Search

There is rising use of recreational nitrous oxide (N₂O) in the community because of its availability as “whippet” canisters. Nitrous oxide use is still legal and outside the purview of the Drug Enforcement Administration (DEA). It is not detected on a routine drug screen, and patient history is key to establishing the diagnosis. We highlight a case of subacute combined degeneration in a young patient secondary to recreational nitrous oxide use, which improved with vitamin B12 replacement. A 19-year-old male with a history of recreational nitrous oxide use presented with progressive bilateral lower extremity paresthesia and ataxia. Neurological examination revealed deficits in vibration and proprioception, motor weakness, and diminished reflexes in the bilateral lower extremities. The laboratory results were significant for pancytopenia, profound vitamin B12 deficiency (55 ng/mL), and elevated methylmalonic acid (2.14 umol/L). The urine drug screen was negative. MRI showed subacute degeneration of the spinal cord dorsal column at C2-C5. Treatment with intramuscular cyanocobalamin resulted in the normalization of pancytopenia and B12 levels (573 ng/mL). The patient had partial resolution of neurological symptoms following the initiation of parenteral vitamin B12 replacement. The mechanism of subacute combined degeneration in the setting of nitrous oxide toxicity appears to be mediated by functional B12 deficiency. Oxidation of cobalt ion of vitamin B12 by nitrous oxide renders it unavailable as a coenzyme, leading to the accumulation of by-products that enter lipid metabolism, resulting in abnormal myelin synthesis, which ultimately manifests as subacute combined degeneration. Vitamin B12 deficiency of unclear etiology should raise suspicion for nitrous oxide toxicity as early initiation of replacement therapy with vitamin B12 can improve neurological function.