Huntington s Disease Hypothalamic, endocrine and metabolic aspects
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1 Huntington s Disease Hypothalamic, endocrine and metabolic aspects N. Ahmad Aziz i
2 ISBN: Design & layout: N. Ahmad Aziz Cover design: Jorien M.M. van der Burg Printed by: GildePrint, Enschede 2010 N.A. Aziz Copyright of each chapter is with the publisher of the journal in which the work has appeared. No part of this book may be reproduced or distributed in any form, by print, photoprint, microfilm, digital file, or any other means without prior written permission from the copyright holder. The studies described in this thesis were partly supported by the Netherlands Organization for Scientific Research (grant number to N.A.Aziz). ii
3 Huntington s Disease Hypothalamic, endocrine and metabolic aspects Proefschrift ter verkrijging van de graad van Doctor aan de Universiteit Leiden op gezag van de Rector Magnificus prof. mr. P.F. van der Heijden volgens besluit van het College der Promoties te verdedigen op woensdag 31 maart 2010 klokke 16:15 uur door Nasir Ahmad Aziz geboren te Kandahar (Afghanistan) in 1981 iii
4 Promotiecommissie Promotores: Prof. dr. R.A.C. Roos Prof. dr. H. Pijl Overige leden: Prof. dr. H.P.H. Kremer (Rijksuniversiteit Groningen) Prof. dr. J.A. Romijn Prof. dr. D.F. Swaab (Universiteit van Amsterdam, Nederlands Instituut voor Neurowetenschappen) iv
5 .ÙëoClÛ ÖCoC éæ ÙìÛCpF ælûq D,PvD Ölµ D íêkßvc éæ ÙìVß (íwøz ) ÍDGÂC løe We are a wave, our calm is our naught, We have no rest, lest we will be not. Muhammad Iqbal ( CE) v
6 vi
7 To my father, who taught me reason and perseverance To my mother, who bestowed me with love and inspiration To Jorien, for sharing the joys and sorrows of life with me vii
8 viii
9 Contents Chapter 1 GENERAL INTRODUCTION & AIMS OF THE THESIS 1 Rev Neurosci (2007); 18: PART I SECONDARY SIGNS OF HUNTINGTON S DISEASE 43 Chapter 2 Weight loss in Huntington s disease increases with higher CAG repeat number 45 Neurology (2008); 71(19): Chapter 3 Normal and mutant HTT interact to affect clinical severity and progression in Huntington s disease 57 Neurology (2009); 73(16): Chapter 4 Sleep and circadian rhythm alterations correlate with depression and cognitive impairment in Huntington s disease 73 Parkinsonism Rel Disorders (in press) Chapter 5 Autonomic symptoms in patients and premanifest mutation carriers of Huntington s disease 87 Eur J Neurol (in press) PART II HYPOTHALAMIC PATHOLOGY IN HUNTINGTON S DISEASE 99 Chapter 6 Hypocretin and melanin-concentrating hormone in patients with Huntington s disease 101 Brain Pathol (2008); 18(4): PART III ENDOCRINE STUDIES IN HUNTINGTON S DISEASE 119 Chapter 7 Increased hypothalamic-pituitary-adrenal axis activity in Huntington s disease 121 J Clinical Endocrinol Metab (2009); 94(4): Chapter 8 Growth hormone and ghrelin secretion are associated with clinical severity in Huntington s disease 135 ix
10 Eur J Neurol (in press) Chapter 9 Altered thyrotropic and lactotropic axes regulation in Huntington s disease 149 Clinical Endocrinol (Oxf.) (in revision) Chapter 10 Leptin secretion rate increases with higher CAG repeat number in Huntington s disease patients 161 Clinical Endocrinol (Oxf.) (in press) Chapter 11 Delayed onset of the diurnal melatonin rise in patients with Huntington s disease 173 J Neurol (2009) 256: PART IV METABOLIC STUDIES IN HUNTINGTON S DISEASE 183 Chapter 12 Systemic energy homeostasis in Huntington s disease patients 185 J Neurol Neurosurg Psychiatry (in press) Chapter 13 SYNOPSIS, CONCLUSIONS & FUTURE PERSPECTIVES 197 APPENDICES 205 A Summary and conclusions in Dutch 207 B Excerpt in Persian 215 C Acknowledgments 217 D Curriculum vitae 219 E List of publications 221 x
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