Motor Neuron Disease: Biology and Management

ISBN-13: 9781447118732 / Angielski / Miękka / 2011 / 468 str.

P. N. Leigh; Michael Swash

Opis

Here is the first book to provide a comprehensive overview of the clinical, pathological, and research aspects of motor neuron disease (MND). The text contains all essential features of the anatomy, physiology, pharmacology and toxicology of the motor system, a full description of MND and its variants, as well as historical developments and a review of the current concepts and controversies. This book comes at a time of increasing interest in neurodegenerative disorders and MND in particular. It will prove a key reference book with an integrated overview of the field, and will be indispensable to practicing neurologists, researchers, and all those with an interest in MND.

Recenzje

"This book is worthwhile to every neurologist and particularly those interested in ALS. It is an interesting book to everybody involved in research on motor neuron diseases. it certainly is one of the better volumes on MND available." Acta Neurologica Belgica

Spis treści

1 Motor Neuron Disease: The Clinical Syndrome.- Classification of Motor Neuron Diseases.- Spinal Muscular Atrophies.- Motor Neuron Disease (Amyotrophic Lateral Sclerosis).- Clinical Features.- Other Clinical Syndromes of MND.- Outcome of MND.- Possible Associations of MND with Other Diseases.- Poliomyelitis.- Hexosaminidase Deficiency (GM2 Gangliosidosis).- MND and Plasma Cell Dyscrasia.- Hyperparathyroidism and Thyrotoxicosis.- AIDS.- Creutzfeldt-Jakob Disease.- Other Disorders.- Diagnosis and Investigation.- Differential Diagnosis.- 2 Epidemiology of Motor Neuron Disease.- Some Important Clinical Patterns of Motor Neuron Disease/Amyotrophic Lateral Sclerosis (MND/ALS).- Frequency of MND/ALS and its Determinants.- Prevalence Rate.- Incidence Rate.- Mortality Rate.- High-Risk Foci.- Risk Factors.- Case-Control Studies.- Ecological Studies.- Definite Risk Factors for MND/ALS.- Familial Aggregation of MND/ALS and Separation of Genetic Entities.- Aetiological Hypotheses.- 3 Familial Motor Neuron Disease.- The Case for Studying Familial Motor Neuron Disease: Rapid Development of Techniques of Molecular Genetics and their Successful Application.- The Problems: Few Families, Clinical and Pathological Heterogeneity and Incomplete Penetrance.- Profile of Familial Motor Neuron Disease.- Phenotypic Variation in FMND.- Neuropathology.- Linkage Analysis in Familial Motor Neuron Disease.- What is Involved in Locating a Defective Gene?.- Linkage to Chromosome 21 Markers.- Identification of Mutations in FMND.- Mutations of Human Cu,Zn SOD in FMND.- The Significance of Mutations of Cu,Zn SOD.- The Next Steps: Identification of other MND genes.- Improvements in DNA Markers.- Choice of Families — Informative Families.- Statistical Analysis.- Candidate Genes.- Other Motor Neuron Disorders: the Spinal Muscular Atrophies.- Androgen Receptors and Typical Motor Neuron Disease (ALS).- Summary and Future Prospects.- 4 Pathology of Motor System Disorder.- Physiological Anatomy of the Motor System.- Axonal Transport in the Motor System.- Macroscopic Pathology of ALS.- Microscopic Pathology of ALS.- Motoneuron Loss.- “Senescent Changes” in ALS.- Cytoplasmic Inclusions in ALS.- Proximal and Distal Axonopathy in ALS.- Tract Degeneration.- Conclusions.- 5 The Pathology of Motor Neuron Disease.- General Autopsy and Neuropathological Findings.- Motor Cortex.- Subcortical White Matter and Cortical Pyramidal Tracts.- Central Grey Matter and Basal Ganglia.- Brainstem and Cranial Nerve Nuclei.