The literature on acute disseminated encephalomyelitis (ADEM) is reviewed in an update by researchers at the University of San Francisco, CA; University of Texas Southwestern Medical Center, Dallas; and Universities in Germany. The clinical onset of ADEM is preceded by a febrile infection, usually upper respiratory, in about 50% to 75% of cases. Viral infections include herpes simplex, in 10% of cases in one series; measles (1/1000); rubella (1/10,000 to 1/20,000); varicella zoster (1/10,000 to 1/20,000); varicella, mumps, HIV, human herpesvirus 6, hepatitis virus (A and C), Epstein-Barr, coronavirus, cocksackie B, and dengue viruses. Bacterial infections include streptococcus, mycoplasma pneumoniae, and rickettsia rickettsii. Vaccinations include hepatitis B (2 of 31 patients vaccinated 3-6 weerks prior to onset of ADEM); pertussis (0.9/100,000 following DPT-triple vaccine); measles (0.1/100,000 for live measles vaccination); polio, and rabies. Neurologic symptoms and signs appear days to weeks after an infection or vaccination, with an average latency of 4 to 13 days; these include fever, headache, lethargy, ataxia, obtundation, and brainstem involvement. Bickerstaff encephalitis and postinfectious transverse myelitis, where inflammation and demyelination are confined to the brainstem and spinal cord, respectively, are considered subgroups of ADEM. Bilateral optic neuritis is characteristic of varicella-related ADEM. The clinical diagnosis usually requires confirmation by MRI, showing disseminated CNS demyelination, and follow-up MRI after 6 months to exclude new lesions suggestive of MS. CSF to rule out acute viral, bacterial, or parasitic meningoencephalitis may show lymphocytic pleocytosis and elevated albumin. Oligoclonal banding occurs in an average of 12.5% cases in children (range 0-29%), often transiently. PCR results may be positive for an inciting pathogen, but proof of a causative relation to ADEM is difficult. Brain biopsy is considered in cases with insidious onset and mass effect. The most common differential diagnosis is MS. ADEM is considered a monophasic disease, but 25% to 33% of patients have relapses, usually within 1 year of the initial event, and significantly shorter than MS relapse interval of 3.1 years. Treatment consists of IV high-dose corticosteroids, and if necessary, the addition of IV immunoglobulin and plasmapheresis, and immunosuppressive agents. Prognosis today is favorable, and contrasts with 25% mortality and 35% morbidity reported in pre-vaccination, measles-induced ADEM cases. Early use of high-dose steroids has also contributed to the improved outcome. 
COMMENT. Although ADEM is considered a relatively rare disorder, with an estimated annual prevalence rate of 0.8/100,000 of the population , the diagnosis is increasingly important because of the expanded usage of vaccination, the need for early steroid therapy, and the risks of permanent neurologic sequelae. The poor prognosis of patients with measles-related ADEM should be a warning to parents who are persuaded to forego immunization of a child because of unsubstantiated reports of potential risks of autism.
Patients with onset of ADEM before 5 years of age have a lower mean intelligence quotient (p<0.01), significantly lower scores on reading and spelling tests (p<0.001), and a higher incidence of severe behavioral and emotional problems, compared to controls of the same age and socioeconomic status . This study finds standard scores on spelling significantly lower in a young onset group compared to older onset patients with ADEM (p<0.05). Long-term neuropsychological dysfunction may occur in children who develop ADEM in early childhood, despite the absence of persisting neurologic deficits. (see Ped Neur Briefs 2004; 18:66).