We have read with interest the recent article by de Seze et al1 titled “Acute Fulminant Demyelinating Disease: A Descriptive Study of 60 Patients.” The article mainly tackles the problem of different diagnosis criteria between acute disseminated encephalomyelitis (ADEM) and multiple sclerosis (MS) during the acute phase of the first episode in a population aged 15 years and older. From this study, it has emerged that the following variables help to distinguish patients with ADEM from patients with MS: atypical symptoms, oligoclonal bands, and gray matter involvement. When referring to adults, de Seze and colleagues cite only the work by Schwarz et al,2 underlining some differential characteristics having to do with age and the distribution of lesions on magnetic resonance imaging. The same topic appears among our subjects of interest, as can be seen from our articles published in 2005,3 2006,4 and 2007,5 which were not cited by de Seze and colleagues. To date, our study concerned approximately 80 adult patients with an average follow-up of more than 2 years, with data collected from 1997 to 2007. Twenty-six percent of ADEM cases showed a recurrent or multiphasic course, causing us to consider differential diagnosis vs the relapsing-remitting form of MS. The following features, already notable at disease onset, are helpful in addressing the diagnosis: age at onset, cerebrospinal fluid findings, consciousness disturbances, peripheral nervous system involvement, visual evoked potentials, and chemokine profile (Table). Interestingly, the same variables, with the inclusion of the degree of neurological impairment, allow us to identify the subgroup of patients with ADEM who have a higher risk of relapse. During follow-up, we noticed some other useful characteristics in addressing the differential diagnosis with MS: (1) the recurrent forms of ADEM, also when characterized by brain involvement during the first stage, recur exclusively in the form of myelitis or myeloradiculitis; and (2) brain magnetic resonance imaging during relapses shows the definitive disappearance of lesions, contrary to what is observed in the typical MS pattern. Moreover, the subgroup of patients with a higher risk of recurrence shows a major degree of functional impairment and a less favorable long-term outcome than that with the classic form of MS. In conclusion, based on our data, the differential diagnosis between ADEM and MS in an adult population can be achieved with acceptable accuracy early in the acute phase of the disease.