Pediatric Multiple Sclerosis

 

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Abstract

Pediatric multiple sclerosis (MS) is a chronic inflammatory neurologic disease that is challenging to diagnose and treat. Although there are many clinical parallels between pediatric-onset MS and adult-onset MS, there is also accumulating evidence of distinguishing clinical features that may, in part, arise from development-specific, neuroimmune processes governing MS pathogenesis in children. Here the authors describe the clinical features, diagnosis, and treatment of pediatric MS, with a particular focus on describing clinical features and highlighting new developments that promise a better understanding of pediatric MS pathogenesis. An important task that lies ahead for pediatric neurologists is better understanding the early gene–environment interaction that precipitates the first demyelinating event in pediatric MS. This area is of particular importance for understanding the MS etiology and the natural history of pediatric MS. Such understanding should in turn inform new developments in diagnostic tools, long-term therapies, and much-needed biomarkers. Such biomarkers are not only valuable for defining the disease onset, but also for monitoring both the treatment response and a disease evolution that spans multiple decades in children with MS.

• References

• 1 Banwell B, Kennedy J, Sadovnick D , et al. Incidence of acquired demyelination of the CNS in Canadian children. Neurology 2009; 72 (3) 232-239
  CrossrefPubMedGoogle Scholar
• 2 Pohl D, Hennemuth I, von Kries R, Hanefeld F. Paediatric multiple sclerosis and acute disseminated encephalomyelitis in Germany: results of a nationwide survey. Eur J Pediatr 2007; 166 (5) 405-412
  CrossrefPubMedGoogle Scholar
• 3 Ness JM, Chabas D, Sadovnick AD, Pohl D, Banwell B, Weinstock-Guttman B ; International Pediatric MS Study Group. Clinical features of children and adolescents with multiple sclerosis. Neurology 2007; 68 (16) (Suppl. 02) S37-S45
  CrossrefPubMedGoogle Scholar
• 4 Deiva K, Absoud M, Hemingway C , et al; United Kingdom Childhood Inflammatory Demyelination (UK-CID) Study and French Kidbiosep Study. Acute idiopathic transverse myelitis in children: early predictors of relapse and disability. Neurology 2015; 84 (4) 341-349
  CrossrefPubMedGoogle Scholar
• 5 Meyer P, Leboucq N, Molinari N , et al. Partial acute transverse myelitis is a predictor of multiple sclerosis in children. Mult Scler 2014; 20 (11) 1485-1493
  CrossrefPubMedGoogle Scholar
• 6 Banwell B, Bar-Or A, Arnold DL , et al. Clinical, environmental, and genetic determinants of multiple sclerosis in children with acute demyelination: a prospective national cohort study. Lancet Neurol 2011; 10 (5) 436-445
  CrossrefPubMedGoogle Scholar
• 7 Benson LA, Healy BC, Gorman MP , et al. Elevated relapse rates in pediatric compared to adult MS persist for at least 6 years. Mult Scler Relat Disord 2014; 3 (2) 186-193
  CrossrefPubMedGoogle Scholar
• 8 Gorman MP, Healy BC, Polgar-Turcsanyi M, Chitnis T. Increased relapse rate in pediatric-onset compared with adult-onset multiple sclerosis. Arch Neurol 2009; 66 (1) 54-59
  CrossrefPubMedGoogle Scholar
• 9 Mikaeloff Y, Suissa S, Vallée L , et al; KIDMUS Study Group. First episode of acute CNS inflammatory demyelination in childhood: prognostic factors for multiple sclerosis and disability. J Pediatr 2004; 144 (2) 246-252
  CrossrefPubMedGoogle Scholar
• 10 Fay AJ, Mowry EM, Strober J, Waubant E. Relapse severity and recovery in early pediatric multiple sclerosis. Mult Scler 2012; 18 (7) 1008-1012
  CrossrefPubMedGoogle Scholar
• 11 Malik MT, Healy BC, Benson LA , et al. Factors associated with recovery from acute optic neuritis in patients with multiple sclerosis. Neurology 2014; 82 (24) 2173-2179
  CrossrefPubMedGoogle Scholar
• 12 Renoux C, Vukusic S, Mikaeloff Y , et al; Adult Neurology Departments KIDMUS Study Group. Natural history of multiple sclerosis with childhood onset. N Engl J Med 2007; 356 (25) 2603-2613
  CrossrefPubMedGoogle Scholar
• 13 Julian L, Serafin D, Charvet L , et al; Network of Pediatric MS Centers of Excellence. Cognitive impairment occurs in children and adolescents with multiple sclerosis: results from a United States network. J Child Neurol 2013; 28 (1) 102-107
  CrossrefPubMedGoogle Scholar
• 14 MacAllister WS, Belman AL, Milazzo M , et al. Cognitive functioning in children and adolescents with multiple sclerosis. Neurology 2005; 64 (8) 1422-1425
  CrossrefPubMedGoogle Scholar
