A 29-year-old, non-vegetarian woman was admitted to our hospital because of hyperpigmentation over the dorsa of the fingers, toes (fig. ), and trunk (fig. ), along with intermittent numbness in the plantar region of the foot that began 2 months before admission. The numbness and hypoesthesia were initially limited to the plantar region of the foot; subsequently, these symptoms ascended to both lower legs 2 weeks before admission. The patient noted weakness in both legs, an unsteady gait, and a tendency to fall when walking. Numbness in the fingertips was also noted. The patient's medical history was not significant, and her family history was unremarkable.\nOn physical examination, her conjunctivae and mucous membranes were slightly pale, whereas her tongue appeared normal. Multiple, asymptomatic, hyperpigmented macular patches were noted on the trunk (fig. ), and no rash or dermatitis had preceded the onset of hyperpigmentation. Neurological examination revealed weakness based on hyporeflexia in all limbs and the results of manual muscle tests (MMT 4+/5). Impaired pinprick sensations below the second thoracic dermatome, poor joint positions, and vibration sensations over both lower limbs were recorded. A broad-based ataxic gait and a positive Romberg sign were also noted. There were no atypical cerebellar signs. In addition to the observed symptoms, the patient reported mild constipation, a bitter taste in the mouth, and hair loss.\nLaboratory investigations revealed normocytic anemia (hemoglobin, 10.7 g/dl [normal range, 12.0–16.0 g/dl]; mean corpuscular volume, 94.1 fl [normal range, 79–100 fl]), leukopenia (white blood count, 4.41 × 103/µl [normal range, 4.5 × 103−11 × 103/µl]), and thrombocytopenia (platelet count, 114 × 103/µl [normal range 150 × 103−400 × 103/µl]). A low vitamin B12 level (204 pg/ml [normal range 211–911 pg/ml]) and high serum homocysteine level (33.35 µmol/l [normal range 3.70–13.90 µmol/l]) were noted. Levels of human immunodeficiency virus antibody, the autoimmune profile, and levels of folic acid and endocrine hormones were within the normal ranges. A nerve conduction velocity test revealed polyneuropathy in the lower legs. Analysis of the cerebrospinal fluid revealed normal protein levels and cell counts. Examination of skin biopsy specimens showed basal layer hyperpigmentation with melanin incontinence and focal mild acanthosis.\nWe reevaluated the patient's medical history, taking into account the possibility of a vitamin B12 deficiency. The patient reported that she had started using N2O at parties in recent years. The frequency of N2O use was half a whipped cream propellant cartridge (approximately 7.0 liters of N2O may be released from each cartridge) daily for the last 2 years, and 1 month before admission, this had increased to 1 propellant cartridge daily. The patient received intramuscular injections of 1,000 µg vitamin B12 daily for 1 week and then weekly for 1 month. After 4 weeks of treatment, the pigmented lesions showed clinically significant improvement (fig. , fig. ).
A 45-year-old male with no significant past medical or psychiatric history presented with sudden onset of numbness below the umbilicus and unsteady gait. At the time of admission, the patient also had cognitive impairment with a Montreal cognitive assessment (MoCA) score of 22/30. There was no associated phonophobia or photophobia. During the hospital stay, the patient had experienced urinary retention with subsequent Foley catheterization. On physical examination, he had no vibratory sensation or proprioception in bilateral (B/L) lower extremities with cold temperature and spared pinprick. Reflexes were 2+ in B/L knees and ankle (left) with non-sustained clonus on left ankle, big toes were down going, with diminished sensation around T10, increased muscle tone in B/L lower extremities, and no obvious muscle weakness in lower extremities. He had a normal anal tone and post-void residual. Findings were suggestive of a spinal cord lesion mainly affecting the posterior column.\nAll laboratory findings were unremarkable except mean corpuscular volume of 111 fl (80-100 fl), B12 level of 311 pg/mL (160-950 pg/ml), methylmalonic acid (MMA) level of 7397 nmol/L (< 370 nmol/L), and a homocysteine level of 89.7 umol/L (< 15 umol/L). He had a recent history of abuse of nitrous oxide due to recreational usage. Magnetic resonance imaging (MRI) C spine (with and without contrast), T spine (with and without contrast), L spine (with and without contrast), and MRI brain (with and without contrast) were unremarkable. Cerebrospinal fluid (CSF) analysis revealed the presence of immunoglobulin G (IgG) oligoclonal bands. Electromyography showed left non-localizable peroneal neuropathy with a small peroneal compound muscle action potential (CMAP) and small superficial peroneal CMAP with no evidence of polyneuropathy. Based on all these findings, the final diagnosis of “myelopathy secondary to vitamin B12 deficiency induced by nitrous oxide abuse” was made.\nLater, the patient was treated with intramuscular vitamin B12 followed by oral formulation, and discharged to a rehabilitation center. Upon follow-up after 16 weeks, the patient's memory loss and confusion had improved with repeat B12 and MMA values of 1409 pg/mL and 139 nmol/L, respectively. The patient was able to ambulate without the assistance of a walking device and was able to perform all other activities of daily living. The patient's only remaining symptom was mild vibratory sensation deficits below the knees B/L, which was no longer noted at his 24-week follow-up.