peer reviewed ; Objectives: To emphasize physio-pathological, clinical and prognosis differences between conditions causing serious and sometimes very similar clinical manifestations: anti-aquaporin-4 (AQP4) and anti-myelin oligodendrocyte glycoprotein (MOG) antibodies related diseases, and seronegative NMOSD (neuromyelitis optica spectrum disorders). Methods: Based on diagnostic criteria for NMOSD and MOGAD (MOG associated disorders), we retrospectively surveyed 10 AQP4-NMOSD, 8 MOGAD and 2 seronegative NMOSD, followed at the specialized neuroimmunology unit of the CHU Liege. Results: Female predominance was only observed in AQP4 group. Age at onset was 37.8 and 27.7 years old for AQP4-NMOSD and MOGAD, respectively. In both groups, the first clinical event most often consisted of optic neuritis (ON), followed by isolated myelitis. Fifteen of our 20 patients encountered a relapsing course with 90% relapses in AQP4-NMOSD, 62.5% in MOGAD and 50% in the seronegative group, and a mean period between the first and second clinical event of 7.1 and 4.8 months for AQP4-NMOSD and MOGAD, respectively. In total, we counted 54 ON, with more ON per patient in MOGAD. MOG-associated ON mainly affected the anterior part of the optic nerve with a papilledema in 79.2% of cases. Despite a fairly good visual outcome after MOG-associated ON, retinal nerve fiber layer (RNFL) thickness decreased, suggesting a fragility of the optic nerve toward further attacks. Conclusion: As observed in larger cohorts, our MOGAD and AQP4-NMOSD cases differ by clinical and prognostic features. A better understanding of these diseases should encourage prompt biological screening and hasten proper diagnosis and treatment.