Neurological disorders caused by recreational use of nitrous oxide—a retrospective study from a German metropolitan area and review of the literature

Abstract

The recreational use of nitrous oxide (N2O) has seen a worldwide rise in the recent years, resulting in an increased incidence of neurological complications due to N2O-induced functional vitamin B12 deficiency. Here, we report on a cohort of patients admitted to a tertiary care center with neurological symptoms in the context of recreational N2O use between 2020 and 2024. We screened the database of the University Hospital Frankfurt for patients ≥ 18 years of age who presented with neurological deficits and a history of N2O consumption between January 2020 and December 2024. We analyzed the spectrum of neurological deficits as well as radiological and laboratory findings. We identified a total of 20 patients, 16 males and 4 females, with a median age of 21 years. We found a steady increase in the number of cases, with no cases in 2020 and 2021 and a definite peak in 2024. The mean daily N2O consumption was 2500 g. All patients reported sensory deficits; 85% had gait disturbances and 70% had motor deficits. Less frequent symptoms included pain, bladder or bowel dysfunction, fatigue and spasticity. The median score on the modified Rankin scale (mRS) was 2, with some patients being wheelchair-bound. The most frequently observed lesion pattern was combined myelo-polyneuropathy. T2-hyperintense myelon lesions were observed in 11 of 15 patients (73.3%). Surprisingly, laboratory work-up revealed normal vitamin B12 levels in nearly all patients (95%), whereas homocysteine and methylmalonic acid levels were prominently elevated in all patients (100%). In addition, 13 patients (65%) presented with hematological abnormalities. All of the patients who presented for follow-up (20%) reported continued use of N2O. There was no neurological improvement in any of these cases. Our study confirms that the increasing incidence of N2O-induced neurotoxicity reported in other countries can also be observed in Germany. Therefore, it underlines the relevance of the current debate on health policies. In addition, our study highlights the pitfalls of vitamin B12 laboratory testing and emphasizes the need to address substance addiction in treatment.