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Nitrous Oxide Neurological Damage — MRCPsych Paper B MCQ

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HardSubstance MisuseNitrous Oxide Neurological DamageMRCPsych Paper B

A 25-year-old woman reports several months of heavy recreational nitrous oxide use. She develops distal paraesthesia, sensory ataxia and cognitive slowing. Her mean corpuscular volume is 108 fL, but serum total vitamin B12 is within the laboratory reference range. Plasma homocysteine and methylmalonic acid are elevated, and MRI shows symmetrical signal abnormality in the posterior columns of the cervical cord. Which mechanism best accounts for her neurological syndrome?

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Correct answer: B — Functional cobalamin inactivation causing methionine synthase inhibition and impaired myelin maintenance

Nitrous oxide oxidises the cobalt ion in methylcobalamin, functionally inactivating vitamin B12 and inhibiting methionine synthase. The resulting disturbance of methionine-dependent methylation and myelin maintenance causes myeloneuropathy or subacute combined degeneration. Serum total B12 may remain normal, so raised homocysteine and methylmalonic acid support functional deficiency. NMDA receptor antagonism explains acute psychoactive and anaesthetic effects, not this delayed myeloneuropathy. Thiamine deficiency causes Wernicke encephalopathy or beriberi rather than the characteristic posterior-column syndrome. Folate deficiency can cause megaloblastic anaemia but does not typically cause subacute combined degeneration. Oxygen displacement can cause acute hypoxic injury, but would not explain macrocytosis and the abnormal cobalamin-dependent metabolic markers.

Reference: Advisory Council on the Misuse of Drugs. Nitrous oxide: updated harms assessment, sections 4.11–4.12 and 4.25. 2023. https://www.gov.uk/government/publications/nitrous-oxide-updated-harms-assessment/nitrous-oxide-updated-harms-assessment-accessible