Greenfield's Neuropathology Two Volume Set, 9th Edition

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 Greenfield’s Ninth Edition

Neuropathology
Volume 1
Edited by
Seth Love MBBCh PhD FRCP FRCPath
Professor of Neuropathology
Institute of Clinical Neurosciences
School of Clinical Sciences
University of Bristol
Southmead Hospital
Bristol, UK

Herbert Budka MD
Professor of Neuropathology
Consultant, Institute of Neuropathology
University Hospital Zurich
Zurich, Switzerland

James W Ironside CBE BMSc FRCPath FRCPEdin FMedSci FRSE

Professor of Clinical Neuropathology and Honorary
Consultant in Neuropathology
National Creutzfeldt–Jakob Disease Surveillance Unit
University of Edinburgh
Western General Hospital
Edinburgh, UK

Arie Perry MD
Professor of Pathology and Neurological Surgery
Director of Neuropathology
Director of Neuropathology Fellowship Training Program
University of California, San Francisco
San Francisco, CA, USA

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CRC Press
Taylor & Francis Group
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Boca Raton, FL 33487-2742
© 2015 by Taylor & Francis Group, LLC
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 Contents
Preface................................................................................vii Chapter 15: Ageing of the brain........................................ 849
Contributors........................................................................ ix James Lowe
Abbreviations......................................................................xiv
Chapter 16: Dementia....................................................... 858
James Lowe and Raj Kalaria
Volume 1
Chapter 1: General pathology of the central nervous Volume 2
system..................................................................................1
Chapter 17: Psychiatric diseases..................................... 975
Harry V Vinters and BK Kleinschmidt-DeMasters
Margaret M Esiri, Steven A Chance, Jean
Debarros and Tim J Crow
Chapter 2: Vascular disease, hypoxia and related
­conditions........................................................................... 59
Chapter 18: Prion diseases............................................. 1016
Raj Kalaria, Isidro Ferrer and Seth Love
Mark W Head, James W Ironside, Bernardino Ghetti, ­
Martin Jeffrey, Pedro Piccardo and Robert G Will
Chapter 3: Disorders of the perinatal period.................... 210
Rebecca D Folkerth and Marc R Del Bigio
Chapter 19: Viral infections............................................. 1087
Seth Love, Clayton A Wiley and Sebastian Lucas
Chapter 4: Malformations................................................. 270
Brian N Harding and Jeffrey A Golden
Chapter 20: Bacterial infections..................................... 1192
Martina Deckert
Chapter 5: Metabolic and neurodegenerative diseases
of childhood..................................................................... 399
Chapter 21: Parasitic infections...................................... 1230
Thomas S Jacques and Brian N Harding
Sebastian Lucas
Chapter 6: Lysosomal diseases....................................... 439
Chapter 22: Fungal infections......................................... 1281
Steven U Walkley, Kinuko Suzuki and Kunihiko Suzuki
Sebastian Lucas
Chapter 7: Mitochondrial disorders.................................. 523
Chapter 23: Demyelinating diseases.............................. 1297
Patrick F Chinnery, Nichola Z Lax, Evelyn Jaros, Robert W
G R Wayne Moore and Christine Stadelmann-Nessler
Taylor, Douglas M Turnbull and Salvatore DiMauro

Chapter 8: Peroxisomal disorders.................................... 562 Chapter 24: Diseases of peripheral nerves..................... 1413
Phyllis L Faust and James M Powers Robert E Schmidt and Juan M Bilbao

Chapter 25: Diseases of skeletal muscle........................ 1515

Chapter 9: Nutritional and toxic diseases........................ 589
Caroline A Sewry, Susan C Brown, Rahul Phadke and
Jillian Kril, Leila Chimelli, Christopher M Morris and ­Francesco Muntoni
John B Harris
Chapter 26: Introduction to tumours.............................. 1623
Chapter 10: Trauma.......................................................... 637
Arie Perry and David N Louis
Colin Smith, Susan S Margulies and Ann-Christine Duhaime
Chapter 27: Astrocytic tumours...................................... 1638
Chapter 11: Epilepsy........................................................ 683 Daniel J Brat
Maria Thom and Sanjay Sisodiya
Chapter 28: Oligodendroglial tumours............................ 1673
Chapter 12: Extrapyramidal diseases of Guido Reifenberger
movement......................................................................... 740
Tamas Revesz, H Brent Clark, Janice L Holton, Henry H Chapter 29: Ependymal tumours.................................... 1693
Houlden, Paul G Ince and Glenda M Halliday Guido Reifenberger

Chapter 13: Degenerative ataxic disorders...................... 799 Chapter 30: Choroid plexus tumours............................. 1709
H Brent Clark Hope T Richard, Jason F Harrison and Christine E Fuller

Chapter 14: Motor neuron disorders................................ 817 Chapter 31: Other glial neoplasms................................. 1717
Paul G Ince, J Robin Highley and Stephen B Wharton Daniel J Brat

