Evan Brickner, MS4* Patrick Herndon, MS3* Alexis Kerl, MS4* Adrian Michel, M.D.^ Francisco Davila, M.D.*^ *Oakland University William Beaumont School of Medicine, Rochester, Michigan ^Internal Medicine Department at Beaumont Health System, Royal Oak, Michigan
Commonly known as “laughing gas”, nitrous oxide (N2O) is an anesthetic frequently used in medical and dental settings. It is also sold as “whippet” canisters for making homemade whipped-cream; however, whippets are commonly used as recreational drugs due to their rapid onset and euphoric, relaxant properties. High systemic levels of N2O can cross-react with vitamin B12 stores resulting in irreversible oxidation of the cobalt ion within vitamin B12, which causes inactivation of vitamin B12, an important coenzyme of methionine synthase and methylmalonyl-CoA mutase. These enzymes aid in the generation of important biomolecules including DNA, RNA, myelin, and heme. Therefore, inactivation of vitamin B12 may ultimately lead to a functional vitamin B12 deficiency and development of subacute combined degeneration (SCD) of the spinal cord, as well as macrocytic anemia.
A 26-year old female with a history of anxiety and depression presented to the emergency department with paresthesias and ataxia. She initially experienced paresthesias in her toes and feet following a panic attack 2.5 weeks prior to admission, which progressively ascended to her legs, abdomen, and hands. She also reported worsening gait and multiple falls. Further history revealed that she began using whippets one year prior but increased her usage to 100-150 canisters daily over the prior three months following an emotional, relationship breakup. The patient's vitals were stable on arrival. Neurological exam showed absent vibratory and proprioceptive sensation to the knees, dysmetria on heel to shin testing, and preserved reflexes bilaterally. Laboratory investigations included: hemoglobin 12.3 g/dL, MCV 98 fL, unremarkable BMP, normal folate, and normal vitamin B12 level at 298 pg/mL (reference range 271-1,000 pg/mL). Urine drug screen tested positive for cannabinoids. CT head did not show any acute intracranial process. An MRI of the entire neuraxis with and without contrast noted T2 signal changes in the dorsal column from C1 to T1 and associated edema, without contrast enhancement. SCD was suspected and the patient was started on vitamin B12 replacement. Days later, homocysteine levels >50 mcmol/L (reference range 4-10 mcmol/L) and methylmalonic acid at 2.50 nmol/mL (reference range = 0.40 nmol/mL) resulted, confirming the diagnosis of functional vitamin B12 deficiency. The patient participated in an intense, inpatient rehabilitation program for seventeen days. She was eventually discharged, able to walk 60 meters and climb 15 stairs with a rolling walker.
This presentation of acute neurological symptoms following an emotional trigger was initially consistent with a primary psychiatric condition, such as conversion disorder. However, further investigations revealed a biological origin for her symptoms. Importantly, functional vitamin B12 deficiency needs to be suspected in patients with N2O use, particularly if initial blood levels of vitamin B12 are normal. A thorough social history including drug use is essential for initial suspicion of this disease process. Increased homocysteine and methylmalonic acid can yield the diagnosis, along with characteristic imaging findings for SCD. Vitamin B12 supplementation and intense physical rehabilitation are the main therapeutic modalities to try to reverse the disease course.
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