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Semin Neurol 2008; 28(1): 069-083
DOI: 10.1055/s-2007-1019129
© Thieme Medical Publishers

Multiple Sclerosis in Children

Terrence Thomas1 , Brenda Banwell1
  • 1Pediatric Multiple Sclerosis Clinic, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
Further Information

Publication History

Publication Date:
07 February 2008 (online)

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ABSTRACT

Multiple sclerosis (MS) is being increasingly diagnosed in children and adolescents. Clinical and magnetic resonance imaging (MRI) features of MS in the pediatric population are similar to adult-onset disease, with some important distinctions. Case vignettes, recently published clinical definitions, and an approach to disorders considered in the differential diagnoses are provided in this article. Immunomodulatory therapies approved for use in adults with MS are safe and well-tolerated in children, although monitoring of liver function is of particular importance. Finally, this article presents recent research studies performed in an MS population for whom disease onset occurs in unique temporal proximity to the events involved in MS pathogenesis.

KEYWORDS

Multiple sclerosis - children - demyelination

REFERENCES

  • 1 Boiko A, Vorobeychik G, Paty D et al.. Early onset multiple sclerosis: a longitudinal study.  Neurology. 2002;  59(7) 1006-1010
    CrossrefPubMedGoogle Scholar
  • 2 Duquette P, Murray T J, Pleines J et al.. Multiple sclerosis in childhood: clinical profile in 125 patients.  J Pediatr. 1987;  111(3) 359-363
    CrossrefPubMedGoogle Scholar
  • 3 Simone I L, Carrara D, Tortorella C et al.. Course and prognosis in early-onset MS: comparison with adult-onset forms.  Neurology. 2002;  59(12) 1922-1928
    CrossrefPubMedGoogle Scholar
  • 4 Ruggieri M, Polizzi A, Pavone L, Grimaldi L M. Multiple sclerosis in children under 6 years of age.  Neurology. 1999;  53(3) 478-484
    PubMedGoogle Scholar
  • 5 Ghezzi A, Pozzilli C, Liguori M et al.. Prospective study of multiple sclerosis with early onset.  Mult Scler. 2002;  8(2) 115-118
    CrossrefPubMedGoogle Scholar
  • 6 Mikaeloff Y, Caridade G, Assi S, Suissa S, Tardieu M. Prognostic factors for early severity in a childhood multiple sclerosis cohort.  Pediatrics. 2006;  118(3) 1133-1139
    CrossrefPubMedGoogle Scholar
  • 7 Dessa Sadovnick A. The genetics of multiple sclerosis.  Clin Neurol Neurosurg. 2002;  104 199-202
    CrossrefPubMedGoogle Scholar
  • 8 Wingerchuk D M, Weinshenker B G. Neuromyelitis optica.  Curr Treat Options Neurol. 2005;  7(3) 173-182
    PubMedGoogle Scholar
  • 9 Wingerchuk D M, Lennon V A, Pittock S J, Lucchinetti C F, Weinshenker B G. Revised diagnostic criteria for neuromyelitis optica.  Neurology. 2006;  66(10) 1485-1489
    CrossrefPubMedGoogle Scholar
  • 10 Krupp L B, Banwell B, Tenembaum S. International Pediatric MS Study Group . Consensus definitions proposed for pediatric multiple sclerosis.  Neurology. 2007;  68 S7-S12
    CrossrefPubMedGoogle Scholar
  • 11 Tenembaum S, Chamoles N, Fejerman N. Acute disseminated encephalomyelitis: a long-term follow-up study of 84 pediatric patients.  Neurology. 2002;  59(8) 1224-1231
    CrossrefPubMedGoogle Scholar
  • 12 Rust R S. Multiple sclerosis, acute disseminated encephalomyelitis, and related conditions.  Semin Pediatr Neurol. 2000;  7(2) 66-90
    CrossrefPubMedGoogle Scholar
  • 13 Wilejto M, Shroff M, Buncic J R, Kennedy J, Goia C, Banwell B. The clinical features, MRI findings, and outcome of optic neuritis in children.  Neurology. 2006;  67(2) 258-262
