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Neuropediatrics 2018; 49(03): 165-172
DOI: 10.1055/s-0038-1635123
Review Article
Georg Thieme Verlag KG Stuttgart · New York

Imaging Pediatric Multiple Sclerosis—Challenges and Recent Advances

Katrin Parmar
1   Department of Neurology, University Hospital Basel, Basel, Switzerland
,
Brenda L. Banwell
2   Division of Neurology, Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, Pennsylvania, United States
,
Nadine Akbar
3   School of Rehabilitation Therapy, Queen's University, Kingston, Ontario, Canada
,
Sandra Bigi
4   Division of Child Neurology, Department of Pediatrics, University Children's Hospital Bern, University of Bern, Bern, Switzerland
› Author Affiliations Funding This study did not receive funding.
Further Information

Publication History

02 October 2017

21 January 2018

Publication Date:
26 February 2018 (online)

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Abstract

Pediatric onset multiple sclerosis (POMS) is a rare disease with an incidence of 0.07 to 2.9/100'000 children per year. It follows a relapsing–remitting disease course and is characterized by rapid accrual of inflammatory lesions, high relapse frequency, and early cognitive impairment. Magnetic resonance imaging (MRI) plays a pivotal role in the diagnosis of POMS, and in the exclusion of other disorders mimicking POMS. Furthermore, MRI aids in disease monitoring, and in the evaluation of therapeutic efficacy in both clinical practice and clinical trials. Volumetric MRI studies, diffusion tensor imaging, resting-state, and task-based functional MRI provide deeper insight into the impact of POMS on maturing neural networks. This review article aims to highlight the importance of MRI in the care of POMS patients and to provide an overview on the different MRI techniques used in the management of POMS.

Keywords

pediatric multiple sclerosis - magnetic resonance imaging - acute demyelinating syndromes

Ethical Approval

This article does not contain any studies with human participants or animals performed by any of the authors.


Informed Consent

Not applicable.


 

