is far lower than the risk of developing ADEM from an actual measles infection, which is about 1 per 1,000 cases. For a rubella infection, the risk is 1 per 5,000 cases. Some early vaccines, later shown to have been contaminated with host animal CNS tissue, had ADEM incident rates as high as 1 in 600. In rare cases, ADEM seems to follow from organ transplantation. Diagnosis ADEM term has been inconsistently used at different times. Currently, the commonly accepted international standard for the clinical case definition is the one published by the International Pediatric MS Study Group, revision 2007. Given that the definition is clinical, it is currently unknown if all the cases with ADEM are positive for anti-MOG autoantibody, but in any case, it seems strongly related to ADEM diagnosis. Differential diagnosis Multiple sclerosis While ADEM and MS both involve autoimmune demyelination, they differ in many clinical, genetic, imaging, and histopathological aspects. Some authors consider MS and its borderline forms to constitute a spectrum, differing only in chronicity, severity, and clinical course, while others consider them discretely different diseases. Typically, ADEM appears in children following an antigenic challenge and remains monophasic. Nevertheless, ADEM does occur in adults, and can also be clinically multiphasic. Problems for differential diagnosis increase due to the lack of agreement for a definition of multiple sclerosis. If MS were defined just by the separation in time and space of the demyelinating lesions as McDonald did, it would not be enough to make a difference, as some cases of ADEM satisfy these conditions. Therefore, some authors propose to establish the separation line in the shape of the lesions around the veins, being therefore "perivenous vs. confluent demyelination". The pathology of ADEM is very similar to that of MS with some differences. The pathological hallmark of ADEM is perivenular inflammation with limited "sleeves of demyelination". Nevertheless, MS-like plaques (confluent demyelination) can appear Plaques in the white matter in MS are sharply delineated, while the glial scar in ADEM is smooth. Axons are better preserved in ADEM lesions. Inflammation in ADEM is widely disseminated and ill-defined, and finally, lesions are strictly perivenous, while in MS they are disposed around veins, but not so sharply. Nevertheless, the co-occurrence of perivenous and confluent demyelination in some individuals suggests pathogenic overlap between acute disseminated encephalomyelitis and multiple sclerosis and misclassification even with biopsy or even postmortem ADEM in adults can