A 25-year-old Chinese woman presented with headache and difficulty in speaking and moving the right arm for the last eight hours. She used oral contraceptives once ten days ago and inhaled nitrous oxide outside with friends in the last week.\nThe patient began to use oxide intermittently twenty months ago. She gradually developed numbness and weakness of distal limbs, and balance difficulty, which significantly improved after vitamin B12 intake of one month. One year ago her numbness in the distal limbs subacutely deteriorated and ascended to both proximal thighs and the upper trunk. Medical record showed she had impaired superficial sensation of both hands, feet and the thorax region from T4 to T8 dermatome, impaired deep sensation of the lower limbs, and areflexia. MRI showed hyper-intensities involving the posterior and lateral column of the spine cord ranging from T5 to T11 vertebral body on T2 sequence (not shown). A diagnosis of peripheral neuropathy and subacute combined degeneration was made and her symptoms again improved significantly with vitamin B12 intake.\nThe patient did not use other substances and had no family history.\nThe patient had significant motor aphasia, mild right facial paralysis and right deviation of tongue. Muscle strength of the right upper limb is 0/5 with reduced tendon reflex compared with the left side. No apparent abnormalities in mental status, sensations and coordination were found.\nErythrocyte sedimentation rate (34 mm/H), c-reaction protein (21.1 mg/L), D-Dimer (1.14 ug/ml) and lactate dehydrogenase (314 U/L) were elevated. Complete blood count, liver enzyme, creatinine, urea nitrogen, troponin I, protein C, protein S, antinuclear antibodies, autoantibodies to extractable nuclear antigens, antiphospholipid antibodies, anti-neutrophil cytoplasmic antibodies, and beta-HCG were all within normal limits. Folate and vitamin B12 levels were normal. Homocysteine level was within the upper limit (13.6 umol/L; normal range 6–14 umol/L). No mutation of Factor V Leiden was found. Methylenetetrahydrofolate reductase (MTHFR) genotype of C677T and A1298C, and plasminogen activator inhibitor 1 (PAI-1) genotype of 4G/5G were confirmed.\nHead CT showed hemorrhagic infarction (Fig. a&b, arrow) and subarachnoid hemorrhage (Fig. b, arrow heads) mainly involving the left parietal lobe. MR angiography and venography were normal (not shown) and excluded major abnormalities of the large and medium arteries as well as the venous sinus system. Since the patient did not experience any major symptomatic improvement during the hospital stay and there was the concern about the existence of isolated cortical vein thrombosis, MRI head with 0.1 mm thickness demonstrated expanding hematoma and edema causing cingulate herniation, and confirmed isolated cortical vein thrombosis over the frontal cortical surface in the sagittal, coronal and axial section (Fig. a-c) ten days after admission.\nVitamin B6, B12, folate, mannitol and Low Molecular Weight Heparin were initiated. The sizes of thrombus, hematoma and edema reduced continuously after treatment of five (Fig. d-f) and twelve days (Fig. g-i), respectively, and the patient achieved significant improvement in muscle strength (grade 3/5) and verbal fluency in the meantime. Anticoagulation was switched from Low Molecular Weight Heparin to oral anticoagulant after another two weeks and the patient was discharged.\nDuring the last follow-up (6 weeks after symptom onset), the patient had further improvement in muscle strength (grade 4/5) and almost normalized verbal fluency. The patient was satisfied with her recovery and no adverse effects were reported.
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. ).