Neurophysiological Characteristics of Nitrous Oxide-Induced Polyneuropathy: A Case Series

Nitrous oxide (N₂O) misuse is a growing health concern, with N₂O-induced neurological disorders increasingly reported across Europe. Among these, N₂O-induced polyneuropathy (PNP) can lead to permanent deficits, yet its neurophysiological characteristics remain inconsistently described. This retrospective case series aimed to characterize the electrophysiological pattern of N₂O-induced polyneuropathy.

We reviewed the records of 12 patients with acute neurological symptoms and a history of N₂O abuse, all of whom underwent electrophysiological testing at a German tertiary care hospital between July 2023 and December 2024. Data were analyzed descriptively.

Conduction studies revealed evidence of PNP in eight out of 12 patients and the most common pattern was pure motor (5/8). No distinct clinical phenotype could be identified for patients with electrophysiologically confirmed PNP or Pure-Motor PNP. SSEPs were abnormal in all assessable patients, whereas signs of SCD on MRI were present in a smaller proportion. Only three of 10 tested patients had reduced vitamin B12 levels, while all showed elevated methylmalonic acid (MMA) levels. Mean MMA levels were higher in patients with PNP than in those without.

The reason why N₂O leads to different patterns of PNP remains unclear and a distinct phenotype for N₂O-induced PNP or Pure-Motor PNP was not found in this cohort. MMA represents a more reliable biomarker than serum vitamin B12 in the diagnostic workup of N₂O-induced neurotoxicity. These findings highlight the need for further research into additional neurotoxic properties of N₂O and individual predisposing factors underlying the different electrophysiological patterns of N₂O-induced PNP.