Acute encephalomyelitis in children refers to an insult of cortical white matter leading to acute disseminated encephalomyelitis, insult of the spinal cord leading to multifocal myelopathy, or a combined form of encephalomyelitis. We report here the clinical presentations and outcome of 16 children with severe acute encephalomyelitis analyzing the effect of high-dose methylprednisolone or intravenous immunoglobulins, administered separately or in combination. Five children developed acute disseminated encephalomyelitis alone, eight developed severe multifocal myelopathy accompanied in two of them by radiculoneuropathy, and three developed the most severe form of combined encephalomyeloradiculoneuropathy. The indications for treatment with either high-dose methylprednisolone, intravenous immunoglobulin, or a combination of the two were severe acute disseminated encephalomyelitis, visual loss, or severe flaccid weakness accompanied by bladder and bowel incontinence. Overall, 10 children had remarkably responded to high-dose methylprednisolone alone and recovered within 10 days. One patient with severe myelopathy, developing paraplegia, who failed oral corticosteroids completely recovered following intravenous immunoglobulin. Of the isolated acute disseminated encephalomyelitis group, all patients were initially treated with high-dose intravenous methylprednisolone and recovered within 10 days, including visual remission in the child with severe optic neuritis. All six children with solitary severe multifocal myelopathy were treated with high-dose methylprednisolone alone and recovered within the first week. Two patients had severe myeloradiculoneuropathy and were therefore treated with combined high-dose methylprednisolone and intravenous immunoglobulin: one remains paraplegic, whereas the second was ventilated for 3 weeks and recovered after 2 months. The three children with the most severe form of encephalomyeloradiculoneuropathy were treated with combined high-dose methylprednisolone and intravenous immunoglobulin; two remain severely handicapped, of whom one is paraplegic, and the third unexpectedly recovered within 3 months. Therefore, our experience indicates that either high-dose methylprednisolone or intravenous immunoglobulin, given separately or combined, may be efficacious in severe debilitating pediatric-onset acute encephalomyelitis. In children with the most severe form of encephalomyeloradiculoneuropathy, we suggest initially administering high-dose methylprednisolone and intravenous immunoglobulin combined, given the poorer outcome of our patients with combined severe central and peripheral demyelination.