• 15 Amato MP, Goretti B, Ghezzi A , et al; Multiple Sclerosis Study Group of the Italian Neurological Society. Cognitive and psychosocial features in childhood and juvenile MS: two-year follow-up. Neurology 2010; 75 (13) 1134-1140
  CrossrefPubMedGoogle Scholar
• 16 Charvet LE, O'Donnell EH, Belman AL , et al; US Network of Pediatric MS Centers. Longitudinal evaluation of cognitive functioning in pediatric multiple sclerosis: report from the US Pediatric Multiple Sclerosis Network. Mult Scler 2014; 20 (11) 1502-1510
  CrossrefPubMedGoogle Scholar
• 17 Polman CH, Reingold SC, Banwell B , et al. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol 2011; 69 (2) 292-302
  CrossrefPubMedGoogle Scholar
• 18 Sadaka Y, Verhey LH, Shroff MM , et al; Canadian Pediatric Demyelinating Disease Network. 2010 McDonald criteria for diagnosing pediatric multiple sclerosis. Ann Neurol 2012; 72 (2) 211-223
  CrossrefPubMedGoogle Scholar
• 19 Krupp LB, Banwell B, Tenembaum S ; International Pediatric MS Study Group. Consensus definitions proposed for pediatric multiple sclerosis and related disorders. Neurology 2007; 68 (16) (Suppl. 02) S7-S12
  CrossrefPubMedGoogle Scholar
• 20 Krupp LB, Tardieu M, Amato MP , et al; International Pediatric Multiple Sclerosis Study Group. International Pediatric Multiple Sclerosis Study Group criteria for pediatric multiple sclerosis and immune-mediated central nervous system demyelinating disorders: revisions to the 2007 definitions. Mult Scler 2013; 19 (10) 1261-1267
  CrossrefPubMedGoogle Scholar
• 21 Kerbrat A, Aubert-Broche B, Fonov V , et al. Reduced head and brain size for age and disproportionately smaller thalami in child-onset MS. Neurology 2012; 78 (3) 194-201
  CrossrefPubMedGoogle Scholar
• 22 Chitnis T, Tenembaum S, Banwell B , et al; International Pediatric Multiple Sclerosis Study Group. Consensus statement: evaluation of new and existing therapeutics for pediatric multiple sclerosis. Mult Scler 2012; 18 (1) 116-127
  CrossrefPubMedGoogle Scholar
• 23 Tenembaum SN, Segura MJ. Interferon beta-1a treatment in childhood and juvenile-onset multiple sclerosis. Neurology 2006; 67 (3) 511-513
  CrossrefPubMedGoogle Scholar
• 24 Ghezzi A, Amato MP, Capobianco M , et al; Immunomodulatory Treatment of Early-onset MS (ITEMS) Group. Treatment of early-onset multiple sclerosis with intramuscular interferonbeta-1a: long-term results. Neurol Sci 2007; 28 (3) 127-132
  CrossrefPubMedGoogle Scholar
• 25 Banwell B, Krupp L, Kennedy J , et al. Clinical features and viral serologies in children with multiple sclerosis: a multinational observational study. Lancet Neurol 2007; 6 (9) 773-781
  CrossrefPubMedGoogle Scholar
• 26 Mowry EM, Krupp LB, Milazzo M , et al. Vitamin D status is associated with relapse rate in pediatric-onset multiple sclerosis. Ann Neurol 2010; 67 (5) 618-624
  PubMedGoogle Scholar
• 27 Yeh EA, Waubant E, Krupp LB , et al; National Network of Pediatric MS Centers of Excellence. Multiple sclerosis therapies in pediatric patients with refractory multiple sclerosis. Arch Neurol 2011; 68 (4) 437-444
  CrossrefPubMedGoogle Scholar
• 28 Lulu S, Julian L, Shapiro E, Hudson K, Waubant E. Treatment adherence and transitioning youth in pediatric multiple sclerosis. Mult Scler Relat Disord 2014; 3 (6) 689-695
  CrossrefPubMedGoogle Scholar
• 29 Ghezzi A, Moiola L, Pozzilli C , et al; MS Study Group-Italian Society of Neurology. Natalizumab in the pediatric MS population: results of the Italian registry. BMC Neurol 2015; 15: 174
  CrossrefPubMedGoogle Scholar
• 30 Huppke P, Stark W, Zürcher C, Huppke B, Brück W, Gärtner J. Natalizumab use in pediatric multiple sclerosis. Arch Neurol 2008; 65 (12) 1655-1658
  CrossrefPubMedGoogle Scholar
• 31 Dale RC, Brilot F, Duffy LV , et al. Utility and safety of rituximab in pediatric autoimmune and inflammatory CNS disease. Neurology 2014; 83 (2) 142-150
  CrossrefPubMedGoogle Scholar
• 32 Chitnis T, Waubant E. B-cell depletion in children with neuroimmunologic conditions: the learning curve. Neurology 2014; 83 (2) 111-112
  CrossrefPubMedGoogle Scholar
• 33 Makhani N, Gorman MP, Branson HM, Stazzone L, Banwell BL, Chitnis T. Cyclophosphamide therapy in pediatric multiple sclerosis. Neurology 2009; 72 (24) 2076-2082
  CrossrefPubMedGoogle Scholar
• 34 Kornek B, Bernert G, Rostasy K , et al. Long-term follow-up of pediatric patients treated with mitoxantrone for multiple sclerosis. Neuropediatrics 2011; 42 (1) 7-12
  Article in Thieme ConnectPubMedGoogle Scholar
• 35 Chitnis T, Tardieu M, Amato MP , et al. International Pediatric MS Study Group Clinical Trials Summit: meeting report. Neurology 2013; 80 (12) 1161-1168
  CrossrefPubMedGoogle Scholar