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

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).

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.

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.

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.

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.