    CrossrefPubMedGoogle Scholar
  • 14 Riikonen R, Donner M, Erkkila H. Optic neuritis in children and its relationship to multiple sclerosis: a clinical study of 21 children.  Dev Med Child Neurol. 1988;  30(3) 349-359
    PubMedGoogle Scholar
  • 15 Pohl D, Rostasy K, Reiber H, Hanefeld F. CSF characteristics in early-onset multiple sclerosis.  Neurology. 2004;  63(10) 1966-1967
    CrossrefPubMedGoogle Scholar
  • 16 McDonald W I, Compston A, Edan G et al.. Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis.  Ann Neurol. 2001;  50(1) 121-127
    CrossrefPubMedGoogle Scholar
  • 17 Hahn C D, Miles B S, MacGregor D L, Blaser S I, Banwell B L, Hetherington C R. Neurocognitive outcome after acute disseminated encephalomyelitis.  Pediatr Neurol. 2003;  29(2) 117-123
    CrossrefPubMedGoogle Scholar
  • 18 Mikaeloff Y, Adamsbaum C, Husson B et al.. MRI prognostic factors for relapse after acute CNS inflammatory demyelination in childhood.  Brain. 2004;  127(Pt 9) 1942-1947
    CrossrefPubMedGoogle Scholar
  • 19 Banwell B, Shroff M, Ness J et al.. MRI features of pediatric multiple sclerosis.  Neurology. 2007;  68 S46-S53
    CrossrefPubMedGoogle Scholar
  • 20 Shiraishi K, Higuchi Y, Ozawa K, Hao Q, Saida T. Clinical course and prognosis of 27 patients with childhood onset multiple sclerosis in Japan.  Brain Dev. 2005;  27(3) 224-227
    CrossrefPubMedGoogle Scholar
  • 21 Ozakbas S, Idiman E, Baklan B, Yulug B. Childhood and juvenile onset multiple sclerosis: clinical and paraclinical features.  Brain Dev. 2003;  25(4) 233-236
    PubMedGoogle Scholar
  • 22 Mikaeloff Y, Suissa S, Vallee L et al.. 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
  • 23 Mikaeloff Y, Caridade G, Huson B, Suissa S, Tardieu M. Acute disseminated encephalomyelitis cohort study: prognostic factors for relapse.  Eur J Paediatr Neurol. 2007;  11(2) 90-95
    CrossrefPubMedGoogle Scholar
  • 24 Banwell B L. Pediatric multiple sclerosis.  Curr Neurol Neurosci Rep. 2004;  4(3) 245-252
    CrossrefPubMedGoogle Scholar
  • 25 Sindern E, Haas J, Stark E, Wurster U. Early onset MS under the age of 16: clinical and paraclinical features.  Acta Neurol Scand. 1992;  86(3) 280-284
    PubMedGoogle Scholar
  • 26 Banwell B L, Anderson P E. The cognitive burden of multiple sclerosis in children.  Neurology. 2005;  64(5) 891-894
    CrossrefPubMedGoogle Scholar
  • 27 MacAllister W S, Belman A L, Milazzo M et al.. Cognitive functioning in children and adolescents with multiple sclerosis.  Neurology. 2005;  64(8) 1422-1425
    CrossrefPubMedGoogle Scholar
  • 28 Kalb R C, DiLorenzo T A, LaRocca N A, Caruso L S, Shawaryn M A, Elkin R DWM. The impact of early onset multiple sclerosis on cognitive and social indices.  Int J MS Care. 1999;  1 2-17
    PubMedGoogle Scholar
  • 29 Mikaeloff Y, Moreau T, Debouverie M et al.. Interferon-beta treatment in patients with childhood-onset multiple sclerosis.  J Pediatr. 2001;  139(3) 443-446
    CrossrefPubMedGoogle Scholar
  • 30 Banwell B. Treatment of children and adolescents with multiple sclerosis.  Expert Rev Neurother. 2005;  5(3) 391-401
    CrossrefPubMedGoogle Scholar
  • 31 Zelnik N, Gale A D, Shelburne Jr S A. Multiple sclerosis in black children.  J Child Neurol. 1991;  6(1) 53-57
    PubMedGoogle Scholar
  • 32 Harel L, Sandborg C, Lee T, von Scheven E. Neuropsychiatric manifestations in pediatric systemic lupus erythematosus and association with antiphospholipid antibodies.  J Rheumatol. 2006;  33(9) 1873-1877
    PubMedGoogle Scholar
