000_Valk_Titelei 18.04.2005 10:09 Uhr Seite I

M.S. van der Knaap, J.Valk Magnetic Resonance of Myelination and Myelin Disorders Third Edition 000_Valk_Titelei 18.04.2005 10:09 Uhr Seite III

Marjo S. van der Knaap Jaap Valk

Magnetic Resonance of Myelination and Myelin Disorders

Third Edition

With 647 Figures in 3873 parts

With contributions by: F. Barkhof R. van den Berg V.Gieselmann J.M.C. van Dijk G.J. Lycklama à Nijeholt R.J.Vermeulen E. Morava R.J.A. Wanders P.J.W.Pouwels R.A. Wevers J.A.M. Smeitink

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Marjo S. van der Knaap, MD, PhD Department of Child Neurology VU University Medical Center De Boelelaan 1117 1081 HV Amsterdam The Netherlands

Jaap Valk, MD, PhD Department of Radiology VU University Medical Center De Boelelaan 1117 1081 HV Amsterdam The Netherlands

Third Edition ISBN-10 3-540-22286-3 Springer Berlin Heidelberg New York ISBN-13 978-3-540-22286-6 Springer Berlin Heidelberg New York Second Edition ISBN 3-540-59277-6 Springer Berlin Heidelberg New York

Library of Congress Control Number: 2004117334

This work is subject to copyright. All rights are reserved, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilm or in any other way, and storage in data banks. Duplication of this publication or parts thereof is permitted only under the provision of the German Copyright Law of September 9, 1965, in its current version, and permission for use must always be obtained from Springer-Verlag. Violations are liable to prosecution under the German Copyright Law. Springer is a part of Springer Science+Business Media springeronline.com © Springer-Verlag Berlin Heidelberg, 1989, 1995, 2005 Printed in Germany The use of designations, trademarks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. Product liability: The publisher can not guarantee the accuracy of any information about dosage and application contained in this book. In every individual case the user must check such information by consulting the relevant literature. Editor: Dr. Ute Heilmann, Heidelberg, Germany Desk editor: Dörthe Mennecke-Bühler, Heidelberg, Germany Production: PRO EDIT GmbH, Heidelberg, Germany Cover-Design: Frido Steinen-Broo, Pau, Spain Typesetting and Reproduction: AM-productions GmbH, Wiesloch, Germany Printing and Binding: Stürtz GmbH, Würzburg, Germany Printed on acid-free paper 21/3151Di - 5 4 3 2 1 0 000_Valk_Titelei 18.04.2005 10:09 Uhr Seite V

Preface

Preface to the Third Edition Our thanks go to our colleagues at the VU Univer- sity Medical Center and to those in other hospitals Reading through the prefaces of the two previous edi- who referred their patients to us. We are indebted to tions,we can say that much of what was said there still all colleagues who allowed us to use their MR images, holds. At the same time, however, much has changed. published or unpublished,making it possible for us to There has been immense progress in the technical present illustrations of nearly all known white matter possibilities of magnetic resonance and in the know- disorders. Two colleagues were particularly helpful ledge of genetic defects, biochemical abnormalities, and provided us with essential and unpublished fig- and cellular processes underlying myelin disorders. ures: our friends Susan Blaser, from the Hospital for This immense progress has prompted us to embark Sick Children in Toronto, and Zoltán Patay, from the upon the enormous task of rewriting the previous King Faisal Hospital in Riyadh. edition and adding 40 chapters. In doing so we have Many people at the VU University Medical Center tried to cover most white matter disorders,hereditary have been of great technical help to us in producing and acquired, and to present a collection of images to high quality images and in providing secretarial illustrate the field to the fullest possible extent. This assistance. The contributions of these people are edition will therefore be more complete than the pre- mentioned separately in the acknowledgements. vious ones. The number of illustrations has increased Our special thanks go to patients with white mat- considerably. This was necessary to reflect not only ter disorders and their families. They came to see us the typical patterns of a disease, but to show also the and were willing to work with us and to go through variability that exists in some disorders. The best ex- the procedure of diagnostic testing, including MR ample of this is found in Alexander disease. Genetic examinations. Many patients and families were also verification now makes it possible to recognize very willing to participate in our research projects to different patterns of imaging abnormalities, all relat- advance the understanding of white matter disorders. ed to a defect in the same gene. Today’s increased in- Patients with white matter disorders are the focus of sight into disease classification based on increased our work.They are our most important collaborators. knowledge of related genes and proteins is best re- Often they are children. To show our gratitude to flected in the chapter on congenital muscular dystro- them,we have decided that all profits of this book will phies. go to the Foundation for Children with White Matter This is the first time that we have invited a number Disorders. of experts in special fields to write or co-write a chap- ter, in order to assure the highest level of scientific Amsterdam, May 2005 accuracy. To assemble the knowledge presented in this work we have also harvested the literature, prof- M.S. van der Knaap iting from the work and discoveries of many others. J. Valk 000_Valk_Titelei 18.04.2005 10:09 Uhr Seite VI

