McAlpine's Multiple Sclerosis, 4th Edition

McAlpine's Multiple Sclerosis

4th Edition

By Alastair Compston, PhD, MBBS, FRCP, Professor of Neurology, University of Cambridge, Cambridge, UK; Ian R. McDonald, University of Cambridge; John Noseworthy, MD, Chair, Department of Neurology, Mayo Clinic, Rocherster, MN; Hans Lassmann, MD, Professor of Neuropathology, Institute of Neurology, University of Vienna, Vienna, Austria; David H. Miller, MBChB, MD, FRCP, FRACP, Professor of Clinical Neurology, Institute of Neurology; Consultant Neurologist, The National Hospital for Neurology and Neurosurgery, London; Kenneth J. Smith, PhD, Department of Neuroimmunology, Guy's King's & St. Thomas' School of Medicine, London, UK; Hartmut Wekerle, PhD, MD, Director, Max-Planck-Institut fur Psychiatrie (Theoretisches Institut), Martinsried, Germany; and Christian Confavreux, MD, Service de Neurologie, Hopital Neurologique, BP Lyon Montchat, France


SECTION ONE: THE STORY OF MULTIPLE SCLEROSIS


1. The story of multiple sclerosis

The evolving concept of multiple sclerosis

Naming and classifying the disease: 1868-1983

Clinical descriptions of multiple sclerosis: 1838-1981

Personal accounts of multiple sclerosis: 1824-1991

The social history of multiple sclerosis: 1945-1998

The pathogenesis and clinical anatomy of multiple sclerosis: 1849-1977

The laboratory science of multiple sclerosis: 1912-1981

Discovery of glia and remyelination: 1858-1988

The aetiology of multiple sclerosis: 1883-1976

Attitudes to the treatment of multiple sclerosis: 1841-1983


SECTION TWO: THE CAUSE AND COURSE OF MULTIPLE SCLEROSIS


2. The distribution of multiple sclerosis

The rationale for epidemiological studies in multiple sclerosis

Definitions and statistics in epidemiology

Strategies for epidemiological studies in multiple sclerosis

The geography of multiple sclerosis

Epidemics and clusters of multiple sclerosis

The environmental factor in multiple sclerosis


3. The genetics of multiple sclerosis:

Genetic analysis of multiple sclerosis

Methods of genetic analysis

Racial susceptibility

Sex differences in susceptibility

Familial multiple sclerosis

Candidate genes in multiple sclerosis

Systematic genome screening

Lessons from genetic studies of experimental allergic encephalomyelitis

Conclusions


4. The natural history of multiple sclerosis

Introduction

Definitions

Onset

Course

Inter-individual variability

Factors affecting the prognosis

General considerations

Environmental influences


Chapter 5: The aetiology of multiple sclerosis: an epitome


SECTION THREE: THE CLINICAL FEATURES AND DIAGNOSIS OF MULTIPLE SCLEROSIS


6. The symptoms and signs of multiple sclerosis.

Multiple sclerosis as a neurological illness

Initial symptoms

Symptoms and signs in the course of the disease

Individual symptoms and sign

Associated diseases

Conclusion


7. The diagnosis of multiple sclerosis

Diagnostic criteria for multiple sclerosis

Selection of investigations

Magnetic resonance imaging

Evoked potentials

Examination of the cerebrospinal fluid

A strategy for the investigation of demyelinating disease


8. The differential diagnosis of multiple sclerosis

The spectrum of disorders mimicking multiple sclerosis

Diseases that may cause multiple lesions of the CNS and also often follow a relapsing remitting course

Systematized central nervous system diseases

Isolated or monosymptomatic CNS syndromes

Non organic symptoms

How accurate is the diagnosis of multiple sclerosis?


