Table Of ContentGreenfield’s Neuropathology
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Greenfield’s Neuropathology
Eighth edition
Edited by
Seth Love MBBCh PhD FRCP FRCPath
Professor of Neuropathology
Institute of Clinical Neurosciences
Frenchay Hospital
Bristol, UK
David N LouisMD
Benjamin Castleman Professor of Pathology
Harvard Medical School; and
Pathologist-in-Chief
James Homer Wright Pathology Laboratories
Massachusetts General Hospital
Boston, MA, USA
David W Ellison MD PhD MA MSc MBBChir MRCP(UK) FRCPath
Department of Pathology
St Jude Children’s Research Hospital
Memphis, TN, USA
Hodder Arnold
www.hoddereducation.com
First published in Great Britain in 1958
Second edition 1963
Third edition 1976
Fourth edition 1984
Fifth edition 1992
Sixth edition 1997
Seventh edition 2002
This eighth edition published in 2008 by Hodder Arnold, an imprint of
Hodder Education, part of Hachette Livre UK, 338 Euston Road, London
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© 2008 Edward Arnold (Publishers) Ltd
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Dedication
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Contents
Contributors xxiii Infratentorial expanding lesions 52
External cerebral herniae 52
Preface xxvii
Hydrocephalus: pathophysiology, causes and consequences
Abbreviations xxix for the central nervous system 52
Treatment of hydrocephalus, and its effects on central
nervous system structure and function 55
Volume 1
Acknowledgements 56
Chapter 1: General pathology of the central References 56
nervous system
Chapter 2: Hypoxia and related conditions
Harry V Vinters and BK Kleinschmidt-DeMasters
Roland N Auer, Jeffrey F Dunn and Garnette R Sutherland
Neurons 1
Astrocytes 8 Introduction 63
Role of astrocytes in central nervous system Oxygen delivery and metabolism 65
development and regeneration 14 Ventilation 66
Trophic effects and influence of astrocytes on vascular Circulation 67
structure, integrity and physiology 17 Respiration 69
Physiology, metabolism and neurochemistry of astrocytes 18 Selective neuronal necrosis versus pan-necrosis 71
Pathological reactions and role in neurological disease 20 Selective neuronal necrosis 71
Oligodendrocytes 22 Pan-necrosis or infarction 73
Ependyma 26 Acidophilic ‘pink’ neurons 74
Microglia and macrophages 29 Delayed neuronal death 76
Identifying microglia and quantifying microgliosis 30 Apoptosis 76
Microglial types 30 The hypoxic insults 76
Functions of microglia 30 Hypoxaemia 76
Pathological reactions of microglia 32 High-altitude hypoxia and brain damage 78
Microglia in disease/injury states 32 Severe hypoxia other than at altitude 78
Distinguishing pathological abnormalities from Anaemia 79
artefacts and incidentals 34 Cardiac arrest encephalopathy (transient global ischaemia) 79
Stem cells in the central nervous system: promise, Hypoxia versus ischaemia 84
potential and reality 34 Ischaemic neuroprotection 87
Concept of the blood–brain barrier and the Excitatory amino acid antagonism 88
neurovascular unit 45 Hyperoxic brain damage 89
Determinants of intracranial pressure and pressure/volume Asphyxia 89
relationships, and causes and consequences of raised Histotoxic hypoxia 90
intracranial pressure 47 Air embolism and decompression sickness 91
Pathology of intracranial expanding lesions 47 Non-perfused brain (respirator brain; permanent global
Supratentorial expanding lesions 48 ischaemia) 92
Supracallosal subfalcine (or cingulate) hernia 48 ‘Swiss cheese brain’ 94
Tentorial (uncal or lateral transtentorial) hernia 48 Dark neurons 95
Central transtentorial herniation 50 Clinical neuropathology 95
Haemorrhage and infarction of the midbrain and pons 51 Experimental neuropathology 95