  • 33 Sibbitt Jr W L, Brandt J R, Johnson C R et al.. The incidence and prevalence of neuropsychiatric syndromes in pediatric onset systemic lupus erythematosus.  J Rheumatol. 2002;  29(7) 1536-1542
    PubMedGoogle Scholar
  • 34 Yu H H, Lee J H, Wang L C, Yang Y H, Chiang B L. Neuropsychiatric manifestations in pediatric systemic lupus erythematosus: a 20-year study.  Lupus. 2006;  15(10) 651-657
    CrossrefPubMedGoogle Scholar
  • 35 Benseler S M, Silverman E, Aviv R I et al.. Primary central nervous system vasculitis in children.  Arthritis Rheum. 2006;  54(4) 1291-1297
    CrossrefPubMedGoogle Scholar
  • 36 Benseler S, Schneider R. Central nervous system vasculitis in children.  Curr Opin Rheumatol. 2004;  16(1) 43-50
    CrossrefPubMedGoogle Scholar
  • 37 Murphy J M, Gomez-Anson B, Gillard J H et al.. Wegener granulomatosis: MR imaging findings in brain and meninges.  Radiology. 1999;  213(3) 794-799
    PubMedGoogle Scholar
  • 38 Krause I, Uziel Y, Guedj D et al.. Childhood Behçet's disease: clinical features and comparison with adult-onset disease.  Rheumatology (Oxford). 1999;  38(5) 457-462
    CrossrefPubMedGoogle Scholar
  • 39 Read R W, Holland G N, Rao N A et al.. Revised diagnostic criteria for Vogt-Koyanagi-Harada disease: report of an international committee on nomenclature.  Am J Ophthalmol. 2001;  131(5) 647-652
    CrossrefPubMedGoogle Scholar
  • 40 Susac J O, Murtagh F R, Egan R A et al.. MRI findings in Susac's syndrome.  Neurology. 2003;  61(12) 1783-1787
    CrossrefPubMedGoogle Scholar
  • 41 Lamy C, Oppenheim C, Meder J F, Mas J L. Neuroimaging in posterior reversible encephalopathy syndrome.  J Neuroimaging. 2004;  14(2) 89-96
    CrossrefPubMedGoogle Scholar
  • 42 Kumar R, Singh S N, Kohli N. A diagnostic rule for tuberculous meningitis.  Arch Dis Child. 1999;  81(3) 221-224
    PubMedGoogle Scholar
  • 43 Garcia H H, Del Brutto O H. Neurocysticercosis: updated concepts about an old disease.  Lancet Neurol. 2005;  4(10) 653-661
    CrossrefPubMedGoogle Scholar
  • 44 Singhi P, Ray M, Singhi S, Khandelwal N. Clinical spectrum of 500 children with neurocysticercosis and response to albendazole therapy.  J Child Neurol. 2000;  15(4) 207-213
    PubMedGoogle Scholar
  • 45 Morgado C, Ruivo N. Imaging meningo-encephalic tuberculosis.  Eur J Radiol. 2005;  55(2) 188-192
    CrossrefPubMedGoogle Scholar
  • 46 Shaw C M, Alvord Jr E C. Multiple sclerosis beginning in infancy.  J Child Neurol. 1987;  2(4) 252-256
    PubMedGoogle Scholar
  • 47 Iannetti P, Falconieri P, Imperato C. Acquired immune deficiency syndrome in childhood. Neurological aspects.  Childs Nerv Syst. 1989;  5(5) 281-287
    CrossrefPubMedGoogle Scholar
  • 48 Offiah C E, Turnbull I W. The imaging appearances of intracranial CNS infections in adult HIV and AIDS patients.  Clin Radiol. 2006;  61(5) 393-401
    CrossrefPubMedGoogle Scholar
  • 49 Garcia-Suarez J, de Miguel D, Krsnik I, Banas H, Arribas I, Burgaleta C. Changes in the natural history of progressive multifocal leukoencephalopathy in HIV-negative lymphoproliferative disorders: impact of novel therapies.  Am J Hematol. 2005;  80(4) 271-281
    CrossrefPubMedGoogle Scholar
  • 50 Lewis D W. Toward the definition of childhood migraine.  Curr Opin Pediatr. 2004;  16(6) 628-636
    CrossrefPubMedGoogle Scholar
  • 51 Swartz R H, Kern R Z. Migraine is associated with magnetic resonance imaging white matter abnormalities: a meta-analysis.  Arch Neurol. 2004;  61(9) 1366-1368
    CrossrefPubMedGoogle Scholar
