Disease-Modifying Treatment Options in Very Early Onset Multiple Sclerosis—What Choices Are There for Onset Under 5 Years of Age? A Systematic Review

Background/Objectives: Very early pediatric-onset multiple sclerosis (POMS) is rare; clinical studies using disease-modifying treatments (DMTs) have not been performed. Clinicians rely on studies performed at older ages. This review resulted from difficulties faced by clinicians and the off-label use of DMTs at this age. Methods: A literature review of studies dated between 1982 and 2025 on very early POMS, specifically with onset before age 5, has been performed, searching for outcomes without or with DMTs. The curated database of the selected patients was analyzed using computed descriptive and integrated cohort-level estimates. The clinical, paraclinical, treatment, and outcome characteristics were analyzed. Statistical analysis used JASP, with GenAI-assisted verification. The treatment outcome of a 16-year-old patient with very early POMS starting at 2 years 4 months that consecutively received interferon, immunoglobulin, and Natalizumab is presented. Results: A total of 101 patients with very early POMS presented, at onset, with ataxic syndrome (57.4%), pyramidal syndrome (41.4%), ophthalmoplegia (10.3%), and optic neuritis (6.9%). In evolution, 22.7% had seizures. Half of the patients were not treated. Among those treated, acute steroid therapy was administered; 11 received the DMTs interferon, Glatiramer acetate, Dimethyl fumarate, and Azathioprine (three), with only two high-efficacy therapies (Natalizumab and Rituximab). Our patient had partial remission under interferon, relapses when stopped and replaced by immunoglobulin and 9 years relapse-free interval when Natalizumab was introduced. Conclusions: Early treatment with high-efficiency DMTs should be considered in very early POMS; association with known increased neuroplasticity at this age may improve prognosis, allowing good recovery of acquired disability.