Prognostic factors in paediatric-onset multiple sclerosis: a narrative review

Background Paediatric-onset multiple sclerosis (POMS) accounts for 3–10% of multiple sclerosis (MS) cases and differs from adult-onset disease in course, treatment response and long-term outcomes. Risk stratification is essential, yet the literature frequently conflates three distinct questions: which children develop MS (susceptibility), which convert from a first demyelinating event (conversion) and which, once diagnosed, will accrue disability (prognosis). Objective This study aimed to provide a narrative overview of candidate prognostic factors in POMS, separated from susceptibility and conversion factors and organised by the outcome each predicts. Methods PubMed and Google Scholar were searched (2002–2025, with hand searching of pivotal 2026 cohorts) using a predefined string and full eligibility criteria. Factors were classified along three axes of inference and graded into four evidence tiers (replicated; preliminary; susceptibility rather than prognosis; inconsistent). No formal risk-of-bias assessment was undertaken, consistent with the narrative design. Results The most reproducible post-diagnosis predictors were early inflammatory activity (relapse number and inter-attack interval in the first two years, annualised relapse rate, early EDSS change), lesion topography (brainstem, spinal cord), T2 lesion accrual, serum neurofilament light chain and treatment-related variables (delayed disease-modifying therapy, early high-efficacy treatment). Advanced MRI metrics, serum glial fibrillary acidic protein and other fluid biomarkers remain preliminary; baseline EDSS was inconsistent. Most dietary, environmental and perinatal exposures relate to susceptibility, not course. Conclusions Current evidence supports candidate predictors, not a validated instrument, and inference is further complicated by confounding by indication. A multidimensional, externally validated POMS-specific prognostic score remains to be developed—the aim of the ongoing PROMISING study.