M. Oehmichen R. N. Auer H.G. König Forensic Neuropathology and Associated Neurology

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M. Oehmichen R. N. Auer H.G. König

Forensic Neuropathology and Associated Neurology

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M. Oehmichen R. N. Auer

H.G. König

Forensic

Neuropathology and Associated Neurology

With a Foreword by Kurt A. Jellinger With 264 Figures and 69 Tables

123

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Manfred Oehmichen

Universitätsklinikum Schleswig-Holstein Institut Rechtsmedizin

Kahlhorststrasse 31–35 D-24562 Lübeck Germany

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Germany

ISBN-10 3-540-23500-0 ISBN-13 978-3-540-23500-2

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Foreword

Partly as a result of major recent advances in neurobiology and molecular sciences, but also as a con- sequence of improving methods in clinical neurosciences, general and forensic pathology, forensic neuropathology has become a highly specialized field of modern medicine, which deals with disorders of the nervous system under non-natural, traumatic, exogenous or criminal conditions. Although forensic neuropathology has a long tradition, leading from C.B. Courville (1964) via Leestma (1988), and Unterharnscheidt (1992−94) to Manfred Oeh- michen, and is of eminent importance within the field of forensic sciences, this particular and com- plicated subject has received only little attention within the scientific community. With greater and more precise understanding of the pathological, physical, biochemical, and molecular genetic processes involved in disorders of the nervous system and their relations with causes of death under natural and non-natural circumstances, the prospects of new forms of investigation into fatal processes are becoming more practicable. Based on lifelong experience in the field of general forensic medicine and, in particular, forensic pathology and neuropathology, Forensic Neuropathology and Associated Neurology, written by Manfred Oehmichen, Roland N. Auer, and Hans Günter König presents a timely overview of the state-of-the-art of examination and clarification of diseases of the nervous system under general and forensic circumstances. Like general pathology and neuropathology, its forensic part serves not only to clarify the causes of death due to nervous system disorders, but it is an important method for quality control excluding natural causes of death. Thus, forensic neuropathology, based on recent results, guidelines and standards of modern pathology and neurosciences, has become an inte- gral part of forensic medicine and practice.

The concept and the structure of the book is based on the principles of forensic neuropathology, modern cytology, cell and tissue reactions, modern biophysics, and molecular biology of the nervous system. It is an important and difficult task for the

forensic neuropathologist to differentiate naturally occurring disorders from non-natural and exogenous ones, and he needs extensive experience in order to avoid misinterpretation of cerebral lesions, which becomes more and more difficult with our increasing knowledge of the pathology and pathogenesis of nervous system disorders, the etiology of which remains to be elucidated. On the other hand, basic and clinical neuropathologists not experi- enced in forensic problems often may not be able to differentiate naturally developing disorders from forensic ones, while many forensic pathologists are not acquainted with the current neuropathological literature. The present book, the first one on forensic neuropathology after almost two decades, and the first written by German scientists after Unter- harnscheidt’s handbooks of traumatic lesions of the brain and spinal cord, closes a broad gap between clinical and forensic neuropathology. The coverage of the topics listed in the table of contents is com- prehensive and complete. After dealing with general aspects and basic mechanisms of molecular neuro- science, it reviews the major disorders of the central and peripheral nervous system with impact on lesions most frequently observed in forensic medicine, i.e., physical, ischemic/hypoxic, and toxic damage to the nervous system of adults, and especially of infants and children, but also naturally occurring disorders of the nervous system, including vascular, metabolic, toxic, degenerative, and age-related diseases, all handled in a well-written, concise, and didactic way. The book is based on the senior author’s vast experience in his particular profession, and will provide the reader with a state-of-the-art overview of forensic neuropathology. The illustrations, as one would expect in a Springer book, are outstanding, and the reference lists added to each chapter are informative.

Speaking as one who has spent much of his life- time in neuropathology and applied neurosciences and as a close friend to the senior author of this sem- inal book, I am glad to note that it covers practically the whole field of neuropathology with impact on

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forensic problems. I am happy to recommend this outstanding volume as a first-rate reference book to a wide audience of forensic scientists, general pathologists, clinical neuropathologists as well as to neurologists, neuropediatrists, and psychiatrists, and other health professionals interested and en- gaged in forensic problems of disorders of the nervous system. Indeed, many physicians and health

professionals will find much information within its pages. I am confident that this outstanding and dis- tinguished textbook is assured of full success.

K.A. Jellinger, MD

Professor of Neurology and Neuropathology, Medical University of Vienna

Senior Editor-in-chief of Acta Neuropathologica VI Foreword

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The present textbook was written with the same in- tentions as Leestma introduced his excellent mono- graph (Forensic Neuropathology. Raven, New York, 1988), “to deal with those areas which have the most importance in forensic settings, are typical problem areas, or seem to be poorly understood by most forensic pathologists….” The authors have attempted not only to describe the pathomorphology of insults of the human nervous system, but also the underly- ing pathophysiological, molecular, and biomechanical principles that can help forensic pathologists to understand the pathological changes induced by a traumatic event and enable the expert witness to reconstruct the criminal act; they have tried to in- tegrate the forensic and criminalistic problems and questions as well as − to a certain degree − the clinical features and sequelae. The aim of this volume is to bridge the gap between the ways of thinking of the basic neuroscientist, the researcher, the practicing medicolegal neuropathologist, and the clinical phy-

Preface

sician. We hope the reader will find this approach unique and useful, as well as intriguingly broaden- ing the horizons of what is usually discussed under medicolegal headings and topics.

The clinical aspects are discussed since forensic pathologists are increasingly asked to aid in medicolegal questions in connection with medical lawsuits.

On the other hand we have lost sight of the needs of clinical neurologists, neurosurgeons, neuropediatri- cians, neurotraumatologists, and neuroradiologists, who may also be called to serve as expert witnesses in court. Thus we offer essential information on the pathological processes encountered in survivors of different brain injuries. The present book may therefore be a useful tool for both pathologists and clinicians confronted with forensically relevant injuries and disorders of the human nervous system.

