Title : A case of nitrous oxide induced vitamin B12 deficiency with secondary myelopathy
Abstract:
Objective: To present a unique case of nitrous oxide (NO2)-induced vitamin B12 deficiency with secondary myelopathy.
Background: Nitrous oxide (NO2), commonly known as “laughing gas”, is frequently used as an anesthetic agent, but is also abused recreationally in the form of “whippets”. Whippets are nitrous oxide containing steel cartridges that are inhaled and cause euphoria. Prolonged N2O exposure has been associated with the development of the rare neurological disorder, N2O-induced vitamin B12 myelopathy. We report a case N2O-induced B12 myelopathy and explore the underlying biochemistry to demonstrate how N2O pathologically disrupts the normal metabolic roles of vitamin B12, thus resembling the same clinical phenotype as subacute combined degeneration of the spinal cord (SCDSC).
Case: 47-year-old gentleman without significant medical history presented with three months of ascending numbness and tingling of the bilateral lower extremities which rapidly progressed from the toes to the mid thoracic region and bilateral upper extremities two weeks prior to presentation. This was associated with progressive unsteady gait and bladder retention. Neurological examination revealed normal cortical function and intact cranial nerves with no facial diplegia and reactive pupils bilaterally. Motor exam was significant for only bilateral tibialis anterior 4/5 and otherwise 5/5 strength throughout. No atrophy or fasciculations were observed. Reflexes were absent in the bilateral ankles. No upper motor neuron signs. Plantar responses were equivocal bilaterally. Sensory was significant for decrease in vibration and proprioception in the distal bilateral lower extremities. There was hyperesthesia and allodynia to touch extending proximally toward the torso. He was able to stand without assistance but was not able to ambulate independently secondary to severe gait ataxia. Romberg and tandem gait were unable to be obtained. Labs demonstrated low vitamin B12 level of 192 pg/mL (normal: 300-1200 pg/ml); elevated methyl malonic acid (MMA) level 48,000 nmol/L (normal: l87-318 pg/ml); elevated homocysteine level 26.85 pg/ml (normal: 6.6-14.80). Spinal fluid was normal.
Imaging: MRI brain was unremarkable. MRI cervical spine with and without contrast demonstrated abnormal T2 hyperintensity and enhancement of central gray matter of the Cervical C3 to C7 spinal cord with patchy enhancement at the levels of C2 through MRI thoracic spine with and without contrast demonstrated long segment abnormal enhancement of the entire thoracic spinal cord with involvement of the central and posterior cord.
Discussion: Nitrous oxide (NO2) is a colorless, odorless gas that has been used as an anesthetic for over a century. N2O has gained popularity as a recreational drug, known as “whippets" due to its euphoric effects (1). Abuse of, and prolonged exposure to N2O has been associated with neurological manifestations, specifically, spinal cord myelopathy resembling subacute combined degeneration of the spinal cord (SCDSC), secondary to the impact of N2O on Vitamin B12 metabolism.
Conclusion: “Whippets” are a common, easily accessible, recreational drug that contains nitrous oxide (NO2) which is known to inactivate vitamin B12. Patients can have normal B12 levels but typically have elevated methylmalonic acid (MMA) and homocysteine levels signifying this inactivation- as is true in our case. This patient’s myelopathy effectively appeared as B12 deficiency/SCDSC which was further confirmed by abnormal spinal cord signals on MRI cervical and thoracic imaging secondary to N2O/whippet abuse. Patient recovered after 3 months of high intensity IM B12 to treatment prevent profound long-term peripheral nerve and spinal cord damage.