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 VI Contents

Chapter 32: Neuronal and mixed neuronal-glial Chapter 40: Lymphomas and haemopoietic
tumours.......................................................................... 1726 neoplasms...................................................................... 1850
Daniel J Brat Martina Deckert

Chapter 33: Neuroepithelial tumours of the Chapter 41: Pituitary and suprasellar
pineal region..................................................................... 1756 tumours.......................................................................... 1870
Alexandre Vasiljevic, Anne Jouvet and Sylvia L Asa
Michelle Fevre Montange
Chapter 42: Cysts and tumour-like
Chapter 34: Embryonal tumours..................................... 1765 conditions....................................................................... 1908
Charles Eberhart Arie Perry

Chapter 35: Tumours of the peripheral nerves............... 1788 Chapter 43: Metastatic disease...................................... 1919
Arie Perry and Robin Reid Matthew D Cykowski and Gregory N Fuller

Chapter 36: Tumours of the meninges........................... 1803 Chapter 44: Hereditary tumour
Arie Perry syndromes...................................................................... 1926
Arie Perry
Chapter 37: Mesenchymal non-meningothelial
tumours............................................................................ 1828 Chapter 45: Paraneoplastic syndromes......................... 1945
Christine E Fuller and Knarik Arkun Marc K Rosenblum

Chapter 38: Germ cell tumours...................................... 1834 Chapter 46: CNS reactions to anti-neoplastic
Marc K Rosenblum therapies......................................................................... 1954
Arie Perry
Chapter 39: Melanocytic tumours and
haemangioblastoma....................................................... 1844 Index...................................................................................I-1
Arie Perry

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 Preface
Greenfield’s Neuropathology holds a special place in detailed molecular genetic and phenotypic information
the heart of most neuropathologists. It has long been a that is readily accessible through online resources such
standard-bearer of our specialty. In 1921, Joseph Godwin as OMIM, the database of Genotypes and Phenotypes
Greenfield and Edward Farquhar Buzzard published (dbGaP), AlzGene and PDGene. We expect readers to look
Pathology of the Nervous System, which had a key role to Greenfield’s Neuropathology for guidance and perspec-
in defining neuropathology as a distinct specialty. The tive rather than as a substitute for bibliographic databases
authors set out to ‘describe clearly the anatomical changes and search engines.
which are associated with disorders of nervous function, The changes have involved a great deal of work on the
to discuss briefly questions of pathogenesis, and to indi- part of our authors, who have shown unfailing courtesy
cate in a few words, where it is possible, the relationship and forbearance in responding to requests to condense
between structural alterations and clinical signs and symp- prose, reorganise chapters and be selective in the inclusion
toms.’ In 1958, a book entitled simply Neuropathology, of references. We are in their debt. Throughout, our objec-
by Greenfield, William Blackwood, William McMenemy, tives, much like those of Greenfield and Buzzard, have
Alfred Meyer and Ronald Norman, updated and greatly been to describe clearly the neuropathological changes
expanded on most of the content of Pathology of the that underlie neurological diseases, to discuss briefly their
Nervous System. Unlike Pathology of the Nervous System, pathogenesis, and to try to relate molecular genetic, struc-
however, Neuropathology did not cover neoplastic dis- tural and biochemical alterations to clinical and neurora-
eases (dealt with instead in a companion book, Russell diological manifestations.
and Rubinstein’s Pathology of Tumours of the Nervous Once a full account has been taken of the clinical and
System). However, tumours of the nervous system have neuroradiological manifestations of neurological disease
been included in Greenfield’s Neuropathology since the in a particular patient, a detailed visual examination of
seventh edition in 1997. the diseased tissue is the starting point for almost all neu-
Readers of a succession of editions over many decades ropathological investigations. Much of the excitement of
have dipped into this venerable reference book seek- neuropathology comes from discovering visual clues to
ing definitive advice and instruction on all matters neu- disease, macroscopic or microscopic, whether in a section
ropathological. Producing a new edition of Greenfield’s stained simply with haematoxylin and eosin, a series of
Neuropathology has therefore been both a huge privilege confocal laser scanning images or a transmission electron
and a massive responsibility. It has also been a balancing micrograph. Neuropathology remains a highly visual spe-
act, in which we have had to reconcile the tension between cialty and most of us neuropathologists obtain immense
the physical constraints of a two-volume book and the ever- aesthetic gratification from our work. Not surprisingly,
expanding amount of information encompassed within our therefore, we have placed a strong emphasis on visual
field. Indeed, this may be the last edition of Greenfield’s aspects of this reference book, which includes over one
Neuropathology that can be produced in hardcover thousand completely new photographs and drawings. It
printed format. Accommodating the additional informa- also incorporates new design elements such as the alter-
tion has largely involved a combination of reorganisation nate colour coding of chapters that is intended to allow
and restraint, together with considerably increased use of their easier navigation. To this same end, both volumes
photographs and diagrams. now include full indexes to the whole book. There are
The reorganisation has involved the merging of vascu- also improved search, annotation and bookmarking
lar disease, hypoxia and related conditions into a single facilities in the bundled bonus e-book version of this edi-
chapter; the subdivision of movement disorders into sepa- tion. The e-book frees users from most of the physical
rate chapters on extrapyramidal disorders, ataxias and limitations (not least of which are the size and weight)
motor neuron diseases; the inclusion of separate chap- of the printed version and can be downloaded to a wide
ters on ageing and dementia, the latter encompassing an range of mobile and electronic devices, so that it is not
expanded section on vascular dementia; and the further necessary to be online to have full access to Greenfield’s
subdivision of the tumour section from two chapters in the Neuropathology.
previous edition to twenty-one in the present one, which Publication of this ninth edition of Greenfield’s
we hope will make this part of the book easier to navigate. Neuropathology would not have been possible without
The total number of chapters in the book has increased the support of many people, initially at Hodder Arnold
from twenty-four to forty-six. Restraint has been applied and subsequently at Taylor and Francis. At Hodder
in relation to the inclusion of references and of some very Arnold, Joanna Koster, Editorial Director; Caroline