VI Preface

Preface to the Second Edition been derived both from MRI and from MR spec- troscopy (MRS). This prompted us to review the clin- The first edition of this book was well received by ical,laboratory,biochemical,and pathological data on readers and reviewers and we are very grateful for the this subject in order to integrate all available informa- positive reactions. We were convinced then, and even tion and to provide improved insights into normal more now, that MRI and MRS have much to offer in and disordered myelin and myelination.We will show diagnosis, therapy monitoring and research of hered- how the synthesis of all available information con- itary and acquired myelin disorders. tributes to the interpretation of MR images. In the last few years,a great deal of new information Following a brief historical review of the increas- has become available concerning the genetic basis of ing knowledge on myelin and myelin disorders, we inborn errors of metabolism and neurodegenerative propose a new classification of myelin disorders disorders, the role of subcellular structures, the en- based on the subcellular localization of the enzymat- zyme biochemistry, the pathophysiological mecha- ic defects as far as the inborn errors of metabolism nisms of posthypoxic-ischemic cerebral damage, and are concerned. This classification serves as a guide the inflammatory processes in infectious and inflam- throughout the book. All items of the classification matory disorders. MR images of many rare disorders will be discussed and, whenever relevant and possi- have become available, either in our own experience ble, illustrated by MR images. or published by other groups. MR spectroscopy could We are aware of the fact that in a number of myelin confirm its role in certain clinical applications. Be- disorders MRI is not a part of the usual diagnostic cause of these developments,it was necessary for us to work up because a definite diagnosis is reached by rewrite the book almost completely. In some fields other means, such as biochemical investigations of developments are so fast that we have not have caught blood and urine, enzyme assessment or detection of all the latest developments. The pattern of the new specific antibodies. However, in many disorders MRI approaches has, however, been established, making may facilitate a rapid diagnosis and early instigation the assimilation of newly available information easy. of treatment, thus preventing structural cerebral We are extremely grateful for the help of colleagues damage. In other cases the role of MRI is to visualize to make this book as complete as possible. The posi- the extent of damage and give an indication of tive reactions of those from whom we requested MR the prognosis. In disorders which present in a non- pictures or other forms of support were of enormous specific way,for instance with behavioral problems or encouragement to us during our efforts to complete learning difficulties, MRI can be one of the first-line this project. investigations. It is important to be acquainted with We hope this work will be as warmly welcomed by the various MRI patterns of the myelin disorders, as our colleagues as the first edition. an early diagnosis may be of major importance in young families with a view to the provision of ade- Amsterdam, January 1995 quate genetic counseling. MRS has been of limited clinical importance until M.S. van der Knaap now, and its application in patients only has a short J. Valk history. We do, however, expect it to be a promising technique in the field of myelin and myelin disorders in clinical as well as in basic, experimental research Preface to the First Edition and have, therefore, devoted a separate chapter to this subject. Magnetic resonance imaging (MRI) is now consid- This volume was written by a neuroradiologist and ered to be the imaging modality of choice for the ma- a neurologist/child neurologist. It is the product of jority of disorders affecting the central nervous sys- close cooperation,animated discussions,strong argu- tem. This is particularly true for gray and white mat- ments, restructuring, rewriting, and editing, in which ter disorders,thanks to the superb soft tissue contrast they had an equal share. If the reader finds value in in MRI which allows gray matter, unmyelinated, and this monograph, it is because of this dual effort. myelinated white matter to be distinguished and their respective disorders identified. The present book is Amsterdam and Utrecht, March 1989 devoted to the disorders of myelin and myelination. A growing amount of detailed in vivo information J. Valk about myelin, myelination, and myelin disorders has M.S. van der Knaap 000_Valk_Titelei 18.04.2005 10:09 Uhr Seite VII

