Neurological Recovery Following NOS-SACD

NCT05714917 | Recruiting

• 1 other identifier: 22NS021
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 3

Brief Summary

Nitrous oxide has become an increasingly popular recreational drug amongst young people, particularly at festivals, nightclubs and parties. Considering the drug is not illegal to possess, has low cost in the form of 'whippets' and can be easily purchased online, it has become the second most commonly used recreational drug amongst people aged 16-24 in the UK. However, nitrous oxide is known to irreversibly inactivate the functioning of vitamin B12, a vitamin required for the maintenance and proper functioning of nerves in the spinal cord. Neurological symptoms in this population have been reported in around 3.4% of nitrous oxide users, although the true incidence is expected to be higher as the cases being reported by UK hospitals continues to rise. Patients may present with adverse neurological symptoms like tingling, weakness, coordination and mobility problems. Currently, studies reviewing the functional recovery of these patients have been limited by a retrospective study design, short follow up duration and being limited to small cohort sizes. This is in part linked to patient non-compliance and non-attendance at follow-up appointments. The investigators will therefore prospectively recruit all patients presenting with these symptoms and continue to collect data relating to their neurological recovery for 12 months. Data collection will be remote to ensure it is of low burden to the participants. This will allow the investigating team and others to fully appraise the severity of these toxic neuropathies and understand how best to manage their follow up.

Conditions

Nitrous Oxide Abuse; Subacute Combined Cord Degeneration; Neurologic Symptoms; Paresthesia; B12 Deficiency Vitamin

Keywords

Nitrous oxide; B12; Neurological symptoms; Clinical recovery

Outcome Measures

Primary Outcomes (1)

• Improvement in finger tapping task, baseline to month 12

  To determine whether patients with NOS-induced neurological damage recover their dexterity function over a 12-month period.

  12 months

Secondary Outcomes (3)

• Improvement in cognitive function task, baseline to month 12

  12 months

• Improvement in step counts, baseline to month 12

  12 months

• Improvement in I-RODS and ONLS, baseline to month 12

  12 months

Study Arms (1)

Confirmed diagnosis of NOS-induced neurological damage

Any patient first presented with paraesthesia, weakness, ataxia or gait disturbance with a history of NOS use (age limit 16-40) as of 19/08/2024. Patients who can read and write in English, so that they can complete the questionnaires.

Other: Observational study with no interventions

Interventions

Observational study with no interventions OTHER

This is an observational study and there will be no clinical interventions.

Also known as: Observational Study

Confirmed diagnosis of NOS-induced neurological damage

Eligibility Criteria

• Age: 16 Years - 40 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

NOS induced neurological symptoms may present with either a.) severe neurological impairment to warrant A\&E admission, or b.) milder symptoms which may present to primary care. The investigators team therefore propose recruitment pathways based either on A\&E or GP referral. Participants will be invited to the neurology team in order for them to coordinate the care according to local practices.

You may qualify if:

• Any patient first presented with paraesthesia, weakness, ataxia or gait disturbance with a history of NOS use (age limit 16-40) as of 19/08/2024
• Patients who can read and write in English, so that they can complete the questionnaires.
• Patients must have received a definitive consultant neurologist confirmed diagnosis of NOS-induced neurological damage. This is possible as all eligible patients will have been reviewed by the neurology team prior to study involvement.

You may not qualify if:

• Other causes of previous neuropathy or neurodegeneration indicated.
• Qualitative Interview Study:
• Patients currently taking part in the longitudinal study.
• Patients who report previously (clinical history) or currently (PHQ-2, clinical history) experiencing mental health difficulties.

Sponsors & Collaborators

• Nottingham University Hospitals NHS Trust: lead
• Barts & The London NHS Trust: collaborator
• Northern Care Alliance NHS Foundation Trust: collaborator
• University Hospital Birmingham NHS Foundation Trust: collaborator

Study Sites (3)

University Hospitals Birmingham NHS Foundation Trust

Birmingham, United Kingdom

RECRUITING

Barts Health NHS Trust

London, United Kingdom

RECRUITING

Salford Royal NHS Foundation Trust

Manchester, United Kingdom

RECRUITING

Related Publications (14)

• Kroes AC, Lindemans J, Abels J. [Interaction between nitrous oxide and vitamin B12]. Ned Tijdschr Geneeskd. 1985 Nov 23;129(47):2243-7. No abstract available. Dutch.

  PMID: 4088327 BACKGROUND

• Omotosho YB, Ying GW, Orji R, Patel H. Recreational Nitrous Oxide-Induced Subacute Combined Degeneration. Cureus. 2022 Mar 22;14(3):e23409. doi: 10.7759/cureus.23409. eCollection 2022 Mar.