M. Oehmichen, R.N. Auer, H.G. König

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Acknowledgements

This volume was made possible by the many years the authors have devoted to traumatology of the nervous system in the fields of clinical neuropathology (R.N. Auer), forensic physics (H.G. König), as well as clinical neuropathology and forensic pathology and neuropathology (M. Oehmichen). We would like to thank Dr. med. Carol Falk for advice on the use of medical English. We cannot let this opportu- nity pass without expressing our special gratitude to Mrs. Silke Tychsen-Langer, Mrs. Dagmar Anger- mann and Mrs. Susanne Rath. Mrs. Tychsen-Langer has devoted countless hours to the painstaking task of typing and correcting the manuscript not just once, but many times as the text evolved and grew.

Without her help this book would not exist in its present form. Mrs. Angermannn has been responsible for the figures, from the beginning (autopsy) up to the final electronic processing and management;

thus her documentation is the basic framework of the textbook. Mrs. Rath was responsible for total the histological and immunohistological techniques.

M. Oehmichen owes a great debt of gratitude to his fellow scientists and wishes to express additional acknowledgements, as follows:

▬ Dr. Ivana Gerling/Lübeck, Germany

▬ PD Dr. Christoph Meissner/Lübeck, Germany

▬ Dr. Arthur Reiter/Lübeck, Germany

who over many years of joint effort performed au- topsies and issued expert opinions from which in

part the present volume’s extensive documentation and work-up of case material was cooperatively de- rived.

▬ Professor Dr. Rainer Mattern/Heidelberg, Germany

▬ Professor Dr. Ingo Pedal/Heidelberg, Germany

▬ Professor Dr. Klaus-Steffen Saternus/Göttingen, Germany

▬ Professor Dr. Volker Schmidt/Halle, Germany who have provided many years of expert consul- tation and assistance in clarifying causes of death (neuropathological examinations and reports be- ing entrusted to M.O.) and whose case material has compensated for short falls in our own.

▬ Professor Dr. Hans-Björn Gehl/Lübeck, Germany

▬ Dr. Ulrich van Laak/Kiel, Germany

▬ Professor Dr. Ingo Pedal/Heidelberg, Germany

▬ Professor Dr. Erich Reusche/Lübeck, Germany

▬ Professor Dr. Gisela Skopp/Heidelberg, Germany

▬ Professor Dr. Horst Wiethölter/Stuttgart, Germany

who proffered their critical review of parts of the manuscript and constructive comments and valu- able suggestions. Their joint contribution and sup- port made it possible to complete this volume in its present form.

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Contents

Abbreviations XXI 1 Introduction 1

I Principles of Forensic Neuropathology 5 2 Risks, Responsibilities and Liabilities 7 2.1 Basic Principles 7

2.1.1 Identity of the Victim 8 2.1.2 Manner of Death 8 2.1.3 Cause of Death 8 2.1.4 Process of Dying 9 2.1.5 Causation 10

2.1.5.1 German Theories of Causation 10 2.1.5.2 American Theories of Causation 10 2.2 Role of Expertise and Expert Witness 11 2.2.1 Definition: Expert Witness 11

2.2.2 Standards in (the American) Court 11 2.2.3 Function of Expert Witness 12 2.2.4 Probability of Expert Opinion 12 Bibliography 12

References 12 3 Cytology of the CNS 15 3.1 Neurons 15

3.1.1 Morphology 15 3.1.2 Function 17 3.1.3 Pathology 19 3.2 Astrocytes 20

3.2.1 Morphology, Classification, and Immunoreactivity 20 3.2.2 Function 20

3.2.3 Pathology 23

3.2.3.1 Reactive Astrogliosis 23 3.2.3.2 Piloid Gliosis 24

3.2.3.3 Metabolic (Protoplasmic) Gliosis 24 3.2.3.4 Regressive Alterations 24

3.3 Oligodendrocytes 24

3.3.1 Morphology, Classification, and Immunoreactivity 24 3.3.2 Function 25

3.3.3 Pathology 26

3.4 Microglia and/or Mononuclear Phagocytes of the CNS 27 3.4.1 Morphology, Classification,

and Immunoreactivity 27 3.4.2 Pathology 28

3.4.3 Function 31

3.4.3.1 Resting Microglia 32 3.4.3.2 Perivascular Microglia 32 3.4.3.3 Activated Microglia

(Macrophages) 32 3.5 Additional Cell Types

and Tissue Components 32 3.5.1 Leptomeningeal

and Perivascular Cells 32 3.5.2 Parenchymal Vessels 33

3.5.3 Choroid Plexus and Ependyma 33 3.5.4 Pathology of the CSF

and Cells Within the CNS 33 Bibliography 34

References 34

4 Cell and Tissue Reactions 41

4.1 Increased Brain Volume − Edema 42 4.1.1 Definition 42

4.1.2 Clinical Features 42 4.1.3 Pathogenesis 44

4.1.4 Types of Brain Edema 44 4.1.4.1 Vasogenic Edema 44 4.1.4.2 Cytotoxic Edema 47 4.1.4.3 Conclusion 47 4.1.5 Neuropathology 48

