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Multiple Sclerosis - 1st Edition - ISBN: 9780128007631, 9780128010051

Multiple Sclerosis

1st Edition

A Mechanistic View

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Editor: Alireza Minagar
Hardcover ISBN: 9780128007631
eBook ISBN: 9780128010051
Imprint: Academic Press
Published Date: 1st November 2015
Page Count: 538
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Multiple Sclerosis: A Mechanistic View provides a unique view of the pathophysiology of multiple sclerosis (MS) and related disorders. As the only book on the market to focus on the mechanisms of MS rather than focusing on the clinical features and treatment of the disease, it describes the role of genetic and environmental factors in the pathogenesis of MS, the role of specific cells in the pathophysiology of the disease, and the pathophysiology of inflammatory and neurodegenerative disorders related to MS.

The book provides discussion of neurodegeneration and neuroregeneration, two critical emerging areas of research, as well as detailed discussion of the mechanisms of action of the approved and investigational drugs for treatment of MS and the emerging role of magnetic resonance spectroscopy (MRI) in investigations into MS.

It is the only book on the market to offer comprehensive coverage of the known mechanisms of MS and related diseases, and contains contributions from physicians and researchers who are worldwide experts in the field of study.

Key Features

  • Focuses on the pathophysiologic mechanisms of multiple sclerosis and the mechanisms of action in agents for the treatment of MS
  • Discusses the roles of neurodegeneration and neuroregeneration in MS and related diseases
  • Authored and edited by international leaders in the field of MS research


Researchers and graduate students in neurology, neuroscience, neurosurgery; internists and researchers in neuroinflammation and neuroimmunology

