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This chapter presents the literature review on disease-modifying therapies (DMT) for children with multiple sclerosis (MS). Four first-line DMTs have been approved for treatment of relapsing-remitting (RR) MS in the adult population. They include glatiramer acetate, interferon beta (IFNB)-1a IM, IFNB-1a SC, and IFNB-1b SC. Large phase III studies showed that chronic administration of recombinant IFNB reduced the number of relapses and slowed progression of physical disability in adult patients with RR MS. Abnormalities in liver function tests (LFTs) may be pronounced in younger children taking interferon. The glatiramer acetate is designed to mimic human myelin basic protein and is postulated to induce the myelin-specific response of suppressor T-lymphocytes and to inhibit specific effector T-lymphocytes. Breakthrough disease is a concern in the pediatric MS population. Proposed consensus criteria for breakthrough disease in adults include increase in relapse number, new or recurrent MRI lesions, and worsening of cognitive or motor disability.
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.
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