An international panel has recently proposed consensus definitions for pediatric multiple sclerosis and related disorders. These are important diagnostic improvements, but exceptions have been acknowledged. Further insight about clinical overlap between pediatric multiple sclerosis and all forms of relapsing acute disseminated encephalomyelitis may be gained from long-term follow-up. We report an 8-year follow-up of a girl who developed multiple episodes of central nervous system demyelination at the age of 3 years consistent with multiphasic acute disseminated encephalomyelitis. At 10 years of age (7 years after the first clinical event), she developed progressive cognitive deterioration, mood disorder, and headache, suggesting a secondary progressive form of multiple sclerosis. Magnetic resonance imaging and cerebrospinal fluid analysis were equivocal while visual evoked potentials were the sole test in favor of a diagnosis of multiple sclerosis. A multifaceted approach may be needed when dealing with atypical cases of demyelinating disease in young children.