Clinical Neuropathology

Although most textbooks of neurology contain a certain amount of pathological informa­ tion, neuropathology has often been treated in isolation. However, neuropathology has a close relationship to clinical neurology, neurosurgery and neuroradiology. Thus, advances in the rapidity and accuracy of pathological diagnosis have often led to changes in clinical management and, recently, improvements in clinical diagnosis, particularly CT scanning, have brought about a change in emphasis in the practice of neuropathology. In this textbook we have sought to present a widely based account of neuropathology in combination with information from clinical experience. We chose this approach in order to emphasize the close interrelation between clinician and pathologist. The book grew out of a course organised jointly by two neurologists and two neuropathologists from the Depart­ ments of Neuropathology and Neurology of The London Hospital and The University of Southampton. It is hoped that the book will be useful not only to pathologists, neurologists, neurosurgeons, and neuroradiologists, but also to general physicians. In a period of rapid advance in knowledge it is important to recognise how changes in the clinical and laboratory disciplines overlap. In order to make the most of consultations with pathologist colleagues the clinician must know what skills and techniques are available in the laboratory, and similarly, the pathologist must keep abreast of changes in clinical practice. In the past the clinician and pathologist have often been slow to appreciate advances in each other's fields.

1. Development of Neurology and Neuropathology.- Early concepts of neurological structure and function.- Microscopy of the nervous system.- Development of clinical neurology.- Diagnosis and treatment of neurological disease.- Development of modern neuropathology.- 2. Functional Histology and Anatomy of the Central Nervous System.- Histology of the brain.- Neurons.- Oligodendrocytes.- Astrocytes.- Blood vessels of the brain, and the blood-brain barrier.- Microglia.- Ependyma.- Choroid plexus.- Anatomy of the human brain.- Anatomy of the spinal cord.- Basic neuroanatomy from the study of brain evolution.- Further reading.- 3. The Interpretation of Neurological Symptoms and Signs.- Clinical localisation of brain disorders.- Focal lesions.- Synopsis of regional functions in the cerebral hemispheres.- Disorders of the cerebellum and basal ganglia.- Clinical effects of lesions of the mid-brain, pons and medulla.- Interaction between focal and generalised effects of intracranial lesions.- Altered states of consciousness.- States of arousal.- Discrepancies between apparent state of arousal and content of consciousness.- Epilepsy.- Headache.- Raised intracranial pressure.- Spinal cord lesions.- Extrinsic lesions.- Intrinsic lesions.- Pain.- Radiology.- Peripheral nerve disease.- Symptoms.- Autonomic disturbances.- Distribution of symptoms and signs.- Investigation of peripheral neuropathy.- Correlation of clinical findings, electromyography and biopsy.- Conclusion.- Further reading.- 4. General Pathology of the Central Nervous System.- Reactions of brain cells to disease processes.- Neurons.- Astrocytes.- Microglia.- Reactions to brain tissue damage.- Inflammation and repair.- Breakdown of the blood-brain barrier, and cerebral oedema.- Breakdown of myelin.- Multiple sclerosis.- The secondary effects of intracranial space-occupying lesions and cerebral oedema.- Hydrocephalus.- Further reading.- 5. Cerebral Vascular Disease.- Stroke.- Clinical features.- Clinical classification.- Embolism and cerebral infarction.- Arterial occlusion.- Large and small vessel disease in cerebral infarction.- Risk factors.- Epidemiology.- Treatment.- Vascular territories and infarction.- Physiological aspects of the cerebral circulation.- Cerebral infarcts.- Sequence of histological changes after cerebral infarction.- Blood flow changes after cerebral infarction.- Lacunes.- Carotid artery territory infarction.