  PMID: 35475085 BACKGROUND

• Winstock AR, Ferris JA. Nitrous oxide causes peripheral neuropathy in a dose dependent manner among recreational users. J Psychopharmacol. 2020 Feb;34(2):229-236. doi: 10.1177/0269881119882532. Epub 2019 Nov 4.

  PMID: 31679459 BACKGROUND

• Schilling RF. Is nitrous oxide a dangerous anesthetic for vitamin B12-deficient subjects? JAMA. 1986 Mar 28;255(12):1605-6.

  PMID: 3951096 BACKGROUND

• Flippo TS, Holder WD Jr. Neurologic degeneration associated with nitrous oxide anesthesia in patients with vitamin B12 deficiency. Arch Surg. 1993 Dec;128(12):1391-5. doi: 10.1001/archsurg.1993.01420240099018.

  PMID: 8250714 BACKGROUND

• Patel KK, Mejia Munne JC, Gunness VRN, Hersey D, Alshafai N, Sciubba D, Nasser R, Gimbel D, Cheng J, Nouri A. Subacute combined degeneration of the spinal cord following nitrous oxide anesthesia: A systematic review of cases. Clin Neurol Neurosurg. 2018 Oct;173:163-168. doi: 10.1016/j.clineuro.2018.08.016. Epub 2018 Aug 9.

  PMID: 30144777 BACKGROUND

• Seed A, Jogia M. Lessons of the month: Nitrous oxide-induced functional vitamin B12 deficiency causing subacute combined degeneration of the spinal cord. Clin Med (Lond). 2020 May;20(3):e7-e9. doi: 10.7861/clinmed.2020-0072.

  PMID: 32414730 BACKGROUND

• de Medeiros FC, de Albuquerque LA, de Souza RB, Gomes Neto AP, Christo PP. Vitamin B12 extensive thoracic myelopathy: clinical, radiological and prognostic aspects. Two cases report and literature review. Neurol Sci. 2013 Oct;34(10):1857-60. doi: 10.1007/s10072-013-1335-7. Epub 2013 Mar 7.

  PMID: 23468407 BACKGROUND

• Algahtani H, Shirah B, Abdelghaffar N, Abuhawi O, Alqahtani A. Nitrous oxide recreational abuse presenting with myeloneuropathy and mimicking Guillain-Barre syndrome. Intractable Rare Dis Res. 2020 Feb;9(1):54-57. doi: 10.5582/irdr.2020.01007.

  PMID: 32201677 BACKGROUND

• Swart G, Blair C, Lu Z, Yogendran S, Offord J, Sutherland E, Barnes S, Palavra N, Cremer P, Bolitho S, Michael Halmagyi G. Nitrous oxide-induced myeloneuropathy. Eur J Neurol. 2021 Dec;28(12):3938-3944. doi: 10.1111/ene.15077. Epub 2021 Sep 6.

  PMID: 34427020 BACKGROUND

• Berling E, Fargeot G, Aure K, Tran TH, Kubis N, Lozeron P, Zanin A. Nitrous oxide-induced predominantly motor neuropathies: a follow-up study. J Neurol. 2022 May;269(5):2720-2726. doi: 10.1007/s00415-021-10858-2. Epub 2021 Nov 6.

  PMID: 34741241 BACKGROUND

• 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.

  PMID: 27037733 BACKGROUND

• Zheng D, Ba F, Bi G, Guo Y, Gao Y, Li W. The sharp rise of neurological disorders associated with recreational nitrous oxide use in China: a single-center experience and a brief review of Chinese literature. J Neurol. 2020 Feb;267(2):422-429. doi: 10.1007/s00415-019-09600-w. Epub 2019 Oct 26.

  PMID: 31655888 BACKGROUND

• Peirce J, Gray JR, Simpson S, MacAskill M, Hochenberger R, Sogo H, Kastman E, Lindelov JK. PsychoPy2: Experiments in behavior made easy. Behav Res Methods. 2019 Feb;51(1):195-203. doi: 10.3758/s13428-018-01193-y.

  PMID: 30734206 BACKGROUND

Related Links

• Drug misuse in England and Wales - Office for National Statistics
• Global Drug Survey 2021

MeSH Terms

Conditions

Neurologic Manifestations; Paresthesia; Vitamin B 12 Deficiency

Interventions

Observation

Condition Hierarchy (Ancestors)

Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Somatosensory Disorders; Sensation Disorders; Vitamin B Deficiency; Avitaminosis; Deficiency Diseases; Malnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Methods; Investigative Techniques

Central Study Contacts

Nikos Evangelou, FRCP, DPhil

CONTACT

07715172966; nikos.evangelou@nottingham.ac.uk

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 18, 2023
• First Posted: February 6, 2023
• Study Start: August 19, 2024
• Primary Completion (Estimated): August 19, 2026
• Study Completion (Estimated): August 19, 2026
• Last Updated: July 25, 2025

Record last verified: 2025-07

Locations

GB (3)