VII

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 VIII Preface

Makepeace, Head of Postgraduate and Professional We are pleased to present the ninth edition of Greenfield’s
Publishing; Mischa Barrett, Project Editor; and Miriam Neuropathology. We hope you obtain as much satisfaction
Trent, Editorial Assistant, were closely involved in the from reading this book as we have from editing it.
early stages. At Taylor and Francis, Barbara Norwitz,
Executive Editor; Amy Blalock, Supervisor, Editorial
Project Development; Rachael Russell, Senior Editorial
Assistant; and Linda Van Pelt, Senior Project Manager, S Love
Medical, all worked on different stages of the title, and H Budka
one person who merits special thanks is Sue Hodgson for J W Ironside
her invaluable help as Executive Editor. Glenys Norquay A Perry
provided freelance support and Jayne Jones designed the
cover and interior pages. November 2014

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 Contributors
Knarik Arkun, md Patrick F Chinnery,
Director bmedsci, mbbs, phd, frcp, frcpath, fmedsci
Neuropathology and Autopsy Service Professor of Neurogenetics
Assistant Professor Newcastle University
Department of Pathology Newcastle upon Tyne, UK
Tufts Medical Center
Boston, MA, USA H Brent Clark, md, phd
Director of Neuropathology
Sylvia L Asa, md, phd Professor of Laboratory Medicine and Pathology,
Medical Director Neurology, and Neurosurgery
Laboratory Medicine Program University of Minnesota Medical School
University Health Network Minneapolis, MN, USA
Lakeridge Health & Women’s College Hospital
Senior Scientist Tim J Crow, mbbs, phd, frcp, frcpsych, fmedsci
Ontario Cancer Institute SANE POWIC
Professor University Department of Psychiatry
Department of Laboratory Medicine and Pathobiology Warneford Hospital
University of Toronto Oxford, UK
Toronto, ON, Canada
Matthew D Cykowski, md
Juan M Bilbao, frcp (Canada) Neuropathology Fellowship Program
Professor Emeritus of Neuropathology Houston Methodist Hospital/MD Anderson Cancer Center
St Michael’s and Sunnybrook Hospitals Houston, TX, USA
University of Toronto
Jean Debarros, phd, MBPsS
Toronto, ON, Canada
Research Clinical Psychologist
Counselling Service
Daniel J Brat, md, phd
University of Oxford
Professor and Vice Chair
Oxford, UK
Translational Programs
Department of Pathology and Laboratory Medicine Martina Deckert, md
Emory University School of Medicine Professor
Georgia Research Alliance Distinguished Cancer Scientist Department of Neuropathology
Atlanta, GA, USA University Hospital of Cologne
Cologne, Germany
Susan C Brown, phd
Reader in Translational Medicine Marc R Del Bigio, md, phd, frcpC
Comparative Biomedical Sciences Canada Research Chair in Developmental
Royal Veterinary College Neuropathology
London, UK Professor
Department of Pathology (Neuropathology)
Herbert Budka, md University of Manitoba
Professor of Neuropathology Winnipeg, MB, Canada
Consultant, Institute of Neuropathology
University Hospital Zurich Salvatore DiMauro, md
Zurich, Switzerland Lucy G Moses Professor
Department of Neurology
Steven A Chance, dphil Columbia University Medical Center
Associate Professor in Clinical Neurosciences New York, NY, USA
Department of Neuropathology
University of Oxford Ann-Christine Duhaime, md
Oxford, UK Director
Pediatric Neurosurgery
Leila Chimelli, md, phd Massachusetts General Hospital
Professor of Pathology Nicholas T Zervas Professor of Neurosurgery
Federal University of Rio de Janeiro Harvard Medical School
Rio de Janeiro, Brazil Boston, MA, USA
IX

