Recreational nitrous oxide-related myeloneuropathy in adolescents: a multicenter retrospective case series and systematic literature review.

Lital Cohen-Vig, Noy Hota, Oded Scheuerman, Tamar Steinberg, Maha Zeidan, Jacob Genizi, Eran Rom, Elena Kogan, Sharon Aharoni

Journal: European journal of pediatrics 2026;185(8):

PMID: 42474763

Abstract

UNLABELLED

Nitrous oxide (N2O) is a common recreational drug. Chronic use inactivates vitamin B12 resulting in neurological damage. Most studies have focused on adults. This study aims to describe unique features of N2O-related myeloneuropathy in adolescents. Adolescents aged 14-18 years admitted with N2O-related myeloneuropathy to three tertiary medical centers in 2024 were enrolled. Their medical records were reviewed retrospectively. A systematic review was conducted for N2O-related neurologic complications in adolescents, using Embase, MEDLINE, Scopus and PubMed databases. Clinical data from the case series and systematic review were extracted and analyzed together. Five new and 54 reported patients (2011-2026) were included. All presented with neurological complaints, predominantly sensory. Vitamin B12 deficiency was detected in 45% and elevated homocysteine or methylmalonic acid levels in 92% of them. Intracranial pressure was elevated in two of the new patients. Magnetic resonance imaging demonstrated long posterior column changes in 89%, and nerve conduction studies showed peripheral neuropathy, predominantly axonal sensorimotor, in 88% of the patients. Recovery occurred in 27% and improvement in 61% with B12 treatment.

CONCLUSION

 N2O abuse should be considered in the differential diagnosis of unexplained myelopathy and/or neuropathy in a teenager, even in the absence of anemia. Early diagnosis is important, as timely treatment may improve prognosis. Subclinical B12 deficiency may serve as a predisposing factor; thus, further research is required. This study aims to raise awareness of the clinical picture, risks, and treatment of chronic N2O abuse in adolescents.

WHAT IS KNOWN

• Recreational N2O use is common and may cause myeloneuropathy, primarily due to B12 dysfunction. Homocysteine and methyl-malonic acid levels are better biomarkers of B12 dysfunction. • Information on unique features of neurological complications in adolescents is sparse.

WHAT IS NEW

• Chronic N2O use in adolescents is predominantly associated with sensory symptoms; a potential association with elevated intracranial pressure is suggested. • Subclinical B12 deficiency may serve as a predisposing factor for neurological complications.

© 2026. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Address: Institute of Pediatric Neurology, Schneider Children's Medical Center of Israel, Petach Tikva, 49420235, Israel. [email protected].; Gray Faculty of Medical & Health Sciences, Tel Aviv University, Tel Aviv, 6997801, Israel. [email protected].; Gray Faculty of Medical & Health Sciences, Tel Aviv University, Tel Aviv, 6997801, Israel.; Department of Pediatrics B, Schneider Children's Medical Center of Israel, Petach Tikva, 49420235, Israel.; Institute of Pediatric Neurology, Schneider Children's Medical Center of Israel, Petach Tikva, 49420235, Israel.; Gray Faculty of Medical & Health Sciences, Tel Aviv University, Tel Aviv, 6997801, Israel.; Pediatric Department, Bnai Zion Medical Center, Haifa, 31048, Israel.; Pediatric Department, Bnai Zion Medical Center, Haifa, 31048, Israel.; Bruce Rappaport Faculty of Medicine, Technion, Haifa, 3525433, Israel.; Gray Faculty of Medical & Health Sciences, Tel Aviv University, Tel Aviv, 6997801, Israel.; Department of Pediatrics C, Schneider Children's Medical Center of Israel, Petach Tikva, 49420235, Israel.; Gray Faculty of Medical & Health Sciences, Tel Aviv University, Tel Aviv, 6997801, Israel.; Department of Neurology, Rabin Medical Center-Beilinson Hospital, Petach Tikva, 4941492, Israel.
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