Nitrous Oxide  has been used clinically and recreationally since its discovery in 1772. Since then Nitrous Oxide induced neurotoxicity have been reported, and has been shown to be dose depaendant. With infrequent users unlikely to be at risk of neurotoxicity, while heavier and habitual used at risk of serious neurological conserquences.

With the increase in recreation use of “Whippits” we need to remember to take a detailed recreation drug history when seeing patients presenting to ED with neurological symptoms. As Nitrous Oxide induced neurotoxicity is treatable.

Presentations

Nitrous Oxide induced neurotoxicity can present as either spinal cord demyelination , peripheral neuropathy or a a combination of the two.

• Demyelination of the dorsal columns of spinal cord 
  • Typically onset is subacute  (i.e. weeks), but acute onset has been reported in the literature
  • Typically symmetrical but can be unilateral
  • Signs
    • Pyramidal weakness – weak upper limb extensors, and lower limb flexors
    • Dorsal Column Sensory loss – Vibration, Proprioception, Fine touch
    • Sensory Ataxia – Incoordination due to loss of proprioception and weakness
  • Level – Most frequently cervical 4-6 levels, but can affect any.
• Peripheral Neuropathy
  • Typically Symmetrical (but not always)
  • Sensory loss (often painful)
  • Distal Weakness
• Optic Neuropathy  – has been reported and may present with visual disturbance.

Pathophysiology

Nitrous Oxide usage can render vitamin B12 inactive, which in-turn disrupts myelination, causing the demyelination of nerves.

Differentials

• Deficiencies: B12, Folate, copper, zinc
• Inflammatory: Guillian-Barre syndrome, MS, Neurosarcoidosis
• Infection: HIV, Syphilis
• Cancer
• Vascular: Spinal cord ischaemia, vasculitis

Tests

• Vitamin B12 level (often in normal range)
• Homocysteine and Methylmalonic Acid Level (not available in ED)
• MRI – contrast enhanced

Treatment

Start before Tests are back (i.e. on clinical suspicion)

• IM Vitamine B12 1mg OD
• PO Folic Acid 5mg OD

Follow-up

• Discuss admission with Medical team as potential for SDEC management
• Treat until clinical improvement(King’s Team noted the following)
  • Sometimes treat for 5-7days only
  • Often switch to alternate days IM Bit B12
  • Can teach to self administer
• Further Testing
  • Homocysteine and Methylmalonic Acid levels – often improve quickly
  • MRI often lags clinical improvement endnote necessary to repeat
• Majority Improve clinically – but futureabstinence is often challenging

References

• RACGP
• RCP
• BMJ
• Journal Psychopharmacology
• Frontiers of neurology