  • References

  • 1 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
  • 2 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
    CrossrefPubMedGoogle Scholar
  • 3 Boiko A, Vorobeychik G, Paty D, Devonshire V, Sadovnick D. ; University of British Columbia MS Clinic Neurologists. Early onset multiple sclerosis: a longitudinal study. Neurology 2002; 59 (07) 1006-1010
    CrossrefPubMedGoogle Scholar
  • 4 Banwell B, Kennedy J, Sadovnick D. , et al. Incidence of acquired demyelination of the CNS in Canadian children. Neurology 2009; 72 (03) 232-239
    CrossrefPubMedGoogle Scholar
  • 5 Waldman A, Ness J, Pohl D. , et al. Pediatric multiple sclerosis: clinical features and outcome. Neurology 2016; 87 (09) (Suppl. 02) S74-S81
    CrossrefPubMedGoogle Scholar
  • 6 Ketelslegers IA, Catsman-Berrevoets CE, Neuteboom RF. , et al. Incidence of acquired demyelinating syndromes of the CNS in Dutch children: a nationwide study. J Neurol 2012; 259 (09) 1929-1935
    CrossrefPubMedGoogle Scholar
  • 7 Ghezzi A, Deplano V, Faroni J. , et al. Multiple sclerosis in childhood: clinical features of 149 cases. Mult Scler 1997; 3 (01) 43-46
    CrossrefPubMedGoogle Scholar
  • 8 Huppke B, Ellenberger D, Rosewich H, Friede T, Gärtner J, Huppke P. Clinical presentation of pediatric multiple sclerosis before puberty. Eur J Neurol 2014; 21 (03) 441-446
    CrossrefPubMedGoogle Scholar
  • 9 Disanto G, Berlanga AJ, Handel AE. , et al. Heterogeneity in multiple sclerosis: scratching the surface of a complex disease. Autoimmune Dis 2010; 2011: 932351
    PubMedGoogle Scholar
  • 10 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
  • 11 Cossburn M, Ingram G, Hirst C, Ben-Shlomo Y, Pickersgill TP, Robertson NP. Age at onset as a determinant of presenting phenotype and initial relapse recovery in multiple sclerosis. Mult Scler 2012; 18 (01) 45-54
    CrossrefPubMedGoogle Scholar
  • 12 Harding KE, Liang K, Cossburn MD. , et al. Long-term outcome of paediatric-onset multiple sclerosis: a population-based study. J Neurol Neurosurg Psychiatry 2013; 84 (02) 141-147
    CrossrefPubMedGoogle Scholar
  • 13 Ghassemi R, Antel SB, Narayanan S. , et al; Canadian Pediatric Demyelinating Disease Study Group. Lesion distribution in children with clinically isolated syndromes. Ann Neurol 2008; 63 (03) 401-405
    CrossrefPubMedGoogle Scholar
  • 14 Hennes EM, Baumann M, Schanda K. , et al; BIOMARKER Study Group. Prognostic relevance of MOG antibodies in children with an acquired demyelinating syndrome. Neurology 2017; 89 (09) 900-908
    CrossrefPubMedGoogle Scholar
  • 15 Ketelslegers IA, Van Pelt DE, Bryde S. , et al. Anti-MOG antibodies plead against MS diagnosis in an acquired demyelinating syndromes cohort. Mult Scler 2015; 21 (12) 1513-1520
    CrossrefPubMedGoogle Scholar
  • 16 Baumann M, Hennes EM, Schanda K. , et al. Children with multiphasic disseminated encephalomyelitis and antibodies to the myelin oligodendrocyte glycoprotein (MOG): extending the spectrum of MOG antibody positive diseases. Mult Scler 2016; 22 (14) 1821-1829
    CrossrefPubMedGoogle Scholar
  • 17 Reindl M, Di Pauli F, Rostásy K, Berger T. The spectrum of MOG autoantibody-associated demyelinating diseases. Nat Rev Neurol 2013; 9 (08) 455-461
    CrossrefPubMedGoogle Scholar
  • 18 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 (01) 54-59
    CrossrefPubMedGoogle Scholar
  • 19 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 (02) 186-193
    CrossrefPubMedGoogle Scholar
  • 20 Fay AJ, Mowry EM, Strober J, Waubant E. Relapse severity and recovery in early pediatric multiple sclerosis. Mult Scler 2012; 18 (07) 1008-1012
    CrossrefPubMedGoogle Scholar
  • 21 O'Mahony J, Marrie RA, Laporte A. , et al. Recovery from central nervous system acute demyelination in children. Pediatrics 2015; 136 (01) e115-e123
    CrossrefPubMedGoogle Scholar