4.1.6 Space-Occupying Effects 49 4.1.7 Herniation 51

4.1.7.1 Uncal Herniation 51 4.1.7.2 Cingulate Herniation 53

4.1.7.3 Central Transtentorial Herniation 53 4.1.7.4 Upward Tentorial Displacement 54 4.1.8 Forensic Implications 54

4.2 Hydrocephalus 54

4.2.1 Classification and Pathogenesis 54 4.2.2 Neuropathology 55

4.2.3 Clinical Features 56 4.3 Cell and Tissue Decay 56

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XII Contents

4.3.1 Injury-Induced Cell Death:

Necrosis 56

4.3.1.1 Incomplete Necrosis 57 4.3.1.2 Tissue Necrosis: Infarction 58 4.3.2 Gene-Regulated Cell Death:

Apoptosis 60

4.3.3 Necrosis Versus Apoptosis 62 4.3.4 Penumbra 63

4.3.5 Dendritic Injury 64 4.3.6 Axonal Injury 65 4.3.6.1 Anterograde (Wallerian)

Degeneration 66

4.3.6.2 Retrograde Degeneration 66 4.3.7 Regenerative Capacity 66 4.4 Inflammation 67

4.4.1 Principles of Neuroimmunology 67 4.4.2 Inflammatory Cells 67

4.4.2.1 Polymorphonuclear Leukocytes 69 4.4.2.2 Lymphocytes 69

4.4.2.3 Microglia and Brain Macrophages 69 4.4.2.4 Astrocytes 70

4.4.2.5 Endothelial Cells and Collagen Fibers 70 4.4.3 Inflammatory Mediators 71 4.4.3.1 Cytokines 71

4.4.3.2 Chemokines 71 4.4.3.3 Effector Molecules 71 4.4.4 Types of Inflammation 72 4.4.4.1 Sterile Inflammation 72 4.4.4.2 Cell-Mediated Inflammation 72 4.4.4.3 Antibody-Mediated Inflammation 73 4.4.5 Inflammation-Induced Ischemia 73 4.5 Misinterpretable Findings 73 4.5.1 Gross Findings 73

4.5.2 Microscopic Findings 74 Bibliography 75

References 76

5 Methods in Forensic Neuropathology 83 5.1 Macroscopic Examination 83 5.1.1 Principles of Brain Autopsy 83 5.1.1.1 Biosafety 83

5.1.1.2 Preserved Native Material 83 5.1.1.3 Documentation 84

5.1.2 Brain 84

5.1.2.1 Fixation Procedures 84

5.1.2.2 Examination during Autopsy 85 5.1.2.3 Sectioning

of the Formalin-Fixed Brain 85 5.1.2.4 Block Selection for Microscopy 86 5.1.2.5 Paraffin Embedding 88

5.1.2.6 Special Problems 88 5.1.3 Spinal Cord 89 5.1.4 Peripheral Nerves 89 5.2 Microscopic Examination 90

5.3 Postmortem Imaging 90 Bibliography 92

References 92

II Physical Trauma 95

6 Basic Principles of Mechanical Trauma 97 6.1 Classification 97

6.2 Epidemiology

of Mechanical Brain Injury 98 6.3 Forensic Aspects 98

6.4 Biomechanical Aspects and Pathomorphology 99 6.4.1 Physical Quantities 99 6.4.2 Mechanical Forces 99

6.4.3 Types of Mechanical Brain Injury 101 6.4.4 Pathology 102

6.4.5 Secondary Lesions 103 6.5 Clinical Features 104 6.5.1 Somatic Symptoms 104

6.5.2 Neuropsychological Impairment 105 6.6 Outcome 106

6.7 Medicolegal Principles 106 Bibliography 107

References 107

7 Injuries of the Brain’s Coverings 111 7.1 The Scalp 113

7.1.1 Anatomy 113 7.1.2 Pathophysiology 113 7.1.3 Pathology 113 7.1.3.1 Abrasion Injury 114 7.1.3.2 Contusion Injury 114 7.1.3.3 Hematoma 114 7.1.3.4 Laceration Injury 114 7.1.3.5 Avulsion Injury 114 7.2 The Skull 115 7.2.1 Anatomy 115

7.2.2 Biomechanical Aspects 116 7.2.2.1 Linear Calvarial Fracture 117 7.2.2.2 Depressed Calvarial Fracture 117 7.2.2.3 Combined Fractures 117

7.2.2.4 Basilar Skull Fracture 117 7.2.2.5 Facial Skull Fracture 120 7.2.2.6 Growing Skull Fracture 120 7.2.3 Clinical Features 120 7.3 Dura Mater 120 7.3.1 Anatomy 120 7.3.2 Pathology 120 7.3.3 Secondary Lesion

(Herniation Syndrome) 123 7.4 Epidural Hemorrhage 123 7.4.1 Classification 123

7.4.2 Biomechanical Aspects 123

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7.4.3 Pathology 125 7.4.4 Clinical Features 125 7.4.4.1 Prognosis 125

7.5 Subdural Hemorrhage 126 7.5.1 Classification 126

7.5.2 Biomechanical Aspects 127 7.5.3 Clinical Features 129

7.5.3.1 Types and Causes of SDH 129 7.5.3.2 Prognosis 129

7.5.3.3 Diagnosis 130 7.5.4 Pathology 130 7.5.4.1 Acute SDH 130 7.5.4.2 Subacute SDH 132 7.5.4.3 Chronic SDH 132 7.5.4.4 Internal Hemorrhagic

Pachymeningitis 135 7.5.4.5 Hygroma 135

7.6 Histology and Microscopic Dating of EDH and SDH 135

7.7 Injuries of Intracranial Vessels 138 7.7.1 Mechanically Induced Subarachnoid

Hemorrhage and Intraventricular Hemorrhage 139

7.7.1.1 Biomechanical Aspects 139 7.7.1.2 Clinical Features 141

7.7.1.3 Pathology and Differential Diagnosis 142 7.7.1.4 Delayed Mechanically

Induced Apoplexy 143

7.7.2 Mechanically Induced Aneurysm 143 7.7.2.1 “False” Aneurysm 143

7.7.2.2 Dissecting Aneurysm 144 7.7.3 Mechanically Induced

Arterial Thrombosis 144 7.7.4 Injury of the Veins 145 7.7.4.1 Injury of the Sinuses

(Sinus Thrombosis) 145

7.7.4.2 Carotid Artery − Cavernous Sinus Fistula (Carotid-Cavernous Fistula, CCF) 145 7.8 Injuries of the Extracranial Arteries 146 7.8.1 Injury of the Carotid Artery 146 7.8.2 Injury of the Vertebral Artery 147 Bibliography 147

References 147 8 Open Brain Injuries 151 8.1 Basic Principles 151 8.1.1 Classification 151

8.1.2 Biomechanical Aspects 151 8.1.3 Pathology 151

8.2 Stabbing and Incision Wounds 152 8.3 Gunshot Wounds 154

8.3.1 Clinical Features and Capability to Act 155 8.3.2 Biomechanical Aspects 159 8.3.3 Pathology 161

8.3.3.1 Scalp 161 8.3.3.2 Skull 162 8.3.3.3 Brain 165

8.3.4 Postmortem Imaging 167 8.3.5 Homicide, Suicide, Accident 168 8.3.6 Dating of Gunshot Wounds 169 8.4 Secondary Lesions 171

