Pediatric Multiple sclerosis

Year 2013, Volume: 5 , - , 13.12.2013

Anastasia Gkampeta , Efterpi Pavlidou , Panagiotis Saravakos Evangelos Pavlou

Abstract

Multiple sclerosis (MS) is considered as the major cause of acquired neurological insult in young adults and the most common demyelinating disease of the central nervous system (CNS). It is an inflammatory disease characterized by multiple areas of demyelination, rupture of the blood-brain barrier and diffused disorder of the white matter. MS is relatively rare in childhood. However, 3-10% of children develop the first episode of MS before the 16^th year of age. Diagnosis of MS in childhood requires clinical and laboratory data, that localize the demyelinating episodes of the CNS, helping to exclude other pathological conditions. The therapeutic options vary and mainly focus on the use of steroids and intravenous immunoglobulins, while recent data suggest the use of interferon. In this review, we present the latest bibliographic data concerning the epidemiological characteristics, the etiology, the clinical course, the available diagnostic methods and the main treatment options of MS.

Keywords

multiple sclerosis; demyelinating disorders; childhood

References

• Pirko I, Noseworthy JH. Demyelinating Disorders of the Central Nervous System. In: Goetz CG, editor. Textbook of Clinical Neurology 3rd ed. Philadelphia: Saunders; 2007.
• Hanefeld F. Pediatric multiple sclerosis: a short history of a long story. Neurology. 2007;68(16 Suppl 2):S3-6.
• Ghezzi A, Deplano V, Faroni J, Grasso MG, Liguori M, Marrosu G, et al. Multiple sclerosis in childhood: clinical features of 149 cases. Mult Scler. 1997;3(1):43-6.
• Pinhas-Hamiel O, Barak Y, Siev-Ner I, Achiron A. Juvenile multiple sclerosis: clinical features and prognostic characteristics. J Pediatr. 1998;132(4):735-7.
• Ghezzi A, Pozzilli C, Liguori M, Marrosu MG, Milani N, Milanese C, et al. Prospective study of multiple sclerosis with early onset. Mult Scler. 2002;8(2):115-8.
• Simone IL, Carrara D, Tortorella C, Liguori M, Lepore V, Pellegrini F, et al. Course and prognosis in early-onset MS: comparison with adult-onset forms. Neurology. 2002;59(12):1922
• Banwell B, Ghezzi A, Bar-Or A, Mikaeloff Y, Tardieu M. Multiple sclerosis in children: clinical diagnosis, therapeutic strategies, and future directions. Lancet Neurol. 2007;6(10):887-902.
• Renoux C, Vukusic S, Mikaeloff Y, Edan G, Clanet M, Dubois B, et al. Natural history of multiple sclerosis with childhood onset. N Engl J Med. 2007;356(25):2603-13.
• 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):54-9.
• Chitnis T, Glanz B, Jaffin S, Healy B. Demographics of pediatric-onset multiple sclerosis in an MS center population from the Northeastern United States. Mult Scler. 2009;15(5):627-31.
• McDonald WI, Compston A, Edan G, Goodkin D, Hartung HP, Lublin FD, et al. Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann Neurol. 2001;50(1):121-7.
• Montalban X, Tintore M, Swanton J, Barkhof F, Fazekas F, Filippi M, et al. MRI criteria for MS in patients with clinically isolated syndromes. Neurology. 2010;74(5):427-34.
• Sadovnick AD, Ebers GC. Epidemiology of multiple sclerosis: a critical overview. Can J Neurol Sci. 1993;20(1):17-29.
• Tintore M, Arrambide G. Early onset multiple sclerosis: the role of gender. J Neurol Sci. 2009;286(1-2):31-4.
• Confavreux C, Hutchinson M, Hours MM, Cortinovis-Tourniaire P, Moreau T. Rate of pregnancy-related relapse in multiple sclerosis. Pregnancy in Multiple Sclerosis Group. N Engl J Med. 1998;339(5):285-91.
• Cole GF, Stuart CA. A long perspective on childhood multiple sclerosis. Dev Med Child Neurol. 1995;37(8):661-6.
• Sadovnick AD, Dircks A, Ebers GC. Genetic counselling in multiple sclerosis: risks to sibs and children of affected individuals. Clin Genet. 1999;56(2):118-22.
