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 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.