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 X Contributors

Charles Eberhart, md, phd Jeffrey A Golden, md

Professor of Pathology, Ophthalmology and Oncology Chair
Director of Neuropathology and Ophthalmic Pathology Department of Pathology
Johns Hopkins University School of Medicine Brigham and Women’s Hospital
Baltimore, MD, USA Ramzi S Cotran Professor of Pathology
Harvard Medical School
Margaret M Esiri, DM, FRCPath Boston, MA, USA
Neuropathology Department
John Radcliffe Hospital Glenda M Halliday, phd
Emeritus Professor of Neuropathology Professor of Neuroscience and NHMRC Senior Principal
Nuffield Department of Clinical Neurosciences Research Fellow
University of Oxford School of Medical Sciences and Neuroscience Research
Oxford, UK Australia
University of New South Wales
Phyllis L Faust, md, phd Sydney, NSW, Australia
Associate Professor of Clinical Pathology and Cell Biology
Department of Pathology and Cell Biology Brian N Harding, MA, DPhil, BM, BCh, FRCPath
Columbia University Department of Pathology and
New York, NY, USA Laboratory Medicine
Children’s Hospital of Philadelphia
Isidro Ferrer, md, phd Perelman School of Medicine
Professor University of Pennsylvania
Institute of Neuropathology Philadelphia, PA, USA
Bellvitge University Hospital and University of Barcelona
Hospitalet de Llobregat John B Harris, phd, BPharm, FSocBiol, MRPharmSoc
Barcelona, Spain Emeritus Professor of Experimental
Neurology
Rebecca D Folkerth, md
Medical Toxicology Centre
Director of Neuropathology
Newcastle University
Department of Pathology
Newcastle upon Tyne, UK
Brigham and Women’s Hospital
Consultant in Neuropathology
Jason F Harrison, md, phd
Boston Children’s Hospital
Neurosurgery Resident
Associate Professor of Pathology
Department of Neurosurgery
Harvard Medical School
Virginia Commonwealth University
Boston, MA, USA
Richmond, VA, USA
Christine E Fuller, md
Professor Mark W Head, BSc, phd
Pathology and Neurology Reader
Director University of Edinburgh
Neuropathology and Autopsy Pathology Deputy Director
Department of Pathology National CJD Research & Surveillance Unit
Virginia Commonwealth University Edinburgh, Scotland
Richmond, VA, USA
J Robin Highley, DPhil, FRCPath
Gregory N Fuller, md, phd Senior Clinical Lecturer in Neuropathology
Professor and Chief Department of Neuroscience
Section of Neuropathology Sheffield Institute of Translational Neuroscience
The University of Texas University of Sheffield
MD Anderson Cancer Center Sheffield, UK
Department of Pathology
Houston, TX, USA Janice L Holton, BSc, MBChB, phd, FRCPath
Professor of Neuropathology
Bernardino Ghetti, MD, FANA, FAAAS Department of Molecular Neuroscience
Distinguished Professor University College London Institute of Neurology
Indiana University London, UK
Chancellor’s Professor
Indiana University-Purdue University Indianapolis Henry H Houlden, md, phd
Department of Pathology and Laboratory Medicine Professor of Neurology and Neurogenetics
Division of Neuropathology Department of Molecular Neuroscience
Indiana University School of Medicine University College London Institute of Neurology
Indianapolis, IN, USA London, UK