References 173

9 Closed Brain Injuries 177 9.1 Classification 177 9.2 Concussion Injury

and Cortical Hemorrhage 179 9.2.1 Biomechanical Aspects 179 9.2.1.1 Injury by Fall 183

9.2.1.2 Injury by Blow 184

9.2.2 Cellular and Molecular Mechanisms 185 9.2.2.1 Cytological Reaction 185

9.2.2.2 Necrosis 187 9.2.2.3 Apoptosis 188 9.2.2.4 ApoE-Genotype 189 9.2.3 Pathology 189

9.2.3.1 Concussion Injury 189 9.2.3.2 Contusion Injury 189

9.2.3.3 Posterior Fossa Hemorrhage 190 9.2.3.4 Scar Formation 190

9.2.4 Dating of Cortical Hemorrhages 190 9.3 Intracerebral Hemorrhages 194 9.3.1 Classification 194

9.3.2 Pathology and Differentiation 196 9.3.3 Brain Stem Hemorrhages 198 9.3.3.1 Primary Brain Stem Hemorrhage 199 9.3.3.2 Secondary Brain Stem Hemorrhage 200 9.3.4 Intraventricular Hemorrhage 201 9.4 Diffuse Brain Injuries 202 9.4.1 Edema 202

9.4.2 Ischemia 204 9.4.3 Axonal Injury 205 9.4.4 Vascular Lesion 207 9.4.5 Boxing Brain Injury

(Punch Drunk Syndrome) 207 9.5 CNS Involvement in Mechanical Injury

without Primary Brain Injury 208 9.5.1 Fat Embolism 208

9.5.2 Air Embolism 209 9.5.3 Vascular Injury 210 9.5.4 Coagulation Disorders 210 9.5.5 Ischemic Injury 210 Bibliography 210 References 210

10 Injuries of Spine and Spinal Cord 217 10.1 Basic Principles 217

10.1.1 Epidemiology 217 10.1.2 Anatomy 218

Contents XIII

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10.1.3 Pathophysiology 219 10.1.4 Clinical Features 219 10.1.5 Biomechanical Aspects 220 10.2 Spinal Cord Injury (SCI) 221

10.2.1 Subdural and Epidural Hemorrhage 221 10.2.2 Penetrating SCI 221

10.2.2.1 Stab Wound 223 10.2.2.2 Gunshot Wound 223 10.2.2.3 Disruption

of the Craniocervical Junction 223 10.2.2.4 Pathology of Penetrating Injury 224 10.2.3 Closed Cord Injury 225

10.2.3.1 Biomechanical Aspects 225 10.2.3.2 Clinical Features 225 10.2.4 Neuropathology 226

10.2.4.1 Contusional Injury of the Cord 226 10.2.4.2 Compression Injury of the Cord 229 10.2.4.3 Vascular Myelopathy 231

10.2.4.4 Iatrogenic Cord Injury 231 10.3 Injury of the Cervical Spine 233 10.3.1 Biomechanical Features 233 10.3.1.1 Direct Injury 233

10.3.1.2 Indirect Injury 234

10.3.2 Indirect (“Whiplash”) Injury 234 10.3.3 Chiropractic Manipulation 235 Bibliography 236

References 236

11 Injuries of Peripheral Nerves 241 11.1 Anatomy 241

11.2 Types of Morphological Reactions 242 11.2.1 Wallerian Degeneration 242

11.2.2 Retrograde Reaction (Axonal Degeneration) 242 11.2.3 Remote Effects 242 11.2.4 Edema 243 11.2.5 Regeneration 243 11.3 Types of Injury 243 11.3.1 Injuries by Compression

and Percussion 243 11.3.2 Injuries by Traction

and Elongation 243 11.3.3 Injuries by Transection 244 Bibliography 244

References 244

12 Special Physical Trauma 245 12.1 Thermal Trauma 245 12.1.1 Hypothermia 246 12.1.1.1 Incidence 246 12.1.1.2 Pathophysiology 246 12.1.1.3 Clinical Features 247 12.1.1.4 Neuropathology 248 12.1.2 Hyperthermia 248 12.1.2.1 Incidence 248

12.1.2.2 Pathophysiology 249 12.1.2.3 Clinical Features

and Neuropathology 249 12.1.2.4 Heat Exhaustion 250 12.1.2.5 Sunstroke (Insolation) 250 12.1.2.6 Heatstroke 250

12.1.3 Trauma by Fire and Burns 251 12.1.3.1 Incidence 251

12.1.3.2 Clinical Features 251 12.1.3.3 Neuropathology 251 12.2 Electrical Trauma 254 12.2.1 Incidence 254

12.2.2 Clinical Features 254 12.2.3 Pathogenesis 255 12.2.4 Neuropathology 255 12.2.5 Electric Shock Devices 256 12.2.6 Electromagnetic Radiation 256 12.3 Lightning Trauma 256

12.3.1 Incidence 256 12.3.2 Clinical Features 256 12.2.3 Neuropathology 257 12.4 Irradiation Trauma 257 12.4.1 Pathogenesis 257

12.4.2 Types of CNS Reaction 258 12.4.3 Acute Radiation Injury 258 12.4.3.1 Radiation Necrosis 258

12.4.3.2 Transitory Radiation Myelopathy 259 12.4.3.3 Radiation Neuropathy 259

12.4.4 Early Delayed Reaction 259 12.4.5 Chronic Radiation Injury 259 12.4.5.1 Acute Onset 259

12.4.5.2 Chronic Progressive Injury 259 12.5 Special Mechanical Trauma 259 12.5.1 Ultrasound Injury 259

12.5.2 Pressure Injury 260 12.5.2.1 Barotrauma 260

12.5.3 Toxicity of Hyperbaric Gases 261 12.5.4 Decompression Sickness (DCS) 261 12.5.4.1 Incidence 261

12.5.4.2 Pathophysiology 261 12.5.4.3 Clinical Features 261 12.5.4.4 Neuropathology 262 12.5.5 Gas Embolism 262 12.5.5.1 Pathophysiology

and Clinical Features 262 12.5.5.2 Neuropathology 263 12.5.6 High-Altitude Illness 263 12.5.6.1 Incidence 263

