Contents 1 Immunology for the Non-immunologist 2 Neurology for the Non-neurologist 3 Neuroimmunology for the Non-neuroimmunologist

Transcription

1 1 Immunology for the Non-immunologist The Beginnings of Immunology The Components of the Healthy Immune Response White Blood Cells Molecules... 8 References Neurology for the Non-neurologist Organization of the Nervous System Electrical Nature: Nerve Transmission and Neurotransmitters Cells of the Nervous System Structure of the Nervous System: CNS, PNS, Upper and Lower Motor Neurons The Neurological Evaluation Neurological Examination Imaging of the Nervous System EEG and EMG References Neuroimmunology for the Non-neuroimmunologist The Beginnings of Neuroimmunology: Post-vaccinial Encephalomyelitis Semple Rabies Vaccine Autoimmune Encephalomyelitis: Temporal Progression. Interplay Between the Nervous and Immune Systems Stage 1. DAY 0: Exposure to the Antigen Stage 2. Days 0 7: Lymph Node Drainage and Processing of Antigen in Peripheral Lymph Node Stage 3. Days 7 10: Recruitment of Myelin-Specific Lymphocytes into the CNS Stage 4. Days 10 20: Maximal Inflammation with Involvement of Local CNS Immunity, Including Cervical Lymph Nodes Stage 5. Days 20 and Later: Recovery ix

2 x 3 The Tools of the Neuroimmunologist Aspects of Inflammation in Neuroimmunology Unique to the Nervous System The Necessity for Great Care in Classifying a Neuroimmunological Disease as Autoimmune The Importance of Antibodies References The Prototypic Neuroimmunological CNS Disease: Multiple Sclerosis, a Precis Definition Etiopathogenesis Pathology Genetics and Epidemiology Clinical Manifestations Initial Symptoms The MS Attack Natural History and Prognosis MS Clinical Classifications Form of MS Disability Activity Severity References Multiple Sclerosis: Diagnosis History and Examination Laboratory Findings Routine Studies: Blood, Urine, Chest X-Ray CNS Imaging Cerebrospinal Fluid Analysis References Multiple Sclerosis Mimics Cerebrovascular Disease/Stroke Neurological Infections HIV Neurosyphilis Neurocysticercosis Lyme Disease Tropical Spastic Paraparesis Tuberculosis Brain Abscess NMO ADEM Leukodystrophies... 63

3 xi 6 Other Conditions Neurosarcoidosis Subacute Combined Degeneration Other Neuroinflammatory Diseases References Multiple Sclerosis Therapy Disease-Modifying Drugs How Medications Become Approved for Use in MS The Primary Endpoint When Should One Treat with DMDs? General Approach to Therapy Current Agents Symptomatic Therapies References Experimental Models of MS Animal Models of MS Autoimmune Viral Demyelination Induced by Toxins In Vitro Models of MS Animal Models of Neuromyelitis Optica (NMO) and the Use of Passive Transfer Models References Guillain Barré Syndrome (GBS) and Other Immune-Mediated Neuropathies Definition Etiopathogenesis Pathology Epidemiology and Etiopathogenesis Clinical Manifestations Natural History and Prognosis Classification Diagnosis Therapy GBS s Cousin: Chronic Inflammatory Demyelinating Polyneuropathy Neuropathy Associated with Monoclonal Gammopathy Experimental Neuritis References Neuromuscular Neuroimmunological Diseases: Myasthenia Gravis Definition Etiopathogenesis Pathology Genetics and Epidemiology