• Sadovnick AD AH, Rice GP, et al. A populationbased study of multiple sclerosis in twins: update. Ann Neurol. 1993;33:281-5.
• Dyment DA, Ebers GC, Sadovnick AD. Genetics of multiple sclerosis. Lancet Neurol. 2004;3(2):104-10.
• Sadovnick AD, Yee IM, Ebers GC, Canadian Collaborative Study G. Factors influencing sib risks for multiple sclerosis. Clin Genet. 2000;58(6):431-5.
• Allen M, Sandberg-Wollheim M, Sjogren K, Erlich HA, Petterson U, Gyllensten U. Association of susceptibility to multiple sclerosis in Sweden with HLA class II DRB1 and DQB1 alleles. Hum Immunol. 1994;39(1):41-8.
• Barcellos LF, Oksenberg JR, Begovich AB, Martin ER, Schmidt S, Vittinghoff E, et al. HLADR2 dose effect on susceptibility to multiple sclerosis and influence on disease course. Am J Hum Genet. 2003;72(3):710-6.
• Dyment DA, Sadovnick AD, Ebers GC. Genetics of multiple sclerosis. Hum Mol Genet. 1997;6(10):1693-8.
• Ligers A, Dyment DA, Willer CJ, Sadovnick AD, Ebers G, Risch N, et al. Evidence of linkage with HLA-DR in DRB1*15-negative families with multiple sclerosis. Am J Hum Genet. 2001;69(4):900-3.
• Husain S, Yildirim-Toruner C, Rubio JP, Field J, Southern MSGC, Schwalb M, et al. Variants of ST8SIA1 are associated with risk of developing multiple sclerosis. PLoS ONE. 2008;3(7):e2653.
• Banwell B, Krupp L, Kennedy J, Tellier R, Tenembaum S, Ness J, et al. Clinical features and viral serologies in children with multiple sclerosis: a multinational observational study. Lancet Neurol. 2007;6(9):773-81.
• Marrie RA, Wolfson C, Sturkenboom MC, Gout O, Heinzlef O, Roullet E, et al. Multiple sclerosis and antecedent infections: a case-control study. Neurology. 2000;54(12):2307-10.
• Confavreux C, Suissa S, Saddier P, Bourdes V, Vukusic S, Vaccines in Multiple Sclerosis Study G. Vaccinations and the risk of relapse in multiple sclerosis. Vaccines in Multiple Sclerosis Study Group. N Engl J Med. 2001;344(5):319-26.
• Mikaeloff Y, Caridade G, Assi S, Tardieu M, Suissa S, Society KsgotFN. Hepatitis B vaccine and risk of relapse after a first childhood episode of CNS inflammatory demyelination. Brain. 2007;130(Pt 4):1105-10.
• Mikaeloff Y, Suissa S, Vallee L, Lubetzki C, Ponsot G, Confavreux C, et al. First episode of acute CNS inflammatory demyelination in childhood: prognostic factors for multiple sclerosis and disability. J Pediatr. 2004;144(2):246-52.
• Hayes CE. Vitamin D: a natural inhibitor of multiple sclerosis. The Proceedings of the Nutrition Society. 2000;59(4):531-5.
• Mikaeloff Y, Caridade G, Tardieu M, Suissa S, group Ks. Parental smoking at home and the risk of childhood-onset multiple sclerosis in children. Brain. 2007;130(Pt 10):2589-95.
• Hedstrom AK, Sundqvist E, Baarnhielm M, Nordin N, Hillert J, Kockum I, et al. Smoking and two human leukocyte antigen genes interact to increase the risk for multiple sclerosis. Brain. 2011;134(Pt 3):653-64.
• Venkateswaran S, Banwell B. Pediatric multiple sclerosis. Neurologist. 2010;16(2):92-105.
• Ozakbas S, Idiman E, Baklan B, Yulug B. Childhood and juvenile onset multiple sclerosis: clinical and paraclinical features. Brain Dev. 2003;25(4):233-6.
• Ruggieri M, Polizzi A, Pavone L, Grimaldi LM. Multiple sclerosis in children under 6 years of age. Neurology. 1999;53(3):478-84.
