Rapid-Onset Subacute Combined Degeneration After Short-Term, High-Dose Nitrous Oxide Use

Recreational nitrous oxide (N2O) use has risen in recent years and is increasingly accessible in high-volume cartridges and canisters. N2O oxidizes cobalamin and functionally inhibits methionine synthase disrupting methylation pathways essential for myelin maintenance and DNA metabolism. Serum vitamin B12 levels may be normal despite functional deficiency, making markers such as homocysteine and methylmalonic acid helpful to confirm the diagnosis. Clinical manifestations range from peripheral neuropathy and megaloblastic anemia to subacute combined degeneration (SCD), a demyelinating myelopathy classically involving the dorsal columns (and sometimes corticospinal tracts). Although SCD is often associated with chronic exposure, brief but high-dose use may precipitate rapid neurologic decline. Early recognition and prompt parenteral vitamin B12 replacement may reduce the risk of irreversible deficits.