  • 52 Desmond D W, Moroney J T, Lynch T, Chan S, Chin S S, Mohr J P. The natural history of CADASIL: a pooled analysis of previously published cases.  Stroke. 1999;  30(6) 1230-1233
    CrossrefPubMedGoogle Scholar
  • 53 Valanne L, Ketonen L, Majander A, Suomalainen A, Pihko H. Neuroradiologic findings in children with mitochondrial disorders.  AJNR Am J Neuroradiol. 1998;  19(2) 369-377
    PubMedGoogle Scholar
  • 54 Moore D F, Kaneski C R, Askari H, Schiffmann R. The cerebral vasculopathy of Fabry disease.  J Neurol Sci. 2007;  257 258-263
    CrossrefPubMedGoogle Scholar
  • 55 Ries M, Ramaswami U, Parini R et al.. The early clinical phenotype of Fabry disease: a study on 35 European children and adolescents.  Eur J Pediatr. 2003;  162(11) 767-772
    CrossrefPubMedGoogle Scholar
  • 56 van der Knaap M S. Magnetic resonance in childhood white-matter disorders.  Dev Med Child Neurol. 2001;  43(10) 705-712
    CrossrefPubMedGoogle Scholar
  • 57 Horster F, Surtees R, Hoffmann G F. Disorders of intermediary metabolism: toxic leukoencephalopathies.  J Inherit Metab Dis. 2005;  28(3) 345-356
    CrossrefPubMedGoogle Scholar
  • 58 Barkovich J A. Pediatric Neuroimaging. 2nd ed. New York; Raven Press 2000
    Google Scholar
  • 59 Porto L, Kieslich M, Schwabe D, Yan B, Zanella F E, Lanfermann H. Central nervous system lymphoma in children.  Pediatr Hematol Oncol. 2005;  22(3) 235-246
    CrossrefPubMedGoogle Scholar
  • 60 Haddad E, Sulis M L, Jabado N, Blanche S, Fischer A, Tardieu M. Frequency and severity of central nervous system lesions in hemophagocytic lymphohistiocytosis.  Blood. 1997;  89(3) 794-800
    PubMedGoogle Scholar
  • 61 Pande A R, Ando K, Ishikura R et al.. Disseminated necrotizing leukoencephalopathy following chemoradiation therapy for acute lymphoblastic leukemia.  Radiat Med. 2006;  24(7) 515-519
    CrossrefPubMedGoogle Scholar
  • 62 Chan Y L, Leung S F, King A D, Choi P H, Metreweli C. Late radiation injury to the temporal lobes: morphologic evaluation at MR imaging.  Radiology. 1999;  213(3) 800-807
    CrossrefPubMedGoogle Scholar
  • 63 Boyd J R, MacMillan L J. Multiple sclerosis in childhood: understanding and caring for children with an “adult” disease.  Axone. 2000;  22(2) 15-21
    PubMedGoogle Scholar
  • 64 Hahn J S, Siegler D J, Enzmann D. Intravenous gammaglobulin therapy in recurrent acute disseminated encephalomyelitis.  Neurology. 1996;  46(4) 1173-1174
    PubMedGoogle Scholar
  • 65 Nishikawa M, Ichiyama T, Hayashi T, Ouchi K, Furukawa S. Intravenous immunoglobulin therapy in acute disseminated encephalomyelitis.  Pediatr Neurol. 1999;  21(2) 583-586
    CrossrefPubMedGoogle Scholar
  • 66 Murthy S N, Faden H S, Cohen M E, Bakshi R. Acute disseminated encephalomyelitis in children.  Pediatrics. 2002;  110(2 Pt 1) e21
    CrossrefPubMedGoogle Scholar
  • 67 Apak R A, Anlar B, Saatci I. A case of relapsing acute disseminated encephalomyelitis with high dose corticosteroid treatment.  Brain Dev. 1999;  21(4) 279-282
    CrossrefPubMedGoogle Scholar
  • 68 Weinshenker B G, O'Brien P C, Petterson T M et al.. A randomized trial of plasma exchange in acute central nervous system inflammatory demyelinating disease.  Ann Neurol. 1999;  46(6) 878-886
    CrossrefPubMedGoogle Scholar
  • 69 The IFNB Multiple Sclerosis Study Group . Interferon beta-1b is effective in relapsing-remitting multiple sclerosis. I. Clinical results of a multicenter, randomized, double-blind, placebo-controlled trial.  Neurology. 1993;  43(4) 655-661
    PubMedGoogle Scholar
  • 70 PRISMS . Randomised Double-Blind Placebo-Controlled Study of Interferon beta-1a in Relapsing-Remitting MS.  Lancet. 1998;  352 1498-1504