• Tardieu M, Mikaeloff Y. Multiple sclerosis in children. Int MS J. 2004;11(2):36-42.
• Patel Y, Bhise V, Krupp L. Pediatric multiple sclerosis. Annals of Indian Academy of Neurology. 2009;12(4):238-45.
• MacAllister WS, Krupp LB. Multiple sclerosisrelated fatigue. Phys Med Rehabil Clin N Am. 2005;16(2):483-502.
• Amato MP, Goretti B, Ghezzi A, Lori S, Zipoli V, Portaccio E, et al. Cognitive and psychosocial features of childhood and juvenile MS. Neurology. 2008;70(20):1891-7.
• Banwell BL, Anderson PE. The cognitive burden of multiple sclerosis in children. Neurology. 2005;64(5):891-4.
• MacAllister WS, Belman AL, Milazzo M, Weisbrot DM, Christodoulou C, Scherl WF, et al. Cognitive functioning in children and adolescents with multiple sclerosis. Neurology. 2005;64(8):1422-5.
• Banwell B, Tremlett H. Coming of age: the use of immunomodulatory therapy in children with multiple sclerosis. Neurology. 2005;64(5):778-9.
• Wilejto M, Shroff M, Buncic JR, Kennedy J, Goia C, Banwell B. The clinical features, MRI findings, and outcome of optic neuritis in children. Neurology. 2006;67(2):258-62.
• Pohl D, Rostasy K, Reiber H, Hanefeld F. CSF characteristics in early-onset multiple sclerosis. Neurology. 2004;63(10):1966-7.
• Dale RC dSC, Chong WK, Cox TC, Harding B, Neville BG. Acute disseminated encephalomyelitis, multiphasic disseminated encephalomyelitis and multiple sclerosis in children. Brain. 2000;13:2407–22.
• Ghezzi A, Bergamaschi R, Martinelli V, Trojano M, Tola MR, Merelli E, et al. Clinical characteristics, course and prognosis of relapsing Devic's Neuromyelitis Optica. J Neurol. 2004;251(1):47-52. Zaffaroni M, Italian Devic's Study G. Cerebrospinal fluid findings in Devic's neuromyelitis optica. Neurol Sci. 2004;25 Suppl 4:S368-70.
• Pohl D RK, Treiber-Held S, et al. Pediatric multiple sclerosis: detection of clinically silent lesions by multimodal evoked potentials. J Pediatr. 2006;149:125–7.
• Miller DH, Rudge P, Johnson G, Kendall BE, Macmanus DG, Moseley IF, et al. Serial gadolinium enhanced magnetic resonance imaging in multiple sclerosis. Brain. 1988;111 ( Pt 4):927-39.
• Waubant E, Chabas D. Pediatric multiple sclerosis. Current Treatment Options in Neurology. 2009;11(3):203-10.
• Callen DJ, Shroff MM, Branson HM, Lotze T, Li DK, Stephens D, et al. MRI in the diagnosis of pediatric multiple sclerosis. Neurology. 2009;72(11):961-7.
• Callen DJ, Shroff MM, Branson HM, Li DK, Lotze T, Stephens D, et al. Role of MRI in the differentiation of ADEM from MS in children. Neurology. 2009;72(11):968-73.
• Compston A, Coles A. Multiple sclerosis. Lancet. 2008;372:1502-17.
• Yeh EA, Chitnis T, Krupp L, Ness J, Chabas D, Kuntz N, et al. Pediatric multiple sclerosis. Nat Rev Neurol. 2009;5(11):621-31.
• Leary SM, Porter B, Thompson AJ. Multiple sclerosis: diagnosis and the management of acute relapses. Postgrad Med J. 2005;81(955):302-8.
• Gold R, Buttgereit F, Toyka KV. Mechanism of action of glucocorticosteroid hormones: possible implications for therapy of neuroimmunological disorders. J Neuroimmunol. 2001;117(1-2):1-8.
• Royal College of Physicians/NICE. Multiple Sclerosis: national clinical guideline for diagnosis and management in primary and secondary care 200 Schilling S, Linker RA, Konig FB, Koziolek M, Bahr M, Muller GA, et al. [Plasma exchange therapy for steroid-unresponsive multiple sclerosis relapses: clinical experience with 16 patients]. Nervenarzt. 2006;77(4):430-8.
