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Background: The spectrum of differential diagnosis of acquired demyelinating disorders of the central nervous system has been recently broadened. There is now growing evidence that supports anti-myelin oligodendrocyte antibodies associated demyelination as a distinct disease entity, with some clinical characteristics that somehow overlap those of Multiple Sclerosis (MS) and anti-AQP4+ Neuromyelitis Optica Spectrum Disorders (AQP4+NMOSD) but different pathogenesis and treatment strategies., Summary: We hereby present 3 cases of anti-MOG+ patients with different disease courses - ranging from mild to severe - all presenting with Optic neuritis (ON) at the onset. Optic neuritis (ON) is a common manifestation of different central nervous system (CNS) inflammatory disorders and can represent the first clinical event of MS and NMOSD. ON is also the most common presentation of antiMOG demyelinating disorders, followed by - and sometimes associated with - myelitis, most commonly extended over more than 2 spinal cord segments and defined as longitudinally extended transverse myelitis (LETM). All the three patients tested negative for oligoclonal bands in CSF and anti-AQP4 Ab in serum, had a relapsing disease course characterized by prominent involvement of the optic nerve and spinal cord, with good recovery after treatment with high-dose corticosteroids. However, they had a different disease course at follow-up and underwent different treatment approaches., Conclusions: Since anti-MOG+ patients can have a multiphasic disease course and accumulate disability over time, a high degree of suspicion and early diagnosis are of critical importance for treatment decision-making in clinical practice., Aim: The aim of this case report is to enhance focus on an emerging disease spectrum among acquired CNS demyelinating disorders., (Copyright © 2019 Elsevier B.V. All rights reserved.)