BACKGROUND: Early-onset multiple sclerosis (MS) typically has a more favorable course than adult-onset disease. OBJECTIVE: To assess the extent of microscopic tissue damage in the brain and cervical cord of patients with early-onset MS. DESIGN: During a single magnetic resonance imaging session, images of the brain and spinal cord were obtained using diffusion tensor and magnetization transfer magnetic resonance imaging. PATIENTS: We studied 13 patients with early-onset MS and 10 healthy volunteers. RESULTS: Compared with control subjects, patients with early-onset MS showed only a slight increase of the average mean diffusivity of the normal-appearing brain tissue. CONCLUSION: The relatively modest central nervous system damage detected in these patients might explain why early-onset MS typically has a more favorable clinical course than adult-onset MS.