Neuroimmune disorders of the central nervous system (CNS) encompass a heterogeneous group of conditions affecting the brain, spinal cord, and optic nerves. Among these, acquired demyelinating syndromes (ADS) represent a significant subset, characterized by inflammatory processes that primarily target the white matter, resulting in symptoms corresponding to the affected CNS area (Hardy, 2023).

The global incidence of pediatric ADS is estimated at 0·87 (95 % CI 0·35–1·40) per 100 000 children per year (Yan et al., 2020). These syndromes are usually classified based on the number of lesions (mono- or poly-focal) and disease course (monophasic or relapsing demyelinating syndrome) (Goldman and Brenton, 2022; Neuteboom et al., 2017).

In children, a first episode of CNS demyelination may remain a single event in life or signal the onset of a chronic relapsing disorders, including multiple sclerosis (MS), myelin-oligodendrocyte glycoprotein antibody-associated disease (MOGAD), seronegative multiphasic disseminated encephalomyelitis (MDEM) or neuromyelitis optica spectrum disorder (NMOSD) (Fadda et al., 2021).

Timely diagnosis is essential when a child presents with a first episode of CNS inflammation. Treatment strategies differ between pediatric onset multiple sclerosis (POMS) and other demyelinating disorders. Moreover, antibody mediated ADS or seronegative acquired demyelinating conditions frequently present more severely in the acute phase and a prompt aggressive treatment may also be beneficial for long-term outcomes (Bonnan et al., 2018).

Recently, several studies have examined the frequency and clinico-radiological characteristics of ADS in pediatric populations and the distribution of MOG and aquaporin-4 (AQP4) antibodies among them, in the attempt to find prognostic factors for relapse and outcomes. (Eusebi et al., 2021; Fonseca et al., 2025; Kilic et al., 2022; Moseley et al., 2024; Prithviraj et al., 2024; Rempe et al., 2021; Rutatangwa et al., 2023; Wassmer et al., 2024). Some of these papers did not consider MOG-antibodies status (Eusebi et al., 2021; Rutatangwa et al., 2023) or selected only specific clinic-neuroradiological phenotypes, such as optic neuritis or MOG-IgG positive restricted cases (Boesen et al., 2019; Virupakshaiah et al., 2024). At present, differentiating ADS subtypes at onset and recognizing future trajectories remains complex and challenging, as clinical presentations frequently overlap in the early stages. In this study, we retrospectively evaluated all pediatric patients diagnosed with ADS at our tertiary-care pediatric hospital over the past 12 years. We analyzed their clinical and neuroradiological features at onset to better characterize the acute presentation in relation to final diagnosis aiming to identify which presentations may support early and aggressive immunotherapy.