12.5.6.2 Clinical Features

and Pathophysiology 263

12.5.6.3 Pathology and Neuropathology 264 Bibliography 264

References 264 XIV Contents

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III Ischemia and Asphyxia 271

13 Hypoxia, Ischemia (Hypoglycemia) 273 13.1 Basic Principles 273

13.2 Metabolic Disturbances 275 13.3 Hypoxia 276

13.3.1 High-Altitude Mountaineering 277 13.3.2 Respiratory Disease 278

13.3.3 Anemic Hypoxia 279 13.3.4 Histotoxic Hypoxia 279 13.3.5 Neuropathology 279 13.4 Ischemia 280 13.4.1 Pathophysiology 280 13.4.2 Neuropathology 281 13.4.2.1 Cerebral Cortex 281 13.4.2.2 Hippocampus 282 13.4.2.3 Basal Ganglia 284 13.4.2.4 Brain Stem 284 13.4.2.5 Cerebellum 285 13.4.2.6 Spinal Cord 285 13.4.2.7 White Matter Lesions

(Leukoencephalopathy) 286 13.5 Hypoglycemia 286

13.5.1 Neuropathology 287 Bibliography 288 References 288

14 Forensic Types of Ischemia and Asphyxia 293 14.1 Suffocation 294

14.1.1 Environmental Suffocation 294

14.1.2 Smothering, Choking, and Gagging 295 14.1.3 Drowning 295

14.1.4 Mechanical Asphyxia 296

14.1.5 Neuropathology of Suffocation 296 14.1.5.1 Acute Death after Suffocation 296 14.1.5.2 Delayed Death after Suffocation 296 14.2 Strangulation 297

14.2.1 Hanging 297

14.2.2 Ligature Strangulation 298 14.2.3 Manual Strangulation 298

14.2.4 Neuropathology of Strangulation 298 14.2.4.1 Acute Death after Strangulation 299 14.2.4.2 Delayed Death after Strangulation 299 14.2.5 Cervical Spine and Strangulation 300 14.3 Time Course of Ischemia 301

14.3.1 Macroscopic Findings 301 14.3.2 Edema 301

14.3.3 Microthrombosis and Fibrin Deposition 303 14.3.4 Neurons 303

14.3.5 Neuronal Proteins 305 14.3.6 Astrocytes 306

14.3.7 Polymorphonuclear Leukocytes 307 14.3.8 Mononuclear Phagocytes/Microglia 307 14.3.9 Mesenchymal Reaction 308

14.3.10 Cytokines 308

14.3.11 Enzymes 309

14.4 Clinical Features of Acute Asphyxia 310 14.5 Transient Ischemia 311

14.6 Selective Neuronal Necrosis 312 14.7 Apallic Syndrome 312

14.8 Ethical Implications 312 Bibliography 313 References 313

15 Permanent Global Ischemia 319 15.1 Classification 319

15.2 Pathophysiology 319 15.3 Clinical Features 321 15.4 Neuropathology 321 15.4.1 Gross Examination 321 15.4.2 Microscopic Examination 322 15.5 Forensic Implications 323 15.5.1 Respirator Brain

and/or Postmortem Autolysis 323 15.5.2 Declaration of Death 325

15.5.3 Time of Brain Death 326 15.5.4 Time of Causal Event

Leading to Brain Death 327 15.5.5 Morphological Statement

of Intracranial Circulatory Arrest 328 Bibliography 328

References 328

IV Intoxication 331

16 Introductory Remarks 333 16.1 Biological Principles 333 16.2 Toxic Encephalopathy 335

16.3 Toxic Neuropathy/Polyneuropathy 336 Bibliography 337

References 337

17 Specific Types of Neurotoxins 339 17.1 Metals and Metallic Compounds 339 17.1.1 Aluminum (Al) 339

17.1.2 Arsenic (As) 341

17.1.2.1 Inorganic Arsenicals 341 17.1.2.2 Organic Arsenicals 341 17.1.3 Bismuth (Bi) 341 17.1.4 Cadmium (Cd) 342 17.1.5 Gold (Au) 342 17.1.6 Lead (Pb) 342

17.1.6.1 Inorganic Lead Compounds 342 17.1.6.2 Organic Lead Compounds 343 17.1.7 Lithium (Li) 343

17.1.8 Manganese (Mn) 344 17.1.9 Mercury (Hg) 344 17.1.9.1 Elementary Mercury

and Inorganic Mercury Compounds 344

Contents XV

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17.1.9.2 Organic Mercury Compounds 344 17.1.10 Platinum (Pt) 345

17.1.11 Thallium (Tl) 346

17.1.12 Tin (Sn) and Tin Compounds 346 17.1.12.1 Triethyltin 346

17.1.12.2 Trimethyltin 346

17.2 Non-Metallic Inorganic Neurotoxins 347 17.2.1 Phosphorus (P)

and Phosphorous Compounds 347 17.2.2 Sulfur (S) 347

17.2.2.1 Carbon Disulfide 347 17.2.3 Tellurium (Te) 347 17.3 Gases 347

17.3.1 Carbon Monoxide (CO) 347 17.3.1.1 Acute Intoxication 349 17.3.1.2 Intermittent Exposure 350 17.3.1.3 Chronic Intoxication 351

17.3.2 Cyanides and Cyanide Compounds 351 17.3.3 Hydrogen Sulfide (H2S) 352

17.3.4 Nitrous Gases and Nitrites 352 17.3.5 Oxygen (O2) 352

17.4 Industrial and Environmental Toxins 353 17.4.1 Acrylamide 353

17.4.2 Aliphatic Hydrocarbons 353 17.4.3 Halogenated Hydrocarbons 353 17.4.3.1 Methyl Chloride 353

17.4.3.2 Trichloroethylene 353

17.4.4 Chlorinated Cyclic Hydrocarbons 354 17.4.4.1 Hexachlorophene (HCP) 354

17.4.4.2 Lindane 354

17.4.5 Methyl Alcohol (Methanol) 354 17.4.6 Organophosphorus Compounds 355 17.4.7 Toxic Oil 356

17.5 Nerve Agents 356

17.6 Drugs and Pharmaceutical Products 357 17.6.1 Sedatives, Hypnotics and Analgesics 357 17.6.2 Antiprotozoal Agents 358

