Some of these terms, used originally to refer to the neurologic sequelae of infectious fevers, were introduced into medicine in the late 19th century but it was not until the late 1920s that Perdrau, Pette, Greenfield, and others identified a type of pathologic reaction common to a number of monophasic inflammatory syndromes following exanthems and vaccines. The current view of the entity known as ADEM is that it is distinguished pathologically by numerous foci of demyelination scattered throughout the brain and spinal cord. These lesions vary in diameter from miniscule to several millimeters (when confluent) and invariably surround small and medium-sized veins. The axons and nerve cells remain more or less intact. The perivenular inflammatory reaction consists primarily of lymphocytes and mononuclear cells. The adjacent regions of white matter are invaded by monocytes and microglia corresponding to the zones of demyelination. Multifocal meningeal infiltration is another invariable feature but is rarely severe. With the exception of this last feature, ADEM is indistinguishable on histopathologic grounds from acute MS. It is the postinfectious setting and temporal course that are the main features that set them apart. On the other hand, even the monophasic nature of ADEM has been questioned by Schwarz and colleagues, who found that 14 of 40 adults initially diagnosed with ADEM later developed clear signs of MS, usually within a year. A larger and more recent retrospective study of 228 patients with ADEM by Koelman and colleagues likewise showed that 25 percent had a multiphasic course, and that a relapsing course in adults (and women, in particular) was more likely to correspond to a transition to MS than in children with ADEM. The transition to MS in children with typical ADEM is less common.
An acute encephalitic, myelitic, or encephalomyelitic process of this type is observed in a number of clinical settings and is more common in children. In our experience, the disease in children follows a febrile illness by days or infrequently up to 2 weeks; this is less often the case in adults. In the originally described form, it occurred within a few days of onset of the exanthem of measles, rubella, smallpox, or chickenpox. Prior to widespread immunization against measles, an epidemic in a large city might have resulted in 100,000 cases of measles and clinically evident neurologic complications in 1 in 800 to 1 in 2,000 cases.
The mortality among patients with such complications ranged from 10 to 20 percent; about an equal number were left with persistent neurologic damage. The neurologic complications of measles alone provide sufficient justification for immunization against the disease. The incidence of encephalomyelitis was less following chickenpox and rubella, and much less following mumps. In the past, a similar illness was observed to follow vaccination against rabies and smallpox and, reportedly, after administration of tetanus antitoxin (rare), as discussed further on. Now, however, most cases, clinically and pathologically indistinguishable from these 2 categories of ADEM, appear to develop after seemingly banal respiratory infections and after documented infections with Epstein-Barr, cytomegalovirus, Mycoplasma pneumoniae, and even HIV (Narisco et al); occasionally there is no clearly defined preceding illness or inoculation. Many, if not most, instances of acute transverse myelitis may represent the same postinfectious process. The neurologic illness may coincide with the later stages of the manifestations of the infection, in which case the term parainfectious may be appropriate.