Nitrous oxide–related neurotoxicity: Clinical features, key investigations, and a proposed diagnostic approach from a single-center cohort

Background: Recreational use of nitrous oxide (N2O) is a growing public health concern. Its neurological complications include peripheral neuropathy and posterior column myelopathy. Our study aims to characterize the clinical, laboratory, and radiological features of N2O neurotoxicity, and to explore the clinical relevance of various commonly employed investigations in real-world setting. Methods: We conducted a retrospective study of 52 consecutive patients diagnosed with N2O-related neurological disorders admitted between 2019 and 2024. Clinical characteristics, serum markers, spinal MRI, and electrodiagnostic (EDX) data were collected. Analyses were primarily descriptive. Exploratory unadjusted associations between MRI findings, EDX classifications, homocysteine status, and symptom-onset variables were assessed using appropriate statistical tests. Results: The median age was 24.0 21.8;28.0 years, with a female-to-male ratio of 1.7:1. Acute onset (< 4 weeks) was observed in 61.5% of cases. Sensory symptoms occurred in 94.2% and gait ataxia in 86.5%, with 88.5% exhibited a pattern of distal weakness exceeding proximal. Elevated homocysteine was present in 43 (89.6%), whereas low total B12 was found in only 10.4%. MRI abnormalities were detected in 31/48 (64.6%), with the “inverted V” sign in 17 cases (54.8%). Reduced CMAPS with intact sensory potentials was the most common EDX pattern 17 (32.7%), and needle electromyography showed ongoing denervation in 66%. Exploratory association analyses did not identify any significant relationships between EDX classifications, MRI findings, symptom onset, or homocysteine levels. Conclusion: Nitrous oxide neurotoxicity is characterized by predominant sensory symptoms, gait ataxia and elevated homocysteine. EDX patterns are heterogenous and non-specific. A combined approach using spinal MRI, serum homocysteine and EDX could play a key role in differentiating this pathology from other mimickers and achieving a timely and accurate diagnosis.