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 Contributors XI

Paul G Ince, MBBS, md, FRCPath B K Kleinschmidt-DeMasters, md

Professor of Neuropathology Professor of Pathology, Neurology, and
Head of Department of Neuroscience Neurosurgery
University of Sheffield Department of Pathology
Sheffield, UK University of Colorado School of Medicine
Aurora, CO, USA
James W Ironside, CBE, BMSc, FRCPath,
FRCPEdin, FMedSci, FRSE Jillian Kril, phd, FFSc (RCPA)
Professor of Clinical Neuropathology and Honorary Professor of Neuropathology
Consultant in Neuropathology Sydney Medical School
National Creutzfeldt–Jakob Disease Surveillance Unit The University of Sydney
University of Edinburgh Sydney, NSW, Australia
Western General Hospital
Edinburgh, UK Nichola Z Lax, phd
Research Associate
Thomas S Jacques, phd, MRCP, FRCPath Wellcome Trust Centre for Mitochondrial
Higher Education Funding Council for England Research
Clinical Senior Lecturer Institute of Neuroscience
Honorary Consultant Newcastle University
Paediatric Neuropathologist Newcastle upon Tyne, UK
University College London Institute of Child Health and
Great Ormond Street Hospital David N Louis, md
Department of Histopathology Pathologist-in-Chief
Great Ormond Street Hospital for Children NHS Massachusetts General Hospital
Foundation Trust Benjamin Castleman Professor of
London, UK Pathology
Harvard Medical School
Evelyn Jaros, phd James Homer Wright Pathology
Clinical Scientist in Neuropathology Laboratories
Neuropathology/Cellular Pathology Massachusetts General Hospital
Newcastle upon Tyne Hospitals NHS Foundation Trust Boston, MA, USA
Honorary Senior Research Associate
Institute of Neuroscience and Institute for Ageing Seth Love, MBBCh, phd, FRCP, FRCPath
Newcastle University Professor of Neuropathology
Campus for Ageing and Vitality Institute of Clinical Neurosciences
Newcastle upon Tyne, UK School of Clinical Sciences
University of Bristol
Martin Jeffrey, BVMS, DVM, Dip ECVP, Southmead Hospital
MRCVS, FRCPath Bristol, UK
Consultant Pathologist
Pathology Department James Lowe, DM, FRCPath
Animal Health and Veterinary Laboratories Agency Professor of Neuropathology
(AHVLA-Lasswade) University of Nottingham
Penicuik, UK Honorary Consultant in Neuropathology to
the Nottingham University Hospitals
Anne Jouvet, md, phd NHS Trust
Associate Professor of Pathology School of Medicine
Centre de Pathologie et Neuropathologie Est Faculty of Medicine and Health Sciences
Centre de Biologie et Pathologie Est University of Nottingham
Groupement Hospitalier Est Nottingham, UK
Hospices Civils de Lyon
Lyon, France Sebastian Lucas, FRCP, FRCPath
Emeritus Professor of Histopathology
Raj Kalaria, phd, FRCPath Department of Histopathology
Professor of Cerebrovascular Pathology St Thomas’ Hospital
(Neuropathology) London, UK
Institute of Neuroscience
Newcastle University Susan S Margulies, phd
National Institute for Health Research Biomedical George H Stephenson Professor
Research Building Department of Bioengineering
Campus for Ageing and Vitality University of Pennsylvania
Newcastle upon Tyne, UK Philadelphia, PA, USA

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 XII Contributors

Michelle Fevre Montange, phd James M Powers, md

Centre de Recherche en Neuroscience de Lyon Professor Emeritus
INSERM U1028 Department of Pathology
CNRS UMR 5292 University of Rochester School of Medicine
Equipe Neuro-oncologie et Neuro-inflammation and Dentistry
Université de Lyon Rochester, NY, USA
Lyon, France
Robin Reid, BSc, MBChB, FRCPath
G R Wayne Moore, BSc, md, CM, FRCPC, FRCPath Formerly Consultant Pathologist
Clinical Professor Western Infirmary
Department of Pathology and Laboratory Medicine Glasgow, UK
International Collaboration on Repair Discoveries (ICORD)
University of British Columbia Guido Reifenberger, md
Vancouver General Hospital Professor
Vancouver, BC, Canada Department of Neuropathology
Heinrich Heine University
Christopher M Morris, phd Düsseldorf, Germany
Senior Lecturer
Medical Toxicology Centre Tamas Revesz, md, FRCPath
National Institutes of Health Research Professor Emeritus in Neuropathology
Health Protection Research Unit in Chemical and UCL Institute of Neurology
Radiation Threats and Hazards University College London
Institute of Neuroscience London, UK
Newcastle University
Newcastle upon Tyne, UK Hope T Richard, md, phd
Neuropathology Fellow
Francesco Muntoni, FRCPCH, FMedSci
Department of Pathology
Director
Virginia Commonwealth University
Dubowitz Neuromuscular Centre
Richmond, VA, USA
MRC Centre for Neuromuscular Diseases
University College London Institute of Child Health and
Marc K Rosenblum, md
Great Ormond Street Hospital for Children (GOSH)
Founder’s Chair and Chief
London, UK
Neuropathology and Autopsy Service
Arie Perry, md Memorial Sloan-Kettering Cancer Center
Professor of Pathology and Neurological Surgery Professor of Pathology and Laboratory
Director of Neuropathology Medicine
Director of Neuropathology Fellowship Training Program Weill Medical College of Cornell
University of California, San Francisco University
San Francisco, CA, USA New York, NY, USA

Rahul Phadke, MBBS, md, FRCPath Robert E Schmidt, md, phd

Consultant Neuropathologist Professor of Pathology and Immunology
University College London Institute of Neurology Director
National Hospital for Neurology and Neurosurgery and Division of Neuropathology
Dubowitz Neuromuscular Centre Medical Director
Great Ormond Street Hospital for Children Electron Microscope Facility
London, UK Washington University School of Medicine
St Louis, MO, USA
Pedro Piccardo, md
Senior Investigator Caroline A Sewry, phd, FRCPath
Chief Transmissible Spongiform Encephalopathy Professor of Muscle Pathology
Pathogenesis Section Dubowitz Neuromuscular Centre
Laboratory of Bacterial and TSE Agents Institute of Child Health and Great Ormond Street
Office of Blood Research and Review Hospital
Center for Biologics Evaluation and Research London
U.S. Food and Drug Administration Wolfson Centre for Inherited Neuromuscular
Silver Spring, MD, USA Diseases
Professor Robert Jones and Agnes Hunt Orthopaedic
Neurobiology Division Hospital
The Roslin Institute Oswestry, UK
University of Edinburgh
Easter Bush, UK

