International Pediatric Multiple Sclerosis Study Group criteria for pediatric multiple sclerosis and immune-mediated central nervous system demyelinating disorders: Revisions to the 2007 definitions

Lourie Center for Pediatric MS. Stony Brook University Medical Center, USA.
Multiple Sclerosis (Impact Factor: 4.82). 09/2013; 19(10):1261-1267. DOI: 10.1177/1352458513484547


Background: There has been tremendous growth in research in pediatric multiple sclerosis (MS) and immune mediated central nervous system demyelinating disorders since operational definitions for these conditions were first proposed in 2007. Further, the International Pediatric Multiple Sclerosis Study Group (IPMSSG), which proposed the criteria, has expanded substantially in membership and in its international scope. Objective: The purpose of this review is to revise the 2007 definitions in order to incorporate advances in delineating the clinical and neuroradiologic features of these disorders. Methods: Through a consensus process, in which input was sought from the 150 members of the Study Group, criteria were drafted, revised and finalized. Final approval was sought through a web survey. Results: Revised criteria are proposed for pediatric acute disseminated encephalomyelitis, pediatric clinically isolated syndrome, pediatric neuromyelitis optica and pediatric MS. These criteria were approved by 93% or more of the 56 Study Group members who responded to the final survey. Conclusions: These definitions are proposed for clinical and research purposes. Their utility will depend on the outcomes of their application in prospective research.

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Available from: Silvia Tenembaum, Jan 04, 2014
    • "Briefly, children with an incident demyelinating attack meeting the 2010 McDonald criteria (Polman et al., 2011) and/or International Pediatric MS Study Group (IPMSSG) consensus criteria for MS (Krupp et al., 2013) were included as MS patients (n = 17) retrospectively after a mean follow-up of 2.5 ± 1.4 years. Patients meeting the IPMSSG consensus criteria for a diagnosis of ADEM (n = 9), ON (n = 4) or TM (n = 4) (as defined in Krupp et al. (Krupp et al., 2013)) who have normal brain magnetic resonance imaging (MRI) and negative CSF oligoclonal bands (n = 12) were grouped as monophasic ADS patients (n = 17) and had a mean follow-up of 2.4 ± 1.4 years. Characteristics of included children are summarized in Table 1. "
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    ABSTRACT: Acquired demyelinating syndromes (ADS) in children evolve either as a monophasic disease diagnosed as acute demyelinating encephalomyelitis (ADEM), transverse myelitis (TM) or optic neuritis (ON), or a multiphasic one with several relapses most often leading to the diagnosis of multiple sclerosis (MS) or neuromyelitis optica (NMO). These neuroinflammatory disorders are increasingly associated with autoantibodies against proteins such as aquaporin-4 in rare instances, and more frequently against myelin oligodendrocyte glycoprotein (MOG). Recently, in adult NMO patients, C5a levels were shown to be elevated in cerebrospinal fluid (CSF) during acute exacerbation. We investigated the CSF levels of anaphylatoxins and pro-inflammatory cytokines, and plasma MOG antibodies in onset samples from children with ADS. Thirty four children presenting with a first episode of ADS, 17 with monophasic ADS (9 with ADEM, 4 with TM and 4 with ON) and 17 with MS, who had paired blood and CSF samples at onset were included and compared to 12 patients with other non-inflammatory neurological disorders (OND). Cytokines and anaphylatoxins in CSF were measured by Cytometric Bead Array immunoassay. MOG antibody titers in plasma were tested by flow cytometry using a stable cell line expressing full-length human MOG. We found a significant increase in C5a levels in the CSF of patients with monophasic ADS (n = 17) compared to OND (n = 12, p = 0.0036) and to MS (n = 17, p = 0.0371). The C5a levels in MS were higher than in OND without reaching significance (p = 0.2). CSF IL-6 levels were significantly increased in monophasic ADS compared to OND (p = 0.0027) and to MS (p = 0.0046). MOG antibody plasma levels were significantly higher in monophasic ADS (p < 0.0001) and, to a lesser extent, in MS compared to OND (p = 0.0023). Plasma MOG antibodies and CSF IL-6 levels were significantly correlated (r = 0.51, p = 0.018). CSF C5a and IL-6 levels are increased in monophasic ADS but not in MS when compared to OND, suggesting that these markers may help to predict monophasic or relapsing fate of ADS at onset. MOG antibody titers, which were higher in monophasic ADS than in MS, correlated with IL-6 levels, but not with C5a, suggesting an association between MOG antibodies and neuroinflammation in pediatric ADS.
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    • "This distinction is important as NMO responds to different immunomodulating agents than does MS. The spectrum of pediatric MS has also been the focus of extensive nosographic revision in recent years, and diagnostic criteria have been recently revised by the International Pediatric Multiple Sclerosis Study Group (IPMSSG) [6]. "

    Full-text · Article · Jan 2014
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    • "In 2007, an international committee proposed provisional consensus definitions that included a range of clinical and laboratory findings to facilitate unification of criteria for accurate diagnosis and to encourage and promote clinical research in pediatric demyelinating disease [4]. The original definitions have been recently reviewed and updated [5]. "
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    ABSTRACT: Multiple sclerosis (MS), a chronic inflammatory autoimmune disease of the central nervous system (CNS) commonly diagnosed in adults, is being recognized increasingly in children. An estimated 1.7%-5.6% of all patients with MS have clinical symptoms before reaching the age of 18 years. In comparison with adults, the diagnosis of MS in children can be more difficult, being dismissed or misdiagnosed as other clinical disorders. Although adults and children share basic aspects of the disorder, children have distinctive clinical features, neuroimaging, laboratory, and courses of the disease. The 2010 McDonald criteria have simplified the requirements for establishing the diagnosis of MS and have been proposed to be applicable for the diagnosis of pediatric MS, mainly in children 12 years and older. This paper describes the distinctive features of common pediatric demyelinating disorders, including MS, and summarizes the most recent advances based on the available literature.
    Full-text · Article · Nov 2013
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