- Lower Motor Neurons and Corticospinal Tracts.- Spinocerebellar Pathways.- Sensory Systems.- Autonomic Nervous System.- Peripheral Nerve.- Muscle.- Intellect, the Frontal Lobe and Parkinsonism.- Relation to Other Neuronal Degenerations.- 6 Alternative Approaches to the Pathology of Motor Neuron Disease.- Animal Models in the Study of MND.- Naturally Occurring Animal Models of MND.- Neurotoxic Substances.- Neurotropic Viruses.- Axonal Sprouting and the Motor End Plate.- Axonal Transport.- Slow Axonal Transport.- Fast Axonal Transport.- Axonal Transport in MND.- Selective Neuronal Vulnerability in MND: Onuf’s Nucleus and Other Nuclei.- Conclusion.- 7 The Molecular Pathology of Motor Neuron Disease.- The Cytoskeleton and Cytoskeletal Pathology in Neurodegenerative Disorders.- Neurofilaments and Neurofilamentous Pathology in MND.- Ubiquitin, the Stress Response and Neuronal Damage in MND.- The Ubiquitin Conjugation Pathway.- Selection of Substrates for Conjugation and Degradation.- Ubiquitin-Protein Ligase.- Protein Degradation and Regeneration of Free Ubiquitin.- Ubiquitin and MND.- Morphological Features of Ubiquitin-Immunoreactive Inclusions in MND.- Clinicopathological Correlations.- Pathogenic Significance of Ub-IR Inclusions in MND.- Conclusions.- 8 Neurochemistry of Motor Neuron Disease.- Excitatory Amino Acids in Plasma and CSF in MND.- Glutamate, Glutamate Dehydrogenase (GDH) and Excitotoxicity.- N-Acetyl-Aspartyl-Glutamate (NAAG) and MND.- Plasma Cysteine and Metabolism of Sulphur-Containing Compounds.- Glycine and GABA.- Spinal Cholinergic Systems.- Monoamines.- Neuropeptides.- Thyrotropin-Releasing Hormone (TRH).- Substance P.- Calcitonin Gene-Related Peptide (CGRP).- Neurotrophic Factors and Motoneuronal Death.- Summary and Conclusions.- 9 Calcium and Aluminium in the Chamorro Diet: Unlikely Causes of Alzheimer-Type Neurofibrillary Degeneration on Guam.- Geology, Villages and Water Sources of Guam and Rota.- Implications of These Findings.- Conclusions.- 10 Toxicology of Motor Systems.- Mechanistic Basis of Neuronotoxicity.- General Considerations.- Neuroexcitatory Amino Acid Receptors in the Central Nervous System.- The Excitotoxic Hypothesis of Neuronal Death.- Glutamate as an Endogenous and Exogenous Factor in Neurological Disease.- General Considerations.- Neurotoxicity of Exogenous Glutamate.- Glutamate Metabolism and Neurological Disease.- Glutamate Metabolism in Motor Neuron Disease.- Other Endogenous Factors: Sulphur-Containing Amino Acids.- Amino Acids Containing Oxidised Sulphur Atoms.- Cysteine and Cystine.- Cystine and Glutamate Transport.- Cysteine, Sulphate and Motor Neuron Disease.- Exogenous Factors.- General Considerations.- Lathyrus sativus Seed.- Cycas circinalis Seed.- Nitschia pungens.- Non-NMDA Receptors on Glia.- Summary.- 11 Theories of Causation.- Toxins.- Ageing.- Trophic Factors.- Viruses.- Metabolic Abnormalities.- Autoimmunity.- 12 Neurotrophic Factors and Neurodegeneration.- The Neurotrophins.- Nerve Growth Factor.- Brain-Derived Neurotrophic Factor.- Neurotrophins -3, -4, and -5.- Ciliary Neurotrophic Factor and Related Cytokines.- Platelet-Derived Growth Factor.- The Fibroblast Growth Factors.- Insulin-like Growth Factors.- Epidermal Growth factor.- Growth Factor Receptors and Signal Transduction Pathways.- Neurotrophic Factors and Neurodegeneration.- NGF and Alzheimer’s Disease.- Motor Neuron Disease and Neurotrophic Factors.- CNTF and Motor Neuron Disease.- BDNF, Motor Neurons and Parkinson’s Disease.- 13 Somatic Motoneurons and Descending Motor Pathways. Limbic and Non-limbic Components.