Case Presentation:

A 42 year old female noticed numbness and a tingling sensation over her feet bilaterally. This sensation progressed to involve the entire lower extremities and was accompanied by unsteady gait and weakness over the next 24 hours. Four days after her symptoms began she presented to the emergency department at St. Joseph Mercy Hospital because of the lack of ability to perform activities of daily living. Further history revealed that she had been inhaling 46 to 100 canisters of nitrous oxide daily for 2 months for recreational use. Physical examination was significant for bilateral lower extremity giveaway weakness, loss of vibratory sensation and proprioception at the great toes, positive Romberg test and brisk knee reflexes bilaterally. Although initial studies showed normal hemoglobin, vitamin B12 (1322 pcg/mL) and folic acid levels, physical examination and high hemoglobin mean corpuscular volume (105 fL) suggested functional vitamin B12 (B12) deficiency. She was given an immediate dose of 1,000 mcg B12 as an injection prior to hospitalization. High blood homocysteine, methylmalonic acid levels and magnetic resonance imaging findings confirmed the diagnosis of subacute combined degeneration of the spinal cord (SCD) (Figure). She received daily B12 injections for four days prior to discharge. After 4 weekly B12 injections, daily oral B12 supplementation and abstinence from nitrous oxide for three months, her symptoms completely resolved. 

Discussion:

Eggs, meat and dairy products make up the majority of B12 intake in humans. The vitamin then needs to be bound to intrinsic factor prior to absorption in the ileum. Because of this, vegans and patients with pernicious anemia are most susceptible to B12 deficiency. They can present with a variety of findings including megaloblastic anemia, neuropsychiatric symptoms such as mood, cognitive changes and SCD. Nitrous oxide irreversibly inactivates methionine synthase, an enzyme that utilizes B12 as a cofactor. This leads to functional deficiency of B12 and results in inhibition of myelin production, which is thought to be the cause of SCD. Inhibition of B12 function leading to symptoms of SCD has been observed in patients who have low or borderline B12 levels but has less commonly been described in patients with high levels. Our patient’s high homocysteine and methylmalonic acid levels suggest functional deficiency despite high B12 levels. Abstaining from nitrous oxide use and B12 supplementation can reverse the disease. However, delay in diagnosis and treatment may lead to irreversible spinal cord damage.

Conclusions:

Nitrous oxide chargers can be purchased without prescription. Because recreational use can lead to serious complications such as SCD, hospitalists who admit patients with symptoms suggestive of spinal cord dysfunction should consider functional B12 deficiency from nitrous oxide toxicity as early therapy can prevent permanent damage to the spinal cord.