- Vertebro-basilar territory infarction.- Boundary zone infarction.- Death due to hypotensive brain damage.- Hypoxic encephalopathy.- Spinal cord infarction.- Venous infarction.- Intracranial haemorrhage.- Hypertensive cerebral and cerebellar haemorrhage.- Subarachnoid haemorrhage.- Cerebral tumour and cerebral haemorrhage.- Further reading.- 6. Trauma to the Nervous System.- Head injuries.- Blunt head injuries.- Pathology of blunt head injuries.- Penetrating head injuries.- Spinal cord trauma.- Pathology of spinal cord injuries.- Prospectus.- Chronic and recurrent trauma to the nervous system.- Nerve root compression, and traumatic radiculopathies.- Root and cord lesions in spondylosis.- Spinal cord and nerve root compression by tumour or infection.- Radiation myelopathy and encephalopathy.- Further reading.- 7. Intracranial and Spinal Tumours.- Classification.- Incidence of intracranial and spinal tumours.- Clinical presentation of intracranial tumours.- Diagnosis of intracranial tumours.- Intracranial tumours of neuro-epithelial origin.- Astrocytomas.- Gioblastomas and anaplastic astrocytomas.- Oligodendrogliomas.- Ependymomas.- Medulloblastomas.- Choroid plexus papillomas.- Colloid cysts of the third ventricle.- Tumours of nerve sheath cells.- Schwannomas.- Neurofibromas.- Meningiomas.- Primary malignant lymphomas of the brain.- Tumours and malformations of blood vessel origin.- Haemangioblastomas.- Capillary telangiectases.- Cavernous angiomas.- Arteriovenous malformations.- Tumours of the pituitary.- Tumours of the pineal.- Metastatic intracranial tumours.- Spinal tumours.- Classification.- Clinical presentation, investigation and treatment.- Pathology.- Further reading.- 8. Pituitary Tumours.- Pituitary adenomas.- Clinical aspects.- Histopathology.- Craniopharyngiomas and suprasellar cysts.- Pathology.- Further reading.- 9. Virus Infections of the Nervous System.- Clinical aspects and pathology.- Viral meningitis.- Viral encephalitis.- Post-infectious encephalitis.- Reye’s syndrome.- Viruses with specific neurotropic characteristics.- Viruses and polyneuropathy.- Slow virus encephalitis.- Virology of nervous system infections.- Viral replication.- Defences against viral infection.- Viruses associated with CNS infections.- Virological investigations in CNS infections.- Meningitis and paralytic disease.- Herpes simplex meningitis.- Investigation of encephalitis.- Post-infectious encephalitis.- Mycoplasma pneumoniae infections.- Acute encephalitis.- Herpes simplex encephalitis.- Diagnosis of other viral encephalitides.- Slow virus encephalitis.- Further reading.- 10. Bacterial, Fungal and Parasitic Infections of the Central Nervous System.- Bacterial infections.- Bacterial meningitis.- Clinical features.- Chronic or subacute forms.- Late complications.- CSF examination.- Bacteriology of meningitis.- Pathology of bacterial meningitis.- Tuberculous meningitis and tuberculomas.- Neurosyphilis.- Shunt-associated meningitis.- Fungal meningitis.- Other causes of meningitis.- Intracranial abscess.- Subdural abscess.- Brain abscess.- Mycotic aneurysms.- Protozoal infections.- Metazoal parasites.- Further reading.- 11. Developmental and Neonatal Neuropathology.- Epidemiology.- Antenatal factors.- Perinatal factors.- Postnatal developmental disability.- Pathogenetic considerations.- Development of the human brain.- Chromosomal abnormalities.- Down’s syndrome (mongolism).- Trisomy 17–18 (trisomy E; Edwards’ syndrome).- Trisomy 13–15 (trisomy D; Pateau’s syndrome).- Destructive lesions.- Infections.- Porencephaly and hydranencephaly.- Chemical agents and CNS malformations.- Radiation.- Dysraphic malformations.- Anencephaly.- Encephalocoeles.- Spina bifida dorsalis.- Arnold-Chiari malformation.- Dandy-Walker malformation.- Hydrocephalus.- Syringomyelia.- Perinatal brain injuries.- Birth trauma.- Cerebral trauma in neonates.- Hypoxia.- Kernicterus: bilirubin encephalopathy.- Neonatal infections.- The phakomatoses.- Neurofibromatosis.- Tuberose sclerosis.- Von Hippel-Lindau’s disease.- Sturge-Weber syndrome.