17.6.2.1 Chloroquine 358 17.6.2.2 Clioquinol 358 17.6.3 Cytostatics

and Antituberculous Agents 359 17.6.3.1 Methotrexate 359

17.6.3.2 Vincristine, Vinblastine 359 17.6.3.3 Isoniacid 360

17.7 Biological Toxins 360 17.7.1 Plants 360

17.7.2 Animals 362 17.7.3 Microorganisms 362 17.7.3.1 Botulinum Toxin 362 17.7.3.2 Tetanospasmin 362 17.7.3.3 Diphtheria Toxin 363 17.7.3.4 Anthrax 363

Bibliography 363 References 363

18 Alcohol, Organic Solvents, and Aerosols 371 18.1 Epidemiology 371

18.2 Metabolism, Kinetics, and Causes of Death 372 18.3 Pharmacology 373 18.4 Clinical Features 374 18.4.1 Acute Intoxication 374

18.4.2 Chronic Intoxication (Alcoholism) 374 18.5 Neuropathology 375

18.5.1 Acute Intoxication 375 18.5.2 Chronic Intoxication 375 18.5.2.1 Diffuse Brain Alterations 376 18.5.2.2 Cerebellar Atrophy 378

18.5.2.3 Wernicke − Korsakoff Syndrome 378 18.5.2.4 Central Pontine Myelinolysis 379 18.5.2.5 Marchiafava − Bignami Syndrome 380 18.5.2.6 Pellagra 380

18.5.2.7 Alcoholic Myelopathy 380 18.5.2.8 Neuropathy

of the Autonomic Nervous System 380 18.5.2.9 Neuropathy/Polyneuropathy 380 18.5.2.10 Myopathy 381

18.5.2.11 Secondary Pathologic Alterations 381 18.5.2.12 Disulfiram Treatment 383

18.6 Alcoholic Fetopathy and Embryopathy 383

18.7 Organic Solvents and Aerosol 384 Bibliography 385

References 385

19 Illegal Drugs and Drug Dependence 391 19.1 Epidemiological and Social Data 391 19.2 Cannabis 392

19.3 Hallucinogens and Entactogens 392 19.3.1 Mescaline 393

19.3.2 Lysergic Acid Diethylamide (LSD) 393 19.3.3 Amphetamine Substitutes 393 19.3.3.1 MDMA (3,4-methylenedioxmeth-

amphetamine) 393

19.3.3.2 MDEA (3,4-methylenedioxyeth- amphetamine) 394

19.3.4 Other Agents 394

19.4 Narcotics: Opium and Opioids 394 19.4.1 Basic Principles 394

19.4.1.1 Epidemiology 394 19.4.1.2 Pathophysiology 395 19.4.1.3 Neuropathology 395 19.4.2 Morphine 397 19.4.3 Heroin 397 19.4.4 Codeine 397

19.4.5 Dihydrocodeine (DHC) 398 19.4.6 Methadone 398

19.4.7 Other Narcotic Agents 398 19.5 Stimulants 398

XVI Contents

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19.5.1 Cocaine 398

19.5.2 Cocaine Freebase: Crack 399 19.5.3 Amphetamine

and Methamphetamine (Speed) 399 19.5.4 Caffeine 400

19.5.5 Ephedrine 400 19.5.6 Khat 400 Bibliography 401 References 401

V Pediatric Neuropathology 405 20 Basic Principles 407

20.1 Epidemiology 407

20.1.1 Injuries During the Perinatal Period 407 20.1.2 Acquired Postnatal Injury 408

20.2 Developmental Neuroanatomy 408 20.2.1 The Coverings 408

20.2.2 The Brain 411 20.3 Autopsy Findings 412

20.3.1 Head and Cranial Contents 413 20.3.2 Cervical Spine 413

20.3.3 Ears and Mastoids 414 20.3.4 Eyes 414

20.4 Microscopic Examination:

Cell Reaction 414

20.5 Postmortem Biochemistry 415 20.6 Diffuse Cerebral Swelling 415 20.6.1 Hyperemia 416

20.6.2 Edema 416

20.6.3 Hydrocephalus 416

20.7 Forensic Aspects (Expert Witness) 417 20.7.1 Medical Malpractice 417

20.7.2 Physical Abuse 419 20.7.3 Ethical Aspects 419 Bibliography 420 References 420

21 Fetal Neuropathology 425 21.1 Malformations 425

21.2 Hypoxic − Ischemic Encephalopathy 427 21.2.1 Neuropathology 428

21.3 Intoxication 429 21.3.1 Cocaine 431 21.3.2 Heroin 431 21.4 Infection 431 Bibliography 432 References 432 22 Perinatal CNS Injury 433

22.1 Ischemic−Asphyxiant Injury 434 22.1.1 Causes of Oxygen Depletion 434 22.1.2 Ischemic Cell Injury 435 22.1.2.1 Pathophysiology 435

22.1.2.2 Cytopathology 436 22.1.3 Neuropathology 436 22.1.3.1 Qualitative Differences 437 22.1.3.2 Topographical Differences 439 22.1.4 Dating of Asphyxiant Injury 441 22.2 Mechanical Injury (Birth Injury) 441 22.2.1 Extracranial Hemorrhages 441 22.2.2 Skull Fracture 443

22.2.3 Intracranial Hemorrhages 443 22.2.3.1 Epidural Hemorrhage (EDH) 443 22.2.3.2 Subdural Hemorrhage (SDH) 443 22.2.3.3 Subarachnoid Hemorrhage (SAH) 444 22.2.3.4 Intraparenchymal Hemorrhage 444 22.2.3.5 Dating of Intracerebral Hemorrhages

in Immature Infants 445 22.2.4 Spinal Cord Injury 445 22.2.5 Peripheral Nerve Injury 445 22.3 Venous Sinus Thrombosis 446 22.4 Late Sequelae

of Perinatal Brain Injury 447 Bibliography 447

References 447

23 Postnatal Natural CNS Death 451 23.1 Metabolic Diseases 451 23.1.1 Bilirubin Encephalopathy 452 23.1.1.1 Pathophysiology 454

