Table of Contents

1 Normal Histology and Commonly Used Stains 1
1.1 Cells of the Nervous System 1
1.1.1 Neurons . 1
1.1.2 Astrocytes 2
1.1.3 Oligodendrocytes . 5
1.1.4 Schwann Cells . 5
1.1.5 Ependyma 6
1.1.6 Microglia . 7
1.1.7 Supporting Tissues 8
1.2 General Architecture of the Nervous System . 8
1.2.1 Grey and White Matter 8
1.2.2 Peripheral Nerve 9
1.2.3 Ganglia 10
1.2.4 Skeletal Muscle . 10
1.3 Commonly Used Stains in Neuropathology . 11
1.3.1 Tinctorial Stains . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
1.3.2 Immunohistochemical Preparations 13
References . 15
2 Basic Pathologic Reactions . 17
2.1 Neurons 17
2.1.1 Neuronal Atrophy and Neuronal Loss . . . . . . . . . . . . . . . 17
2.1.2 Hypoxic-Ischaemic Change 17
2.1.3 Central Chromatolysis . 18
2.1.4 Abnormal Inclusions . 18
2.1.5 Axonal Alterations 19
2.2 Astrocytes . 21
2.2.1 Gliosis 21
2.2.2 Alzheimer Type II Astrocyte . 23
2.2.3 Rosenthal Fibers 23

2.2.4 Eosinophilic Granular Bodies . 23
2.2.5 Corpora Amylacea . 23
2.3 Oligodendrocytes . 25
2.3.1 Demyelination . 25
2.3.2 Inclusions 25
2.4 Ependyma . 26
2.4.1 Atrophy 26
2.4.2 Discontinuity . 26
2.4.3 Granulations 26
2.5 Microglia 27
2.5.1 Diffuse Microglial Activation
and Microglial Nodules 27
References . 28
3 Requesting and Interpreting Pathological Tests 29
3.1 Neurosurgical Specimens . 30
3.2 Muscle and Nerve Biopsies 31
3.3 Cerebrospinal Fluid 32
3.4 Skin Biopsies 33
3.5 Other Samples 33
4 Vascular Diseases 35
4.1 Vascular Anatomy 35
4.1.1 Arterial Supply 35
4.1.2 Venous Drainage 38
4.2 Diseases Affecting the Blood Vessels 38
4.2.1 Atherosclerosis 38
4.2.2 Small Vessel Disease . 38
4.2.3 Amyloid Angiopathy . 40
4.2.4 Hereditary Vascular Diseases 41
4.2.5 Vasculitides 43
4.2.6 Vascular Malformations 46
4.2.7 Aneurysms . 47
4.3 Consequences of Cerebrovascular Diseases 50
4.3.1 Ischaemia and Infarction . 50
4.3.2 Haemorrhage . 54
References . 55
5 Infections 57
5.1 Bacterial Infections 58
5.1.1 Acute Bacterial Meningitis 58
5.1.2 Abscess 60
5.1.3 Chronic Bacterial Infections 62
5.2 Viral Infections . 65
5.2.1 Aseptic Meningitis 65
5.2.2 Encephalitis or Encephalomyelitis 65

