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 I
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
12
3Marjo S. van der Knaap Jaap Valk
Magnetic Resonance of Myelination
and Myelin Disorders
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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
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Editor: Dr. Ute Heilmann, Heidelberg, Germany
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Preface to the Third Edition
Reading through the prefaces of the two previous edi- tions, we can say that much of what was said there still holds. At the same time, however, much has changed.
There has been immense progress in the technical possibilities of magnetic resonance and in the know- ledge of genetic defects, biochemical abnormalities, and cellular processes underlying myelin disorders.
This immense progress has prompted us to embark upon the enormous task of rewriting the previous edition and adding 40 chapters. In doing so we have tried to cover most white matter disorders, hereditary and acquired, and to present a collection of images to illustrate the field to the fullest possible extent. This edition will therefore be more complete than the pre- vious ones. The number of illustrations has increased considerably. This was necessary to reflect not only the typical patterns of a disease, but to show also the variability that exists in some disorders. The best ex- ample of this is found in Alexander disease. Genetic verification now makes it possible to recognize very different patterns of imaging abnormalities, all relat- ed to a defect in the same gene. Today’s increased in- sight into disease classification based on increased knowledge of related genes and proteins is best re- flected in the chapter on congenital muscular dystro- phies.
This is the first time that we have invited a number of experts in special fields to write or co-write a chap- ter, in order to assure the highest level of scientific accuracy. To assemble the knowledge presented in this work we have also harvested the literature, prof- iting from the work and discoveries of many others.
Our thanks go to our colleagues at the VU Univer- sity Medical Center and to those in other hospitals who referred their patients to us. We are indebted to all colleagues who allowed us to use their MR images, published or unpublished, making it possible for us to present illustrations of nearly all known white matter disorders. Two colleagues were particularly helpful and provided us with essential and unpublished fig- ures: our friends Susan Blaser, from the Hospital for Sick Children in Toronto, and Zoltán Patay, from the King Faisal Hospital in Riyadh.
Many people at the VU University Medical Center have been of great technical help to us in producing high quality images and in providing secretarial assistance. The contributions of these people are mentioned separately in the acknowledgements.
Our special thanks go to patients with white mat- ter disorders and their families. They came to see us and were willing to work with us and to go through the procedure of diagnostic testing, including MR examinations. Many patients and families were also willing to participate in our research projects to advance the understanding of white matter disorders.
Patients with white matter disorders are the focus of our work. They are our most important collaborators.
Often they are children. To show our gratitude to them, we have decided that all profits of this book will go to the Foundation for Children with White Matter Disorders.
Amsterdam, May 2005 M.S. van der Knaap J. Valk
Preface
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Preface to the Second Edition
The first edition of this book was well received by readers and reviewers and we are very grateful for the positive reactions. We were convinced then, and even more now, that MRI and MRS have much to offer in diagnosis, therapy monitoring and research of hered- itary and acquired myelin disorders.
In the last few years, a great deal of new information has become available concerning the genetic basis of inborn errors of metabolism and neurodegenerative disorders, the role of subcellular structures, the en- zyme biochemistry, the pathophysiological mecha- nisms of posthypoxic-ischemic cerebral damage, and the inflammatory processes in infectious and inflam- matory disorders. MR images of many rare disorders have become available, either in our own experience or published by other groups. MR spectroscopy could confirm its role in certain clinical applications. Be- cause of these developments, it was necessary for us to rewrite the book almost completely. In some fields developments are so fast that we have not have caught all the latest developments. The pattern of the new approaches has, however, been established, making the assimilation of newly available information easy.
We are extremely grateful for the help of colleagues to make this book as complete as possible. The posi- tive reactions of those from whom we requested MR pictures or other forms of support were of enormous encouragement to us during our efforts to complete this project.
We hope this work will be as warmly welcomed by our colleagues as the first edition.