Acknowledgements

The preparation of this book was a project of several Annuska Houtappels, who digitized older films and years and could not have been concluded successfully helped us improve the quality of the images. without the support and collaboration of many peo- Excellent secretarial help was provided by Sigrid ple. Thanks to all. Bruinsma, who single-handedly took care of the ref- Special thanks go to our colleagues: Jeroen Ver- erence section. Staff members of the VUMC Library meulen and Leo Smit, pediatric neurologists, and Els van Deventer,Linda Glas,Margreet Bosshardt,and Frederik Barkhof and Jonas Castelijns, neuroradiolo- Cisca Frederiks were very helpful in providing us gists, at the VU University Medical Center (VUMC) with the necessary literature. in Amsterdam; Martin Heitbrink and Bart Wiarda, Technical support and guidance with computer radiologists at the Medical Center Alkmaar; and Erik programs and settings were provided by the Depart- Veldhuizen, radiologist at the MRI center, Amster- ment of Informatics of the VUMC.We are grateful for dam, for their continuous support during this en- their kind and prompt assistance.Special thanks go to deavor. We are grateful to the MRI technicians at the Michiel Sprenger, Guido Zonneveld, and Peter Theijs- VUMC, who guaranteed the quality of the MR exam- meijer. inations and had the patience and empathy to deal We acknowledge the continuous friendly and with very sick children and their parents. We want to encouraging support of the editorial staff of Springer- mention especially the help of Karin Barbiers and Er- Verlag, Dr. Ute Heilmann and Mrs Dörthe Mennecke- win Kist,who headed this team and carried out the re- Bühler. trieval of older examinations to the Image Manage- ment System. Amsterdam, May 2005 We received great support from the audiovisual center at the VUMC. We are especially indebted M.S. van der Knaap to Daan van Eijndhoven, Rene den Engelsman, and J. Valk 000_Valk_Titelei 18.04.2005 10:09 Uhr Seite IX

Contents

1 Myelin and White Matter ...... 1 33 Trichothiodystrophy 2 Classification of Myelin Disorders . . . . 20 with Photosensitivity ...... 268 3 Selective Vulnerability ...... 25 34 Pelizaeus–Merzbacher Disease 4 Myelination and Retarded Myelination 37 and X-linked Spastic Paraplegia Type 2 ...... 272 5 Lysosomes and Lysosomal Disorders . . 66 35 18q– Syndrome ...... 281 6 Metachromatic Leukodystrophy. . . . . 74 36 ...... 284 7 Multiple Sulfatase Deficiency ...... 82 37 Glutaric Aciduria Type 1...... 294 8 Globoid Cell Leukodystrophy (Krabbe Disease) ...... 87 38 ...... 300 39 Nonketotic Hyperglycinemia ...... 306 9GM1 Gangliosidosis ...... 96 40 Maple Syrup Urine Disease ...... 311 10 GM2 Gangliosidosis ...... 103 11 Fabry Disease ...... 112 41 3-Hydroxy 3-Methylglutaryl-CoA Lyase Deficiency ...... 321 12 Fucosidosis ...... 119 42 Canavan Disease ...... 326 13 Mucopolysaccharidoses ...... 123 43 L-2-Hydroxyglutaric Aciduria ...... 334 14 Free Sialic Acid Storage Disorder . . . . 133 44 D-2-Hydroxyglutaric Aciduria ...... 338 15 Neuronal Ceroid Lipofuscinoses . . . . 137 45 Hyperhomocysteinemias ...... 342 16 Adult Polyglucosan Body Disease . . . . 147 46 Defects ...... 360 17 Peroxisomes and Peroxisomal Disorders ...... 151 47 Serine Synthesis Defect Caused by 3-Phosphoglycerate 18 Peroxisome Biogenesis Defects . . . . . 154 Dehydrogenase Deficiency ...... 369 19 Peroxisomal D-Bifunctional 48 Molybdenum Cofactor Protein Deficiency ...... 167 Deficiency and Isolated Sulfite 20 Peroxisomal Acyl-CoA Oxidase Deficiency...... 372 Oxidase Deficiency...... 172 49 Galactosemia ...... 377 21 X-linked Adrenoleukodystrophy . . . . 176 50 Sjögren–Larsson Syndrome ...... 383 22 Refsum Disease...... 191 51 Lowe Syndrome ...... 387 23 Mitochondria 52 Wilson Disease ...... 392 and Mitochondrial Disorders...... 195 53 Menkes Disease ...... 400 24 Mitochondrial Encephalopathy with Lactic Acidosis 54 Fragile X Premutation ...... 406 and Stroke-like Episodes ...... 204 55 Hypomelanosis of Ito ...... 409 25 Leber Hereditary Optic Neuropathy . . 212 56 Incontinentia Pigmenti ...... 412 26 Kearns–Sayre Syndrome ...... 215 57 Alexander Disease ...... 416 27 Mitochondrial Neurogastrointestinal 58 Giant Axonal Neuropathy...... 436 Encephalomyopathy...... 221 59 Megalencephalic Leukoencephalo- 28 Leigh Syndrome and Mitochondrial pathy with Subcortical Cysts ...... 442 Leukoencephalopathies ...... 224 60 Congenital Muscular Dystrophies . . . . 451 29 Pyruvate Carboxylase Deficiency . . . . 245 61 Myotonic Dystrophy Type I ...... 469 30 Multiple Carboxylase Deficiency . . . . 248 62 Myotonic Dystrophy Type 2 ...... 473 31 Cerebrotendinous Xanthomatosis . . . 252 63 X-linked Charcot–Marie–Tooth 32 Cockayne Syndrome ...... 259 Disease ...... 476 000_Valk_Titelei 18.04.2005 10:09 Uhr Seite X

