Case Presentation: A 50-year-old female with a history of alcohol use disorder presented to the emergency department with a one-day history of unsteady gait, decreased lower extremity sensation, and slurred speech. She reported using 20 whippits (recreational inhaled nitrous oxide) daily for the preceding 3-4 weeks. She denied any dietary restrictions. Exam revealed 3+ patellar reflexes, upgoing toes, decreased sensation to light touch and vibration and decreased proprioception in distal lower extremities, dysmetria in upper extremities, wide-based, ataxic gait, and positive Romberg sign. Labs were notable for macrocytosis (MCV 101.4 fL), normal vitamin B1, low-normal vitamin B12 (291 pg/mL), elevated homocysteine (>130 µmol/mL), and elevated methylmalonic acid (MMA, 89 nmol/mL). Brain magnetic resonance imaging (MRI) without contrast showed no acute intracranial abnormalities. With high-dose vitamin B12 replacement, homocysteine and MMA levels normalized, but neurologic recovery was only modest, with some persistent ataxia and decreased sensation. The cause of her sensory ataxia was nitrous oxide-induced vitamin B12 myelopathy.
Discussion: Misuse of nitrous oxide (N2O), also known as “laughing gas” or “whippits,” is a growing public health concern. It causes transient analgesic, euphoric, and hallucinogenic effects, making it an ideal drug for abuse [1]. N2O irreversibly inactivates vitamin B12, affecting the biochemical pathways in which B12 is a cofactor, leading to decreased myelin production and demyelination of the brain, spinal cord, and peripheral nervous system [1-3]. Vitamin B12 deficiency is an infrequent cause of neurologic symptoms in hospitalized patients, but one that hospitalists should readily identify. Patients present with paresthesias, numbness, weakness, unsteady gait, and/or neuropsychiatric effects. Serum B12 may be normal, but homocysteine and MMA are often elevated, and nerve conduction studies show axonal sensorimotor neuropathy and spinal MRI shows characteristic dorsal column T2 hyperintensities. Treatment with vitamin B12 replacement often improves neurologic symptoms, but many patients have persistent paresthesias or ataxias, including this patient [1,4-5].
Conclusions: It is important to consider N2O abuse as a cause of acute dorsal column myelopathy, as symptoms can improve or be reversed with high dose vitamin B12 replacement.