Amsterdam, January 1995 M.S. van der Knaap J. Valk
Preface to the First Edition
Magnetic resonance imaging (MRI) is now consid- ered to be the imaging modality of choice for the ma- jority of disorders affecting the central nervous sys- tem. This is particularly true for gray and white mat- ter disorders, thanks to the superb soft tissue contrast in MRI which allows gray matter, unmyelinated, and myelinated white matter to be distinguished and their respective disorders identified. The present book is devoted to the disorders of myelin and myelination.
A growing amount of detailed in vivo information about myelin, myelination, and myelin disorders has
been derived both from MRI and from MR spec- troscopy (MRS). This prompted us to review the clin- ical, laboratory, biochemical, and pathological data on this subject in order to integrate all available informa- tion and to provide improved insights into normal and disordered myelin and myelination. We will show how the synthesis of all available information con- tributes to the interpretation of MR images.
Following a brief historical review of the increas- ing knowledge on myelin and myelin disorders, we propose a new classification of myelin disorders based on the subcellular localization of the enzymat- ic defects as far as the inborn errors of metabolism are concerned. This classification serves as a guide throughout the book. All items of the classification will be discussed and, whenever relevant and possi- ble, illustrated by MR images.
We are aware of the fact that in a number of myelin disorders MRI is not a part of the usual diagnostic work up because a definite diagnosis is reached by other means, such as biochemical investigations of blood and urine, enzyme assessment or detection of specific antibodies. However, in many disorders MRI may facilitate a rapid diagnosis and early instigation of treatment, thus preventing structural cerebral damage. In other cases the role of MRI is to visualize the extent of brain damage and give an indication of the prognosis. In disorders which present in a non- specific way, for instance with behavioral problems or learning difficulties, MRI can be one of the first-line investigations. It is important to be acquainted with the various MRI patterns of the myelin disorders, as an early diagnosis may be of major importance in young families with a view to the provision of ade- quate genetic counseling.
MRS has been of limited clinical importance until now, and its application in patients only has a short 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 and have, therefore, devoted a separate chapter to this subject.
This volume was written by a neuroradiologist and a neurologist/child neurologist. It is the product of close cooperation, animated discussions, strong argu- ments, restructuring, rewriting, and editing, in which they had an equal share. If the reader finds value in this monograph, it is because of this dual effort.
Amsterdam and Utrecht, March 1989 J. Valk
M.S. van der Knaap
Preface VI
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The preparation of this book was a project of several years and could not have been concluded successfully without the support and collaboration of many peo- ple. Thanks to all.
Special thanks go to our colleagues: Jeroen Ver- meulen and Leo Smit, pediatric neurologists, and Frederik Barkhof and Jonas Castelijns, neuroradiolo- gists, at the VU University Medical Center (VUMC) in Amsterdam; Martin Heitbrink and Bart Wiarda, radiologists at the Medical Center Alkmaar; and Erik Veldhuizen, radiologist at the MRI center, Amster- dam, for their continuous support during this en- deavor. We are grateful to the MRI technicians at the VUMC, who guaranteed the quality of the MR exam- inations and had the patience and empathy to deal with very sick children and their parents. We want to mention especially the help of Karin Barbiers and Er- win Kist, who headed this team and carried out the re- trieval of older examinations to the Image Manage- ment System.
We received great support from the audiovisual center at the VUMC. We are especially indebted to Daan van Eijndhoven, Rene den Engelsman, and
Annuska Houtappels, who digitized older films and helped us improve the quality of the images.
Excellent secretarial help was provided by Sigrid Bruinsma, who single-handedly took care of the ref- erence section. Staff members of the VUMC Library Els van Deventer, Linda Glas, Margreet Bosshardt, and Cisca Frederiks were very helpful in providing us with the necessary literature.
Technical support and guidance with computer programs and settings were provided by the Depart- ment of Informatics of the VUMC. We are grateful for their kind and prompt assistance. Special thanks go to Michiel Sprenger, Guido Zonneveld, and Peter Theijs- meijer.
We acknowledge the continuous friendly and encouraging support of the editorial staff of Springer- Verlag, Dr. Ute Heilmann and Mrs Dörthe Mennecke- Bühler.