23.1.1.2 Neuropathology 454

23.1.2 Hypoglycemic Encephalopathy 454 23.1.2.1 Pathophysiology 455

23.1.2.2 Neuropathology 455 23.1.3 Hemorrhagic Shock

and Encephalopathy Syndrome (HSES) 455

23.1.4 Iron Deficiency 456 23.2 Stroke 456

23.3 Infectious Diseases 457 23.3.1 Bacterial Meningitis 457

23.3.2 Abacterial Meningoencephalitis 458 23.4 Tumor 459

23.5 Sudden Infant

Death Syndrome (SIDS) 460 23.5.1 Definition and Incidence 460 23.5.2 Neuropathology

and Pathophysiology 461 23.5.2.1 Primary CNS Changes 461

23.5.2.2 Perfusion Disturbance or Ischemia 463 23.5.3 Conclusion 465

Bibliography 465 References 465

24 Postnatal Mechanical Brain Injury (MBI) 471 24.1 Incidence 471

24.2 Clinical Features 472

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24.3 Biomechanical Aspects and Causal Events 472 24.4 Skull Fracture 474 24.4.1 Growing Fracture 478 24.5 Dural Hemorrhages 478

24.5.1 Epidural Hemorrhage (EDH) 478 24.5.2 Subdural Hemorrhage (SDH) 479 24.5.3 Chronic Subdural

Hemorrhage (SDH) 479 24.5.4 Subdural Hygroma 479

24.6 Subarachnoid Hemorrhage (SAH) 480 24.7 Cerebral Contusion

and Laceration Injury 480 24.7.1 Neuropathology 481 24.7.2 Biomechanics 481 24.7.3 Clinical Features 481

24.8 Mechanical Vessel Injury 481 24.9 Secondary Alterations 481 24.9.1 Edema and Hypoxia 481 24.9.2 Inflammation 482 24.10 Late Sequelae 482 24.10.1 Hydrocephalus 482 24.10.2 Seizures 483

24.11 Spinal Cord Injury 484 Bibliography 484 References 484 25 Physical Abuse 489 25.1 Basic Principles 489 25.1.1 Sociopsychological/

Forensic Considerations 489 25.1.2 Definition 491

25.1.3 Incidence 492

25.1.4 Types of Brain Injuries 492

25.2 Mechanically Caused Brain Injury 493 25.3 Shaken Infant Syndrome 493

25.3.1 Clinical Features 493 25.3.2 Autoptic Findings 496 25.3.2.1 Intracranial Hemorrhage 497 25.3.2.2 Retinal Hemorrhage 497 25.3.2.3 Brain Edema 500 25.3.2.4 Cervical Cord Injury:

Dural Hemorrhage and Cord Lesion 500 25.3.2.5 Skull Fracture 501

25.3.2.6 Further Morphological Alterations 502 25.3.2.7 The Repeated Shaking 502

25.3.3 Shaking Impact Syndrome 502 25.3.4 “Tin-Ear” Syndrome 502 25.3.5 Cause of Death 503 25.3.6 Clinical Outcome 503 25.3.7 Differential Diagnosis 504 25.3.7.1 Wounding by Birth 505 25.3.7.2 Dehydration 505

25.3.7.3 Physiotherapy in Premature Infants 506

25.3.7.4 Sudden Infant

Death Syndrome (SIDS) 506 25.3.7.5 Resuscitation 506

25.3.7.6 “Rebleed” of Chronic Subdural Hematoma 507

25.3.8 Shaking versus Fall 507 25.3.8.1 Epidemiologic Evaluation 507 25.3.8.2 Biomechanical Aspects 508 25.3.8.3 Conclusion 510

25.4 Asphyxiant Brain Injury 511 25.4.1 Types of Violence 511 25.4.2 Compression of the Chest 511 25.4.3 Drowning 512

25.4.4 Neuropathology 513 25.5 Toxic Brain Injury 513 25.5.1 Incidence 513

25.5.2 Clinical Features and Neuropathology 514

25.6 Obligations of an Expert Witness 514 Bibliography 515

References 515

VI Clinical Neuropathology 523 26 Basic Principles 525

26.1 Sudden, Unexpected Death 525 26.1.1 Definition 525

26.1.2 Epidemiology 526 26.1.3 Classification 526

26.1.3.1 Neuronal-Mediated Death 526 26.1.3.2 Death Associated

with Vascular Diseases 527 26.1.3.3 Death Associated

with Inflammatory Diseases 527 26.2 Further Cerebral Diseases

of Forensic Significance 527 Bibliography 528

References 528

27 Seizures and Epilepsy 529 27.1 Classification 529 27.2 Clinical Features 531

27.3 Etiology of Symptomatic Epilepsy 531 27.4 Pathogenesis 532

27.5 Pathophysiology 532 27.6 Epidemiology 532 27.7 Neuropathology 533 27.7.1 Hippocampal Pathology 534 27.7.2 Temporal Lobe Epilepsy 535 27.7.3 Myoclonic Epilepsy 535 27.7.4 Status Epilepticus 535 27.8 Cause of Death 535 27.8.1 Sudden Unexpected Death

in Epilepsy (SUDEP) 536 XVIII Contents

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27.8.1.1 Risk Factors 536

27.8.1.2 Pathogenetic Considerations 536 27.8.1.3 Diagnosis of SUDEP 537

27.9 Additional Forensic Implications 537 Bibliography 537

References 537 28 Vascular Diseases 541 28.1 Physiology

of the Cerebral Circulation 542 28.2 Anatomy of Cerebral Vessels 543 28.3 Pathology of Cerebral Arteries 543 28.3.1 Cerebral Atherosclerosis 543 28.3.2 Brain Calcinosis 545

