Although there are evident differences in the etiology, induction, and probably also maintenance between EAE and human inflammatory demyelinating diseases, there is a striking similarity between both conditions regarding the structural features and the evolution of the lesions in the central nervous system. These similarities make possible the conclusion that immunopathological mechanisms play a key role in the pathogenesis of human inflammatory demyelinating diseases. Thus our knowledge of the pathogenetic mechanisms involved in the animal model may be relevant for the understanding of the human diseases. There is a large number of original studies and reviews dealing with this topic available (Frick 1979; Lisak 1980; Wisniewski et al. 1982). For this reason only a few aspects will be discussed in the following chapters; these seem to be the most relevant for an understanding of the pathohistology of inflammatory demyelinating lesions.
1 Introduction.- 2 The Spectram of Inflammatory Demyelinating Diseases.- 2.1 Experimental Models.- 2.2 Human Diseases.- 3 Allergic Encephalomyelitis in Humans.- 4 The Pathology of Inflammatory Demyelinating Lesions.- 4.1 Inflammatory Reaction.- 4.1.1 Inflammation in Experimental Allergic Encephalomyelitis.- 4.1.2 The Inflammatory Response in Human Inflammatory Demyelinating Diseases.- 4.2 Vascular Pathology.- 4.2.1 Vascular Pathology in EAE.- 4.2.2 Vascular Pathology in Multiple Sclerosis.- 4.3 Blood-Brain Barrier.- 4.3.1 Blood-Brain Barrier and Blood-CSF Barrier Leakage Under Physiological Conditions.- 4.3.2 The Diffusion of Proteins in the Extracellular Space of the Brain.- 4.3.3 Mechanisms and Structural Correlates of Blood- Brain Barrier Damage.- 4.3.4 The Blood-Brain Barrier in Experimental Allergic Encephalomyelitis.- 4.3.5 Implications of Blood-Brain Barrier Permeability on the Distribution of EAE Lesions Within the CNS.- 4.3.6 The Blood-Brain Barrier in Multiple Sclerosis.- 4.4 Demyelination and Myelin Degradation.- 4.4.1 Initial Stages of Demyelination in EAE.- 4.4.2 Myelin Degradation and Removal of Debris in EAE.- 4.4.3 Demyelination and Myelin Degradation in Multiple Sclerosis.- 4.5 The Fate of Oligodendroglia.- 4.5.1 Oligodendrocytes in EAE Lesions.- 4.5.2 Oligodendroglia in Multiple Sclerosis.- 4.6 Remyelination.- 4.6.1 Remyelination in Acute and Chronic EAE.- 4.6.2 Remyelination in Multiple Sclerosis.- 4.7 Sclerosis.- 4.7.1 Astroglial Reaction in the Lesions of Acute and Chronic EAE.- 4.7.2 Gliosis in Multiple Sclerosis.- 4.8 Axonal and Neuronal Pathology.- 4.8.1 Experimental Allergic Encephalomyelitis.- 4.8.2 Multiple Sclerosis.- 4.9 Meningeal Pathology.- 4.9.1 Experimental Allergic Encephalomyelitis.- 4.9.2 Multiple Sclerosis.- 4.10 Peripheral Nervous System Pathology.- 4.10.1 PNS Involvement in Different Models of Chronic EAE.- 4.10.2 Peripheral Nervous System Involvement in Multiple Sclerosis.- 4.11 Patterns of Plaque Growth.- 4.11.1 Plaque Growth in Chronic EAE.- 4.11.2 Mechanisms of Plaque Growth in Multiple Sclerosis.- 4.12 Lesional Topography in the CNS.- 4.12.1 Lesional Distribution in EAE.- 4.12.2 Lesional Topography in Human Inflammatory Demyelinating Diseases.- 4.13 The Variability of Inflammatory Demyelinating Lesions.- 4.14 EAE as a Model of Human Inflammatory Demyelinating Diseases.- 5 Immunopathogenetic Considerations.- 5.1 Transfer Studies.- 5.2 The Possible Role of Autoantigens in the Pathogenesis of Inflammatory Demyelinating Lesions.- 5.3 Conclusions.- 5.3.1 The Variability of EAE Lesions as an Expression of Multiple Antigens and Effector Mechanisms.- 5.3.2 The Compartmentalization of the Immune Reaction and Its Consequences for the Study of Chronic EAE Pathogenesis.- 5.3.3 Implications for Future Research in Human Inflammatory Demyelinating Diseases.- 6 Addendum: Material and Methods - Models of Chronic EAE.- 6.1 Material and Methods.- 6.1.1 Animal Care.- 6.1.2 Clinical Grading.- 6.1.3 Sensitization Procedure.- 6.1.4 Sampling of Animals.- 6.1.5 Human Material.- 6.2 Factors Modifying the Development of Chronic EAE Models.- 6.2.1 Guinea Pig Strains.- 6.2.2 Antigen Dose.- 6.2.3 Age of the Animals at the Time of Sensitization.- 6.2.4 Inoculation Site.- 6.2.5 Amount of Mycobacterium in the Adjuvant.- 6.2.6 Spinal Cord Subfractions.- 6.2.7 Chronic EAE in Sprague Dawley Rats.- 6.2.8 Conclusions.- 7 References.
