BACKGROUND Osmotic demyelination syndrome (ODS) is an uncommon neurological disorder. Until the mid-1980s, the mortality rate was 90-100%, but more than half of patients now have a good prognosis. Early suspicion of ODS is important. However, radiologic findings of ODS are variable and scintigraphy findings have not been reported. CASE REPORT A 38-year-old man with alcohol abuse history was admitted due to electrolyte imbalance. On the 10th day of his hospital stay, he had a generalized tonic-clonic seizure. Brain perfusion SPECT showed asymmetrically hyperperfused and hypoperfused lesions. Brain MRI revealed diffuse T2 hyperintensity with mild diffusion restriction in the pons and hyperperfused lesions on brain SPECT. He was treated based on the diagnosis of hyponatremia and osmotic demyelination. After treatment, the asymmetric hyperperfusion was decreased. MRI showed that the cortical hyperintensity had resolved, with encephalomalacic change shown in the pons. CONCLUSIONS To the best of our knowledge, this is the first report showing changes in brain perfusion SPECT and MRI in an ODS patient with a seizure. This case report may be helpful to neurologists, radiologists, and nuclear physicians.