    CrossrefPubMedGoogle Scholar
  • 71 Jacobs L D, Cookfair D L, Rudick R A et al.. Intramuscular interferon beta-1a for disease progression in relapsing multiple sclerosis. The Multiple Sclerosis Collaborative Research Group (MSCRG) [see comments] [published erratum appears in Ann Neurol 1996;40(3):480].  Ann Neurol. 1996;  39(3) 285-294
    CrossrefPubMedGoogle Scholar
  • 72 Johnson K P, Brooks B R, Cohen J A et al.. Copolymer 1 reduces relapse rate and improves disability in relapsing-remitting multiple sclerosis: results of a phase III multicenter, double-blind placebo-controlled trial.  The Copolymer 1 Multiple Sclerosis Study Group . Neurology. 1995;  45(7) 1268-1276
    CrossrefPubMedGoogle Scholar
  • 73 Jacobs L D, Beck R W, Simon J H et al.. Intramuscular interferon beta-1a therapy initiated during a first demyelinating event in multiple sclerosis.  CHAMPS Study Group . N Engl J Med. 2000;  343(13) 898-904
    CrossrefPubMedGoogle Scholar
  • 74 Comi G, Filippi M, Barkhof F et al.. Effect of early interferon treatment on conversion to definite multiple sclerosis: a randomised study.  Lancet. 2001;  357(9268) 1576-1582
    CrossrefPubMedGoogle Scholar
  • 75 Kappos L, Traboulsee A, Constantinescu C et al.. Long-term subcutaneous interferon beta-1a therapy in patients with relapsing-remitting MS.  Neurology. 2006;  67(6) 944-953
    CrossrefPubMedGoogle Scholar
  • 76 Banwell B, Reder A T, Krupp L et al.. Safety and tolerability of interferon beta-1b in pediatric multiple sclerosis.  Neurology. 2006;  66(4) 472-476
    CrossrefPubMedGoogle Scholar
  • 77 Waubant E, Hietpas J, Stewart T et al.. Interferon beta-1a in children with multiple sclerosis is well tolerated.  Neuropediatrics. 2001;  32(4) 211-213
    Article in Thieme ConnectPubMedGoogle Scholar
  • 78 Etheridge L J, Beverley D W, Ferrie C, McManus E. The use of interferon beta in relapsing-remitting multiple sclerosis.  Arch Dis Child. 2004;  89(8) 789-791
    CrossrefPubMedGoogle Scholar
  • 79 Kornek B, Bernert G, Balassy C, Geldner J, Prayer D, Feucht M. Glatiramer acetate treatment in patients with childhood and juvenile onset multiple sclerosis.  Neuropediatrics. 2003;  34(3) 120-126
    Article in Thieme ConnectPubMedGoogle Scholar
  • 80 Ghezzi A, Amato M P, Capobianco M et al.. Disease-modifying drugs in childhood-juvenile multiple sclerosis: results of an Italian co-operative study.  Mult Scler. 2005;  11(4) 420-424
    CrossrefPubMedGoogle Scholar
  • 81 Pohl D, Rostasy K, Gartner J, Hanefeld F. Treatment of early onset multiple sclerosis with subcutaneous interferon beta-1a.  Neurology. 2005;  64 888-890
    CrossrefPubMedGoogle Scholar
  • 82 Tenembaum S N, Segura M J. Interferon beta-1a treatment in childhood and juvenile-onset multiple sclerosis.  Neurology. 2006;  67 511-513
    CrossrefPubMedGoogle Scholar
  • 83 Pakdaman H, Fallah A, Sahraian M A, Pakdaman R, Meysamie A. Treatment of early onset multiple sclerosis with suboptimal dose of interferon beta-1a.  Neuropediatrics. 2006;  37(4) 257-260
    Article in Thieme ConnectPubMedGoogle Scholar
  • 84 Smith D. Preliminary analysis of a trial of pulse cyclophosphamide in IFN-beta-resistant active MS.  J Neurol Sci. 2004;  223(1) 73-79
    CrossrefPubMedGoogle Scholar
  • 85 Hauser S L, Dawson D M, Lehrich J R et al.. Intensive immunosuppression in progressive multiple sclerosis. A randomized, three-arm study of high-dose intravenous cyclophosphamide, plasma exchange, and ACTH.  N Engl J Med. 1983;  308(4) 173-180
    PubMedGoogle Scholar