X Contents

64 Oculodentodigital Dysplasia ...... 479 86 Whipple Disease ...... 658 65 Leukoencephalopathy 87 Toxic Encephalopathies ...... 664 with Vanishing White Matter ...... 481 88 Iatrogenic Toxic Encephalopathies . . . 679 66 Aicardi–Goutières Syndrome ...... 496 89 Central Pontine and Extrapontine 67 Leukoencephalopathy Myelinolysis ...... 684 with Calcifications and Cysts ...... 505 90 Hypernatremia ...... 690 68 Leukoencephalopathy with Brain Stem 91 Marchiafava–Bignami Syndrome . . . . 695 and Spinal Cord Involvement 92 Posterior Reversible and Elevated White Matter Lactate . . . 510 Encephalopathy Syndrome ...... 699 69 Hypomyelination with Atrophy 93 Langerhans Cell Histiocytosis ...... 709 of the and Cerebellum . . 519 94 Post-Hypoxic–Ischemic Damage . . . . 714 70 Hereditary Diffuse Leukoencephalo- 95 Post-Hypoxic–Ischemic pathy with Neuroaxonal Spheroids . . . 526 Leukoencephalopathy of Neonates . . . 718 71 Dentatorubropallidoluysian Atrophy . 530 96 Neonatal Hypoglycemia ...... 749 72 Cerebral Amyloid Angiopathy ...... 535 97 Delayed Posthypoxic 73 Cerebral Autosomal Dominant Leukoencephalopathy ...... 755 Arteriopathy with Subcortical Infarcts 98 White Matter Lesions of the Elderly . . . 759 and Leukoencephalopathy ...... 541 99 Subcortical Arteriosclerotic 74 Cerebral Autosomal Recessive Encephalopathy ...... 767 Arteriopathy with Subcortical Infarcts and Leukoencephalopathy ...... 549 100 Vasculitis ...... 773 75 Polycystic Lipomembranous 101 Leukoencephalopathy Osteodysplasia with Sclerosing and Dural Venous Fistula ...... 801 Leukoencephalopathy 102 Leukoencephalopathy after Chemo- (Nasu-Hakola Disease)...... 552 therapy and/or Radiotherapy ...... 808 76 Pigmentary Orthochromatic 103 Gliomatosis Cerebri ...... 818 Leukodystrophy ...... 557 104 Diffuse Axonal Injury ...... 823 77 Adult-Onset Autosomal Dominant 105 Wallerian Degeneration Leukoencephalopathies ...... 559 and Myelin Loss Secondary 78 Inflammatory to Neuronal and Axonal and Infectious Disorders ...... 561 Degeneration ...... 832 79 Multiple Sclerosis ...... 566 106 Diffusion-Weighted Imaging ...... 839 80 Acute Disseminated Encephalomyelitis 107 Magnetization Transfer Imaging . . . . 854 and Acute Hemorrhagic 108 Magnetic Resonance Spectroscopy: Encephalomyelitis ...... 604 Basic Principles, and Application 81 Acquired Immunodeficiency in White Matter Disorders...... 859 Syndrome ...... 616 109 Pattern Recognition 82 Progressive Multifocal in White Matter Disorders...... 881 Leukoencephalopathy ...... 628 References ...... 905 83 Brucellosis ...... 635 84 Subacute Sclerosing Panencephalitis . 640 Subject Index ...... 1075 85 Congenital and Perinatal Cytomegalovirus Infection ...... 645 000_Valk_Titelei 18.04.2005 10:09 Uhr Seite XI

