A 27-year-old man of North African descent attended the emergency room of our tertiary percutaneous coronary intervention centre because of chest pain. Since 12 h, he had experienced severe retrosternal chest pain with sweating, nausea, and vomiting. Electrocardiography demonstrated ST-elevation in the anterior leads (Figure ). Detailed history revealed that in the hours prior to presentation, he had been recreationally using high amounts of N2O by inhalation from balloons. For the last 24–48 h, he had been sleep-deprived and, while sitting in a car, he had inhaled approximately 3.3 kg (or 420 balloons) of N2O and smoked 4 joints of cannabis. The patient had not experienced recent trauma, had no co-morbidities and was not under any prescription. He had never experienced chest pain before, there were no signs of acute heart failure. Besides smoking nicotine and cannabis, he did not have any other cardiovascular risk factors. There was no family history of coronary disease or sudden cardiac death. Drug screening upon presentation was positive for tetrahydrocannabinol (THC). Patient admitted to regularly smoke cannabis but denied consumption of alcohol or any other recreational drugs.\nAs per hospital protocol, he received 180 mg ticagrelor orally, 300 mg aspirin intravenously (i.v.) and 5000 EH heparin i.v. and was referred for immediate coronary angiography (CAG). This showed a normal aspect of the left main, right coronary and circumflex artery. The distal left anterior descending artery (LAD) was totally occluded, and thrombus was angiographically visible in the proximal segment, with maintained flow (TIMI 3) (Figure and ). Despite successful wire passage into the distal LAD and multiple balloon dilatations, no recanalization was achieved. Therefore, mechanical thrombectomy by means of AngioJet was attempted without distal recanalization, nor angiographical resolution of the proximal thrombus. Optical coherence tomography of the proximal LAD confirmed the presence of residual thrombus but excluded atherosclerotic media thickening. Plaque/endothelial erosion underneath the thrombus could not be excluded (Figure and ). Because of a minimal lumen area of 10.75 mm2 no further intervention was undertaken. The procedure was discontinued, and the patient received tirofiban i.v. for 48 h, on top of standard dual antiplatelet therapy (DAPT: ticagrelor and aspirin).\nThe first high-sensitive troponin T and CK-MB levels were 0.418 μg/L and 77 μg/L, peaking at 5.35 μg/L (upper limit of reference range: 0.014 μg/L) and >300 μg/L (upper limit of reference range: 7.6 μg/L). Transthoracic echocardiogram (TTE) showed a reduced (30–40%) left ventricular ejection fraction (LVEF) with apical and mid septal akinesia, a normal right ventricular function and no valvular abnormalities (). Migration of a venous thromboembolism due to intracardiac right-left shunt was excluded by using right-sided contrast. Vitamin B12 (114 pmol/L; reference range: 160–700 pmol/L), folic acid (7.7 nmol/L; 8.8–40 nmol/L), and homocysteine (205 μmol/L; <15 μmol/L) levels were measured upon admission.\nAfter 5 days, serum homocysteine levels had decreased to 86 μg/L. Additional analysis excluded the presence of a methylenetetrahydrofolate reductase (MTHFR)-gene polymorphism. To evaluate the effect of the initiated antiplatelet therapy CAG was repeated after 7 days. The size of the thrombus in the proximal LAD was slightly reduced, but the distal LAD remained occluded. (Figure and ). After initiation of heart failure medication, he was discharged with the advice to take DAPT for 1 year, discontinue drug abuse and take oral folic acid and vitamin B12 supplementation. Upon discharge persistent ST-elevation with negative T- (V2–V6) and pathological Q-waves (V2–V6) in the anterior leads was shown on the electrocardiogram (Figure ).\nAfter 3 months, a repeat TTE showed improvement of LVEF (53%), with remaining anteroseptal wall motion abnormalities (). He did not report recurrent angina or symptoms of heart failure.
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. ).