The term post-infectious encephalomyelitis (PIEM) is frequently used interchangeably with acute disseminated encephalomyelitis (ADEM), although technically PIEM occurs after a known infection whereas with ADEM there is no antecedent infection. PIEM represents one of the primary demyelinating disorders of the central nervous system, along with multiple sclerosis and Devic's disease. There is no specific diagnostic test for any of these conditions and at onset it may be difficult to differentiate between ADEM and the first attack of multiple sclerosis. However, there are clinical and magnetic resonance imaging features that allow differentiation between PIEM/ADEM and a relapsing disease such as multiple sclerosis. Some patients improve spontaneously; most improve with methylprednisolone. If that fails, plasma exchange or intravenous immunoglobulin may be effective.