Wir möchten in diesem Kapitel nicht auf Einzelheiten der klinischen Symptomatologie und der diagnostischen Methoden eingehen, sondern mehr auf ihre Bedeutung in therapeutischer und prognostischer Hinsicht. Ferner werden die für die Beurteilung des Therapieerfolges wichtigen Parameter und die Differentialdiagnose des Rezidivs beschrieben und diskutiert.
A. Formulation of the Problem and Relevant Literature.- I. Phagocyte Conclusion.- II. Literature Dealing with Mononuclear Phagocytes in the Central Nervous System.- 1. Progressive Microglia.- 2. Perivascular Cells of Intracerebral Vessels.- 3. Free Subarachnoidal Cells.- 4. Epiplexus Cells.- Conclusion.- III. Considerations on the Origin of Mononuclear Phagocytes in the Central Nervous System.- 1. Homoplastic Genesis.- a) Resting and Progressive Microglia.- b) Perivascular Cells of Intracerebral Vessels.- c) Free Subarachnoidal Cells.- d) Epiplexus Cells.- 2. Local Heteroplastic Genesis.- a) Progressive Microglia and Neuroglia.- b) Microglia and Subependymal Glia.- c) Progressive Microglia and Perivascular Cells.- d) Progressive Microglia and Free Subarachnoidal Cells.- e) Progressive Microglia and Epiplexus Cells.- f) Progressive Microglia, Perivascular Cells, and Free Subarachnoidal Cells..- g) Progressive Microglia, Perivascular Cells, and Epiplexus Cells.- h) Progressive Microglia, Free Subarachnoidal Cells, and Epiplexus Cells.- i) Perivascular Cells and Free Subarachnoidal Cells.- j) Free Subarachnoidal Cells and Epiplexus Cells.- k) Epiplexus Cells and Epithelial Cells of the Choroid Plexus.- 3. Hematogenesis.- a) Progressive Microglia and Blood Cells.- b) Progressive Microglia, Perivascular Cells, and Blood Cells.- c) Progressive Microglia, Perivascular Cells, and Free Subarachnoidal Cells, and Blood Cells.- d) Free Subarachnoidal Cells and Blood Cells.- e) Free Subarachnoidal Cells, Epiplexus Cells, and Blood Cells.- f) Epiplexus Cells and Blood Cells.- Conclusion.- B. Author's Investigation.- Materials and Methods Consistently Used.- I. Origin of Mononuclear Phagocytes of the Nervous System.- 1. Local Proliferation.- 2. Hematogenesis.- 3. Monocytic Origin.- a) Investigations of the Hematogenesis of Mononuclear Phagocytes in the Central Nervous System of Rabbits.- b) Investigations of the Monocytic Origin of Mononuclear Phagocytes in the Central Nervous System.- c) Investigations of the Monocytic Origin of Mononuclear Phagocytes in the Nervous System which Avoid Tracer Reutilization.- 4. Lymphocytic Origin.- Conclusion.- II. Mode of Distribution and Possible Lymphatic Efflux of Intracerebrally Injected Corpuscular Particles and Cellular Elements.- 1. Corpuscular Particles.- 2. Cellular Elements.- Conclusion.- III. Functional Activity of Mononuclear Phagocytes of the Central Nervous System.- 1. Phagocytosis Experiments.- a) Phagocytic Reaction of Local Cells Following Intracerebral Application of Labeling Material.- b) Giant Cell Formation.- c) Phagocytic Reaction of Human Cerebrospinal Fluid Cells.- 2. Cytochemical Investigations.- 3. Investigations with Immunologic Markers.- a) Leptomeningeal Membrane Specimens.- b) Cells of the Subarachnoid, Ventricular, and Perivascular Spaces.- c) Human Cerebrospinal Fluid Cells.- d) Glass-Induced Inflammatory Cells in the Sense of Progressive Microglia.- e) Brain of the Athymic or So-Called Nude Mouse.- f) Application of Anti-Lymphocyte and Anti-Monocyte Sera to Human Brain Tissue.- Conclusion.- C. Discussion and Conclusion.- I. Explanation of the Author's Findings.- 1. Cytogenesis.- a) Undamaged Animals.- b) Animals with a Lesion of the Nervous System.- 2. Distribution and Fate.- a) Intracerebral Distribution.- b) Lymphatic Efflux.- 3. Function.- a) Nonimmunologic Activity.- b) Immunologic Activity.- II. Mononuclear Phagocytes of the Central Nervous System and the Phagocyte 1. Identity.- 2. Significance.- III. Summary of the Author's Investigations.- References.
