Introduction

Pediatric-onset multiple sclerosis (POMS) accounts for approximately 3–5% of all MS cases [1], with an annual incidence ranging from 0.07 to 2.9 per 100,000 children [2]. Compared with adult-onset MS (AOMS), POMS typically exhibits a more inflammatory phenotype, characterized by higher relapse activity and greater MRI lesion burden [3, 4]. Although recovery from acute attacks is often substantial and disability accrual tends to be slower, individuals with POMS may nonetheless reach disability milestones at a younger age due to earlier disease onset [5]. Importantly, only approximately one-third of children presenting with acquired demyelinating syndromes are ultimately diagnosed with MS [6]. Consequently, early diagnosis of POMS relies on accurately distinguishing MS from other pediatric demyelinating disorders and alternative diagnoses, including acute disseminated encephalomyelitis (ADEM), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), and infectious, metabolic, or genetic conditions [1]. The 2010, 2017, and 2024 versions of the international McDonald criteria for MS have formally included consideration of the diagnosis of MS in children and adolescents, and have supported the concept of MS being a single disease across pediatric and adult-onset.

Advanced MRI biomarkers, notably the central vein sign (CVS) and paramagnetic rim lesions (PRLs), have emerged as tools to improve diagnostic specificity in MS. Identified on susceptibility-based MRI, CVS reflects perivenular inflammatory demyelination, whereas PRLs represent a subset of chronically active lesions characterized by iron-laden microglia and macrophages at the lesion edge [7, 8]. In AOMS, both biomarkers improve differentiation of MS from other conditions, leading to their incorporation into the 2024 revisions of the McDonald criteria [9].

In adults, CVS is defined using the Select-6 rule, considered positive when ≥6 white matter lesions are CVS-positive, or when most lesions are CVS-positive if fewer than 10 lesions are present. In POMS, given that lesion burden is often high and that absolute lesion-count approaches have not been appropriately validated, a more conservative threshold is recommended: CVS is considered supportive of MS when ≥50% of lesions are CVS-positive [9, 10].

The McDonald panel further noted that the diagnostic value of PRLs in POMS remains uncertain due to the paucity of pediatric-specific studies.

To determine whether CVS and PRLs convey the same specificity in POMS as has been shown in AOMS, we conducted a systematic review and meta-analysis to evaluate their prevalence in POMS, critically appraise the existing literature, identify methodological limitations, and highlight priorities for future research.