  • 22 Renoux C, Vukusic S, Confavreux C. The natural history of multiple sclerosis with childhood onset. Clin Neurol Neurosurg 2008; 110 (09) 897-904
    CrossrefPubMedGoogle Scholar
  • 23 MacAllister WS, Belman AL, Milazzo M. , et al. Cognitive functioning in children and adolescents with multiple sclerosis. Neurology 2005; 64 (08) 1422-1425
    CrossrefPubMedGoogle Scholar
  • 24 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
  • 25 Amato MP, Goretti B, Ghezzi A. , et al; MS Study Group of the Italian Neurological Society. Neuropsychological features in childhood and juvenile multiple sclerosis: five-year follow-up. Neurology 2014; 83 (16) 1432-1438
    CrossrefPubMedGoogle Scholar
  • 26 Till C, Racine N, Araujo D. , et al. Changes in cognitive performance over a 1-year period in children and adolescents with multiple sclerosis. Neuropsychology 2013; 27 (02) 210-219
    CrossrefPubMedGoogle Scholar
  • 27 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
  • 28 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 (01) 116-127
    CrossrefPubMedGoogle Scholar
  • 29 Ghezzi A, Banwell B, Boyko A. , et al. The management of multiple sclerosis in children: a European view. Mult Scler 2010; 16 (10) 1258-1267
    CrossrefPubMedGoogle Scholar
  • 30 Chitnis T, Ghezzi A, Bajer-Kornek B, Boyko A, Giovannoni G, Pohl D. Pediatric multiple sclerosis: escalation and emerging treatments. Neurology 2016; 87 (09) (Suppl. 02) S103-S109
    CrossrefPubMedGoogle Scholar
  • 31 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
  • 32 Kornek B, Aboul-Enein F, Rostasy K. , et al. Natalizumab therapy for highly active pediatric multiple sclerosis. JAMA Neurol 2013; 70 (04) 469-475
    CrossrefPubMedGoogle Scholar
  • 33 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
    PubMedGoogle Scholar
  • 34 Arnal-Garcia C, García-Montero MR, Málaga I. , et al. Natalizumab use in pediatric patients with relapsing-remitting multiple sclerosis. Eur J Paediatr Neurol 2013; 17 (01) 50-54
    CrossrefPubMedGoogle Scholar
  • 35 Waubant E, Chabas D, Okuda DT. , et al. Difference in disease burden and activity in pediatric patients on brain magnetic resonance imaging at time of multiple sclerosis onset vs adults. Arch Neurol 2009; 66 (08) 967-971
    PubMedGoogle Scholar
  • 36 Banwell BL. The long (-itudinally extensive) and the short of it: transverse myelitis in children. Neurology 2007; 68 (18) 1447-1449
    CrossrefPubMedGoogle Scholar
  • 37 Chabas D, Castillo-Trivino T, Mowry EM, Strober JB, Glenn OA, Waubant E. Vanishing MS T2-bright lesions before puberty: a distinct MRI phenotype?. Neurology 2008; 71 (14) 1090-1093
    CrossrefPubMedGoogle Scholar
  • 38 Polman CH, Reingold SC, Banwell B. , et al. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol 2011; 69 (02) 292-302
    CrossrefPubMedGoogle Scholar
  • 39 Bigi S, Marrie RA, Verhey L, Yeh EA, Banwell B. 2010 McDonald criteria in a pediatric cohort: is positivity at onset associated with a more aggressive multiple sclerosis course?. Mult Scler 2013; 19 (10) 1359-1362
    CrossrefPubMedGoogle Scholar
  • 40 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 (02) 211-223
    CrossrefPubMedGoogle Scholar
  • 41 Tantsis EM, Prelog K, Brilot F, Dale RC. Risk of multiple sclerosis after a first demyelinating syndrome in an Australian Paediatric cohort: clinical, radiological features and application of the McDonald 2010 MRI criteria. Mult Scler 2013; 19 (13) 1749-1759
    CrossrefPubMedGoogle Scholar
  • 42 Williams MT, Tapos DO, Juhász C. Use of the 2010 McDonald criteria can facilitate early diagnosis of pediatric multiple sclerosis in a predominantly black cohort. Pediatr Neurol 2014; 51 (06) 826-830
    CrossrefPubMedGoogle Scholar
  • 43 Verhey LH, Signori A, Arnold DL. , et al. Clinical and MRI activity as determinants of sample size for pediatric multiple sclerosis trials. Neurology 2013; 81 (14) 1215-1221
    CrossrefPubMedGoogle Scholar