1. Introduction.- 1.1 The Need for a New Documentation System.- 1.2 Current Methods of Documentation in General Neurology.- 1.3 Documentation of Special Neurologic Diseases.- 2. Methods.- 2.1 Different Forms of Documentation.- 2.1.1 Punched Cards.- 2.1.2 Modern Methods.- 2.2 Choice of Documentation Method for Multiple Sclerosis.- 2.2.1 Development of the Documentation Sheet for Multiple Sclerosis.- 2.2.2 Handling of the Sheet.- 2.3 Quality Control of the Data.- 2.4 Management of the Forms.- 2.4.1 The Process of Registration.- 2.4.2 Description of the Program.- 2.4.3 Access to the Data.- 2.4.4 Correction of Errors.- 2.5 Analysis of the Data.- 2.6 Distribution of the Data.- 2.7 The New Set of Documentation Sheets.- 2.8 Statistical Methods.- 2.8.1 Significance Tests.- 2.8.2 Graphic Presentation.- 3. Results.- 3.1 Size of the Study.- 3.2 Comments on the Method.- 3.2.1 Analysis of Errors.- 3.2.2 The Precision of Recording.- 3.2.3 Free Text.- 3.2.4 Validity of the System.- 3.3 Documentation of Disease Course.- 3.4 Analysis of All Examinations Performed.- 3.5 Analysis of First Examinations.- 3.5.1 Month of Onset.- 3.5.2 Age at Onset, Present Age, and Differences Between Males and Females.- 3.5.3 Disturbances of the Functional Systems.- 3.5.4 Selection of Certain Groups.- 3.5.5 Statistical Analysis of Symptoms.- 3.6 Correlations.- 3.6.1 Correlation Between Mental Changes and Other Disturbances.- 3.6.2 Duration of Disease and Symptoms.- 3.6.3 Duration of Disease and Performance.- 3.6.4 Age at Onset and Performance.- 3.6.5 Disease Course and Performance.- 3.6.6 Analysis of Bouts.- 3.7 Diagnostic Classification.- 3.8 Laboratory Results.- 3.8.1 CSF Findings.- 3.8.2 Serologic Studies.- 3.9 Different Samples.- 3.9.1 The Epidemiologic Study.- 3.9.2 Subgroups.- 4. Discussion.- 4.1 Clinical Questions.- 4.1.1 Prognosis.- 4.1.2 The Problem of Diagnosis.- 4.1.3 Statistics on Signs and Symptoms.- 4.1.4 Follow-Up Examinations.- 4.2 Critical Comments on the Method.- 4.3 The Contribution of the New Documentation System to MS Research.- 5. Outlook.- 5.1 Neuropathology.- 5.2 Virology.- 5.3 Immunology.- 5.4 Relevance of CSF Findings.- 5.5 Epidemiology.- 5.6 The Standardized Medical Record.- Summary.- References.
The electrosensitive examination consists of the determination of sensory nerve conduction velocity and the somatosensory cortical evoked potentials above the contralateral postcentralarea after segmental skin stimu-contralateral postcentral area after segmental skin stimulation. This method records the total sensory system. The results received from normal persons and patients demonstrate that this riskless method is suitable for localization of peripheral neurogenic cerebral and especially localized spinal diseases. With the aid of cauda equina neurography additionally a new possibility is indicated to encircle the area of damage in the cases of lumbosacral root affections.
