Case Presentation: A 47-year-old woman with alcohol use disorder, history of methamphetamine use, and tobacco exposure presented with two months of progressive bilateral lower-extremity weakness and numbness, as well as new gait instability. Notably, her husband had presented to the emergency department several days earlier with similar symptoms, but no diagnosis was made. On exam, mental status and cranial nerves were normal. Upper-extremity strength was 5/5, and lower-extremity strength was 2/5 proximally. Reflexes were brisk in the upper extremities, patellar reflexes were absent, and Achilles reflexes were diminished. Sensory deficits to light touch, pinprick, and temperature extended below the mid-thighs bilaterally; proprioception was impaired at the toes. Romberg was positive. Serum B12 was 71 pg/mL. MRI of the cervical spine demonstrated a long-segment, symmetric dorsal column T2 hyperintensity from C1–C6 without enhancement or compression, consistent with subacute combined degeneration (SCD). Differential diagnoses included nutritional neuropathy, alcohol-related neurotoxicity, demyelinating disease, and infectious myelopathy. With further questioning, she disclosed frequent nitrous oxide (N2O) use with her husband. She subsequently initiated daily intramuscular cyanocobalamin of 1,000 µg and physical therapy, while also discontinuing N2O. At the three-week follow-up visit, she demonstrated improvement in strength, increased gait stability, and resolution of paresthesias.
Discussion: N2O-induced SCD is an increasingly prevalent and under-recognized cause of reversible myelopathy. Unlike classic B12 deficiency, neurologic injury arises from functional inactivation rather than depletion, meaning serum B12 can appear deceptively normal in some cases. Symmetric dorsal column hyperintensity on MRI can serve as a radiologic hallmark. Social history is essential to uncovering substance exposures, and neurologic symptoms in multiple household members should prompt consideration of shared environmental or toxic causes. Early recognition of such patterns can prevent unnecessary immunologic or surgical interventions. When identified promptly, B12 therapy combined with cessation of N2O use can result in clinical improvement. Ultimately, this case illustrates one of the neurologic conditions where timely clinical vigilance can dramatically reverse severe and initially disabling deficits.
Conclusions: Recreational use of N2O, colloquially known as “whippets,” has emerged as a growing cause of SCD by irreversibly oxidizing active cobalamin, inactivating methionine synthase, and destabilizing myelin, producing clinical and radiographic findings indistinguishable from a traditional B12 deficiency. Timely recognition by hospitalists is critical, as this syndrome is one of the few rapidly progressive myelopathies that can be reversible with prompt intervention. This case underscores diagnostic challenges if social history is initially incomplete, characteristic MRI features of N2O exposure, and the prognostic benefit of early B12 therapy.