  • 44 Verhey LH, Branson HM, Shroff MM. , et al; Canadian Pediatric Demyelinating Disease Network. MRI parameters for prediction of multiple sclerosis diagnosis in children with acute CNS demyelination: a prospective national cohort study. Lancet Neurol 2011; 10 (12) 1065-1073
    CrossrefPubMedGoogle Scholar
  • 45 Waldman AT, Stull LB, Galetta SL, Balcer LJ, Liu GT. Pediatric optic neuritis and risk of multiple sclerosis: meta-analysis of observational studies. J AAPOS 2011; 15 (05) 441-446
    CrossrefPubMedGoogle Scholar
  • 46 Heussinger N, Kontopantelis E, Gburek-Augustat J. , et al; for GRACE-MS (German-speaking Research Alliance for ChildrEn with Multiple Sclerosis). Oligoclonal bands predict multiple sclerosis in children with optic neuritis. Ann Neurol 2015; 77 (06) 1076-1082
    CrossrefPubMedGoogle Scholar
  • 47 Thomas T, Branson HM, Verhey LH. , et al. The demographic, clinical, and magnetic resonance imaging (MRI) features of transverse myelitis in children. J Child Neurol 2012; 27 (01) 11-21
    CrossrefPubMedGoogle Scholar
  • 48 Callen DJ, Shroff MM, Branson HM. , et al. Role of MRI in the differentiation of ADEM from MS in children. Neurology 2009; 72 (11) 968-973
    CrossrefPubMedGoogle Scholar
  • 49 Fernandez-Carbonell C, Vargas-Lowy D, Musallam A. , et al. Clinical and MRI phenotype of children with MOG antibodies. Mult Scler 2016; 22 (02) 174-184
    CrossrefPubMedGoogle Scholar
  • 50 Zecca C, Disanto G, Sormani MP. , et al. Relevance of asymptomatic spinal MRI lesions in patients with multiple sclerosis. Mult Scler 2016; 22 (06) 782-791
    CrossrefPubMedGoogle Scholar
  • 51 Kanda T, Matsuda M, Oba H, Toyoda K, Furui S. Gadolinium deposition after contrast-enhanced MR imaging. Radiology 2015; 277 (03) 924-925
    CrossrefPubMedGoogle Scholar
  • 52 Sormani MP, Bonzano L, Roccatagliata L, Cutter GR, Mancardi GL, Bruzzi P. Magnetic resonance imaging as a potential surrogate for relapses in multiple sclerosis: a meta-analytic approach. Ann Neurol 2009; 65 (03) 268-275
    CrossrefPubMedGoogle Scholar
  • 53 Schiffmann R, van der Knaap MS. Invited article: an MRI-based approach to the diagnosis of white matter disorders. Neurology 2009; 72 (08) 750-759
    CrossrefPubMedGoogle Scholar
  • 54 Abla O, Weitzman S, Blay JY. , et al. Primary CNS lymphoma in children and adolescents: a descriptive analysis from the International Primary CNS Lymphoma Collaborative Group (IPCG). Clin Cancer Res 2011; 17 (02) 346-352
    CrossrefPubMedGoogle Scholar
  • 55 van der Knaap MS, Naidu S, Breiter SN. , et al. Alexander disease: diagnosis with MR imaging. AJNR Am J Neuroradiol 2001; 22 (03) 541-552
    PubMedGoogle Scholar
  • 56 van der Knaap M, Valk J. Magnetic Resonance of Myelination and Myelin Disorders. 3 ed. Berlin Heidelberg: Springer-Verlag; 2005
    Google Scholar
  • 57 Parikh S, Bernard G, Leventer RJ. , et al; GLIA Consortium. A clinical approach to the diagnosis of patients with leukodystrophies and genetic leukoencephalopathies. Mol Genet Metab 2015; 114 (04) 501-515
    CrossrefPubMedGoogle Scholar
  • 58 Koné-Paut I. Behçet's disease in children, an overview. Pediatr Rheumatol Online J 2016; 14 (01) 10
    CrossrefPubMedGoogle Scholar
  • 59 Hynson JL, Kornberg AJ, Coleman LT, Shield L, Harvey AS, Kean MJ. Clinical and neuroradiologic features of acute disseminated encephalomyelitis in children. Neurology 2001; 56 (10) 1308-1312
    CrossrefPubMedGoogle Scholar
  • 60 Lekoubou A, Viaccoz A, Didelot A. , et al. Anti-N-methyl-D-aspartate receptor encephalitis with acute disseminated encephalomyelitis-like MRI features. Eur J Neurol 2012; 19 (02) e16-e17
    CrossrefPubMedGoogle Scholar
  • 61 Weisfeld-Adams JD, Katz Sand IB, Honce JM, Lublin FD. Differential diagnosis of Mendelian and mitochondrial disorders in patients with suspected multiple sclerosis. Brain 2015; 138 (Pt 3): 517-539
    CrossrefPubMedGoogle Scholar