5.3 Fungal Infections 72
5.4 Parasitic Infections . 72
5.4.1 Protozoal Infections . 72
5.4.2 Metazoal/Helminthic Infections 76
5.5 Role of Brain Biopsy in Infectious Diseases 77
References . 78
6 Tumours of Central Nervous System 79
6.1 Classification 79
6.2 Sending Specimens to the Laboratory 80
6.3 Gliomas 81
6.3.1 Astrocytic Tumours . 81
6.3.2 Genetics of Gliomas 85
6.3.3 Non-astrocytic Gliomas . 86
6.4 Neuronal Tumours With or Without Glial Features . 89
6.4.1 Gangliocytoma and Ganglioglioma . 89
6.4.2 Dysembryoplastic Neuroepithelial Tumour 90
6.4.3 Central Neurocytoma 90
6.4.4 Desmoplastic Infantile Astrocytoma/Ganglioglioma 91
6.4.5 Dysplastic Gangliocytoma of the Cerebellum
(Lhermitte-Duclos
Syndrome) 91
6.5 Embryonal Tumours . 92
6.5.1 Medulloblastoma . 92
6.5.2 Primitive Neuroectodermal Tumour 93
6.5.3 Atypical Teratoid/Rhabdoid Tumour . . . . . . . . . . . . . . . . 93
6.6 Pineal Region Tumours 93
6.7 Choroid Plexus Tumours 93
6.8 Meningeal Tumours . 94
6.8.1 Meningiomas . 94
6.8.2 Other Tumours of the Meninges 95
6.9 Pituitary Region Tumours 96
6.10 Lymphomas 98
6.11 Tumours of the Peripheral Nerves 99
6.12 Other Tumours Affecting the CNS 101
References . 102
7 Demyelinating Diseases 103
7.1 Multiple Sclerosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103
7.1.1 Classic Multiple Sclerosis . 104
7.1.2 Acute Multiple Sclerosis . 105
7.1.3 Concentric Sclerosis 105
7.2 Neuromyelitis Optica (Devic’s Disease) 106
7.3 Acute Disseminated Encephalomyelitis . 109
7.4 Acute Haemorrhagic Leukoencephalopathy 109
7.5 Trigeminal Neuralgia . 110
References . 111

8 Epilepsy 113
8.1 Rasmussen’s Encephalitis 114
8.2 Focal Cortical Dysplasia 114
8.3 Hippocampal Sclerosis . 115
8.4 Sudden Unexpected Death in Epilepsy (SUDEP) 116
References . 117
9 Muscle Diseases . 119
9.1 Muscle Biopsy Technique 120
9.2 Laboratory Preparation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 120
9.3 Normal Structure of Muscle . 122
9.4 General Pathological Reactions . 126
9.5 Muscular Dystrophies 128
9.5.1 Dystrophin-Related Muscular Dystrophies . 128
9.5.2 Limb Girdle Muscular Dystrophies . 130
9.5.3 Congenital Muscular Dystrophies . 132
9.5.4 Other Muscular Dystrophies . 132
9.6 Congenital Myopathies 133
9.7 Myofibrillar Myopathies 137
9.8 Metabolic Myopathies 137
9.9 Inflammatory Muscle Disease 139
9.10 Toxic Myopathies . 145
9.11 Neurogenic Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 145
References . 146
10 Peripheral Nerve Diseases 147
10.1 Nerve Biopsy Technique 149
10.2 Laboratory Preparation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 149
10.3 Normal Structure of Peripheral Nerve . 150
10.4 General Pathological Reactions . 150
10.5 Inflammatory Neuropathies 153
10.5.1 Guillain-Barre Syndrome 153
10.5.2 Chronic Inflammatory Demyelinating
Polyradiculoneuropathy (CIDP) . 153
10.5.3 Multifocal Motor Neuropathy with Conduction
Block . 153
10.5.4 Idiopathic Perineuritis . 154
10.5.5 Sarcoidosis 154
10.5.6 Vasculitis . 154
10.6 Neuropathies Associated with Infectious Disease . 155
10.6.1 Leprosy 155
10.6.2 Human Immunodeficiency Virus . 156
10.6.3 Lyme Disease 156
10.6.4 Diphtheria 156
10.7 Toxic Neuropathies 156
10.8 Metabolic and Nutritional Neuropathies 157

