggered peripheral neuropathy. Front Neurol. 2022;13:1033327. PubMed

ED Trends • Australia

Increasing emergency visits for nitrous oxide in Australia

State-wide surveillance shows steep rise in N₂O-related presentations—evidence for public-health intervention.

Bethmont A, Short D, Macdonald N, et al. Increasing illicit use of nitrous oxide in presentations to NSW emergency departments. Med J Aust. 2019;211(9):429-429.e1. PubMed

Public Health • Europe

Under-recognition of N₂O poisonings across Europe

Cross-sectional Italian survey finds frequent but under-reported N₂O misuse; identifies major gaps in clinician awareness.

Riccò M, Ferraro P, Ranzieri S, et al. Nitrous Oxide Inhalant Abuse: Preliminary Results from a Cross-Sectional Survey. Int J Environ Res Public Health. 2023;20(21):7096. PubMed

Peripheral Neurotoxicity • Review

Comprehensive review of N₂O-induced peripheral neurotoxicity

Summarizes peripheral nerve findings, diagnostics, and management pearls; practical for neurologists and ED teams.

Brunt T M, van Amsterdam J G C. Nitrous oxide and peripheral neurotoxicity: what do we know? Front Neurol. 2024;15:11520302. PubMed

Service Pathway • Ambulatory Care

Ambulatory care pathway for N₂O-induced myeloneuropathy

Describes outcomes of a structured outpatient protocol—template for hospitals facing rising N₂O cases.

Summary

Multidisciplinary pathway reduced admissions and improved follow-up compliance; offers model for neurology and addiction-medicine collaboration.

Zaloum S A, Thompson V, Paris A, et al. Evaluation of an Ambulatory Care Pathway for Patients with Nitrous Oxide-Induced Myeloneuropathy. BMJ Neurol Open. 2024;6(1):e000737. PubMed

Informational only — not medical advice. Nitrous oxide misuse can cause irreversible neurologic injury; seek evaluation and stop exposure immediately.