Background Nitrous oxide has become a popular inhalant as abused substance by young Chinese people in recent years. It has been mainly associated with medical conditions including megaloblastic anemia and myeloneuropathy. Case presentation We report a case of a 25-year-old high school graduate who had been abusing nitrous oxide for twenty months. She had a history of peripheral neuropathy and subacute combined degeneration in between. The young woman presented with headache, motor aphasia and right arm paralysis of eight hours after intermittently consuming nitrous oxide for one week. D-dimer was increased (1.1 mg/ml). Blood vitamin B12, folate, homocysteine and beta-HCG levels were normal. Head CT showed hemorrhagic infarction and subarachnoid hemorrhage. MR angiography and venography were normal. Head MRI identified left frontal isolated cortical vein thrombosis. Her muscle strength and verbal fluency significantly improved after initiation of Low Molecular Weight Heparin and serial head MRI showed continuous reduction in the size of thrombus. Conclusions For the first time nitrous oxide use is found to be related to isolated cortical vein thrombosis. Public education regarding the potential consequences of abusing nitrous oxide especially in high-risk individuals is urgently needed.