1;Preface;5 2;Contents;11 3;Contributors;13 4;Benign Multiple Sclerosis: A Distinct Clinical Entity with Therapeutic Implications;15 4.1;1 Introduction;16 4.2;2 Natural History of Multiple Sclerosis: Disability Progression;16 4.3;3 Benign MS: A Fallacy or a Distinct Clinical Entity?;17 4.4;4 Does Benign MS Stay Benign with Increasing Disease Duration?;18 4.5;5 Other Clinical Predictors of MS Outcome;20 4.6;6 Neuroimaging Studies in Benign MS;21 4.7;7 The Currently FDA-Approved Disease-Modifying Agents: Efficacy, Mode of Action, and Side Effects;23 4.8;8 Should All MS Patients Be Treated with Disease- Modifying Therapies? ;27 4.9;References;28 5;Pathological Heterogeneity of Idiopathic Central Nervous System Inflammatory Demyelinating Disorders;32 5.1;1 Introduction;33 5.2;2 Heterogeneity of Multiple Sclerosis White Matter Lesions;34 5.3;3 Remyelination in MS;44 5.4;4 The Clinicopathologic Spectrum of CNS Idiopathic Inflammatory Demyelinating Disorders;45 5.5;Conclusions;51 5.6;References;51 6;Multiple Sclerosis Genetics;57 6.1;1 Introduction;58 6.2;2 Major Histocompatibility Complex and Multiple Sclerosis;59 6.3;3 Genetic Analyses;61 6.4;4 Microarray Studies;69 6.5;5 Future Directions;73 6.6;References;75 7;Imaging of Remyelination and Neuronal Health;85 7.1;Abbreviations;86 7.2;1 Introduction ;86 7.3;2 Conventional MRI of Remyelination;88 7.4;3 Magnetization Transfer Imaging of Remyelination ;92 7.5;4 Diffusion Imaging of Remyelination ;95 7.6;5 Spectroscopy of Remyelination ;98 7.7;6 Other Imaging Modalities ;100 7.8;Conclusions;102 7.9;References;102 8;Immunological Aspects of Axon Injury in Multiple Sclerosis;105 8.1;1 Introduction;106 8.2;2 Changes in Axon Function During Demyelination ;106 8.3;3 Axonal Degeneration During Demyelination;115 8.4;4 Immune-Mediated Mechanisms of Axon Injury During Demyelination ;119 8.5;5 Stress and the Naked Axon - A Hypothesis;130 8.6;References;130 9;The Multiple Sclerosis Degradome: Enzymatic Cascades in Development and Progression of Central Nervous System Inflammatory Disease;144 9.1;1 Introduction;145 9.2;2 Multiple Classes of Protease Implicated in MS;146 9.3;3 Functional Roles of Proteases in MS;158 9.4;4 Novel Hypothesis Regarding Role of Proteases in MS;167 9.5;5 Proteases as Targets for Rationale Drug Design;168 9.6;Conclusion;170 9.7;References;170 10;Genetic Analysis of CNS Remyelination;187 10.1;1 Introduction;188 10.2;2 Mouse Models of Demyelinating Disease;189 10.3;3 Cellular Events in Remyelination;190 10.4;4 Genetic Analysis in the Mouse;190 10.5;5 Reverse Genetic Analysis of CNS Remyelination;192 10.6;6 Forward Genetic Analysis of CNS Remyelination;197 10.7;References;200 11;Remyelination in Experimental Models of Toxin- Induced Demyelination;203 11.1;1 Introduction;204 11.2;2 Demyelinating Toxins ;206 11.3;3 What is the Place of Toxin Models in the Study of CNS Demyelination and Remyelination?;215 11.4;References;218 12;Remyelination-Promoting Human IgMs: Developing a Therapeutic Reagent for Demyelinating Disease;223 12.1;1 Multiple Sclerosis is a Disease of Myelin;224 12.2;2 Remyelination as a Normal Reparative Response;224 12.3;3 Strategies to Augment Remyelination;226 12.4;4 Antibodies Directed Against CNS Antigens Can be Pathogenic or Reparative;229 12.5;5 Human Antibodies that Promote Remyelination;231 12.6;6 Role of Anti-CNS Antibodies in Endogenous Repair;233 12.7;7 A Recombinant Human IgM Promotes Remyelination in vivo at Doses Comparable to Growth Factors;233 12.8;8 The IgM Character of Remyelination Promoting Antibodies is Vital for Function;236 12.9;9 Mechanisms of Antibody-Mediated CNS Repair;237 12.10;10 Therapeutic Goal: Alter the Balance of Inflammation to Favor Regeneration;239 12.11;References;240 13;Neuroimaging of Demyelination and Remyelination Models;250 13.1;1 Introduction ;251 13.2;2 Conventional MRI Studies ;253 13.3;3 Advanced MRI Methods for Visualizing Demyelinating Diseases ;260 13.4;4 T1 and T2 Relaxometry;264 13.5;5 Magnetic Resonance Spectr