204 - N.O. Laughing Matter: A Case Series of Nitrous Oxide-Induced Neurotoxicity

A 42-year-old non-binary individual with generalized anxiety disorder and a 10-year history of recreational nitrous oxide use presented after a fall with head strike, worsening shortness of breath, progressive paresthesias, and balance issues following recent discontinuation of supplemental vitamin B12 due to social stressors. Labs were consistent with nitrous oxide-induced subacute combined degeneration. 

A 25-year-old man with major depressive disorder and a 6-year history of recreational nitrous oxide use presented with ascending paresthesias, neuropathy, and inability to ambulate. Examination revealed decreased sensation to light touch, vibration, and proprioception in the distal lower extremities with sensory ataxia. Labs showed macrocytic anemia consistent with functional vitamin B12 deficiency secondary to nitrous oxide use. 

Both patients received vitamin B12 supplementation and were discharged to acute inpatient rehabilitation where they regained motor and sensory function with mild residual deficits.


Discussions: Nitrous oxide inactivates vitamin B12 which disrupts methionine synthase-dependent myelin synthesis and causes subacute combined degeneration of the spinal cord. The dorsal columns and lateral corticospinal tracts are preferentially demyelinated resulting in gait instability, weakness,  paresthesias, and sensory deficits. While chronic use of nitrous oxide can result in severe neurologic impairment, early recognition and treatment can markedly improve functional outcomes. Both patients had underlying mood disorders and psychosocial stressors that contributed to their substance use disorders and neurologic conditions. These cases highlight the importance of using a multidisciplinary approach involving PM&R, addiction medicine, psychiatry, and social work to promote functional recovery. 

Conclusions: Nitrous oxide use can cause reversible but potentially severe neurologic injury. Early recognition, prompt vitamin B12 supplementation, and multidisciplinary support is essential for optimal rehabilitation.