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 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.