Abstract
OBJECTIVE: To describe the demographic, clinical, laboratory, and radiological findings, and the clinical course of seven patients with severe N2O-induced subacute combined degeneration of the spinal cord (SACD). METHODS: Retrospective study with prospective follow-up of patients with SACD associated with N2O abuse presenting at a single center between 2014 and 2024. RESULTS: The median age (range) of the seven patients (one woman, six men) was 24 (18-33) years. Prior to disease onset, patients had consumed N2O daily over a median (range) of 12 (3-20) weeks, with a mean (SD; range) inhalation dosage of 2376.7 (2872.7; 160-9000) g of N2O per day. Clinical presentations included paresthesia and paresis in the legs and gait disturbances. All patients exhibited characteristic signal alterations in the posterior columns spanning from C1 to T10 on T2-weighted spinal MRIs. Electrophysiology demonstrated polyneuropathies in all but one patient. Vitamin B12 levels were decreased in four, but normal in three patients. Methylmalonic acid levels were elevated in all patients. Although the median (interquartile range [IQR]) modified Rankin Scale score improved from 3.0 (3.0-4.0) at baseline to 1.0 (1.0-2.0; p < 0.05, Wilcoxon matched-pairs signed-rank test) at follow-up after the start of vitamin B12 supplementation, all five patients who could be examined on follow-up exhibited persistent deficits on the last follow-up assessment at a median (range) of 5 (3-116) months after disease onset. CONCLUSIONS: N2O abuse over a few weeks can lead to severe SACD. The diagnosis is supported by characteristic findings on spinal MRI and elevated methylmalonic acid levels, while normal vitamin B12 levels do not rule out N2O-induced SACD. Although there was some clinical improvement upon cessation of N2O abuse and vitamin B12 supplementation, residual deficits persisted.