Neurological complications of excessive recreational nitrous oxide use: a case series based on a text mining algorithm

Background: The recreational use of nitrous oxide (N ₂O) has gained popularity over recent years. We present a case series of excessive N ₂O users with neurological complications. Methods: In this retrospective three-centre study, we used a text mining algorithm to search for patients who used N ₂O recreationally and visited a neurologist. Results: We identified 251 patients. The median duration of N ₂O use was 11 months (interquartile range [IQR], 3–24) and the median amount of N ₂O used per occasion 1.6 kg (IQR 0.5–4.0). Clinically, polyneuropathy (78%), myelopathy (41%), and encephalopathy (14%) were the most common diagnoses. An absolute vitamin B12 deficiency of < 150 pmol/L was found in 40% of cases. In 90%, at least one indicator of functional vitamin B12 status (vitamin B12, homocysteine, or methylmalonic acid) was abnormal. MRI showed signs of myelopathy in 30/55 (55%) of cases. In 28/44 (64%) of those who underwent electromyography, evidence of axonal polyneuropathy was found. Most (83%) patients were treated with vitamin B12 supplementation, and 23% were admitted to the hospital. Only 41% had follow-up for ≥ 30 days, and 79% of those showed partial or complete recovery. Conclusions: In this case series of excessive N ₂O users, we describe a high prevalence of polyneuropathy, myelopathy, and encephalopathy. Stepwise testing for serum levels of vitamin B12, homocysteine, and methylmalonic acid may support the clinical diagnosis. Due to low sensitivity, MRI of the spinal cord and electromyography have limited value. Effective treatment should incorporate supplementation of vitamin B12 and strategies to prevent relapses in N ₂O use.