Contributors

F. Barkhof, MD PhD R. van den Berg, MD PhD Department of Radiology Department of Radiology and MR Center for MS Research VU University Medical Center, Amsterdam VU University Medical Center and Department of Radiology Amsterdam, The Netherlands Leiden University Medical Center Leiden, The Netherlands V. Geiselmann, PhD Institut fur Physiologische Chemie M.S. van der Knaap, MD PhD Rheinische Friedrich-Wilhelms-Universität Department of Child Neurology Bonn, Germany VU University Medical Center Amsterdam, The Netherlands G.J. Lycklama à Nijeholt, MD PhD Department of Radiology J.M.C. van Dijk, MD PhD VU University Medical Center Department of Neurosurgery Amsterdam, The Netherlands Leiden University Medical Center Leiden, The Netherlands E. Morava, MD Nijmegen Center for Mitochondrial Disorders R.J. Vermeulen, MD PhD and Department of Pediatrics Department of Child Neurology University Medical Center Nijmegen VU University Medical Center Nijmegen, The Netherlands Amsterdam, The Netherlands

P.J.W. Pouwels, PhD R.J.A. Wanders, PhD Department of Clinical Physics and Informatics Department of Clinical Chemistry VU University Medical Center and Department of Pediatrics Amsterdam, The Netherlands Academic Medical Center Amsterdam, The Netherlands J.A.M. Smeitink, MD PhD Nijmegen Center for Mitochondrial Disorders R.A. Wevers, PhD and Department of Pediatrics Laboratory of Pediatrics and Neurology University Medical Center Nijmegen University Medical Center Nijmegen St Radboud Nijmegen, The Netherlands Nijmegen, The Netherlands

J. Valk, MD PhD Department of Radiology VU University Medical Center Amsterdam, The Netherlands 000_Valk_Titelei 18.04.2005 10:09 Uhr Seite XIII

List of Abbreviations

ACE angiotensin converting enzyme CAMFAK cataracts–microcephaly–failure ACTH adrenocorticotropic hormone to thrive–kyphoscoliosis (syndrome) AD Alexander disease CD Canavan disease; cluster determinant ADC apparent diffusion coefficient Cho choline ADEM acute disseminated encephalomyelitis CIPO chronic intestinal pseudo-obstruction ADP adenosine diphosphate CIS clinically isolated symptom AD PEO autosomal dominant progressive CK kinase external ophthalmoplegia CMD congenital muscular dystrophy AHEM acute hemorrhagic encephalomyelitis CMT Charcot–Marie–Tooth disease AIDS acquired immunodeficiency syndrome CMTX X-linked form of CMT ALD adrenoleukodystrophy CMV cytomegalovirus ALDP ALD protein CNP 2’3’-cyclic nucleotide ALL acute lymphocytic leukemia 3’-phosphodiesterase AMN adrenomyeloneuropathy CNS central nervous system ANCAs anti-neutrophil cytoplasm antibodies COFS cerebro-oculofacioskeletal (syndrome) ANCL adult neuronal ceroid lipofuscinosis COX cytochrome-c oxidase (or Kufs disease) CPEO chronic progressive external