Tonsillar hernia (foraminal impaction, cerebellar cone) 51 Carbon monoxide 96
Diffuse brain swelling 52 Epidemiology 96
viii Contents
Carbon monoxide levels 96 Vascular diseases of the pituitary gland 219
Brain appearance in carbon monoxide poisoning 96 Acknowledgements 220
Mechanisms of brain damage in carbon monoxide References 220
poisoning 96
Low dose carbon monoxide exposure and psychic akinesia 98 Chapter 4: Disorders of the perinatal period
White matter damage in carbon monoxide poisoning 99
Hypoglycaemic brain damage 99 Rebecca D Folkerth and Hannah C Kinney
History of hypoglycaemic brain damage 99
Introduction 241
Biochemical basis of hypoglycaemic brain damage 100
Approach to evaluation of perinatal specimens 244
Pharmacology of hypoglycaemic brain damage 101
Brain growth 245
Morphology of hypoglycaemic brain damage 101
Cellular components of the developing human
Selective vulnerability 103
central nervous system 247
Selective vulnerability in general neuropathology 103
Neurons 247
Selective vulnerability in hypoxic and ischaemic states 104
Astrocytes 254
References 105
Oligodendrocytes and central nervous system myelination 256
Microglia 260
Chapter 3: Vascular diseases Ependyma 262
Cellular mechanisms of damage to the developing brain 263
Isidro Ferrer, Markku Kaste and Hannu Kalimo
Grey matter lesions 264
Introduction 121 Hypoxic–ischaemic neuronal cell injury 264
Development and anatomy 121 Factors contributing to neuronal vulnerability to
Development of cerebral vasculature 121 hypoxia–ischaemia in the perinatal brain 267
Arterial blood supply 123 Neuropathology of neuronal injury in perinatal
Venous drainage 127 hypoxia–ischaemia 269
Physiology of the cerebral circulation 131 White matter lesions 273
Definitions and epidemiology of vascular disorders Vascular zones, cerebral autoregulation and
of the central nervous system 131 susceptibility to ischaemia 277
Stroke in general 131 Maturation-related vulnerability of oligodendrocytes
Stroke incidence rates 132 to injury in periventricular leukomalacia 278
Stroke mortality rates 133 Axonal injury in periventricular leukomalacia 282
Risk factors for stroke 133 Cerebral diffuse white matter gliosis 283
Diseases affecting the blood vessels 134 Long-term consequences of perinatal white matter damage284
Atherosclerosis 134 Combined grey and white matter lesions 285
Diseases of small arteries 138 Parasagittal cerebral injury 285
Small vessel disease 139 Neonatal ‘stroke’ 285
Cerebral amyloid angiopathy 142 Porencephaly 289
Hereditary small vessel diseases 146 Near-total asphyxia and multicystic encephalopathy 289
Inflammatory diseases 151 Cerebral haemorrhages 290
Vascular malformations and aneurysms 161 Intraventricular haemorrhage 290
Miscellaneous diseases of blood vessels 173 Cerebellar haemorrhages 294
Haematological disorders 176 Intracerebral haemorrhage 294
Thrombosis and antithrombosis 176 Hypoglycaemia 295
Thrombophilia 177 Kernicterus 296
Antiphospholipid antibodies 178 Infection 297
Polycythaemia and hyperviscosity 179 Neonatal meningitis 298
Anaemias 179 Meningitis in the infant 300
Platelet abnormalities 180 Fungal infections 300
Consequences of cerebrovascular disorders 180 TORCH infections 300
Focal cerebral arterial ischaemia 180 Birth trauma 304
Venous thrombosis and infarction 203 Head and brain injuries 304
Parenchymal brain haemorrhage 204 Nerve injury 305
Subarachnoid haemorrhage 211 Spinal cord and brain stem injury 305
Vascular diseases of the spinal cord 214 Arthrogryposis multiplex congenita 306
Atherosclerosis of spinal cord arteries 214 Sudden infant death syndrome 306