Amsterdam, May 2005 M.S. van der Knaap J. Valk
Acknowledgements
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1 Myelin and White Matter . . . 1
2 Classification of Myelin Disorders . . . . 20
3 Selective Vulnerability . . . 25
4 Myelination and Retarded Myelination 37 5 Lysosomes and Lysosomal Disorders . . 66
6 Metachromatic Leukodystrophy. . . 74
7 Multiple Sulfatase Deficiency . . . 82
8 Globoid Cell Leukodystrophy (Krabbe Disease) . . . 87
9 GM1Gangliosidosis . . . 96
10 GM2Gangliosidosis . . . 103
11 Fabry Disease . . . 112
12 Fucosidosis . . . 119
13 Mucopolysaccharidoses . . . 123
14 Free Sialic Acid Storage Disorder . . . . 133
15 Neuronal Ceroid Lipofuscinoses . . . . 137
16 Adult Polyglucosan Body Disease . . . . 147
17 Peroxisomes and Peroxisomal Disorders . . . 151
18 Peroxisome Biogenesis Defects . . . 154
19 Peroxisomal D-Bifunctional Protein Deficiency . . . 167
20 Peroxisomal Acyl-CoA Oxidase Deficiency. . . 172
21 X-linked Adrenoleukodystrophy . . . . 176
22 Refsum Disease . . . 191
23 Mitochondria and Mitochondrial Disorders . . . 195
24 Mitochondrial Encephalopathy with Lactic Acidosis and Stroke-like Episodes . . . 204
25 Leber Hereditary Optic Neuropathy . . 212
26 Kearns–Sayre Syndrome . . . 215
27 Mitochondrial Neurogastrointestinal Encephalomyopathy. . . 221
28 Leigh Syndrome and Mitochondrial Leukoencephalopathies . . . 224
29 Pyruvate Carboxylase Deficiency . . . . 245
30 Multiple Carboxylase Deficiency . . . . 248
31 Cerebrotendinous Xanthomatosis . . . 252
32 Cockayne Syndrome . . . 259
33 Trichothiodystrophy with Photosensitivity . . . 268
34 Pelizaeus–Merzbacher Disease and X-linked Spastic Paraplegia Type 2 . . . 272
35 18q–Syndrome . . . 281
36 Phenylketonuria . . . 284
37 Glutaric Aciduria Type 1 . . . 294
38 Propionic Acidemia . . . 300
39 Nonketotic Hyperglycinemia . . . 306
40 Maple Syrup Urine Disease . . . 311
41 3-Hydroxy 3-Methylglutaryl-CoA Lyase Deficiency . . . 321
42 Canavan Disease . . . 326
43 L-2-Hydroxyglutaric Aciduria . . . 334
44 D-2-Hydroxyglutaric Aciduria . . . 338
45 Hyperhomocysteinemias . . . 342
46 Urea Cycle Defects . . . 360
47 Serine Synthesis Defect Caused by 3-Phosphoglycerate Dehydrogenase Deficiency . . . 369
48 Molybdenum Cofactor Deficiency and Isolated Sulfite Oxidase Deficiency. . . 372
49 Galactosemia . . . 377
50 Sjögren–Larsson Syndrome . . . 383
51 Lowe Syndrome . . . 387
52 Wilson Disease . . . 392
53 Menkes Disease . . . 400
54 Fragile X Premutation . . . 406
55 Hypomelanosis of Ito . . . 409
56 Incontinentia Pigmenti . . . 412
57 Alexander Disease . . . 416
58 Giant Axonal Neuropathy . . . 436
59 Megalencephalic Leukoencephalo- pathy with Subcortical Cysts . . . 442
60 Congenital Muscular Dystrophies . . . . 451
61 Myotonic Dystrophy Type I . . . 469
62 Myotonic Dystrophy Type 2 . . . 473
63 X-linked Charcot–Marie–Tooth Disease . . . 476
Contents
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64 Oculodentodigital Dysplasia . . . 479 65 Leukoencephalopathy
with Vanishing White Matter . . . 481 66 Aicardi–Goutières Syndrome . . . 496 67 Leukoencephalopathy
with Calcifications and Cysts . . . 505 68 Leukoencephalopathy with Brain Stem
and Spinal Cord Involvement
and Elevated White Matter Lactate . . . 510 69 Hypomyelination with Atrophy