10.8.1 Diabetes Mellitus . 157
10.8.2 Uraemia . 157
10.9 Neuropathies Associated with Paraprotein 157
10.10 Amyloid Neuropathies . 159
10.11 Miscellaneous Neuropathies 161
10.11.1 Paraneoplastic Neuropathy 161
10.11.2 Critical Illness Neuromyopathy . . . . . . . . . . . . . . . . . . . . 161
10.11.3 Carpal Tunnel Syndrome . 161
10.12 Hereditary Neuropathies 161
10.13 Skin Biopsy in Small Fibre Neuropathies 163
References . 165
11 Metabolic, Toxic and Nutritional Diseases . 167
11.1 Metabolic Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 167
11.1.1 Hypoglycaemia 167
11.1.2 Electrolyte Imbalance 168
11.1.3 Hepatic Encephalopathy 171
11.1.4 Wilson’s Disease . 171
11.1.5 Uraemic Encephalopathy 172
11.1.6 Amino Acid Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . 172
11.1.7 Urea Cycle Disorders 172
11.1.8 Porphyrias 173
11.1.9 Lysosomal and Peroxisomal Disorders . 173
11.1.10 Mitochondrial Disorders 177
11.2 Toxic Disorders 177
11.2.1 Ethanol 177
11.3 Nutritional Deficiencies . 178
References . 182
12 Neurodegenerative Disorders . 183
12.1 Dementia 185
12.1.1 Alzheimer’s Disease 185
12.1.2 Dementia with Lewy Bodies . 187
12.1.3 Frontotemporal Lobar Degeneration . 188
12.1.4 Prion Diseases . 191
12.2 Disorders Predominantly Affecting the Basal Ganglia 195
12.2.1 Huntington’s Disease . 196
12.2.2 Neurodegeneration with Brain Iron Accumulation . 196
12.2.3 Neuroacanthocytosis . 196
12.3 Disorders Predominantly Affecting the Midbrain 197
12.3.1 Parkinson’s Disease . 197
12.3.2 Progressive Supranuclear Palsy . 199
12.3.3 Multiple System Atrophy 200
12.3.4 Corticobasal Degeneration 201
12.3.5 Other Disorders . 201

12.4 Cerebellar Degeneration . 202
12.5 Motor Neuron Diseases 202
12.5.1 Motor Neuron Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . 202
12.5.2 X-Linked Bulbar Spinal Muscular Atrophy
(Kennedy’s Disease) . 204
12.5.3 Spinal Muscular Atrophy 204
12.6 Hereditary Spastic Paraparesis . 205
References . 205
13 Trauma . 207
13.1 Focal Injury 208
13.1.1 Scalp Injury . 208
13.1.2 Skull Fractures . 208
13.1.3 Brain Contusions and Lacerations . 209
13.2 Traumatic Intracranial Haemorrhage . 210
13.2.1 Extradural Haemorrhage . 210
13.2.2 Subdural Haemorrhage 210
13.2.3 Subarachnoid Haemorrhage 211
13.2.4 Parenchymal Haemorrhage . 211
13.2.5 Intraventricular Haemorrhage . 211
13.3 Other Localised Injury . 211
13.3.1 Focal Vascular Injury . 211
13.3.2 Pituitary Gland Infarction 212
13.3.3 Brain Stem Avulsion . 212
13.3.4 Cranial Nerve Avulsion . 212
13.4 Diffuse Brain Injury . 213
13.4.1 Diffuse Axonal Injury . 213
13.4.2 Diffuse Vascular Injury . 213
13.4.3 Brain Swelling and Ischaemia . 213
13.4.4 Fat Embolism 215
13.5 Missile Head Injury 217
13.6 Inflicted Head Injury in Childhood 217
13.7 Chronic Traumatic Encephalopathy . 217
13.8 Spinal Cord Injury 218
References . 218
14 Paediatric Diseases 219
14.1 Congenital Malformations . 219
14.1.1 Neural Tube Defects 220
14.1.2 Chiari Malformations 221
14.1.3 Disorders of Forebrain Induction 221
14.1.4 Neuronal Migration Disorders . . . . . . . . . . . . . . . . . . . . . 223
14.1.5 Encephaloclastic Defects . 226
14.1.6 Microcephaly, Megalencephaly,
Hemi-megalencephaly 227
14.1.7 Cerebellar, Brainstem and Spinal Cord
Malformations 227

14.2 Hydrocephalus 229
14.3 Perinatal Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 229
14.3.1 Hypoxic-Ischaemic Neuronal Injury . 229
14.3.2 White Matter Lesions 230
14.3.3 Cerebral Haemorrhages . 231
14.3.4 Hypoglycaemia 231
14.3.5 Kernicterus 232
14.3.6 Infections . 232
14.3.7 Rare Neurodegenerative Diseases . 232
References . 233
15 Autopsies 235
References . 236
Appendix 1. Suggested Reading . 239
Index . 241