Vascular malformations of the spinal cord 214 Neuropathology of the stillborn 312
Spinal cord ischaemia 216 References 315
Contents ix
Chapter 5: Malformations Aicardi–Goutières leukoencephalopathy 493
Megalencephalic leukoencephalopathy with
Brian N Harding and Andrew J Copp subcortical cysts 494
Introduction 335 Vanishing white matter disease, or childhood
Principles of nervous system development 335 ataxia with central hypomyelination syndrome 495
Aetiology 336 Pigmentary type of orthochromatic leukodystrophy 497
Pathogenesis 348 Inborn errors of intermediary metabolism 497
A guide to interpreting the pathogenesis of malformations 356 The hyperphenylalaninaemic syndromes 497
Pathology of malformations 356 Non-ketotic hyperglycinaemia 498
Neural tube defects: dysraphic disorders 356 The homocystinurias 499
Chiari malformations 363 Organic acid disorders 501
Disorders of forebrain induction 368 Urea cycle disorders 503
Neuronal migration disorders 379 Congenital disorders of glycosylation 504
Encephaloclastic defects 403 CDG-Ia (phosphomannomutase deficiency) 506
Microcephaly 408 CDG-IIa (N-acetylglucosaminyltransferase II deficiency) 506
Environmental factors 410 References 506
Megalencephaly 412
Hemi-megalencephaly 412 Chapter 7: Lysosomal diseases
Anomalies of the wall of the lateral ventricles 412
Third ventricular obliteration 413 Kinuko Suzuki and Kunihiko Suzuki
Malformations of the cerebellum 413 Introduction 515
Brain stem malformations 425 Sphingolipidoses 515
Malformations of the spinal cord 429 Gangliosidoses 516
Syringobulbia 431 Niemann–Pick disease types A and B 528
Vascular malformations 434 Gaucher disease 530
Arachnoid cysts 437 Farber disease 533
Phakomatosis 439 Fabry disease 534
Hydrocephalus 444 Metachromatic leukodystrophy and multiple sulphatase
Congenital disorders of the pituitary 448 deficiency 535
Ectopic adenohypophysis 448 Krabbe disease (globoid cell leukodystrophy) 539
Pituitary aplasia/hypoplasia 448 Sphingolipid activator protein deficiencies 543
Pituitary duplication or dystopia 448 Mucopolysaccharidoses 544
Empty sella syndrome 449 Mucopolysaccharidosis I (Hurler and Scheie syndromes) 544
Acknowledgements 449 Mucopolysaccharidosis II (Hunter syndrome) 547
References 449 Mucopolysaccharidosis III (Sanfilippo disease) 551
Mucopolysaccharidosis IVA (Morquio A disease) 551
Chapter 6: Metabolic and neurodegenerative
Mucopolysaccharidosis VI (Maroteaux–Lamy disease) 553
diseases of childhood Mucopolysaccharidosis VII (Sly disease) 553
Mucopolysaccharidosis IX 554
Brian N Harding and Robert AH Surtees
Glycoprotein storage disorders 554
Introduction 481 Sialidase (neuraminidase) deficiency (sialidosis,
Grey matter disorders 481 mucolipidosis I) 554
Alpers–Huttenlocher syndrome (progressive neuronal α-Mannosidosis and β-mannosidosis 555
degeneration of childhood with liver disease) 481 Fucosidosis 557
Rett’s syndrome 484 Aspartylglycosaminuria (aspartylglucosaminuria) 558
Infantile neuroaxonal dystrophy 485 Schindler disease (α-N-acetylgalactosaminidase
Hallervorden–Spatz syndrome (pantothenate deficiency) 559
kinase-associated neurodegeneration or Galactosialidosis 561
neurodegeneration with brain iron accumulation Neuronal ceroid lipofuscinosis (Batten disease) 562
type I) 485 Congenital neuronal ceroid lipofuscinosis 563
Leukoencephalopathy 488 Infantile neuronal ceroid lipofuscinosis (Haltia–Santavuori
Alexander’s disease 488 disease) 563
Spongy leukodystrophy (Canavan or van Bogaert–Bertrand Late infantile neuronal ceroid lipofuscinosis
disease) 490 (Jansky–Bielschowsky disease) 565
Pelizaeus–Merzbacher disease 491 Juvenile neuronal ceroid lipofuscinosis
Cockayne syndrome 491 (Spielmeyer–Vogt–Sjøgren–Batten disease) 568