AP4 2-amino-4-phosphonobutyrate ophthalmoplegia APLA anti-phospholipid antibodies CPM central pontine myelinolysis APBD adult polyglucosan body disease CPSD carbamyl phosphate synthetase apoE apolipoprotein E deficiency APP amyloid precursor protein CPT palmitoyl transferase aPTT activated partial thromboplastin time Cr creatine ASLD argininosuccinate lyase deficiency CREST calcinosis, Raynaud syndrome, ASSD argininosuccinate synthetase deficiency esophageal problems, sclerodactylia, ATP adenosine triphosphate and telangiectasia (syndrome) BAEP brain stem auditory evoked potential CS Cockayne syndrome; concentric BCNU bis-chloroethyl-nitrosourea sclerosis (or Baló disease) BDNF brain-derived neurotrophic factor CSF cerebrospinal fluid bFGF basic fibroblast growth factor CSI chemical shift imaging BIDS brittle hair, impaired intelligence, CT computed tomography/tomogram decreased fertility, short stature CTX cerebrotendinous xanthomatosis (syndrome) DAB diaminobenzidine BMAA β-N-methylamino-L-alanine DAGC dystrophin-associated BOMAA β-N-oxalylmethylamino-L-alanine glycoprotein complex BPD D-bifunctional protein deficiency DAI diffuse axonal injury CAA cerebral amyloid angiopathy DAVF cranial dural arteriovenous fistula CACH childhood ataxia with central nervous DHAPAT dihydroxyacetonephosphate system hypomyelination acyltransferase CACT mitochondrial carnitine/acylcarnitine DM 1 myotonic dystrophy type 1 transporter DM 2 myotonic dystrophy type 2 CADASIL cerebral autosomal dominant DNA deoxyribonucleic acid arteriopathy with subcortical infarcts DNC deoxynucleotide carrier and leukoencephalopathy dNTP deoxyribonucleoside triphosphate cANCA cytoplasmic form of ANCA DOA dominant optic atrophy CARASIL cerebral autosomal recessive DOPA dihydroxyphenylalanine arteriopathy with subcortical infarcts DPHL delayed posthypoxic and leukoencephalopathy leukoencephalopathy DRPLA dentatorubropallidoluysian atrophy 000_Valk_Titelei 18.04.2005 10:09 Uhr Seite XIV