of the Basal Ganglia and Cerebellum . . 519 70 Hereditary Diffuse Leukoencephalo-
pathy with Neuroaxonal Spheroids . . . 526 71 Dentatorubropallidoluysian Atrophy . 530 72 Cerebral Amyloid Angiopathy . . . 535 73 Cerebral Autosomal Dominant
Arteriopathy with Subcortical Infarcts and Leukoencephalopathy . . . 541 74 Cerebral Autosomal Recessive
Arteriopathy with Subcortical Infarcts and Leukoencephalopathy . . . 549 75 Polycystic Lipomembranous
Osteodysplasia with Sclerosing Leukoencephalopathy
(Nasu-Hakola Disease). . . 552 76 Pigmentary Orthochromatic
Leukodystrophy . . . 557 77 Adult-Onset Autosomal Dominant
Leukoencephalopathies . . . 559 78 Inflammatory
and Infectious Disorders . . . 561 79 Multiple Sclerosis . . . 566 80 Acute Disseminated Encephalomyelitis
and Acute Hemorrhagic
Encephalomyelitis . . . 604 81 Acquired Immunodeficiency
Syndrome . . . 616 82 Progressive Multifocal
Leukoencephalopathy . . . 628 83 Brucellosis . . . 635 84 Subacute Sclerosing Panencephalitis . 640 85 Congenital and Perinatal
Cytomegalovirus Infection . . . 645
86 Whipple Disease . . . 658 87 Toxic Encephalopathies . . . 664 88 Iatrogenic Toxic Encephalopathies . . . 679 89 Central Pontine and Extrapontine
Myelinolysis . . . 684 90 Hypernatremia . . . 690 91 Marchiafava–Bignami Syndrome . . . . 695 92 Posterior Reversible
Encephalopathy Syndrome . . . 699 93 Langerhans Cell Histiocytosis . . . 709 94 Post-Hypoxic–Ischemic Damage . . . . 714 95 Post-Hypoxic–Ischemic
Leukoencephalopathy of Neonates . . . 718 96 Neonatal Hypoglycemia . . . 749 97 Delayed Posthypoxic
Leukoencephalopathy . . . 755 98 White Matter Lesions of the Elderly . . . 759 99 Subcortical Arteriosclerotic
Encephalopathy . . . 767 100 Vasculitis . . . 773 101 Leukoencephalopathy
and Dural Venous Fistula . . . 801 102 Leukoencephalopathy after Chemo-
therapy and/or Radiotherapy . . . 808 103 Gliomatosis Cerebri . . . 818 104 Diffuse Axonal Injury . . . 823 105 Wallerian Degeneration
and Myelin Loss Secondary to Neuronal and Axonal
Degeneration . . . 832 106 Diffusion-Weighted Imaging . . . 839 107 Magnetization Transfer Imaging . . . . 854 108 Magnetic Resonance Spectroscopy:
Basic Principles, and Application
in White Matter Disorders. . . 859 109 Pattern Recognition
in White Matter Disorders. . . 881 References . . . 905 Subject Index . . . 1075
Contents X
000_Valk_Titelei 18.04.2005 10:09 Uhr Seite X
F. Barkhof,MD PhD Department of Radiology and MR Center for MS Research VU University Medical Center Amsterdam, The Netherlands V. Geiselmann,PhD
Institut fur Physiologische Chemie
Rheinische Friedrich-Wilhelms-Universität Bonn, Germany
G.J. Lycklama à Nijeholt, MD PhD Department of Radiology VU University Medical Center Amsterdam, The Netherlands E. Morava,MD
Nijmegen Center for Mitochondrial Disorders and Department of Pediatrics
University Medical Center Nijmegen Nijmegen, The Netherlands
P.J.W. Pouwels,PhD
Department of Clinical Physics and Informatics VU University Medical Center
Amsterdam, The Netherlands J.A.M. Smeitink,MD PhD
Nijmegen Center for Mitochondrial Disorders and Department of Pediatrics
University Medical Center Nijmegen Nijmegen, The Netherlands
J. Valk, MD PhD
Department of Radiology VU University Medical Center Amsterdam, The Netherlands
