Background Acute disseminated encephalomyelitis (ADEM) followed by optic neuritis (ADEM-ON) is characterized by the following features: early onset, monophasic or multiphasic ADEM followed by one or more episodes of ON, and the presence of serum anti-myelin oligodendrocyte glycoprotein (MOG) antibodies. Case report We report a case of ADEM-ON without anti-MOG antibodies in a 78-year-old woman. The patient developed acute-onset neurological findings and was diagnosed with ADEM. She was treated with intravenous methylprednisolone (IVMP), and oral corticosteroids. Her clinical symptoms and MRI findings subsequently improved. Left optic neuritis emerged 6 months later, and we made a diagnosis of ADEM-ON. A brain biopsy performed during the acute phase of ADEM showed perivascular infiltration of macrophages with demyelination. Conclusion The majority of the reported ADEM-ON cases are pediatric cases with serum anti-MOG antibodies, but our patient was the elderly, without anti-MOG antibodies. Moreover, the pathological features of our case were similar to those observed in patients with typical ADEM and in patients with anti-MOG antibody-positive ADEM. Although ADEM-ON is related to the presence of anti-MOG antibodies, factors other than anti-MOG antibodies could contribute to the development of ADEM-ON.