XIV List of Abbreviations

DS diffuse sclerosis (or Schilder disease) HCHWA-D Dutch type of hereditary cerebral DSA digital subtraction angiography hemorrhage with amyloidosis DTI diffusion tensor imaging HDL high-density lipoproteins DWI diffusion-weighted imaging HDLS hereditary diffuse leukoencephalopathy EAA excitatory with spheroids EAE experimental allergic encephalomyelitis 5HIAA 5-hydroxyindoleacetic acid ECD ethyl cysteinate dimer HIV-1 human immunodeficiency virus type 1 ECG electrocardiography/electrocardiogram HLA human leukocyte antigen EDSS Expanded Disability Status Scale HMG-CoA 3-hydroxy-3-methylglutaryl- EEG electroencephalogram coenzyme A EGF epidermal growth factor HMI hypomelanosis of Ito eIF eukaryotic initiation factor HMPAO hexamethylpropyleneamine oxime ELISA enzyme-linked immunosorbent assay HSP hereditary spastic paraplegia; heat EMG electromyogram shock protein EPI echo planar imaging HTLV human T-cell lymphotropic virus EPM extrapontine myelinolysis HUS hemolytic–uremic syndrome EPMR progressive epilepsy HVA homovanillic acid with mental retardation IBIDS ichthyosis, brittle hair, impaired ERG electroretinography/electroretinogram intelligence, decreased fertility, FA fractional anisotropy short stature (syndrome) FAD flavin adenine dinucleotide IFN interferon FADH2 flavin adenine dinucleotide, reduced Ig immunoglobulin FCMD Fukuyama congenital muscular IGF insulin-like growth factor dystrophy INCL infantile neuronal ceroid lipofuscinosis FD Fabry disease (or Santavuori disease) FISH fluorescent in situ hybridization IP incontinentia pigmenti FLAIR fluid-attenuated inversion recovery IQ intelligence quotient FSE fast spin echo IR inversion recovery FSH follicle-stimulating hormone IRD infantile Refsum disease 5-FU 5-fluorouracil ISIS image-selective in vivo spectroscopy FvLINCL Finnish variant of late-infantile ISSD severe infantile sialic acid neuronal ceroid lipofuscinosis storage disease GA gestational age IVL intravascular lymphomatosis GABA γ-aminobutyric acid JNCL juvenile neuronal ceroid lipofuscinosis GAMT guanidinoacetate methyltransferase (or Spielmeyer–Vogt disease, or Batten GAN giant axonal neuropathy disease) GDP guanosine diphosphate KA kainate GE gradient echo kDa kiloDalton GEF guanine-nucleotide exchange factor KSS Kearns–Sayre syndrome GFAP glial fibrillary acidic protein LAMP lysosome-associated membrane protein GIP general insertion protein LBSL leukoencephalopathy with brain stem GLD globoid cell leukodystrophy and spinal cord involvement and elevat- Glx , glutamate, GABA ed white matter lactate GOM granular osmiophilic material LCC leukoencephalopathy with calcifications GRACILE growth retardation, , and cysts cholestasis, iron overload, lactic LCH Langerhans cell histiocytosis acidosis, and early death (syndrome) LDL low-density lipoproteins GROD granular osmiophilic deposits LGMD limb girdle muscular dystrophy GTE glyceryl trierucate LH luteinizing hormone GTO glyceryl trioleate LHON Leber hereditary optic neuropathy GTP guanosine triphosphate LINCL late-infantile neuronal ceroid GVHD graft-versus-host disease lipofuscinosis (or Jansky– HAART highly active/aggressive Bielschowsky disease) anti-retroviral treatment MAG myelin-associated glycoprotein HABC hypomyelination with atrophy MAP microtubule-associated protein of the basal ganglia and cerebellum MBS Marchiafava–Bignami syndrome MBP myelin basic protein 000_Valk_Titelei 18.04.2005 10:09 Uhr Seite XV

List of Abbreviations XV

MCE multicystic encephalopathy NCL neuronal ceroid lipofuscinosis MD Menkes disease; myotonic dystrophy nDNA nuclear DNA MDC1A merosin-deficient congenital NKH nonketotic hyperglycinemia muscular dystrophy NMDA N-methyl-D-aspartate MEB muscle–eye–brain disease NMO neuromyelitis optica (or Devic disease) MELAS mitochondrial encephalomyopathy, NRTI nucleoside analogue reverse lactic acidosis, and stroke-like episodes transcriptase inhibitor MEPOP mitochondrial encephalomyopathy NT neurotrophin with sensorimotor polyneuropathy, OCRL oculocerebrorenal syndrome of Lowe ophthalmoplegia, and pseudo- ODDD oculodentodigital dysplasia obstruction OGIMD oculogastrointestinal muscular MERRF myoclonic epilepsy dystrophy with ragged red fibers OHS occipital horn syndrome MHC major histocompatibility complex OMgp oligodendrocyte myelin glycoprotein MHPG 3-methoxy-4-hydroxyphenylglycol ONMR onychotrichodysplasia, neutropenia, MICS microcephaly–intracranial mental retardation (syndrome) calcifications syndrome OSP oligodendrocyte-specific protein MIL multifocal inflammatory OTCD ornithine transcarbamylase deficiency leukoencephalopathy PACNS primary angiitis of the CNS mIns myo-inositol PAF platelet activating factor MLC megalencephalic leukoencephalopathy PAN polyarteritis nodosa with subcortical cysts pANCA perinuclear form of ANCA MLD metachromatic leukodystrophy PAS periodic acid–Schiff MNGIE mitochondrial neurogastrointestinal PCD pyruvate carboxylase deficiency encephalomyopathy PCr phosphocreatine MOBP myelin-associated oligodendrocytic PCR polymerase chain reaction basic protein PDE phosphodiesters MOG myelin oligodendrocyte glycoprotein PDGF platelet-derived growth factor MOM mitochondrial outer membrane PDHc pyruvate dehydrogenase complex MOSP myelin-/oligodendrocyte-specific PEP processing enhancing protein protein PET positron emission tomography MPP mitochondrial processing peptidase Pi inorganic phosphate MPS mucopolysaccharidoses; mucopoly- PIBIDS photosensitivity, ichthyosis, brittle hair, saccharidoses impaired intelligence, decreased MPTP methylphenyltetrahydropyridine fertility, short stature (syndrome) MR magnetic resonance PIP2 phosphatidylinositol 4,5-biphosphate MRA magnetic resonance angiography PKU phenylketonuria MRI magnetic resonance imaging PLOSL polycystic lipomembranous osteo- mRNA messenger RNA dysplasia with sclerosing leuko- MRS magnetic resonance spectroscopy encephalopathy MS multiple sclerosis PLP proteolipid protein MSD multiple sulfatase deficiency PMD Pelizaeus–Merzbacher disease; MSUD maple syrup urine disease proximal myotonic dystrophy MT magnetization transfer PME phosphomonoesters mtDNA mitochondrial DNA PML progressive multifocal leuko- MTI magnetization transfer imaging encephalopathy MTR magnetization transfer ratio PMP peroxisomal membrane protein NAA N-acetylaspartate PNS peripheral nervous system NAAG N-acetylaspartyl glutamate POLD pigmentary orthochromatic NAD nicotinamide adenine dinucleotide leukodystrophy NADH nicotinamide adenine dinucleotide, POLIP polyneuropathy, ophthalmoplegia, reduced leukoencephalopathy, and intestinal NALD neonatal adrenoleukodystrophy pseudo-obstruction NARP neurogenic muscle weakness, ataxia, PPAR peroxisome proliferator activating and retinitis pigmentosa receptor NAWM normal-appearing white matter ppm parts per million NBCA n-butyl cyanoacrylate 000_Valk_Titelei 18.04.2005 10:09 Uhr Seite XVI