  • 62 Tzoulis C, Engelsen BA, Telstad W. , et al. The spectrum of clinical disease caused by the A467T and W748S POLG mutations: a study of 26 cases. Brain 2006; 129 (Pt 7): 1685-1692
    CrossrefPubMedGoogle Scholar
  • 63 Hartley J, Westmacott R, Decker J, Shroff M, Yoon G. Childhood-onset CADASIL: clinical, imaging, and neurocognitive features. J Child Neurol 2010; 25 (05) 623-627
    CrossrefPubMedGoogle Scholar
  • 64 Dörr J, Krautwald S, Wildemann B. , et al. Characteristics of Susac syndrome: a review of all reported cases. Nat Rev Neurol 2013; 9 (06) 307-316
    CrossrefPubMedGoogle Scholar
  • 65 Wingerchuk DM, Banwell B, Bennett JL. , et al; International Panel for NMO Diagnosis. International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology 2015; 85 (02) 177-189
    CrossrefPubMedGoogle Scholar
  • 66 Matthews L, Enzinger C, Fazekas F. , et al; MAGNIMS Network. MRI in Leber's hereditary optic neuropathy: the relationship to multiple sclerosis. J Neurol Neurosurg Psychiatry 2015; 86 (05) 537-542
    CrossrefPubMedGoogle Scholar
  • 67 Deiva K, Mahlaoui N, Beaudonnet F. , et al. CNS involvement at the onset of primary hemophagocytic lymphohistiocytosis. Neurology 2012; 78 (15) 1150-1156
    CrossrefPubMedGoogle Scholar
  • 68 Rao R, Dimitriades VR, Weimer M, Sandlin C. Neurosarcoidosis in pediatric patients: a case report and review of isolated and systemic neurosarcoidosis. Pediatr Neurol 2016; 63: 45-52
    CrossrefPubMedGoogle Scholar
  • 69 Yeh EA, Weinstock-Guttman B, Ramanathan M. , et al. Magnetic resonance imaging characteristics of children and adults with paediatric-onset multiple sclerosis. Brain 2009; 132 (Pt 12): 3392-3400
    CrossrefPubMedGoogle Scholar
  • 70 Ghassemi R, Narayanan S, Banwell B, Sled JG, Shroff M, Arnold DL. ; Canadian Pediatric Demyelinating Disease Network. Quantitative determination of regional lesion volume and distribution in children and adults with relapsing-remitting multiple sclerosis. PLoS One 2014; 9 (02) e85741
    CrossrefPubMedGoogle Scholar
  • 71 Vishwas MS, Healy BC, Pienaar R, Gorman MP, Grant PE, Chitnis T. Diffusion tensor analysis of pediatric multiple sclerosis and clinically isolated syndromes. AJNR Am J Neuroradiol 2013; 34 (02) 417-423
    CrossrefPubMedGoogle Scholar
  • 72 Aliotta R, Cox JL, Donohue K. , et al. Tract-based spatial statistics analysis of diffusion-tensor imaging data in pediatric- and adult-onset multiple sclerosis. Hum Brain Mapp 2014; 35 (01) 53-60
    CrossrefPubMedGoogle Scholar
  • 73 Blaschek A, Keeser D, Müller S. , et al. Early white matter changes in childhood multiple sclerosis: a diffusion tensor imaging study. AJNR Am J Neuroradiol 2013; 34 (10) 2015-2020
    CrossrefPubMedGoogle Scholar
  • 74 Tillema JM, Leach J, Pirko I. Non-lesional white matter changes in pediatric multiple sclerosis and monophasic demyelinating disorders. Mult Scler 2012; 18 (12) 1754-1759
    CrossrefPubMedGoogle Scholar
  • 75 Rocca MA, Absinta M, Amato MP. , et al. Posterior brain damage and cognitive impairment in pediatric multiple sclerosis. Neurology 2014; 82 (15) 1314-1321
    CrossrefPubMedGoogle Scholar
  • 76 Absinta M, Rocca MA, Moiola L. , et al. Brain macro- and microscopic damage in patients with paediatric MS. J Neurol Neurosurg Psychiatry 2010; 81 (12) 1357-1362
    CrossrefPubMedGoogle Scholar
  • 77 Vishwas MS, Chitnis T, Pienaar R, Healy BC, Grant PE. Tract-based analysis of callosal, projection, and association pathways in pediatric patients with multiple sclerosis: a preliminary study. AJNR Am J Neuroradiol 2010; 31 (01) 121-128
    CrossrefPubMedGoogle Scholar
  • 78 Bethune A, Tipu V, Sled JG. , et al. Diffusion tensor imaging and cognitive speed in children with multiple sclerosis. J Neurol Sci 2011; 309 (1-2): 68-74
    CrossrefPubMedGoogle Scholar
  • 79 Akbar N, Giorgio A, Till C. , et al. Alterations in functional and structural connectivity in pediatric-onset multiple sclerosis. PLoS One 2016; 11 (01) e0145906