  • 86 Weiner H L, Mackin G A, Orav E J et al.. Intermittent cyclophosphamide pulse therapy in progressive multiple sclerosis: final report of the Northeast Cooperative Multiple Sclerosis Treatment Group.  Neurology. 1993;  43(5) 910-918
    PubMedGoogle Scholar
  • 87 Weiner H L, Cohen J A. Treatment of multiple sclerosis with cyclophosphamide: critical review of clinical and immunologic effects.  Mult Scler. 2002;  8(2) 142-154
    CrossrefPubMedGoogle Scholar
  • 88 Berger T, Deisenhammer F. Progressive multifocal leukoencephalopathy, natalizumab, and multiple sclerosis.  N Engl J Med. 2005;  353(16) 1744-1746
    CrossrefPubMedGoogle Scholar
  • 89 Langer-Gould A, Atlas S W, Green A J, Bollen A W, Pelletier D. Progressive multifocal leukoencephalopathy in a patient treated with natalizumab.  N Engl J Med. 2005;  353(4) 375-381
    CrossrefPubMedGoogle Scholar
  • 90 Caldwell P H, Murphy S B, Butow P N, Craig J C. Clinical trials in children.  Lancet. 2004;  364(9436) 803-811
    CrossrefPubMedGoogle Scholar
  • 91 Alotaibi S, Kennedy J, Tellier R, Stephens D, Banwell B. Epstein-Barr virus in pediatric multiple sclerosis.  JAMA. 2004;  291(15) 1875-1879
    CrossrefPubMedGoogle Scholar
  • 92 Pohl D, Krone B, Rostasy K et al.. High seroprevalence of Epstein-Barr virus in children with multiple sclerosis.  Neurology. 2006;  67(11) 2063-2065
    CrossrefPubMedGoogle Scholar
  • 93 Ascherio A, Munch M. Epstein-Barr virus and multiple sclerosis.  Epidemiology. 2000;  11(2) 220-224
    CrossrefPubMedGoogle Scholar
  • 94 Ascherio A, Munger K L, Lennette E T et al.. Epstein-Barr virus antibodies and risk of multiple sclerosis: a prospective study.  JAMA. 2001;  286(24) 3083-3088
    CrossrefPubMedGoogle Scholar
  • 95 Trowsdale J. Multiple sclerosis: putting two and two together.  Nat Med. 2006;  12(10) 1119-1121
    PubMedGoogle Scholar
  • 96 Correale J, Tenembaum S N. Myelin basic protein and myelin oligodendrocyte glycoprotein T-cell repertoire in childhood and juvenile multiple sclerosis.  Mult Scler. 2006;  12(4) 412-420
    CrossrefPubMedGoogle Scholar
  • 97 Lucchinetti C F, Kiers L, O'Duffy A et al.. Risk factors for developing multiple sclerosis after childhood optic neuritis.  Neurology. 1997;  49(5) 1413-1418
    CrossrefPubMedGoogle Scholar
  • 98 Miyazawa R, Ikeuchi Y, Tomomasa T, Ushiku H, Ogawa T, Morikawa A. Determinants of prognosis of acute transverse myelitis in children.  Pediatr Int. 2003;  45(5) 512-516
    CrossrefPubMedGoogle Scholar
  • 99 Dunne K, Hopkins I J, Shield L K. Acute transverse myelopathy in childhood.  Dev Med Child Neurol. 1986;  28(2) 198-204
    PubMedGoogle Scholar
  • 100 Defresne P, Hollenberg H, Husson B et al.. Acute transverse myelitis in children: clinical course and prognostic factors.  J Child Neurol. 2003;  18(6) 401-406
    CrossrefPubMedGoogle Scholar
  • 101 Jeffery A R, Buncic J R. Pediatric Devic's neuromyelitis optica.  J Pediatr Ophthalmol Strabismus. 1996;  33(5) 223-229
    PubMedGoogle Scholar
  • 102 Wingerchuk D M, Weinshenker B G. Neuromyelitis optica: clinical predictors of a relapsing course and survival.  Neurology. 2003;  60(5) 848-853
    CrossrefPubMedGoogle Scholar
  • 103 Ghezzi A, Deplano V, Faroni J et al.. Multiple sclerosis in childhood: clinical features of 149 cases.  Mult Scler. 1997;  3(1) 43-46
    CrossrefPubMedGoogle Scholar

Brenda BanwellM.D. F.A.A.P. F.R.C.P.C. 

Director, Pediatric Multiple Sclerosis Clinic, The Hospital for Sick Children, University of Toronto

550 University Avenue, Toronto, Ontario, Canada M5G 1X8

Email: Brenda.banwell@sickkids.ca