9. Multiple sclerosis in the individual and in groups: a conspectus

The typical case

Isolated syndromes and their outcome: judicious use of investigations and critique of the new diagnostic criteria

Co-morbidity and associated diseases

Situations in which alternative diagnoses should be considered

When to ignore ?inconvenient? laboratory results or clinical findings: taking the best position

?Pathognomonic? and ?un-heard of? features of multiple sclerosis


SECTION FOUR: THE PATHOGENESIS OF MULTIPLE SCLEROSIS


10. The neurobiology of multiple sclerosis.

Organisation in the central nervous system

Development of the central nervous system

Macroglial lineages in the rodent and human nervous system

Axon-glial interactions and myelination

Demyelination

Axon degeneration and restoration of function
Remyelination


11. The immunology of inflammatory demyelinating disease

Multiple sclerosis as an autoimmune disease

Immune responses: innate and adaptive

T lymphocytes

B lymphocytes

Autoimmunity and self tolerance in the central nervous system

Regulation of central nervous system autoimmune responses

Immune reactivity in the central nervous system

Pathogenesis of demyelination and tissue damage

Peripheral blood biomarkers for multiple sclerosis and disease activity

Markers of multiple sclerosis and disease activity in cerebrospinal fluid

Conclusion


12. The pathology of multiple sclerosis

Introduction

Pathological classification of demyelinating diseases

The demyelinated plaque

Immunopathology of inflammation

Demyelination and oligodendroglial damge

Remyelination

Axonal pathology

Grey matter pathology / cortical plaques

Astroglia reaction

Abnormalities in the ?normal? white matter

Distribution of lesions in the nervous system

Is there evidence for an infectious agent in the lesions of multiple sclerosis?

Dynamic evolution of multiple sclerosis pathology

Differences between acute relapsing and progressive multiple sclerosis

Molecular approaches to the study of the MS lesion: Global profiling of transcriptome and proteome.

Association of multiple sclerosis with other diseases

Conclusions


13. The pathophysiology of multiple sclerosis

Introduction

Methods for exploring the pathophysiology of multiple sclerosis

Relapsing remitting multiple sclerosis: loss of function due to conduction block

Relapsing remitting multiple sclerosis: recovery of function and remission

Physiological explanations for other clinical symptoms in multiple sclerosis

Permanent loss of function in the context of disease progression

Summary


SECTION FIVE: THE TREATMENT OF MULTIPLE SCLEROSIS


15. Care of the person with multiple sclerosis

General approach to the care of people with multiple sclerosis

The early stages of disease: minimal disability

The middle stages of disease: moderate disability

The later stages of disease: severe disability

Guidelines for the management and investigation of multiple sclerosis

Conclusion


16. Treatment of the acute relapse

The features of active multiple sclerosis

The treatment of relapse in multiple sclerosis

Other approaches to the treatment of acute relapse

Treatment of acute optic neuritis

Management of other central nervous system demyelinating disorders

Adverse effects of corticosteroids

Mode of action of corticosteroids

Practice Guidelines


17. The treatment of symptoms in multiple sclerosis and the role of rehabilitation

The general principles of symptomatic treatment in multiple sclerosis

Disturbances of autonomic function

Mobility and gait disturbance

Fatigue

Disturbances of brain stem function

Perturbations of nerve conduction

Cognition

Visual symptoms

Rehabilitation in multiple sclerosis

Summary


18. Disease modifying treatments in multiple sclerosis

The aims of disease modifying treatment

The principles of evidence based prescribing in multiple sclerosis

The role of magnetic resonance imaging in clinical trials

Drugs that stimulate the immune response

Drugs that non-specifically suppress the immune response

The beta interferons

Molecules that inhibit T cell-peptide binding

Specific treatments that target T cells

Agents which inhibit macrophages and their mediators

Recent miscellaneous treatments

Postscript


19: The person with multiple sclerosis: present and future

Empirical versus hypothesis driven therapeutics

New opportunities for immunological intervention

Axon protection; acute and chronic

Treatment in special situations

Remyelination:


Index