    CrossrefPubMedGoogle Scholar
  • 80 Brown RA, Narayanan S, Banwell B, Arnold DL. ; Canadian Pediatric Demyelinating Disease Network. Magnetization transfer ratio recovery in new lesions decreases during adolescence in pediatric-onset multiple sclerosis patients. Neuroimage Clin 2014; 6: 237-242
    CrossrefPubMedGoogle Scholar
  • 81 Rocca MA, Absinta M, Moiola L. , et al. Functional and structural connectivity of the motor network in pediatric and adult-onset relapsing-remitting multiple sclerosis. Radiology 2010; 254 (02) 541-550
    CrossrefPubMedGoogle Scholar
  • 82 Till C, Ghassemi R, Aubert-Broche B. , et al. MRI correlates of cognitive impairment in childhood-onset multiple sclerosis. Neuropsychology 2011; 25 (03) 319-332
    CrossrefPubMedGoogle Scholar
  • 83 Mesaros S, Rocca MA, Absinta M. , et al. Evidence of thalamic gray matter loss in pediatric multiple sclerosis. Neurology 2008; 70 (13 Pt 2): 1107-1112
    CrossrefPubMedGoogle Scholar
  • 84 Aubert-Broche B, Fonov V, Ghassemi R. , et al. Regional brain atrophy in children with multiple sclerosis. Neuroimage 2011; 58 (02) 409-415
    CrossrefPubMedGoogle Scholar
  • 85 Weier K, Fonov V, Aubert-Broche B, Arnold DL, Banwell B, Collins DL. Impaired growth of the cerebellum in pediatric-onset acquired CNS demyelinating disease. Mult Scler 2016; 22 (10) 1266-1278
    CrossrefPubMedGoogle Scholar
  • 86 Aubert-Broche B, Fonov V, Guizard N. , et al. Brain growth rate is reduced in paediatric-onset multiple sclerosis. Paper presented at: Multiple Sclerosis Journal 2012
    PubMedGoogle Scholar
  • 87 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 (03) 194-201
    CrossrefPubMedGoogle Scholar
  • 88 Evans AC. ; Brain Development Cooperative Group. The NIH MRI study of normal brain development. Neuroimage 2006; 30 (01) 184-202
    CrossrefPubMedGoogle Scholar
  • 89 Aubert-Broche B, Fonov V, Narayanan S. , et al; Canadian Pediatric Demyelinating Disease Network. Onset of multiple sclerosis before adulthood leads to failure of age-expected brain growth. Neurology 2014; 83 (23) 2140-2146
    CrossrefPubMedGoogle Scholar
  • 90 Rocca MA, Valsasina P, Absinta M. , et al. Intranetwork and internetwork functional connectivity abnormalities in pediatric multiple sclerosis. Hum Brain Mapp 2014; 35 (08) 4180-4192
    CrossrefPubMedGoogle Scholar
  • 91 Akbar N, Banwell B, Sled JG. , et al. Brain activation patterns and cognitive processing speed in patients with pediatric-onset multiple sclerosis. J Clin Exp Neuropsychol 2016; 38 (04) 393-403
    CrossrefPubMedGoogle Scholar
  • 92 Akbar N, Till C, Sled JG. , et al. Altered resting-state functional connectivity in cognitively preserved pediatric-onset MS patients and relationship to structural damage and cognitive performance. Mult Scler 2016; 22 (06) 792-800
    CrossrefPubMedGoogle Scholar
  • 93 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 (01) 102-107
    CrossrefPubMedGoogle Scholar
  • 94 Till C, Deotto A, Tipu V. , et al. White matter integrity and math performance in pediatric multiple sclerosis: a diffusion tensor imaging study. Neuroreport 2011; 22 (18) 1005-1009
    CrossrefPubMedGoogle Scholar
  • 95 Fuentes A, Collins DL, Garcia-Lorenzo D. , et al. Memory performance and normalized regional brain volumes in patients with pediatric-onset multiple sclerosis. J Int Neuropsychol Soc 2012; 18 (03) 471-480
    CrossrefPubMedGoogle Scholar
  • 96 Sormani MP, Bonzano L, Roccatagliata L, De Stefano N. Magnetic resonance imaging as surrogate for clinical endpoints in multiple sclerosis: data on novel oral drugs. Mult Scler 2011; 17 (05) 630-633
    CrossrefPubMedGoogle Scholar
  • 97 Sormani MP, Bruzzi P. MRI lesions as a surrogate for relapses in multiple sclerosis: a meta-analysis of randomised trials. Lancet Neurol 2013; 12 (07) 669-676
    CrossrefPubMedGoogle Scholar