XVI List of Abbreviations

PPRE peroxisome proliferator response TTesla element TE toxic encephalopathy; echo time PPT1 palmitoyl protein thioesterase 1 TI inversion time PRES posterior reversible encephalopathy TNF-α tumor necrosis factor-alpha syndrome TORCH toxoplasmosis, rubella, cytomegalo- PRESS point-resolved spectroscopy virus, herpes simplex PROMM proximal myotonic myopathy TPP1 tripeptidyl peptidase 1 PTS peroxisome targeting signals TR repetition time PVA polyvinyl alcohol tRNA transfer RNA PVL periventricular leukomalacia TSD Tay–Sachs disease QA quisqualate TSE turbo spin echo RCDP rhizomelic chondrodysplasia punctata TTD trichothiodystrophy with photo- RD Refsum disease sensitivity RF radiofrequency TTP thrombotic thrombocytopenic purpura RNA ribonucleic acid TvLINCL Turkish variant of late-infantile RPLS reversible posterior leukoencephalo- neuronal ceroid lipofuscinosis pathy syndrome TYROBP TYRO protein kinase RPR rapid plasma reagin (test) binding protein RR relapsing remitting UDP uridine diphosphate rRNA ribosomal RNA US ultrasound/ultrasonography RXR retinoic acid receptor UV ultraviolet SAE subcortical arteriosclerotic V-CAM cellular adhesion molecules encephalopathy VDAC voltage-dependent, SAP sphingolipid activator protein anion-selective channel SCA spinocerebellar ataxia VDRL Venereal Disease Research Laboratory SCL subcortical leukomalacia (test) SD Salla disease VEGF vascular endothelial growth factor SE spine echo VEP visual evoked potential SIBIDS osteosclerosis, ichthyosis, brittle hair, VLA-4 very late antigen 4 impaired intelligence, decreased VLCFA very-long-chain fatty acids fertility, short stature (syndrome) vLINCL variant late-infantile neuronal ceroid SLE systemic lupus erythematosus lipofuscinosis SLS Sjögren–Larsson syndrome VMA vanillyl mandelic acid SP secondary progressive VWM vanishing white matter SPECT single photon emission computed WD Wilson disease tomography WM white matter SPG2 spastic paraparesis type 2 WWS Walker–Warburg syndrome SSEP somatosensory evoked potential XALD X-linked adrenoleukodystrophy SSPE subacute sclerosing panencephalitis XP xeroderma pigmentosum STEAM stimulated-echo acquisition mode ZS Zellweger syndrome STIR short tau inversion recovery