Nitrous oxide-induced myeloneuropathy: a case series

Abstract

Background: Nitrous oxide (N₂O) is the second most common recreational drug used by 16- to 24-year-olds in the UK. Neurological symptoms can occur in some people that use N₂O recreationally, but most information comes from small case series.

Methods: We describe 119 patients with N₂O-myeloneuropathy seen at NHS teaching hospitals in three of the UK's largest cities: London, Birmingham and Manchester. This work summarises the clinical and investigative findings in the largest case series to date.

Results: Paraesthesia was the presenting complaint in 85% of cases, with the lower limbs more commonly affected than the upper limbs. Gait ataxia was common, and bladder and bowel disturbance were frequent additional symptoms. The mid-cervical region of the spinal cord (C3-C5) was most often affected on MRI T2-weighted imaging. The number of N₂O canisters consumed per week correlated with methylmalonic acid levels in the blood as a measure of functional B₁₂ deficiency (rho (ρ)=0.44, p=0.04).

Conclusions: Preventable neurological harm from N₂O abuse is increasingly seen worldwide. Ease of access to canisters and larger cylinders of N₂O has led to an apparent rise in cases of N₂O-myeloneuropathy in several areas of the UK. Our results highlight the range of clinical manifestations in a large group of patients to improve awareness of risk, aid early recognition, and promote timely treatment.

Keywords: B12 deficiency; clinical neurology; myelopathy; neuropathy.

Figure 1

The prevalence of presenting symptoms of nitrous oxide-associated myeloneuropathy. Presenting symptoms were defined as the main reason for the patient attending the hospital. The top graph denotes the number (N) of co-occurrences of different presenting symptoms. The left graph denotes the total number of each presenting symptom. Sites of pain included the abdomen, neck, back and leg.

Figure 2

Initial neurological examination findings. (A) Upper limb (UL) sensory examinations mostly revealed no objective sensory abnormalities. The upper graph denotes co-occurrences of losses in sensory modalities, the left graph describes total losses in each sensory modality. (B) Lower limb (LL) sensory examinations revealed notable losses in various modalities. (C) Gait ataxia was described frequently. (D) Power in both upper and lower limbs was documented using the MRC power grading system. (E) Reflexes were graded from brisk to absent. HA, hyperaesthesia; JPS, joint position sense; LT, light touch; MRC, Medical Research Council, ND, not documented; PP, pinprick sensation; Temp, temperature sensation; Vib, vibration sense.

Figure 3

Blood tests according to the quantity of N₂O used per week. (A) There was no correlation between B₁₂ levels and the quantity of N₂O canisters used per week. (B) There was a significant correlation between MMA and the number of N₂O canisters used per week (Spearman’s Rank p=0.04) in those with no previous supplementation. (C) There was no correlation between homocysteine levels and the quantity of N₂O used weekly. (D) Most patients with modest use of N₂O (<100 canisters per week) tended to have MCVs on the upper end of the reference range. Green shaded areas denote reference ranges, with dark green areas representing reference ranges common to all laboratories and light green shaded areas denoting values within the reference range for only some laboratories. MCV, mean corpuscular volume; MMA, methylmalonic acid; N₂O, nitrous oxide.

Figure 4

Distribution of affected spinal cord segments in cases of N₂O-SACD. Fifty-four cases had MRI reports denoting specifically affected regions of the spinal cord within 10 days before or 90 days after diagnosis. Affected regions are summarised above, along with the percentage of the cases with changes in each region. Note that MRI reports described spinal cord regions in relation to spinal vertebrae, so this nomenclature has been continued here. N₂O, nitrous oxide; SACD, subacute combined degeneration.