Table of Contents

  • Contributors
  • Preface
  • Chapter 1. Clinical Manifestations of Multiple Sclerosis: An Overview
    • Introduction
    • Motor and sensory manifestations
    • Fatigue
    • Cognitive decline
    • Psychiatric manifestations
    • Optic neuritis and other neuroophthalmologic manifestations
    • Uveitis
    • Uhthoff phenomenon
    • Pulfrich phenomenon
    • Brain stem involvement in MS
    • Transverse myelitis
    • Cerebellar involvement and tremor in MS
    • Seizures and other paroxysmal features of MS
    • Painful syndromes
    • Bowel and bladder dysfunction
    • Movement disorders
  • Chapter 2. Novel Therapies for Multiple Sclerosis: A Mechanistic View
    • Introduction
    • Laquinimod
    • Monoclonal antibodies as novel therapies for MS
    • Alemtuzumab
    • Daclizumab
    • Ocrelizumab
    • Ofatumumab
    • Rituximab
    • The concept of remyelination as therapy for MS
    • AntiLINGO-1
    • rHIgM22
  • Chapter 3. Role of B Cells in the Pathogenesis of Multiple Sclerosis: Mechanisms of Action
    • Introduction
    • Evidence of B cell involvement in the pathogenesis of MS and factors pointing to the limits of T cell action
    • The mechanism of B cell action in the development and progress of MS
    • The role of clonally expanded B cells
    • Role of B cells in priming/activating T cells
    • Regulatory B cells (Bregs)
    • Memory B cells
    • The role of MHC in triggering MS
    • Conclusion
    • List of abbreviations
  • Chapter 4. Role of CD4+ T Cells in the Pathophysiology of Multiple Sclerosis
    • Summary
    • Traditional CNS inflammation versus “neuroinflammation”
    • Etiology of MS
    • Physiological and pathological roles of CD4+ T cell subsets
    • Classical Th1/Th2 immunoregulatory axis in MS and its animal models
    • Novel Th17/Treg immunoregulatory axis in MS and its animal models
    • Do “gain-of-function” changes affect susceptibility to MS?
    • “T cell exhaustion” as a protective mechanism against immunopathology
    • Protective roles of PD-1 and TIM-3 in MS and its animal models
    • Conclusions
  • Chapter 5. Granulocyte-Macrophage Colony-Stimulating Factor in Central Nervous System Autoimmunity
    • Introduction
    • The role of GM-CSF in EAE
    • GM-CSF production by T cells in MS
    • Conclusion
  • Chapter 6. Role of Cytokine-Mediated Crosstalk between T Cells and Nonimmune Cells in the Pathophysiology of Multiple Sclerosis
    • Introduction
    • Pathogenic roles of CD4+ T cells
    • Pathogenic roles of CD8+ T cells
    • T cell subsets with suppressive functions
    • Pathogenic role of nonimmune cells: the inflammation amplifier
    • The mechanism of autoreactive T cell invasion into the CNS
    • Conclusion
  • Chapter 7. Vitamin D: Role in Pathogenesis of Multiple Sclerosis
    • Introduction
    • Vitamin D and genetic susceptibility to MS
    • Vitamin D deficiency as a risk factor for MS
    • Experimental autoimmune encephalitis
    • Role of vitamin D in disability progression and relapses in MS
    • Supplementation of vitamin D
    • Therapeutic potential of vitamin D
    • Closing remarks
  • Chapter 8. Role of Genetic Factors in Pathophysiology of Multiple Sclerosis
    • A genetic component to multiple sclerosis
    • Identification of genetic risk variants
    • Missing heritability
    • Association with disease phenotype and therapy outcome
    • From gene to function
    • Concluding remarks
  • Chapter 9. Neuropathology of Multiple Sclerosis
    • Introduction
    • Plaque types
    • Mechanisms of white matter demyelination
    • The pathological substrate of MS progression
    • Cortical demyelination in early MS
    • Remyelination
    • Conclusion
  • Chapter 10. Pathophysiology of Acute Disseminated Encephalomyelitis
    • Introduction
    • Epidemiology
    • Immunopathogenesis of ADEM
    • Pathology of ADEM
    • Do ADEM and MS represent a part of immune-mediated spectrum of demyelinating disorders?
    • Conclusion
  • Chapter 11. Pathophysiology of Experimental Autoimmune Encephalomyelitis
    • Introduction
    • Experimental autoimmune encephalomyelitis
    • Immunopathogenesis of EAE
    • Monocytes/macrophages
    • Concluding remarks
  • Chapter 12. Pathophysiology of Optic Neuritis
    • Introduction
    • ON in relation to the risk of MS
    • Epidemiology of ON in MS
    • The afferent visual pathway
    • Clinical features of optic neuritis
    • Inflammation in optic neuritis
    • Demyelination in optic neuritis
    • Axonal and neuronal degeneration in optic neuritis
    • Imaging and electrophysiologic correlates of optic neuritis
    • Conclusions
    • Disclosures
  • Chapter 13. Neurodegeneration and Remyelination in Multiple Sclerosis
    • Introduction
    • Inflammation and neurodegeneration
    • Conclusion
  • Chapter 14. Mechanisms of Action of Glatiramer Acetate in the Treatment of Multiple Sclerosis
    • Section 1. Introduction
    • Section 2. Impact on adaptive immune responses
    • Section 3. Glatiramer acetate as a neuroprotective agent
    • Conclusion
  • Chapter 15. Mechanism of Action of Interferon Beta in Treatment of Multiple Sclerosis
    • Introduction
    • IFNβ signaling pathway
    • Association between molecular defects in IFNβ signaling and MS pathogenesis
    • Modifying the immune response due to effects on multiple cell types
    • Therapeutic effects of IFNβ through targeting B cells’ functions
    • Effects of IFNβ on DCs
    • IFNβ blocks T cell activation
    • Downregulation of MHC II expression
    • Inhibition of coactivators interaction
    • Upregulation of death receptors and CTLA4 on the T cell surface
    • The effect of IFNβ in cytokine shift
    • The BBB in the pathogenesis of MS
    • Mechanisms of action of IFNβ at the BBB
    • ECAMs and junctional proteins
    • Chemokines and chemokines receptors
    • MMPs and CD73 protein
    • The effect of IFNβ in the CNS
    • MS and miRNAs
    • Vitamin D and IFNβ treatments in MS
  • Chapter 16. Mechanisms of Blood–Brain Barrier Disintegration in the Pathophysiology of Multiple Sclerosis
    • The blood–brain barrier: normal anatomy and physiology
    • BBB disintegration in MS: a mechanistic picture
    • Chemokines and cytokines in MS
    • Role of cell-derived microparticles in the pathogenesis of MS
    • MRI and blood–brain disintegration in MS
    • Conclusion
  • Chapter 17. Mechanisms and Potentials of Stem Cells in the Treatment of Multiple Sclerosis: The Unpaved Path
    • Introduction
    • Neural progenitor/stem cells (NP/SCs): mechanism of function
    • Mesenchymal stem cells: mechanisms of function
    • Hematopoetic stem cells
    • Embryonic stem cells and induced pluripotent stem cells
    • Allogenic stem cell therapy
    • Conclusion
    • List of abbreviations
  • Chapter 18. Role of Neuroimaging in Multiple Sclerosis
    • Introduction
    • Conventional MRI techniques
    • Nonconventional MRI techniques
    • Conclusions
    • List of abbreviations
  • Chapter 19. Pathophysiology of Lymphatic Drainage of the Central Nervous System: Implications for the Pathophysiology of Multiple Sclerosis
    • Introduction
    • Lymphatic drainage of CSF
    • Lymphatic drainage of ISF from the brain parenchyma
    • Evidence for lymphatic drainage of the human brain
    • Age-related deterioration of perivascular lymphatic drainage of the brain
    • Motive force for perivascular lymphatic drainage
    • Temporary impairment of perivascular drainage by immune complexes
    • Pathophysiology of perivascular macrophages
    • Interrelationship between CSF and ISF
    • Immunological significance of lymphatic drainage of the brain and implications for MS
    • Conclusions
  • Index


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© Academic Press 2016
1st November 2015
Academic Press
Hardcover ISBN:
eBook ISBN:

About the Editor

Alireza Minagar

Dr. Alireza Minagar is Professor and Chairman of neurology at LSU Health Sciences Center in Shreveport, Louisiana. As a graduate of Department of Neurology at University of Miami, he did a two-year fellowship in multiple sclerosis and clinical neuroimmunology at the Multiple sclerosis Center of University of Miami. Dr. Minagar has significant interest in pathophysiology and neuroimaging features of the inflammatory disease of human central nervous system, in general, and multiple sclerosis, in particular. His life-long passion is to better understand interactions between the inflamed endothelial cells and other cellular components of blood. Dr. Minagar strongly believes in team work and constantly works with other neurologists and neuroscientists around the globe. He has published more than two hundred manuscripts in peer-reviewed journal and textbooks on multiple sclerosis and other neurological diseases.

Affiliations and Expertise

Professor, Department of Neurology, Louisiana State University Health Sciences Center, Shreveport, LA, USA

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