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 Contributors XIII

Sanjay Sisodiya, MA, phd, FRCP, FRCPEdin Alexandre Vasiljevic, md

Professor of Neurology Associate Professor of Pathology
Department of Clinical and Experimental Epilepsy Centre de Pathologie et Neuropathologie Est
UCL Institute of Neurology Centre de Biologie et Pathologie Est
London Groupement Hospitalier Est
Consultant Neurologist Hospices Civils de Lyon
Epilepsy Society Lyon, France
National Hospital for Neurology and Neurosurgery
Chalfton St Peter, UK Harry V Vinters, md
Professor of Pathology and Laboratory Medicine,
Colin Smith, md, FRCPath Neurology
Reader in Pathology Chief of Neuropathology
University of Edinburgh Division of Neuropathology
Edinburgh, UK Member of Brain Research Institute ACCESS
Program
Christine Stadelmann-Nessler, md Department of Cellular and Molecular
Professor Pathology
Department of Neuropathology University of California, Los Angeles
University Medical Center Göttingen Los Angeles, CA, USA
Göttingen, Germany
Steven U Walkley, DVM, phd
Kinuko Suzuki, md Director
Emeritus Professor of Pathology and Laboratory Medicine Rose F Kennedy Intellectual and Developmental
University of North Carolina at Chapel Hill Disabilities Research Center
Chapel Hill, NC, USA Head
Neuropathology Sidney Weisner Laboratory of Genetic
Tokyo Metropolitan Institute of Gerontology Neurological Disease
Tokyo, Japan Departments of Neuroscience, Pathology and
Neurology
Kunihiko Suzuki, md Albert Einstein College of Medicine
Director Emeritus Bronx, NY, USA
Neuroscience Center
University of North Carolina Stephen B Wharton, BSc, MBBS, phd, FRCPath
Chapel Hill, NC, USA Professor and Honorary Consultant in Neuropathology
Department of Neuroscience
Robert W Taylor, phd, DSc, FRCPath Sheffield Institute of Translational Neuroscience
Professor of Mitochondrial Pathology University of Sheffield
Wellcome Trust Centre for Mitochondrial Research Sheffield, UK
Institute of Neuroscience
Newcastle University Clayton A Wiley, md, phd
Newcastle upon Tyne, UK Professor of Pathology
Director of Neuropathology
Maria Thom, BSc, MBBS, MRCPath PERF Endowed Chair
Senior Lecturer Univeristy of Pittsburgh Medical Center
Institute of Neurology Presbyterian Hospital
University College London Pittsburgh, PA, USA
London, UK
Robert G Will, MA, md, FRCP
Douglas M Turnbull, md, phd, FRCP, FMedSc Professor of Clinical Neurology
Professor of Neurology National Creutzfeldt–Jakob Disease Surveillance Unit
Director University of Edinburgh
Wellcome Trust Centre for Mitochondrial Research Western General Hospital
Director Edinburgh, UK
LLHW Centre for Ageing and Vitality
Newcastle University
Newcastle upon Tyne, UK