- Somatic Motoneurons in Spinal Cord and Brainstem.- Somatic Motoneurons in the Spinal Cord.- Somatic Motoneurons in the Brainstem.- Local Projections to Motoneurons.- Recurrent Motoneuronal Axon Collateral Projections to Motoneurons.- Muscle Spindle Afferent Projections to Motoneurons in Spinal Cord and Brainstem.- Propriospinal Pathways.- Bulbospinal Interneurons Projecting to Motoneurons.- Pathways Controlling Respiration and Abdominal Pressure.- Pathways Involved in Micturition Control.- Descending Pathways of Somatic Motor Control Systems.- The Medial Descending System.- The Lateral Descending System.- Descending Pathways Involved in Limbic Motor Control Systems.- Pathways Projecting Diffusely to the Spinal Gray Matter.- Projections from the Mesencephalon to Caudal Brainstem and Spinal Cord.- Projections from the Hypothalamus to Caudal Brainstem and Spinal Cord.- Projections from Amygdala and Bed Nucleus of the Stria Terminalis to Caudal Brainstem and Spinal Cord.- Projections from the Prefrontal Cortex to Caudal Brainstem and Spinal Cord.- Conclusions.- The First Motor System.- The Second Motor System.- The Third Motor System.- 14 Neurophysiological Changes in Motor Neuron Disease.- Electromyography (EMG).- Fasciculations in MND.- Fibrillation Potentials and Positive Sharp Waves.- Other Spontaneous Discharges in MND.- Motor Unit Potentials in MND.- Fatigue, Decrement and Neuromuscular Jitter.- Motor Conduction in MND.- Late Responses in Motor Conduction Studies.- Sensory Conduction in MND.- Central Motor Conduction in MND.- Stages of the Disease: EMG Criteria.- Electrophysiological Assessment in Treatment Trials.- Differential Diagnosis of MND by its Electrophysiological Features.- 15 Clinical Pharmacology of Motor Neurons.- Trophic Factors and Motor Neurons.- Neurotransmitters, Neuropeptides and Receptors in the Ventral Horn.- Excitotoxins and Motor Neurons.- Assessment Tools for Drug Effects on Human Motor Neurons.- Clinical Measurements.- Electrophysiology.- TRH and TRH Analogues.- Trophic and Protective Effects of TRH on Motor Neurons.- Neurophysiological Data.- Spasticity.- Drugs Used in Spasticity.- Conclusion.- 16 The Management of Motor Neuron Disease.- Background.- Epidemiology.- Who Looks After MND Patients?.- The Organisation of Services.- The Hospital.- Keyworker.- Phase I: The Stage of Diagnosis.- The Diagnosis.- “Treatment”.- Prognosis.- Telling the Diagnosis.- Phase II: The Stage of Deterioration Without Major Disability.- Phase III: The Phase of Major Disability With Multiple Problems.- Bulbar Problems in Motor Neuron Disease.- Salivary Dribbling (Drooling).- Dysphagia.- Choking.- Dysarthria and Communication Problems.- Respiratory Failure.- Weight and Nutrition.- Constipation.- Management of Constipation.- Pain.- Control of Pain.- Decreasing Mobility.- Wheelchairs.- Leg Swelling.- Weakness of Muscles.- Sleeping Problems.- Emotional Problems.- Equipment.- Phase IV: The Terminal Stage.- Use of Narcotics.- Audit.- Appendix I. MND Table of Responsibilities.- 17 Clinical Trial Methodology.- Measurement Techniques.- Natural History.- Sample Size Determination.- The Problem of Drop-outs.- Controls.- Statistical Analysis.- Regulatory Processes.- 18 New Therapeutic Approaches: Rationale and Results.- Rationale and Results.- The Use of Thyrotropin-Releasing Hormone (TRH).- Approaches to Counteract Excitatory Amino Acids.- Treatment of Immunological Abnormalities.- Approaches to Trace Metal Intoxication.- Antiviral Agents.- Enhancing Axonal Sprouting and Regeneration.- Neurotrophic Factors.- Other Approaches.- Conclusion.- 19 Living with Motor Neuron Disease.