Case

A 21-year old male visited the emergency department with complaints of imbalance, limb weakness, and numbness from the toes up to the waist and in hands and arms. Several months earlier he had presented himself with similar symptoms and was admitted to the neurology ward. Electromyography performed back then showed signs of demyelination and he was treated with intravenous immunoglobulins (IVIG) for Guillain-Barre Syndrome.

After an initial improvement however, the last few weeks his symptoms had gotten worse.

The patient was again admitted to the neurology ward. A neurological examination revealed a MRC grade 4 weakness in both legs, absent biceps, triceps, knee, and ankle reflexes, as well as a disturbed sense of vibration. An MRI of the cervical and thoracic spine revealed no signs of myelopathy. During his hospital stay, the patient admitted to the frequent use of nitrous oxide (up to 20 canisters per day). After a short period of abstinence following his previous hospital stay, a few weeks ago he started using again. He noted that after he used nitrous oxide, sometimes he could not stay on his feet at all.

New laboratory tests including a methylmalonic acid test revealed a vitamin B12 deficiency. The patient was treated with vitamin B12 injections after which his symptoms rapidly improved. 

Background

Nitrous oxide is an inhaled anesthetic commonly used in dentistry; it is also used as a propellant in the food industry (eg, in whipped cream dispensers). Several reports have described the neurotoxicity of nitrous oxide after abuse by health care professionals and in others after recreational use. Nitrous oxide causes its harmful effects by irreversibly oxidising the cobalt ion of cobalamin (vitamin B12) from the (+) 1 to the (+) 3 valence state. In the normal state after gastrointestinal absorption, the transcobalamin-cobalamin complex is degraded and cobalamin II is released for conversion into the active forms of vitamin B , methylcobalamin, and adenosylcobalamin. Oxidation of the cobalt ion by nitrous oxide prevents methylcobalamin from acting as a co- enzyme in the production of methionine and subsequently S-adenosylmethionine, which is necessary for methylation of myelin sheath phospholipids.

Although vitamin B12 deficiency rarely occurs in well-nourished, healthy, young people, nitrous oxide (N2O) intoxication is an important cause of vitamin B12 deficiency in this cohort. The neurological manifestations of vitamin B12 deficiency include myelopathy, neuropathy, sensory disturbances, gait abnormalities, and weakness, while the psychiatric problems range from cognitive and behavioral disturbances to dementia. Clinical signs may include a loss of vibration sense, absent reflexes, a positive Romberg test, and (anamnestic) Lhermitte phenomenon. 

The treatment of N2O abuse-induced vitamin B12 deficiency is similar to the treatment of pernicious anemia, and comprises 1 of 2 regimens: 

- intramuscular injections of 1,000 µg vitamin B12 (cyanocobalamin) daily for 1 week, followed by weekly injections for 4–8 weeks, and then monthly injections until clinical resolution; or: 

- daily oral administration of 1,000–2,000 µg cyanocobalamin until clinical resolution.