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A 19-year-old man presented with a 1-month history of progressive 4-limb numbness and gait imbalance. Physical examination revealed mild general muscular weakness, areflexia, and wide-based, ataxic, steppage gait. Sensory tests showed diminished superficial sensation below the level of the cervical-thoracic junction and a glove-and-stocking pattern of sensory loss at the 4 extremities. An initial magnetic resonance imaging examination of the cervical spine revealed an increased bilateral signal from the posterior and anterior columns on T2-weighted images. Nerve conduction velocity and electromyographic tests revealed polyneuropathy. On further inquiry, the patient admitted to chronic recreational use of nitrous oxide. The final diagnosis was nitrous oxide-induced neurotoxicity. The patient was treated for 5 days with injections of 1000 μg/day vitamin B12, followed by an additional 2-month treatment at a dose of 1000 μg/week. The numbness resolved after the first week, but there remained a mild sensory ataxic gait. The patient recovered fully after 2 months of treatment and nitrous oxide abstinence. We recommend an investigation of the patient's history of nitrous oxide exposure in cases where an individual presents to the emergency department or outpatient department with acute numbness characterized by megaloblastic red blood cells and symmetric neurologic deficits.