• Takahashi I, Sawaishi Y, Takeda O, Enoki M, Takada G. Childhood multiple sclerosis treated with plasmapheresis. Pediatr Neurol. 1997;17(1):83-7.
• Krupp LB, Macallister WS. Treatment of Pediatric Multiple Sclerosis. Curr Treat Options Neurol. 2005;7(3):191-9.
• Banwell B. Treatment of children and adolescents with multiple sclerosis. Expert Rev Neurother. 2005;5(3):391-401.
• Feasby T, Banwell B, Benstead T, Bril V, Brouwers M, Freedman M, et al. Guidelines on the use of intravenous immune globulin for neurologic conditions. Transfus Med Rev. 2007;21(2 Suppl 1):S57-107.
• Weinstock-Guttman B, Ransohoff RM, Kinkel RP, Rudick RA. The interferons: biological effects, mechanisms of action, and use in multiple sclerosis. Ann Neurol. 1995;37(1):7-15.
• Bermel RA, Rudick RA. Interferon-beta treatment for multiple sclerosis. Neurotherapeutics. 2007;4(4):633-46.
• Noronha A, Toscas A, Jensen MA. Interferon beta decreases T cell activation and interferon gamma production in multiple sclerosis. J Neuroimmunol. 1993;46(1-2):145-53.
• Calabresi PA, Tranquill LR, Dambrosia JM, Stone LA, Maloni H, Bash CN, et al. Increases in soluble VCAM-1 correlate with a decrease in MRI lesions in multiple sclerosis treated with interferon beta-1b. Ann Neurol. 1997;41(5):669
• Ransohoff R. Biological responses to type I interferons: relationship to therapeutic effects in multiple sclerosis. London: Martin Dunitz; 2003.
• Stone LA, Frank JA, Albert PS, Bash C, Smith ME, Maloni H, et al. The effect of interferon-beta on blood-brain barrier disruptions demonstrated by contrast-enhanced magnetic resonance imaging in relapsing-remitting multiple sclerosis. Ann Neurol. 1995;37(5):611-9.
• Banwell B, Bar-Or A, Giovannoni G, Dale RC, Tardieu M. Therapies for multiple sclerosis: considerations in the pediatric patient. Nat Rev Neurol. 2011;7(2):109-22.
• Mikaeloff Yea. Effectiveness of early beta interferon on the first attack after confirmed multiple sclerosis: a comparative cohort study. EurJ Paediatr Neurol. 2008;12:205–9.
• Ghezzi Aea. The management of multiple sclerosis in children: a European view. Mult Scler. 2010;16:1258–67.
• Banwell B, Reder AT, Krupp L, Tenembaum S, Eraksoy M, Alexey B, et al. Safety and tolerability of interferon beta-1b in pediatric multiple sclerosis. Neurology. 2006;66(4):472-6.
• Etheridge LJ, Beverley DW, Ferrie C, McManus E. The use of interferon beta in relapsingremitting multiple sclerosis. Arch Dis Child. 2004;89(8):789-91.
• Ghezzi A, Ruggieri M, Trojano M, Filippi M, Group IS. Italian studies on early-onset multiple sclerosis: the present and the future. Neurol Sci. 2004;25 Suppl 4:S346-9.
• Mikaeloff Y, Moreau T, Debouverie M, Pelletier J, Lebrun C, Gout O, et al. Interferon-beta treatment in patients with childhood-onset multiple sclerosis. J Pediatr. 2001;139(3):443-6.
• Waubant E HJ, Stewart T, Dyme Z, Herbert J, Lacy J, et al. Interferon beta-1a in children with multiple sclerosis is well tolerated. Neuropediatrics. 2001;32:211–3.
• Pohl D, Rostasy K, Gartner J, Hanefeld F. Treatment of early onset multiple sclerosis with subcutaneous interferon beta-1a. Neurology. 2005;64(5):888-90.
• Tenembaum SN, Segura MJ. Interferon beta-1a treatment in childhood and juvenile-onset multiple sclerosis. Neurology. 2006;67(3):511-3.
