A 20-year-old woman suffered right facial paralysis. The patient showed an abnormality in the perception of speech at an age of 25 years. At an age of 32 years, she developed acute headache and fever. Brain magnetic resonance imaging (MRI) showed an expanded high signal intensity lesion with gadolinium enhancement in the white matter of the left frontal lobe, which was suggestive of tumefactive demyelinating lesion (TDL). A brain tumor was suspected because TDL is a large demyelinating brain lesion mimicking a primary brain tumor. After initiation of steroid therapy, the symptoms and MRI abnormalities improved. At an age of 34 years, she was referred to our hospital with the main complaint of weakness of lips on the left side. Brain MRI showed hyperintense lesions involving the left frontal and the right parietal white matter lobes, and the left ventrolateral pons, which was suggestive of acute disseminated encephalomyelitis (ADEM). Analysis of anti-MOG antibodies identified anti-MOG antibodies both in the serum and in the CSF. Steroid therapy led to complete clinical recovery. MOG antibodies in both serum and CSF were negative six months after the previous measurement. The patient fulfilled the diagnostic criteria for multiple sclerosis (MS) and TDL is one of the rare variants of MS. This study suggests that anti-MOG antibodies can be associated with repetitive encephalitis including TDL and ADEM-like presentation.