Can ADEM Be Distinguished from MS During an Acute Episode of Fulminant Demyelination of the CNS?

Abstract & Commentary

By Susan Gauthier, DO, MPH, Assistant Professor of Neurology, Weill Medical College of Cornell University; Dr. Gauthier reports no financial relationships relevant to this field of study.

Synopsis: In adults presenting with an acute episode of fulminant demyelination of the central nervous system (CNS), atypical symptoms for multiple sclerosis (MS), gray matter involvement on MRI, and absence of oligoclonal bands in the cerebrospinal fluid (CSF) can distinguish acute disseminated encephalomyelitis (ADEM) from MS.

Source: de Seze J, et al. Acute fulminant demyelinating disease: a descriptive study of 60 patients. Arch Neurol 2007;64:1426-1432.

Adem is a fulminant demyelinating episode occurring within the central nervous system and is typically monophasic, following an infectious event or vaccination. ADEM has been studied more often in pediatric cohorts due to its higher incidence in children and young adolescents; therefore, information regarding the clinical and MRI manifestations, as well as the rate of conversion to MS in adults, is scant or lacking. The ability to distinguish MS from ADEM would be advantageous given the proven benefit of early treatment of MS.

In this large multi-center, retrospective study, de Seze et al identified 60 adult patients (older than age 16) as having a diagnosis of ADEM within a European MS database. Alterations in consciousness, hypersomnia, aphasia, hemiplegia, paraplegia, seizure, vomiting, bilateral optic neuritis, or confusion were considered atypical for MS. Six patients were categorized as having multi-phasic demyelinating encephalomyelitis (MDEM) due to recurrence of initial symptoms; these patients were not included in the analysis. Thirty-five patients were categorized as having ADEM (monophasic neurologic symptoms), and 19 patients were labeled as having MS based upon the addition of a new clinical symptom least one month after the first episode.

There was a 32% conversion rate to clinically definite MS after a mean of 37 months. MS patients were found to be younger at presentation (27 years versus 36 years, p=0.04), and although prior infections or vaccinations were more common in ADEM compared to MS, the difference was not significant. Patients with ADEM more often had atypical symptoms, although no one symptom was significant for this association. Corpus callosum lesions were more common in MS patients (p<0.001), whereas gray matter lesions (basal ganglia or cortical) were more common in ADEM patients (p<0.001). The numbers of total T2 lesions, periventricular lesions, spinal cord lesions, or gadolinium-enhanced lesions were not significantly different between the two groups. Three patients with ADEM had new gadolinium-enhanced lesions as compared to nine MS patients (p<0.001). Similarly, 11 patients with MS had new T2 hyperintense lesions as compared to only one ADEM patient (p<0.001). Oligoclonal bands more often were found in the CSF of MS patients (84% versus 20%, p<0.001); however, no differences were found in CSF total white blood count (>30/microliter) or protein level (>1g/dL). Based upon the results, a new criterion was proposed to differentiate MS from ADEM. ADEM diagnosis required two of three of the following features: one or more atypical symptoms, absence of oligoclonal bands in the CSF, or gray matter involvement (basal ganglia or cortical lesions). The sensitivity was calculated to be 82.9%, specificity to be 94.7%, and positive predictive value to be 96.7%.


The distinction between MS and ADEM has never been fully described or understood and remains a diagnostic dilemma. This study represents one of the largest descriptive series of adult-onset ADEM, and it identified a set of distinguishing characteristics for ADEM compared to MS. Furthermore, as demonstrated in this study, differences exist between adult-onset and pediatric-onset ADEM. Adult-onset ADEM had a higher conversion rate to MS as compared to pediatric-onset disease, which ranges between 9% and 35%,1 and a less direct association with vaccinations or prior infection. In addition, adult-onset ADEM had a similar number of periventricular lesions as compared to MS, a finding that differs from the pediatric cohort studies.1

Study limitations are unavoidable because of the overlap between ADEM and MS. Specific limitations of this study include the unexplained exclusion of patients with MDEM and the one-month interval to define MS, given that previous work in ADEM had recommended a two-month interval to accurately define MS.1 A small percentage of patients with ADEM have MRI progression, but the significance of this observation in relation to the development of MS has yet to be established. Finally, the predictive potential of the proposed criteria will need to be evaluated in a separate cohort to ensure reliability. Despite these limitations, this study highlights clinical features that might help to identify patients with a clinical presentation of ADEM who could be at risk for developing MS and would benefit from early intervention with immunomodulatory therapy.


1. Menge T, et al. Arch Neurol 2005;62:1673-1680.