28.3.3 Cerebral Thromboembolism 546 28.3.4 Hypertensive Angiopathy 546 28.3.5 Lacunar Infarcts 548

28.3.6 Amyloid Angiopathy 548 28.3.7 Cystic Medial Necrosis 549 28.3.8 Aneurysms 549

28.3.8.1 Saccular (Fusiform) Aneurysm 550 28.3.8.2 Dissecting Aneurysm 552

28.3.8.3 Infectious (Mycotic) Aneurysm 553 28.3.8.4 Mechanically Induced

Aneurysm 553

28.3.9 Inflammatory Vessel Disease (Vasculitis) 553

28.3.9.1 Non-Infectious Primary CNS Vasculitis 553

28.3.9.2 Infectious Vascular Diseases 554 28.4 Pathology of Cerebral Veins 555 28.4.1 Cerebral Venous Thrombosis 555 28.5 Vascular Malformations 557 28.5.1 Cavernous Angioma 557 28.5.2 Capillary Angioma 557 28.5.3 Venous Angioma 557

28.5.4 Arteriovenous Malformation 558 28.5.5 Von Hippel−Lindau

Hemangioblastoma 558 28.6 Tumor-Induced Stroke 558 28.6.1 Thrombosis and Embolism 559 28.6.2 Tumor Vessels and Hemorrhage 559 28.7 Extracerebral Causes of Stroke 561 28.7.1 Coagulopathy, Hemostatic Disorder,

Cerebral Thrombosis 561 28.7.2 Cerebral Embolism 561 28.7.3 Circulatory Disturbance 561 28.7.4 Illegal Drugs 564

28.8 Ischemic Stroke: Infarction 564 28.8.1 Classification of Cerebral Ischemia 565 28.8.2 Clinical Features of Transient and

Permanent Focal Ischemia 565 28.8.3 Neuropathology 566

28.9 Spontaneous Intracerebral Hemorrhage 569

28.9.1 Incidence 569 28.9.2 Clinical Features 569 28.9.3 Neuropathology 571

28.9.3.1 Causes of Spontaneous Intracerebral Hemorrhage 572

28.10 Vascular Diseases of the Spinal Cord 573 28.10.1 Anatomy of the Spinal Vessels 573 28.10.2 Pathology of the Spinal Vessels 573 28.11 Forensic Aspects of Stroke 574 Bibliography 574

References 574

29 Inflammatory Diseases 581 29.1 Bacterial CNS Diseases 582 29.1.1 Purulent Leptomeningitis 582 29.1.1.1 Neuropathology 584

29.1.1.2 Late Complications 585 29.1.1.3 Neonatal Meningitis 585 29.1.1.4 Meningococcal Meningitis 585

29.1.1.5 Haemophilus Influenzae Meningitis 585 29.1.1.6 Pneumococcal Meningitis 585

29.1.2 Epidural Abscess 585

29.1.3 Subdural Abscess and/or Empyema 586 29.1.4 Brain Abscess 586

29.1.5 Tuberculous Brain Infection 587 29.1.6 Septic Encephalopathy 587 29.2 Abacterial CNS Diseases 590 29.2.1 Classification 590

29.2.2 Pathogenesis 591 29.2.3 Clinical Features 591 29.2.4 Neuropathology 591

29.3 AIDS and the Nervous System 593 29.3.1 Primary HIV-Associated Nervous System

Infection 593 29.3.1.1 HIV Encephalopathy

(Subacute Dementia Encephalopathy) 593 29.3.1.2 HIV Myelopathy 593

29.3.1.3 HIV Neuropathy 594 29.3.2 Secondary HIV-Associated

NS Infection 594

29.4 Transmissible Spongiform Encephalopathies 595

29.5 Non-Infectious Inflammatory Diseases 596

29.5.1 Acute Hemorrhagic Leukoencephalitis (Hurst’s Disease) 596

29.5.2 Acute Demyelinating Disease 597 29.5.3 Chronic Demyelinating Disease:

Multiple Sclerosis 598 Bibliography 601 References 601

30 Nutritional and Metabolic Insults 605 30.1 Starvation and Malnutrition 606 30.1.1 Protein Deficiency 606

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30.1.2 Vitamin Deficiencies 606

30.1.3 Disturbances of Glucose Metabolism 607 30.1.3.1 Hypoglycemic Encephalopathy 607 30.1.3.2 Hyperglycemia 608

30.1.3.3 Diagnosis 608 30.2 Dissociation of Water

and Electrolyte Balance 608 30.2.1 Dehydration 608

30.2.2 Hypernatremia 609 30.2.3 Hyponatremia

and Water Intoxication 609 30.2.4 Hyponatremia

and Central Pontine Myelinolysis 610 30.3 Hepatic Encephalopathy 611

30.3.1 Fulminant Hepatic Failure 611 30.3.2 Chronic Liver Disease

and Portal-Systemic Bypass 611 30.3.3 Familial Hepatolenticular

Degeneration (Wilson’s Disease) 612 30.3.4 Reye’s Syndrome 612

30.4 Uremic Encephalopathy 612 30.4.1 Dialysis Encephalopathy 613 Bibliography 614

References 614

31 Aging and Brain Pathology 619 31.1 Basic Principles 619

31.1.1 Biology of Aging 619

31.1.2 Neurobiology of Aging 620 31.1.3 Dementia and Delirium 620 31.1.4 Classification of Age-Dependent

Dementias 621

31.2 Morphology of the Aging Brain 621 31.2.1 Macroscopic Alterations 621 31.2.2 Microscopic Alterations 622 31.2.2.1 Neurofibrillary Tangles 623 31.2.2.2 Senile Plaques 625

31.3 Pathology of the Aging Brain 625 31.3.1 Alzheimer’s Disease (AD) 626 31.3.1.1 Clinical Features 626

31.3.1.2 Neuropathology

and Diagnostic Criteria 627 31.3.1.3 Pathogenesis 629

31.3.2 Neurofibrillary Tangles and Dementia 630 31.3.3 Dementia Pugilistica 630 31.3.4 Dementia in Parkinson’s Disease

(PD) 631

31.3.5 Lewy Body Dementia 632 31.3.6 Frontotemporal Dementia

(Pick’s Disease) 632 31.3.7 Vascular Dementia 634 Bibliography 636 References 636 Subject Index 641 XX Contents