Abstract
Introduction
Vitamin B12, known as cobalamin, is a water soluble vitamin that plays a role in the formation of DNA and myelin. There are four main etiologies of vitamin B12 deficiency, including autoimmune antibodies to intrinsic factor, structural malabsorptive disorders, lack of dietary intake, and toxin mediated deficiency. Deficiency can cause a length-dependent peripheral neuropathy or myelopathy. The central nervous system can be affected in a condition known as subacute combined degeneration, hallmarked by damage to the dorsal columns, corticospinal tracts, and spinocerebellar tracts. This results in sensory ataxia and loss of proprioception. A recent leading cause of B12 deficiency with secondary neurological dysfunction is the recreational use of nitrous oxide, colloquially known as “whippets”.
Case Info
We present the case of a 45 year old female with a past medical history of bipolar 1 disorder, anxiety disorder, and migraines who presented for recurrent falls associated with bilateral lower extremity weakness, sensory changes, and worsening back pain. She had diffuse lower extremity weakness (⅘), mild hyporeflexia at the Achilles tendons, and length-dependent sensory loss to all modalities. She had a shuffling gait with reduced foot clearance. MRI of the cervical, thoracic, and lumbar spine revealed no abnormal cord signal or structural etiology. Laboratory evaluation revealed a vitamin B12 level of 150, with a markedly elevated methylmalonic acid level of 16,242, consistent with severe functional vitamin B12 deficiency. On further history, the patient reported recreational nitrous oxide (“whippet”) use earlier in the year. The clinical presentation, laboratory findings, and absence of structural findings were felt to be most consistent with vitamin B12 deficiency-associated polyneuropathy (versus imaging-negative myelopathy), likely related to nitrous oxide-induced depletion. Her symptoms improved with aggressive vitamin B12 supplementation.
Disc Clinical
While B12 deficiency related neurological damage is historically taught as two distinct entities, peripheral neuropathy vs central subacute combined degeneration, in actuality there is often overlap between polyneuropathy and myelopathy. Findings have shown more significant axonal dysfunction of motor neurons in nitrous oxide abusing patients than sole vitamin B12 deficiency patients, suggesting that there may be pathologic changes unique to nitrous oxide in the pattern of neuronal dysfunction. The degree of motor neuron damage seems to have a disproportionally higher effect on lower distal muscles than proximal muscles, a presentation that differs from the more proximal and minimal loss in those with isolated vitamin B12 deficiency. Spinal cord involvement is also more prevalent in nitrous oxide use than pure vitamin B12 deficiency.
Conclusion
The exact pathophysiologic mechanism of damage from nitrous oxide abuse may be more nuanced than simple induction of vitamin B12 deficiency. While our patient presented with a polyneuropathy and lack of radiologic findings, the literature shows there is no obvious proportion of one or the other associated with nitrous oxide use. Furthermore, the frequently overlapping symptomatology of peripheral neuropathy and central nervous system damage can make a diagnosis even more challenging. Our case highlights the importance of considering nitrous oxide abuse as a possible etiology of vitamin B12 deficiency and neurological impairment.