- Ataxia-telangiectasia.- Other phakomatoses.- Pathology of metabolic disorders of the brain.- Pathology of inborn lysosomal storage disorders.- Neuronal storage disorders.- Leukodystrophies.- Mucolipidoses.- Further reading.- 12. Metabolic Disorders Affecting the Nervous System.- Neonatal hypothyroidism.- Phenylketonuria.- Disorders of the branched chain amino acids.- Maple syrup urine disease.- ?-Methylcrotonyl CoA carboxylase deficiency.- Disorders of sulphur metabolism.- Urea cycle disorders.- Carbohydrate disorders.- Galactosaemia.- Disorders of fructose metabolism.- Glycogen storage disorders.- Inherited disorders of trace metal metabolism.- Wilson’s disease.- Menkes’ disease.- Diagnosis of inherited disorders of sick infants.- References.- 13. Inborn Lysosomal Storage Disorders Affecting the Nervous System.- Lysosomes and lysosomal storage disorders.- Lysosomal disorders affecting the nervous system.- The mucopolysaccharidoses.- The lipidoses.- The gangliosidoses.- Metachromatic leukodystrophy (MLD).- Krabbe leukodystrophy.- Fabry disease (angiokeratoma corporis diffusum).- Gaucher disease.- Niemann-Pick disease.- Ophthalmoplegic lipidoses.- Farber’s lipogranulomatosis.- The mucolipidoses.- Austin sulphatidosis.- I-cell disease.- Mucolipidosis type IV.- Other lysosomal disorders affecting the nervous system.- Mannosidosis.- Fucosidosis.- Aspartyl-glycosaminuria.- Aids to diagnosis of lysosomal disorders.- Management of lysosomal disorders.- References.- 14. Hereditary and System Disorders of the Nervous System.- Clinical features.- Hereditary system degenerations.- Hereditary spastic paraplegia (Strümpell).- Hereditary posterior column ataxia (Biemond).- Charcot-Marie-Tooth disease (peroneal muscular atrophy).- Friedreich’s ataxia.- Spinocerebellar atrophies.- Cortical cerebellar atrophy.- Olivopontocerebellar atrophy.- Shy-Drager syndrome.- Basal ganglia disorders.- Acquired system degenerations.- Subacute combined degeneration of the cord.- Acquired cerebellar degenerations.- Acquired basal ganglia degenerations.- Striato-nigral degeneration.- Progressive supranuclear palsy.- Stiff man syndrome.- Further reading.- 15. Dementia.- Epidemiology.- Causes.- Alzheimer’s disease.- Multi-infarct dementia.- Coexistence of Alzheimer’s dementia and multi-infarct dementia.- Pick’s disease.- Progressive subcortical gliosis.- Huntington’s disease.- Creutzfeldt-Jakob disease (subacute spongiform encephalopathy).- The amnesic syndrome.- Wernicke-Korsakoff syndrome.- Intermittently raised pressure hydrocephalus (IRPH).- Further reading.- 16. Diseases of Peripheral Nerve.- Nerve biopsy.- Autopsy study of peripheral neuropathies.- Techniques for peripheral nerve histology.- Anatomy of peripheral nerves.- Histology of peripheral nerves.- Development and ageing of peripheral nerves.- General pathology of peripheral nerves.- Axon (wallerian) degeneration and regeneration.- Segmental demyelination.- Hypertrophic neuropathy.- Peripheral nerve diseases.- Destructive lesions of the spinal cord.- Diseases affecting motor neurons.- Diseases of sensory ganglia.- Traumatic and compressive nerve lesions.- Neuropathies due to vascular disease.- Toxic neuropathies.- Metabolic neuropathies.- Amyloid neuropathy.- Inflammatory disorders of peripheral nerves.- Peroneal muscular atrophy and hypertrophic neuropathy.- Disorders of lipid metabolism.- Neuropathies in malignant disease.- Autonomic neuropathies.- Further reading.- 17. Diseases of Muscle.- Muscle biopsy technique.- Histological features of neuromuscular disease.- Statistical methods.- Degenerative changes.- Regenerative changes.- Other features.- Classification of neuromuscular disorders.- Myopathic disorders.- Muscular dystrophies.- Congenital myopathies.- Myotonic syndromes.- Metabolic myopathies.- Endocrine myopathies.- End-plate disorders.- Inflammatory myopathies.- Neurogenic disorders.- Spinal muscular atrophies.- Motor neuron disease.- Other anterior horn cell disorders and other diseases causing denervation of muscle.- Further reading.