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 XIV Abbreviations

Abbreviations
AA anaplastic astrocytoma AMSAN acute motor sensory axonal neuropathy
AACD age-associated cognitive decline ANA antinuclear antibody
AAMI age-associated memory impairment ANCA antineutrophil cytoplasmic autoantibody
ABC ATP-binding cassette ANCL adult neuronal ceroid lipofuscinosis
ABCA1 ATP-binding cassette transporter 1 Ang-1 angiopoietin-1
ABRA Aβ-related angiitis Ang-2 angiopoietin-2
ACA anterior cerebral artery ANI asymptomatic neurocognitive impairment
ACC adrenocortical carcinoma AOA1 early-onset ataxia with oculomotor
ACCIS Automated Childhood Cancer apraxia, type 1
Information System APGBD adult polyglucosan body disease
ACh acetylcholine APLA antiphospholipid antibody
AChR acetylcholine receptor ApoE apolipoprotein E
ACTH adrenocorticotropin APP amyloid precursor protein
AD Alzheimer disease APrP amyloid prion protein
ADAMTS13 a disintegrin and metalloproteinase with a APUD amine precursor uptake and
thrombospondin type 1 motif, member 13 decarboxylation
ADC apparent diffusion coefficient AQP4 aquaporin-4
ADCA autosomal dominant cerebellar ataxia AR androgen receptor
ADEM acute disseminated encephalomyelitis ARBD alcohol-related brain damage
ADK adenosine kinase ARFGEF2 adenosine diphosphate (ADP)-
ADNFLE autosomal dominant nocturnal frontal ribosylation factor guanine exchange
lobe epilepsy factor 2
ADP adenosine diphosphate ASA arylsulfatase A
AFP alpha-fetoprotein ASDH acute subdural haematoma
AGA aspartylglucosaminidase ASE acute schistosomal encephalopathy
AGE advanced glycosylation end product ASL arterial spin labelling
AGPS alkylglycerone phosphate synthase AT ataxia telangiectasia
AGS Aicardi-Goutières syndrome ATP adenosine triphosphate
AGU aspartylglucosaminuria ATRT atypical teratoid/rhabdoid tumour
AHLE acute haemorrhagic leukoencephalitis ATTR amyloid transthyretin
AHT abusive head trauma AVM arteriovenous malformation
AIDP acute inflammatory demyelinating BA Brodmann area
polyneuropathy BACE β-site APP-cleaving enzyme
AIDS acquired immunodeficiency syndrome BAC bacterial artificial chromosome
AIP aryl hydrocarbon receptor-interacting BAV Banna virus
protein BBB blood-brain barrier
AIS axon initial segment BDNF brain-derived neurotrophic factor
AISS axonal index sector score BDV Borna disease virus
AL amyloidosis BEAN brain expressed protein associated with
ALCL anaplastic large cell lymphoma NEDD4
ALD adrenoleukodystrophy bFGF basic fibroblast growth factor
ALK anaplastic lymphoma kinase BGC basal ganglia calcification
ALL acute lymphoblastic leukemia BHC benign hereditary chorea
ALS amyotrophic lateral sclerosis BMAA β-N-methylamino-l-alanine
ALT alternative lengthening of telomeres BMD Becker muscular dystrophy
AMAN acute motor axonal neuropathy BMP bone morphogenetic protein
AMN adrenomyeloneuropathy BOLD blood oxygenation dependent
AMPA α-amino-3-hydroxy-5-methyl-4- bp base pair
isoxazolepropionic acid BPAU bromophenylacetylurea
XIV

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 Abbreviations XV

BRC brain reserve capacity CLL chronic lymphatic leukaemia

BRRS Bannayan-Riley-Ruvalcaba syndrome CM cerebral malaria
BSE bovine spongiform encephalopathy CMD congenital muscular dystrophy
CAA cerebral amyloid angiopathy CMRgl cerebral metabolic rate for glucose
CADASIL cerebral autosomal dominant CMRO2 cerebral metabolic rate for oxygen
­arteriopathy with subcortical infarcts CMROGl cerebral metabolic rates of oxygen and
and leukoencephalopathy glucose
CAE childhood absence epilepsy CMT Charcot–Marie–Tooth
CAHS chronic acquired hepatocerebral CMV cytomegalovirus
syndrome CN cystic nephroma
CAMTA1 calmodulin-binding transcription
CNC Carney’s complex
­activator 1
c-ANCA cytoplasmic antineutrophil cytoplasmic CNP 2ʹ,3ʹ-cyclic nucleotide
antibody 3ʹ-phosphodiesterase
CANOMAD chronic ataxic neuropathy, CNS central nervous system
­ophthalmoplegia, M-protein CNS PNET central nervous system primitive
­agglutination, disialosyl antibodies ­neuroectodermal tumour
CAR coxsackievirus and adenovirus receptor CNTF ciliary neurotrophic factor
CARASIL cerebral autosomal recessive ­arteriopathy CO carbon monoxide
with subcortical infarcts and COL4A1 collagen, type IV, alpha 1
leukoencephalopathy COX cytochrome c oxidase
cART combined antiretroviral therapy COX-2 cyclooxygenase-2
CASK calcium-dependent serine protein kinase CP choroid plexus
CBD corticobasal degeneration CPCS chronic post-concussion syndrome
CBF cerebral blood flow CPM central pontine myelinolysis
CBS corticobasal syndrome CPP cerebral perfusion pressure; central
CBTRUS Central Brain Tumor Registry of the ­precocious puberty
United States CPT carnitine palmitoyltransferase
CCM cerebral cavernous malformation CR cognitive reserve
CCSVI chronic cerebrospinal venous CR3 complement receptor type 3
insufficiency
CRABP cellular retinoic acid binding protein
CD Cowden disease
CRBP cytoplasmic retinol binding protein
CDE common data elements
CREB cyclic adenine dinucleotide phosphate
CDI conformation dependent immunoassay response element binding protein
CDK5 cyclin-dependent kinase 5 CRH corticotropin-releasing hormone
CDKI cyclin-dependent kinase inhibitor CRIMYNE critical illness myopathy and
CDKN2C cyclin-dependent kinase inhibitor 2C neuropathy
CDV canine distemper virus CRMP-5 collapsing response mediator protein 5
CEA carcinoembryonic antigen CRV cerebroretinal vasculopathy
CESD cholesteryl ester storage disease CSDH chronic subdural haematoma
CGH comparative genomic hybridization CSF cerebrospinal fluid
cGMP cyclic guanosine monophosphate CSPα cysteine string protein α
CGRP calcitonin gene-related peptide CT computed tomography
CHD5 chromodomain helicase DNA binding CTD connective tissue disease
domain 5 CTE chronic traumatic encephalopathy
CHN congenital hypomyelinating neuropathy CTF Colorado tick fever
CHS classical hippocampal sclerosis CTL cytotoxic lymphocyte
CIM critical illness myopathy CUP cancer of unknown primary
CIP critical illness polyneuropathy CUTE corticotropin upstream ­transcription-
CIPD chronic inflammatory demyelinating binding element
polyneuropathy CuZnSOD copper- and zinc-containing superoxide
CIS clinically isolated syndrome dismutase
CISP chronic immune sensory CVD cardiovascular disease
polyradiculopathy CVS chorionic villus sampling
CK cytokeratin; creatine kinase CVST cerebral venous sinus thrombosis
CLA2 X-linked cerebellar ataxia CVT cerebral venous thrombosis

