Depending on the focus of the study, 50% to 75% of the patients had a febrile infection—in many cases of the upper respiratory tract—in the 4 weeks preceding the onset of the neurological phenotype (Table 2). Note that many pathogens attributed to the etiology of ADEM may cause upper respiratory tract infections (Table 1). Preceding immunizations were less commonly reported.4,34,38 Neurological signs and symptoms appeared days to weeks after an infection or vaccination, with an average latency of 4 to 13 days.3- 5,34 In general, neurological symptoms developed subacutely over a period of days and led to hospitalization within a week.4,5,7,34 Although ataxia,3,5,7,34,39 altered level of consciousness,3,5,7,34 and brainstem symptoms38,39 are frequently present in both pediatric and adult cases, certain signs and symptoms appear age-related. In childhood ADEM, long-lasting fever5 and headaches2,5,6,39 occur more frequently, but in adult cases, motor and sensory deficits predominate. Despite these empirical observations, clinical discrepancies41,42 should not exclude a priori the diagnosis ADEM in the respective age group. It is noteworthy that a number of authors do not consider monosymptomatic presentations, such as transverse myelitis, pure cerebellar dysfunction, and unilateral (but not bilateral) optic neuritis without radiological abnormalities compatible with ADEM.4,7,34,38,43,44 Classically, however, Bickerstaff encephalitis and postinfectious transverse myelitis are considered subgroups of ADEM, where the inflammation and demyelination appear to be confined to the brainstem or spinal cord, respectively.45,46 Bilateral optic neuritis appears to be associated with chickenpox and has a less polysymptomatic disease course.20 The disseminated necrotizing leukoencephalopathy (Weston-Hurst syndrome, acute necrotizing hemorrhagic encephalomyelitis, ANHEM) is considered by some experts the maximal variant of ADEM.7,39,47 The Marburg type of MS (also termed malignant MS) is a rare, acute form of MS that occurs predominantly in young adults. The disease course is typically monophasic, and clinical signs and symptoms worsen rapidly and relentlessly. Because the Marburg type of MS is often preceded by a febrile illness, these particular cases, if truly monophasic, may also present a fulminant form of ADEM.