To report laboratory, radiologic, and clinical findings in a case series of patients hospitalized with subacute combined degeneration (SCD) caused by nitrous oxide (NO) abuse.

NO is legal and widely available as a food additive, making it an easily accessible recreational drug. NO inhibits methionine synthase and inactivates vitamin B12. Prolonged use can lead to B12 deficiency and SCD.

We reviewed hospital records from March 2016 until August 2022 and found three cases of SCD associated with NO abuse.

One 43-year-old male and two females, 27 and 44 years old, had SCD in the setting of NO abuse. All had numbness, weakness, and ataxia. Cognitive and behavioral changes with loss of vibratory sensation and proprioception were not universal. MRI of the cervical cord in all patients demonstrated T2 hyperintensity of the posterior columns in the classic “inverted V” shape consistent with SCD. B12 levels in two patients were 0.54 and 0.73X lower limit of normal (LLN), while in the third patient it was 2.3X the LLN. Methylmalonic acid (MMA) and homocysteine levels were elevated in all patients up to 34X the upper limit of normal. All patients were treated with high-dose B12 repletion, physical therapy, and counseled on nitrous oxide cessation. Two patients were discharged home, while one was discharged to a skilled facility for further rehabilitation.

NO abuse can induce SCD. Patients may have a normal B12 level but still be functionally B12 deficient because NO inactivates the B12 molecule. Elevated MMA and homocysteine levels are consistent with B12 inactivation as well as deficiency, illustrating the utility of these additional diagnostic tests when B12 deficiency is suspected. Profound neurological deficits can persist at the time of hospital discharge in NO-related SCD.