• Yeh EA. Current therapeutic options in pediatric multiple sclerosis. Curr Treat Options Neurol. 2011;13(6):544-59.
• Polman CH, Bertolotto A, Deisenhammer F, Giovannoni G, Hartung H-P, Hemmer B, et al. Recommendations for clinical use of data on neutralising antibodies to interferon-beta therapy in multiple sclerosis. The Lancet Neurology. 2010;9(7):740-50.
• Chen M, Conway K, Johnson KP, Martin R, Dhib-Jalbut S. Sustained immunological effects of Glatiramer acetate in patients with multiple sclerosis treated for over 6 years. J Neurol Sci. 2002;201(1-2):71-7.
• Chen M, Valenzuela RM, Dhib-Jalbut S. Glatiramer acetate-reactive T cells produce brainderived neurotrophic factor. J Neurol Sci. 2003;215(1-2):37-44.
• Duda PW, Schmied MC, Cook SL, Krieger JI, Hafler DA. Glatiramer acetate (Copaxone) induces degenerate, Th2-polarized immune responses in patients with multiple sclerosis. J Clin Invest. 2000;105(7):967-76.
• Hohlfeld R. Therapeutic strategies in multiple sclerosis. I. Immunotherapy. Philosophical transactions of the Royal Society of London Series B, Biological sciences. 1999;354(1390):1697-710.
• Lalive PH, Neuhaus O, Benkhoucha M, Burger D, Hohlfeld R, Zamvil SS, et al. Glatiramer acetate in the treatment of multiple sclerosis: emerging concepts regarding its mechanism of action. CNS Drugs. 2011;25(5):401-14.
• Miller A, Shapiro S, Gershtein R, Kinarty A, Rawashdeh H, Honigman S, et al. Treatment of multiple sclerosis with copolymer-1 (Copaxone): implicating mechanisms of Th1 to Th2/Th3 immune-deviation. J Neuroimmunol. 1998;92(12):113-21.
• Weber MS, Hohlfeld R, Zamvil SS. Mechanism of action of glatiramer acetate in treatment of multiple sclerosis. Neurotherapeutics. 2007;4(4):647-53.
• Ghezzi A, Immunomodulatory Treatment of Early Onset MSG. Immunomodulatory treatment of early onset multiple sclerosis: results of an Italian Co-operative Study. Neurol Sci. 2005;26 Suppl 4(Suppl 4):S183-6.
• Ghezzi A, Amato MP, Capobianco M, Gallo P, Marrosu G, Martinelli V, et al. Disease-modifying drugs in childhood-juvenile multiple sclerosis: results of an Italian co-operative study. Mult Scler. 2005;11(4):420-4.
• 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):120-6.
• Bergamaschi R. Prognostic factors in multiple sclerosis. Int Rev Neurobiol. 2007;79:423-47.
• Fisniku LK, Brex PA, Altmann DR, Miszkiel KA, Benton CE, Lanyon R, et al. Disability and T2 MRI lesions: a 20-year follow-up of patients with relapse onset of multiple sclerosis. Brain. 2008;131(Pt 3):808-17.
• Boiko A, Vorobeychik G, Paty D, Devonshire V, Sadovnick D, University of British Columbia MSCN. Early onset multiple sclerosis: a longitudinal study. Neurology. 2002;59(7):1006
• Gall JC, Jr., Hayles AB, Siekert RG, Keith HM. Multiple sclerosis in children; a clinical study of 40 cases with onset in childhood. Pediatrics. 1958;21(5):703-9.
• Jones CT. Childhood autoimmune neurologic diseases of the central nervous system. Neurologic clinics. 2003;21(4):745-64.
• Banwell B, Anderson PE. Neuropsychological features of pediatric multiple sclerosis. Neurology. 2002;58(5).
• Guilhoto LM, Osorio CA, Machado LR, de Castro CP, Manreza ML, Callegaro D, et al. Pediatric multiple sclerosis report of 14 cases. Brain Dev. 1995;17(1):9-12.
• 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):280-4.
• Kurtzke JF, Beebe GW, Nagler B, Kurland LT, Auth TL. Studies on the natural history of multiple sclerosis--8. Early prognostic features of the later course of the illness. J Chronic Dis. 1977;30(12):819-30.