Childhood onset MS and MS during Pregnancy

Transcription

1 Childhood onset MS and MS during Pregnancy Rinze Frederik Neuteboom

2 -The studies in this thesis were financially supported by Stichting MS Research -Financial support for publication: Erasmus University Rotterdam, Stichting MS Research -Cover: spaceman by Lennart Nilsson, used with permission. ISBN: Layout: Print: Simone Vinke, Ridderprint B.V., Ridderkerk, The Netherlands Ridderprint B.V., Ridderkerk, The Netherlands

3 Childhood onset MS and MS during Pregnancy Debuut van MS op de kinderleeftijd en MS tijdens zwangerschap PROEFSCHRIFT ter verkrijging van de graad van doctor aan de Erasmus Universiteit Rotterdam op gezag van de rector magnificus Prof.dr. H.G. Schmidt en volgens besluit van het College voor Promoties. De openbare verdediging zal plaatsvinden op donderdag 12 april 2012 om 11:30 uur door Rinze Frederik Neuteboom Geboren te Apeldoorn

4 Promotiecommissie Promotoren: Overige leden: Copromotor: Prof.dr. R.Q. Hintzen Prof.dr. J.D. Laman Prof.dr. P.A. Van Doorn Prof.dr. W.F.M. Arts Prof.dr. C.J.M. De Groot Dr. C.E. Catsman-Berrevoets

5 Table of contents Chapter 1 General introduction 7 Chapter 2 Pregnancy and multiple sclerosis 31 Chapter 2.1 Pregnancy in multiple sclerosis: clinical and self-report scales. 33 J Neurol. 2012;259: Chapter 2.2 Breast-feeding, postpartum and prepregnancy disease activity 47 in multiple sclerosis. Neurology 2011;76:1532 Chapter 2.3 First trimester interleukin 8 levels are associated with postpartum 51 relapse in multiple sclerosis. Mult Scler. 2009;15: Chapter 2.4 The monocyte transcriptome during pregnancy in multiple sclerosis: 57 prominent expression of the Fc-receptor CD64. Mult Scler. 2011;17: Chapter 2.5 Pregnancy-induced fluctuations in functional T-cell subsets in 69 multiple sclerosis patients. Mult Scler. 2010;16: Chapter 2.6 Serum leptin levels during pregnancy in multiple sclerosis. 79 Mult Scler. 2009;15: Chapter 3 Childhood onset in multiple sclerosis 91 Chapter 3.1 Prognostic factors after a first attack of inflammatory CNS 93 demyelination in children. Neurology 2008;71: Chapter 3.2 Barkhof MRI criteria predict early relapse in pediatric multiple 105 sclerosis. Pediatr Neurol. 2010;42:53-55 Chapter 3.3 A comparison of MRI criteria for diagnosing paediatric ADEM and MS. 113 Neurology 2010;74: Chapter 4 General discussion and future perspectives 121 Summary 141 Samenvatting 145 List of abbreviations 149 Dankwoord 153 Curriculum vitae 157 List of publications 159 Portfolio 163

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7 Chapter 1 General introduction

8 Chapter 1 Special situations in MS Multiple sclerosis (MS) is a chronic, incurable disease. Currently, treatments offered to patients with MS do not substantially prevent progressive disability. The Holy Grail in MS research is to develop a definitive cure for MS or at least a method for halting disease progression. Greater knowledge about the etiology and pathogenesis is required to be able to move forward towards a better treatment. Central to this thesis is the concept that through study of natural disease course and natural modifiers, crucial lessons can be learned about etiology, pathogenesis, prognosis and perhaps ultimately new treatment options in MS. This thesis will focus on two special and different situations in MS: pregnancy and MS, and childhood onset of MS. Pregnancy strongly influences disease course in MS. The number of relapses in MS is decreased during pregnancy. However, during the first three months after delivery the number of relapses increases. Alterations in the immune system during pregnancy, essential for a successful pregnancy, likely cause this disease amelioration. Studying clinical features and immune functions during and after pregnancy in MS can provide insight into the pathogenesis of MS in general. It can also prove to be of clinical benefit to women with MS that are pregnant or have a childwish, in supplying both patients and doctors with more detailed information about disease course around pregnancy. Furthermore it may reveal possible biomarkers for predicting postpartum relapse. In a small minority of patients clinical debut of MS occurs in childhood. Diagnosis of MS in children can be difficult, because of the many diseases that can mimic MS in childhood. More information about natural disease course could therefore help to improve diagnosis and management of MS in these children. Furthermore, MS in children allows better study of potential risk factors involved in pathogenesis, that are present early in life, than is possible in patients with an adult onset. The subsequent parts of this introduction will discuss respectively in more detail: the general aspects of MS, pregnancy in MS, and childhood onset of MS. This chapter will conclude with the scope and outline of this thesis. 8

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10 Summary Samenvatting L D list of abbreviations dankwoord Curriculum vitae L list of publications Portfolio

11 Portfolio PhD Portfolio: Summary of PhD training and teaching 1. PhD training Year Workload (ECTS) General and specific courses Biemond courses 2002, 2003, 2004, 2005, 2006, 2007, 2008, 2009, 2010, 2011 ESNI neuro-immunology course Seminars and workshops Voorjaarsvergadering NVKN 2007,2008,2009,2010,2011 Presentations MS research dagen (2 oral presentations) ECTRIMS (oral presentation) Voorjaarsvergadering NVKN (oral presentation) Wetenschappelijke vergadering NVN (oral presentation) EPNS (oral presentation) ACTRIMS/ECTRIMS/LACTRIMS ( 2 poster presentations) MS research dagen (oral presentation) ECTRIMS (poster presentation) MS research dagen (oral presentation) ECTRIMS (poster presentation) (Inter)national conferences MS research dagen 2002, 2003, 2004, 2005, 2006, 2008, 2011 ECTRIMS 2006, 2009, 2011 EPNS ACTRIMS/ECTRIMS/LACTRIMS ISPNO 2. Teaching Nascholing regionale neurologen Zuid-West Nederland Najaarsvergadering NVKN Pediatric Neurology Training for residents in pediatrics Training neuro-pediatric nurses 2010, 2011 MOLMED training 2005, 2008, Total

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