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 XVI Abbreviations

CWD chronic wasting disease EDH extradural haematoma

CX32 connexin 32 EEE eastern equine encephalitis
DAB diaminobenzidine EEG electroencephalogram
DAG dystrophin-associated glycoprotein EET epoxyeicosatrienoic acid
DAI diffuse axonal injury EF HS end folium hippocampal sclerosis
DAPAT dihydroxyacetonephosphate EGA estimated gestational age
acyltransferase EGB eosinophilic granular body
DASE developmentally arrested structural EGFR epidermal growth factor receptor
elements
EGL external granule cell layer
DAWM diffusely abnormal white matter
EGR2 early growth response 2 gene
DCX doublecortin
EIEE early infantile epileptic encephalopathy
DEHSI diffuse excessive high-signal intensity
EL encephalitis lethargica
DFFB DNA fragmentation factor subunit beta
ELBW extreme low birth weight
DHA docosahexaenoic acid
DHAP dihydroxyacetone phosphate ELISA enzyme-linked immunosorbent assay
DHPR dihydropyridine receptor EM electron microscopy
Dil dioctadecyl-tetramethylindocarbacyanine EMA epithelial membrane antigen
perchlorate EME early myoclonic encephalopathy
DILS diffuse infiltrative lymphocytosis EMG electromyography
syndrome
DIR double inversion recovery EMT epithelial-mesenchymal transition
DLB dementia with Lewy bodies eNSC embryonic neural stem cell
DLBCL diffuse large B cell lymphoma ENU ethylnitrosourea
DLK dual leucine kinase EPC endothelial progenitor cell
DM dermatomyositis EPMR epilepsy with mental retardation
DMD Duchenne muscular dystrophy ER endoplasmic reticulum
DMNV dorsal motor nucleus of the vagus ERG electroretinogram
DMPK dermatomyositis protein kinase ERK extracellular signal-regulated kinase
DNER delta/notch-like epidermal growth ­factor- ERM ezrin, radixin and moesin
related receptor ESAM endothelial cell-selective adhesion
DNL disseminated necrotizing molecule
leukoencephalopathy ESR erythrocyte sedimentation rate
DNMT DNA methyltransferase ETANTR embryonal tumour with abundant
DNT dysembryoplastic neuroepithelial tumour ­neuropil and true rosettes
DPR dipeptide repeat ETMR embryonal tumor with multilayered
DPX di-n-butylphthalate-polystyrene-xylene rosettes
EVOH ethylene-vinyl alcohol copolymer
DRD dopa-responsive dystonia
FA Friedreich’s ataxia
DRPLA dentatorubropallidoluysian atrophy
FACS fluorescence-activated cell sorting
DSD Dejerine-Sottas disease
FAD familial Alzheimer’s disease
DSPN diffuse sensory polyneuropathy
FAF familial amyloidosis of the Finnish type
DTI diffusion tensor imaging
FAK focal adhesion kinase
DTICH delayed traumatic intracerebral
haemorrhage FALS familial amyotrophic lateral sclerosis
DWI diffusion weighted imaging FAP familial amyloid polyneuropathy; familial
DXC doublecortin polyposis
FBD familial British dementia
EA episodic ataxia
FBXO7 F-box only protein 7
EAAT excitatory amino acid transporter
FCD focal cortical dysplasia; follicular
EAN experimental allergic neuritis
­dendritic cell
EBP elastin-binding protein FCE fibrocartilaginous embolism
EBV Epstein-Barr virus fCJD familial Creutzfeldt-Jakob disease
EC endothelial cell; entorhinal cortex FDD familial Danish dementia
ECGF1 endothelial cell growth factor 1 FDF-2 fibroblast growth factor 2
­(platelet-derived) FFI fatal familial insomnia
ECM extracellular matrix
FFPE formalin-fixed paraffin-embedded tissue
ECMO extracorporeal membrane oxygenation

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