R. van den Berg, MD PhD Department of Radiology
VU University Medical Center, Amsterdam and Department of Radiology
Leiden University Medical Center Leiden, The Netherlands
M.S. van der Knaap,MD PhD Department of Child Neurology VU University Medical Center Amsterdam, The Netherlands J.M.C. van Dijk, MD PhD Department of Neurosurgery Leiden University Medical Center Leiden, The Netherlands
R.J. Vermeulen,MD PhD Department of Child Neurology VU University Medical Center Amsterdam, The Netherlands R.J.A. Wanders, PhD
Department of Clinical Chemistry and Department of Pediatrics Academic Medical Center Amsterdam, The Netherlands R.A. Wevers, PhD
Laboratory of Pediatrics and Neurology
University Medical Center Nijmegen St Radboud Nijmegen, The Netherlands
Contributors
000_Valk_Titelei 18.04.2005 10:09 Uhr Seite XI
ACE angiotensin converting enzyme ACTH adrenocorticotropic hormone AD Alexander disease
ADC apparent diffusion coefficient ADEM acute disseminated encephalomyelitis ADP adenosine diphosphate
AD PEO autosomal dominant progressive external ophthalmoplegia
AHEM acute hemorrhagic encephalomyelitis AIDS acquired immunodeficiency syndrome ALD adrenoleukodystrophy
ALDP ALD protein
ALL acute lymphocytic leukemia AMN adrenomyeloneuropathy
ANCAs anti-neutrophil cytoplasm antibodies ANCL adult neuronal ceroid lipofuscinosis
(or Kufs disease)
AP4 2-amino-4-phosphonobutyrate APLA anti-phospholipid antibodies APBD adult polyglucosan body disease apoE apolipoprotein E
APP amyloid precursor protein
aPTT activated partial thromboplastin time ASLD argininosuccinate lyase deficiency ASSD argininosuccinate synthetase deficiency ATP adenosine triphosphate
BAEP brain stem auditory evoked potential BCNU bis-chloroethyl-nitrosourea
BDNF brain-derived neurotrophic factor bFGF basic fibroblast growth factor BIDS brittle hair, impaired intelligence,
decreased fertility, short stature (syndrome)
BMAA β-N-methylamino-L-alanine BOMAA β-N-oxalylmethylamino-L-alanine BPD D-bifunctional protein deficiency CAA cerebral amyloid angiopathy
CACH childhood ataxia with central nervous system hypomyelination
CACT mitochondrial carnitine/acylcarnitine transporter
CADASIL cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy
cANCA cytoplasmic form of ANCA CARASIL cerebral autosomal recessive
arteriopathy with subcortical infarcts and leukoencephalopathy
CAMFAK cataracts–microcephaly–failure to thrive–kyphoscoliosis (syndrome) CD Canavan disease; cluster determinant
Cho choline
CIPO chronic intestinal pseudo-obstruction CIS clinically isolated symptom
CK creatine kinase
CMD congenital muscular dystrophy CMT Charcot–Marie–Tooth disease CMTX X-linked form of CMT CMV cytomegalovirus CNP 2’3’-cyclic nucleotide
3’-phosphodiesterase CNS central nervous system
COFS cerebro-oculofacioskeletal (syndrome) COX cytochrome-c oxidase
CPEO chronic progressive external ophthalmoplegia
CPM central pontine myelinolysis CPSD carbamyl phosphate synthetase
deficiency
CPT carnitine palmitoyl transferase
Cr creatine
CREST calcinosis, Raynaud syndrome, esophageal problems, sclerodactylia, and telangiectasia (syndrome) CS Cockayne syndrome; concentric
sclerosis (or Baló disease) CSF cerebrospinal fluid CSI chemical shift imaging
