A 32-year-old male with a known history of bipolar disorder was brought to the emergency department with altered mental status. The patient's symptoms started with slurring of speech and left-sided motor weakness a day before the presentation. The patient suffered two episodes of seizures in the emergency department, which were controlled with two intravenous doses of lorazepam. He had no prior history of seizure disorder. He had to be immediately intubated and sedated for airway protection and was transferred to the intensive care unit from the emergency department. Noncontrast computed tomography (CT) of the head was significant for an infarct in the right frontotemporoparietal region of the brain (Figure ). A CT angiogram of the head and neck revealed complete occlusion of the right middle cerebral artery (Figure ) and a nonocclusive thrombus in the right internal carotid artery (Figures -). The etiology of stroke was unclear at this time. There was no personal history of known thrombophilia and family history was not available, as he was an adopted child. Laboratory investigations were pertinent for macrocytic anemia (hemoglobin: 11.2 mg/dl, mean corpuscular volume: 105 fl/cell). The Factor V Leiden, protein C, and protein S levels were within normal limits. A urine toxicology test obtained prior to administering lorazepam to the patient was negative. The vitamin B12 and folate levels were found to be low (198 pg/ml, and 2.5 ng/ml, respectively). The methylmalonic acid level was in the normal range (0.12 mcmol/L; ref. range: 0.0-0.4 mcmol/L) while the homocysteine level was elevated (253 mcmol/L; ref range: 0-10). Laboratory findings were significant for hyperhomocysteinemia, which led us to gather more history in order to understand its etiology. It was ultimately revealed that the patient had been inhaling nitrous oxide as a recreational agent for the past five years. The patient's symptoms at presentation were past the 4.5 hour time window for thrombolytic therapy and, therefore, he was not a candidate for it. He was mechanically ventilated and oral aspirin 81 mg and atorvastatin 80 mg once daily was administered through an orogastric tube for secondary prophylaxis of ischemic stroke. He was also started on intravenous levetiracetam for seizure prophylaxis. On Day 5 of admission, the patient had a successful weaning trial and was subsequently extubated. Physical therapy and speech therapy were provided to the patient, and he was discharged home on Day 11 of admission. The patient continues to follow up in our neurology clinic. On his last follow-up, 12 months after discharge from the hospital, the patient had residual, left-sided motor weakness in both the upper and lower extremities and mild dysarthria without any signs and symptoms of peripheral neuropathy.
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. ).