This chapter discusses how current operational definitions can apply to clinical practice and research settings of pediatric multiple sclerosis (MS) and acute disseminated encephalomyelitis (ADEM). It emphasizes strengths and limitations of these clinical practice and research settings. ADEM requires the presence of both encephalopathy and polysymptomatic presentation. Three major controversies concerning the criteria of dissemination in time relate to the fact that a consensus has not been reached about when to call pediatric MS a recurrent disease in: patients with a first ADEM-like episode who further develop non- ADEM-like episodes, patients with recurrent ADEM including more than two episodes, and patients with recurrent non-ADEM-like events such as optic neuritis (ON) or transverse myelitis (TM) without brain MRI findings and without neuromyelitis optica (NMO) IgG. The first two situations are fairly specific of the pediatric population, given the higher frequency of ADEM or ADEM-like presentations in children, especially before puberty.

This chapter describes the specific magnetic resonance imaging (MRI) features of pediatric multiple sclerosis (MS). It also discusses proposed MRI criteria for pediatric MS and compares these to the MRI diagnostic criteria well established for adult patients who present with a first demyelinating event. MRI studies in children help to understand early pathogenic events that lead to clinical symptoms and signs of MS. MRI detects white matter pathology that represents clinically silent demyelination in adults. The absence of brain or spine lesions on the initial MRI study seems to be associated with very low risk of progression to MS. Studies in adult MS patients have shown that the initial lesion burden on brain imaging may be an important prognostic factor. The MRI criteria for acute disseminated encephalomyelitis (ADEM) include the presence of poorly defined lesions and a high lesion load, associated with thalamus and basal ganglia involvement.

This chapter briefly summarizes the history of pediatric multiple sclerosis (MS) and related diseases, and current clinical and research directions. Pierre Marie observed that MS in children might be related to acute infectious diseases, syphilis or trauma, suggesting that there was some overlap with infectious or post-infectious central nervous system (CNS) diseases such as acute disseminated encephalomyelitis (ADEM). The reported cases of MS in children may have, in fact, been leukodystrophies. ADEM is classically described as monophasic illness, and one that predominantly occurs in childhood, as opposed to MS, a relapsing and remitting disease, which predominantly occurs in young adults. The study of pediatric MS provides a unique opportunity to examine factors contributing to MS pathogenesis in general, since in affected children there is a close temporal proximity between the interplay of biological, genetic and environmental factors leading to clinical expression of the disease.