CT computed tomography/tomogram CTX cerebrotendinous xanthomatosis DAB diaminobenzidine
DAGC dystrophin-associated glycoprotein complex DAI diffuse axonal injury
DAVF cranial dural arteriovenous fistula DHAPAT dihydroxyacetonephosphate
acyltransferase
DM 1 myotonic dystrophy type 1 DM 2 myotonic dystrophy type 2 DNA deoxyribonucleic acid DNC deoxynucleotide carrier
dNTP deoxyribonucleoside triphosphate DOA dominant optic atrophy
DOPA dihydroxyphenylalanine DPHL delayed posthypoxic
leukoencephalopathy
DRPLA dentatorubropallidoluysian atrophy
List of Abbreviations
000_Valk_Titelei 18.04.2005 10:09 Uhr Seite XIII
DS diffuse sclerosis (or Schilder disease) DSA digital subtraction angiography DTI diffusion tensor imaging DWI diffusion-weighted imaging EAA excitatory amino acid
EAE experimental allergic encephalomyelitis ECD ethyl cysteinate dimer
ECG electrocardiography/electrocardiogram EDSS Expanded Disability Status Scale EEG electroencephalogram
EGF epidermal growth factor eIF eukaryotic initiation factor
ELISA enzyme-linked immunosorbent assay EMG electromyogram
EPI echo planar imaging EPM extrapontine myelinolysis EPMR progressive epilepsy
with mental retardation
ERG electroretinography/electroretinogram FA fractional anisotropy
FAD flavin adenine dinucleotide
FADH2 flavin adenine dinucleotide, reduced FCMD Fukuyama congenital muscular
dystrophy FD Fabry disease
FISH fluorescent in situ hybridization FLAIR fluid-attenuated inversion recovery FSE fast spin echo
FSH follicle-stimulating hormone 5-FU 5-fluorouracil
FvLINCL Finnish variant of late-infantile neuronal ceroid lipofuscinosis GA gestational age
GABA γ-aminobutyric acid
GAMT guanidinoacetate methyltransferase GAN giant axonal neuropathy
GDP guanosine diphosphate
GE gradient echo
GEF guanine-nucleotide exchange factor GFAP glial fibrillary acidic protein GIP general insertion protein GLD globoid cell leukodystrophy Glx glutamine, glutamate, GABA GOM granular osmiophilic material GRACILE growth retardation, aminoaciduria,
cholestasis, iron overload, lactic acidosis, and early death (syndrome) GROD granular osmiophilic deposits GTE glyceryl trierucate
GTO glyceryl trioleate GTP guanosine triphosphate GVHD graft-versus-host disease HAART highly active/aggressive
anti-retroviral treatment HABC hypomyelination with atrophy
of the basal ganglia and cerebellum
HCHWA-D Dutch type of hereditary cerebral hemorrhage with amyloidosis HDL high-density lipoproteins
HDLS hereditary diffuse leukoencephalopathy with spheroids
5HIAA 5-hydroxyindoleacetic acid
HIV-1 human immunodeficiency virus type 1 HLA human leukocyte antigen
HMG-CoA 3-hydroxy-3-methylglutaryl- coenzyme A
HMI hypomelanosis of Ito
HMPAO hexamethylpropyleneamine oxime HSP hereditary spastic paraplegia; heat
shock protein
HTLV human T-cell lymphotropic virus HUS hemolytic–uremic syndrome HVA homovanillic acid
IBIDS ichthyosis, brittle hair, impaired intelligence, decreased fertility, short stature (syndrome) IFN interferon
Ig immunoglobulin
IGF insulin-like growth factor
INCL infantile neuronal ceroid lipofuscinosis (or Santavuori disease)
IP incontinentia pigmenti IQ intelligence quotient IR inversion recovery IRD infantile Refsum disease
ISIS image-selective in vivo spectroscopy ISSD severe infantile sialic acid
storage disease
IVL intravascular lymphomatosis
