Epidemiology of Neurological Complications to Nitrous Oxide Poisoning (EPI-NOX)

N2O inactivates vitamin B12, impairing its ability to act as a cofactor of methionine synthase. In addition, the elimination of vitamin B12 is increased. Neurological damage is similar to that described in combined sclerosis of the marrow, and are probably related to induce vitamin B12 deficiency. The use of N2O can then precipitate the rapid appearance of signs (neurological, psychiatric and hematological) related to a true and/ or functional vitamin B12 deficiency.

In 1978, RB Layzer described the first 3 cases of peripheral neuropathy secondary to nitrous oxide (N2O) consumption. In 2016, a team collected the 91 published cases: among these, 72 had neurological complications, and 52 had a concentration of vitamin B12 considered "low" or "normal-low"

Since then, consumption patterns seem changed due to: an increasing ease of access, the change of container (packaging in cartridge 8 grams versus bottle of 600 grams) and a usually occasional and festive consumption that seems to become solitary and regular, This change in consumption patterns is explained by an increased incidence of neurological complications, although no epidemiological work is yet available.

The objective of this work is to describe the epidemiology of this condition, to correlate it with major recent social phenomena (confinement related to the SARS-Cov2 pandemic), and finally to compare the incidence of myelopathies secondary to N2O with the incidence of other frequent inflammatory neurological diseases (autoimmune myelitis and Guillain-Barré syndrome).

Study Overview

• Status: Recruiting
• Conditions: Neurology Department

• Study Type: Observational
• Enrollment (Anticipated): 135

Contacts and Locations

• Study Contact: Name: Mickael BONNAN, MD; Phone Number: 01 42 35 62 97; Email: mickael.bonnan@ch-stdenis.fr
• Study Contact Backup: Name: Thomas DE BROUCKER, MD; Phone Number: 01 42 35 62 97; Email: thomas.debroucker@ch-stdenis.fr

Study Locations

• France
  • ILE DE France
    • Saint-denis, ILE DE France, France, 93200
      • Recruiting
      • Hopital DELAFONTAINE
      • Contact: Stéphanie Cossec; Phone Number: 6962 0142356140; Email: coordination.rechercheclinique@ghtpdfr.fr
      • Principal Investigator: Mickaël Bonnan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

cohort of patients who have been exposed to N2O and have neurological disorders

Description

Inclusion Criteria:

• Adult patient (≥16 years)
• Hospitalized or having consulted with the departments of Neurology or Internal Medicine for neurological phenomena related to the consumption of N2O. The neurological phenomena included are usually: neuropathies or myelopathies, However, the existence of other neurological or psychiatric signs is not a factor of exclusion: for example, headaches or cognitive or psychiatric disorders with acute onset.
• Exposure to N2O for recreational or medical reasons (Meopa anesthesia).
• Lack of alternative diagnosis other than N2O poisoning
• Consultation for neurological disorders between 01/01/2018 and 31/12/2021

Exclusion Criteria:

• Minor subjects or subjects subject to a legal protection measure (guardianship, curators) during the consultation.
• Refusal to include in a study explained in the file
• Absence of N2O consumption during the 6 months preceding the appearance of signs

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
sexe	describe the epidemiology of neurological complications to nitrous oxide poisoning	Day 1
age	describe the epidemiology of neurological complications to nitrous oxide poisoning	Day 1
place to live	describe the epidemiology of neurological complications to nitrous oxide poisoning	Day 1
Occupational status	describe the epidemiology of neurological complications to nitrous oxide poisoning	Day 1
consumption of toxic substances (alcohol, tobacco, cannabis)	describe the epidemiology of neurological complications to nitrous oxide poisoning	Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Date and nature of first symptoms	correlate epidemiology with major recent social phenomena	Day 1
consumption mode and quantity	correlate epidemiology with major recent social phenomena	Day 1

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
detail of symptoms, origin and consequences	compare the incidence of myelopathies secondary to N2O with the incidence of other frequent inflammatory neurological diseases	Day 1

Collaborators and Investigators

• Sponsor: Centre Hospitalier de Saint-Denis

Publications and helpful links

General Publications

• Layzer RB, Fishman RA, Schafer JA. Neuropathy following abuse of nitrous oxide. Neurology. 1978 May;28(5):504-6.
• Sanders RD, Weimann J, Maze M. Biologic effects of nitrous oxide: a mechanistic and toxicologic review. Anesthesiology. 2008 Oct;109(4):707-22. doi: 10.1097/ALN.0b013e3181870a17.
• Garakani A, Jaffe RJ, Savla D, Welch AK, Protin CA, Bryson EO, McDowell DM. Neurologic, psychiatric, and other medical manifestations of nitrous oxide abuse: A systematic review of the case literature. Am J Addict. 2016 Aug;25(5):358-69. doi: 10.1111/ajad.12372. Epub 2016 Apr 1. Review.
• Vollhardt R, Mazoyer J, Bernardaud L, Haddad A, Jaubert P, Coman I, Manceau P, Mongin M, Degos B. Neurological consequences of recreational nitrous oxide abuse during SARS-CoV-2 pandemic. J Neurol. 2022 Apr;269(4):1921-1926. doi: 10.1007/s00415-021-10748-7. Epub 2021 Aug 21.

Study record dates

Study Major Dates

• Study Start (Actual): April 10, 2022
• Primary Completion (Actual): July 10, 2022
• Study Completion (Anticipated): August 31, 2022

Study Registration Dates

• First Submitted: April 8, 2022
• First Submitted That Met QC Criteria: April 8, 2022
• First Posted (Actual): April 15, 2022

Study Record Updates

• Last Update Posted (Actual): August 11, 2022
• Last Update Submitted That Met QC Criteria: August 10, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: nitrous oxide poisoning
• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Poisoning
• Other Study ID Numbers: CHSD_0023_NEURO; 2022-A00718-35 (Registry Identifier: IDRCB)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No