Breakthrough disease requiring a change in therapy is relatively common in this population. == Growing evidence in adult MS research suggests benefit to early treatment using disease-modifying therapies (DMTs). As such, making a timely diagnosis of MS is essential. In pediatric MS, this is particularly in immediate need because recent TY-51469 research points to more aggressive disease in this group, with more frequent relapses5and higher T2 lesion load on brain magnetic resonance imaging (MRI), both early and later in the disease.6,7Importantly, however, not all first-time demyelinating episodes in children will become multiple sclerotic. Indeed, although 45% of all children with a first-time demyelinating episode will later receive a diagnosis of MS,8only one-fifth of children with a first-time episode of acute disseminated encephalomyelitis (ADEM) will eventually be diagnosed with MS.9 Recently, formulated diagnostic criteria for pediatric MS may help to improve diagnostic accuracy for the clinician. According to definitions of the International Pediatric MS Study Group (IPMSSG) published in 2007,10pediatric MS may be diagnosed after two clinical episodes of central nervous system (CNS) demyelination that are separated by at least 30 days. No lower age limit is specified (Table 1). == Table 1. == Diagnostic criteria for pediatric MS Abbreviations:MS, multiple sclerosis; MRI, magnetic resonance imaging; CSF, DGKD cerebrospinal fluid; IgG, immunoglobulin G. According to these definitions, the Barkhof adult brain MRI criteria can be used to meet the requirement for dissemination in space by demonstrating three of the following four features: (1) nine or more white matter lesions or one gadolinium enhancing lesion, (2) three or more periventricular lesions, (3) one juxtacortical lesion, and (4) an infratentorial lesion. The combination of an abnormal CSF and two lesions on MRI, of which one must be in the brain, can also meet the dissemination in space criteria. The CSF must show either at least two oligoclonal bands (OCB) or an elevated IgG index. The MRI may also be used to satisfy criteria for dissemination in time following the initial clinical event, even in the absence of a new clinical demyelinating event; new T2-bright or gadolinium-enhancing foci must develop 3 or more months following the initial clinical event. These definitions are currently under review. The adult MRI criteria mentioned above have been found to have low sensitivity and specificity in pediatric MS.11In response to this, TY-51469 several groups have proposed MRI diagnostic criteria for pediatric TY-51469 MS. According to one set of criteria, more than two of the following criteria must be satisfied: 5 T2 lesions, two periventricular lesions, or one brainstem lesion. The same group has proposed the following criteria for differentiating ADEM from MS, including two or more of the following: absence of diffuse bilateral lesion pattern, black holes, or greater than two periventricular lesions.12,13The ADEM criteria have been found to be highly sensitive (99%) and relatively specific (75%) in differentiating MS from ADEM when evaluated using an outside cohort of children with known MS (Table 2).14 == Table 2. == Barkhof (adult MS) and 2 other recently proposed sets of TY-51469 diagnostic criteria for pediatric MS Note:The new criteria have been found to be sensitive and specific in the diagnosis of pediatric MS.12,13 Abbreviations:MS, multiple sclerosis; MRI, magnetic resonance imaging; ADEM, acute disseminated encephalomyelitis. == Pathophysiology == Pathologic investigations have suggested that MS lesions in the adult population are heterogeneous; although some lesions may show T-cell mediated and antibody-mediated loss, other lesions may show oligodendrocyte dystrophy suggestive of viral-mediated or toxin-mediated demyelination.15Evaluation of childhood MS is complicated by presentation with confluent lesions on MRI, particularly in younger children who may initially be diagnosed with ADEM.16Thus, distinguishing a first attack of MS from the monophasic condition, ADEM is often challenging. Recent work on children and adults with MS and ADEM suggests pathologic overlap TY-51469 between the two: perivenous inflammation was found to be a hallmark of ADEM but was also seen in a small subset of patients with MS.17 MS is believed to be the result of early triggering events to CNS self-antigens in genetically predisposed individuals.18Antimyelin antibodies have been investigated in the adult MS population as a marker for MS.19Recent work suggests that myelin basic protein antibodies in the serum and CSF of children may modulate the clinical presentation of MS in children and are associated with an.