JNCL juvenile neuronal ceroid lipofuscinosis (or Spielmeyer–Vogt disease, or Batten disease)
KA kainate
kDa kiloDalton
KSS Kearns–Sayre syndrome
LAMP lysosome-associated membrane protein LBSL leukoencephalopathy with brain stem
and spinal cord involvement and elevat- ed white matter lactate
LCC leukoencephalopathy with calcifications and cysts
LCH Langerhans cell histiocytosis LDL low-density lipoproteins LGMD limb girdle muscular dystrophy LH luteinizing hormone
LHON Leber hereditary optic neuropathy LINCL late-infantile neuronal ceroid
lipofuscinosis (or Jansky–
Bielschowsky disease)
MAG myelin-associated glycoprotein MAP microtubule-associated protein MBS Marchiafava–Bignami syndrome MBP myelin basic protein
List of Abbreviations XIV
000_Valk_Titelei 18.04.2005 10:09 Uhr Seite XIV
MCE multicystic encephalopathy
MD Menkes disease; myotonic dystrophy MDC1A merosin-deficient congenital
muscular dystrophy MEB muscle–eye–brain disease
MELAS mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes MEPOP mitochondrial encephalomyopathy
with sensorimotor polyneuropathy, ophthalmoplegia, and pseudo- obstruction
MERRF myoclonic epilepsy with ragged red fibers
MHC major histocompatibility complex MHPG 3-methoxy-4-hydroxyphenylglycol MICS microcephaly–intracranial
calcifications syndrome MIL multifocal inflammatory
leukoencephalopathy mIns myo-inositol
MLC megalencephalic leukoencephalopathy with subcortical cysts
MLD metachromatic leukodystrophy MNGIE mitochondrial neurogastrointestinal
encephalomyopathy
MOBP myelin-associated oligodendrocytic basic protein
MOG myelin oligodendrocyte glycoprotein MOM mitochondrial outer membrane MOSP myelin-/oligodendrocyte-specific
protein
MPP mitochondrial processing peptidase MPS mucopolysaccharidoses; mucopoly-
saccharidoses
MPTP methylphenyltetrahydropyridine MR magnetic resonance
MRA magnetic resonance angiography MRI magnetic resonance imaging mRNA messenger RNA
MRS magnetic resonance spectroscopy MS multiple sclerosis
MSD multiple sulfatase deficiency MSUD maple syrup urine disease MT magnetization transfer mtDNA mitochondrial DNA
MTI magnetization transfer imaging MTR magnetization transfer ratio NAA N-acetylaspartate
NAAG N-acetylaspartyl glutamate NAD nicotinamide adenine dinucleotide NADH nicotinamide adenine dinucleotide,
reduced
NALD neonatal adrenoleukodystrophy NARP neurogenic muscle weakness, ataxia,
and retinitis pigmentosa NAWM normal-appearing white matter NBCA n-butyl cyanoacrylate
NCL neuronal ceroid lipofuscinosis nDNA nuclear DNA
NKH nonketotic hyperglycinemia NMDA N-methyl-D-aspartate
NMO neuromyelitis optica (or Devic disease) NRTI nucleoside analogue reverse
transcriptase inhibitor
NT neurotrophin
OCRL oculocerebrorenal syndrome of Lowe ODDD oculodentodigital dysplasia
OGIMD oculogastrointestinal muscular dystrophy
OHS occipital horn syndrome
OMgp oligodendrocyte myelin glycoprotein ONMR onychotrichodysplasia, neutropenia,
mental retardation (syndrome) OSP oligodendrocyte-specific protein OTCD ornithine transcarbamylase deficiency PACNS primary angiitis of the CNS
PAF platelet activating factor PAN polyarteritis nodosa pANCA perinuclear form of ANCA PAS periodic acid–Schiff
PCD pyruvate carboxylase deficiency PCr phosphocreatine