4 xii 5 Clinical Manifestations Natural History and Prognosis Classification Diagnosis Therapy Lambert Eaton Myasthenic Syndrome Neonatal MG and Arthrogryposis Multiplex Congenita Experimental Models of MG References The Prototypic Neuroimmunological Muscle Disease: Dermatomyositis Definition Etiopathogenesis Pathology Genetics and Epidemiology Clinical Manifestations Natural History and Prognosis Classification Diagnosis Therapy Related Neuroimmunological Muscle Diseases Experimental Models of Inflammatory Muscle Disease References A Introduction to Neurological Infections: Neuro-infectious Disease as Part of Neuroimmunology General Rules of Neuro-infectious Diseases Infection of the Nervous System Follows Systemic Infection Neuro-infectious Diseases Should Be in the Differential Diagnosis in Many Patients with Difficult Neurological Syndromes Because of Their Reversibility with Antibiotics Diagnosis by Identification of the Infectious Agent Is Ideal, but Sometimes Impossible Prompt Recognition of Curable Infectious Diseases Is Critical Therapy of Neuro-infectious Diseases Is Frequently More Difficult than Therapy of Infections Elsewhere in the Body Always Keep HIV/AIDS in Mind Lyme Meningitis: The Prototypic Meningitis Definition Etiopathogenesis Clinical Manifestations Natural History/Prognosis

5 xiii 2.5 Diagnosis Therapy Classification Selected Important Infectious Meningitides Herpes Simplex Encephalitis: The Prototypic CNS Parenchymal Infection Definition Etiopathogenesis/Pathology/Genetics/ Epidemiology Clinical Manifestations Natural History and Prognosis Diagnosis Therapy Other Important CNS Parenchymal Infections Rabies, Poliomyelitis, and the Wonder of Vaccination Infectious Neuritis: Neuropathies of Leprosy and Varicella Zoster Virus Leprosy VZV Infection Immunosuppressed Patients References Neurological Manifestations of Systemic Chronic Inflammatory Disease Neurosarcoidosis Systemic Lupus Erythematosus Antiphospholipid Antibody Syndrome Sjogren s Syndrome Vasculitis References The Neuroimmunology of Cancer: Paraneoplastic Syndromes and Primary CNS Lymphoma Paraneoplastic Neurological Disorders Definition Etiopathogenesis Pathology Genetics and Epidemiology Clinical Manifestations Natural History and Prognosis of PND Classification Diagnosis Therapy CNS Lymphoma References

6 xiv 15 Neuroimmunology of Degenerative Diseases and Stroke Introduction Neuroimmunology of Alzheimer s Disease Neuroimmunology of Parkinson s Disease Neuroimmunology of Stroke References Important Rare Neuroimmunological Diseases Infectious/Postinfectious Subacute Sclerosing Panencephalitis Whipple s Post-Varicella Zoster Virus Cerebellar Syndrome Sydenham s Chorea Autoimmune Acquired Neuromyotonia Stiff Person Syndrome Swine-Worker s Neuropathy Idiopathic Hashimoto s Encephalopathy Behcet s Syndrome Rasmussen s Encephalitis Acute Multifocal Placoid Pigment Epitheliopathy References Neuroimmunological Molecules and Translational Medicine Moving from Basic Science Discoveries to FDA-Approved Therapies Biological Molecules as Therapies Therapeutic Monoclonal Antibodies Molecules as Targets of Therapy or of Disease: CD20, Aquaporin-4 Receptor, TNF-a, Sphingosine- 1-Phosphate Receptors, CD52, MOG, Channels Neuroprotection: The Holy Grail of Translational Neurology References Neuroimmunological Diagnostic Tests General Considerations for Testing Validation of Laboratory Tests by Regulatory Authorities Blood Tests Blood Tests for Inflammation Blood Tests for Specific Immunity to Pathogens or Autoantibodies Blood Tests for Detecting Specific Pathogens

7 xv 3 Cerebrospinal Fluid (CSF) Antibodies in the CSF Detection of Pathogens in the CSF Tests of Immune Function Humoral Immunity Cellular Immunity References Therapy in Neuroimmunological Disease Introduction Chemicals Corticosteroids Immunosuppressives Biologics: Large Molecules Produced via Recombinant Technology or from Human Specimens Intravenous Immunoglobulin Cytokines Monoclonal Antibodies (See Sect. 2.1 in Chap. 17) Procedures Plasmapheresis Thymectomy References Index

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