PCR polymerase chain reaction PDE phosphodiesters
PDGF platelet-derived growth factor PDHc pyruvate dehydrogenase complex PEP processing enhancing protein PET positron emission tomography Pi inorganic phosphate
PIBIDS photosensitivity, ichthyosis, brittle hair, impaired intelligence, decreased fertility, short stature (syndrome) PIP2 phosphatidylinositol 4,5-biphosphate PKU phenylketonuria
PLOSL polycystic lipomembranous osteo- dysplasia with sclerosing leuko- encephalopathy
PLP proteolipid protein
PMD Pelizaeus–Merzbacher disease;
proximal myotonic dystrophy PME phosphomonoesters
PML progressive multifocal leuko- encephalopathy
PMP peroxisomal membrane protein PNS peripheral nervous system POLD pigmentary orthochromatic
leukodystrophy
POLIP polyneuropathy, ophthalmoplegia, leukoencephalopathy, and intestinal pseudo-obstruction
PPAR peroxisome proliferator activating receptor
ppm parts per million
List of Abbreviations XV 000_Valk_Titelei 18.04.2005 10:09 Uhr Seite XV
PPRE peroxisome proliferator response element
PPT1 palmitoyl protein thioesterase 1 PRES posterior reversible encephalopathy
syndrome
PRESS point-resolved spectroscopy PROMM proximal myotonic myopathy PTS peroxisome targeting signals PVA polyvinyl alcohol
PVL periventricular leukomalacia
QA quisqualate
RCDP rhizomelic chondrodysplasia punctata RD Refsum disease
RF radiofrequency RNA ribonucleic acid
RPLS reversible posterior leukoencephalo- pathy syndrome
RPR rapid plasma reagin (test) RR relapsing remitting rRNA ribosomal RNA RXR retinoic acid receptor SAE subcortical arteriosclerotic
encephalopathy
SAP sphingolipid activator protein SCA spinocerebellar ataxia SCL subcortical leukomalacia SD Salla disease
SE spine echo
SIBIDS osteosclerosis, ichthyosis, brittle hair, impaired intelligence, decreased fertility, short stature (syndrome) SLE systemic lupus erythematosus SLS Sjögren–Larsson syndrome SP secondary progressive
SPECT single photon emission computed tomography
SPG2 spastic paraparesis type 2 SSEP somatosensory evoked potential SSPE subacute sclerosing panencephalitis STEAM stimulated-echo acquisition mode STIR short tau inversion recovery
T Tesla
TE toxic encephalopathy; echo time TI inversion time
TNF-α tumor necrosis factor-alpha TORCH toxoplasmosis, rubella, cytomegalo-
virus, herpes simplex TPP1 tripeptidyl peptidase 1 TR repetition time tRNA transfer RNA TSD Tay–Sachs disease TSE turbo spin echo
TTD trichothiodystrophy with photo- sensitivity
TTP thrombotic thrombocytopenic purpura TvLINCL Turkish variant of late-infantile
neuronal ceroid lipofuscinosis TYROBP TYRO protein tyrosine kinase
binding protein UDP uridine diphosphate US ultrasound/ultrasonography UV ultraviolet
V-CAM cellular adhesion molecules VDAC voltage-dependent,
anion-selective channel
VDRL Venereal Disease Research Laboratory (test)
VEGF vascular endothelial growth factor VEP visual evoked potential
VLA-4 very late antigen 4
VLCFA very-long-chain fatty acids
vLINCL variant late-infantile neuronal ceroid lipofuscinosis
VMA vanillyl mandelic acid VWM vanishing white matter WD Wilson disease
WM white matter
WWS Walker–Warburg syndrome XALD X-linked adrenoleukodystrophy XP xeroderma pigmentosum ZS Zellweger syndrome
List of Abbreviations XVI
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