Diseases of the Nervous System - Harald Sontheimer

Diseases of the Nervous System (eBook)

Harald Sontheimer (Autor)

eBook Download: PDF | EPUB

2015 | 1. Auflage
520 Seiten
Elsevier Science (Verlag)
978-0-12-800403-6 (ISBN)

Diseases of the Nervous System summarizes the current state of basic and clinical knowledge for the most common neurological and neuropsychiatric conditions. In a systematic progression, each chapter covers either a single disease or a group of related disorders ranging from static insults to primary and secondary progressive neurodegenerative diseases, neurodevelopmental illnesses, illnesses resulting from nervous system infection and neuropsychiatric conditions. Chapters follow a common format and are stand-alone units, each covering disease history, clinical presentation, disease mechanisms and treatment protocols. Dr. Sontheimer also includes two chapters which discuss common concepts shared among the disorders and how new findings are being translated from the bench to the bedside. In a final chapter, he explains the most commonly used neuroscience jargon. The chapters address controversial issues in current day neuroscience research including translational research, drug discovery, ethical issues, and the promises of personalized medicine.

This book provides an introduction for course adoption and an introductory tutorial for students, scholars, researchers and medical professionals interested in learning the state of the art concerning our understanding and treatment of diseases of the nervous system.

Provides a focused tutorial introduction to the core diseases of the nervous system
Includes comprehensive introductions to Stroke, Epilepsy, Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, ALS, Head and Spinal Cord Trauma, Multiple Sclerosis, Brain Tumors, Depression, Schizophrenia and many other diseases of the nervous system
Covers more than 40 diseases from the foundational science to the best treatment protocols
Includes discussions of translational research, drug discovery, personalized medicine, ethics, and neuroscience

Dr. Sontheimer is a researcher and educator with a life-long interest in Neuroscience. A native of Germany, he obtained a Masters degree in evolutionary comparative Neuroscience, where he worked on the development of occulomotor reflexes. In 1989, he obtained a doctorate in Biophysics and Cellular & Molecular Neuroscience form the University of Heidelberg studying biophysical changes that accompany the development of oligodendrocytes, the principle myelinating cells of the nervous system. He moved to the United States, where he later became a citizen, for post-doctoral studies at Yale University. His independent research career began at Yale in 1991 and continued at the University of Alabama Birmingham in 1994 and been focused on the role of glial support cells in health and disease. His laboratory has made major discoveries that led to two clinical trials using novel compounds to treat malignant gliomas. His research led to over 160 peer-reviewed publications. For the clinical development of his discoveries, Dr. Sontheimer started a biotechnologies company, Transmolecular Inc., which conducted both phase I and II clinical trials with the anti-cancer agent chlorotoxin. This technology was recently acquired by Morphotec Pharmaceuticals who will be conducting the phase III clinical trials.
As educator, Dr. Sontheimer has been active in teaching Medical Neuroscience, graduate Cellular and Molecular Neuroscience, and, for the past 10 years, he has offered both graduate and undergraduate courses on Diseases of the Nervous System. In 2005, Dr. Sontheimer became director of the Civitan International Research Center, a philanthropically supported center devoted to the study and treatment of children with developmental disabilities, ranging from Down's syndrome to Autism. In this capacity, Dr. Sontheimer is frequently tasked explaining complex scientific processes to a lay audience. Recognizing the need to further educate the public about neurological disorders using language that is accessible to an educated public motivated Dr. Sontheimer to write a text book on Diseases of the Nervous system. To assure that the material is comprehensive yet readily understandable, he wrote large parts of this text while on sabbatical leave at Rhodes College in Memphis, where he taught undergraduates while testing his book on this group of talented third and fourth year Neuroscience students. Dr. Sontheimer continues to manage a very active research laboratory where he has trained over 50 students and fellows. Dr. Sontheimer is a sought-after speaker and is regularly participating in national and international conferences.

The study of the brain continues to expand at a rapid pace providing fascinating insights into the basic mechanisms underlying nervous system illnesses. New tools, ranging from genome sequencing to non-invasive imaging, and research fueled by public and private investment in biomedical research has been transformative in our understanding of nervous system diseases and has led to an explosion of published primary research articles. Diseases of the Nervous System summarizes the current state of basic and clinical knowledge for the most common neurological and neuropsychiatric conditions. In a systematic progression, each chapter covers either a single disease or a group of related disorders ranging from static insults to primary and secondary progressive neurodegenerative diseases, neurodevelopmental illnesses, illnesses resulting from nervous system infection and neuropsychiatric conditions. Chapters follow a common format and are stand-alone units, each covering disease history, clinical presentation, disease mechanisms and treatment protocols. Dr. Sontheimer also includes two chapters which discuss common concepts shared among the disorders and how new findings are being translated from the bench to the bedside. In a final chapter, he explains the most commonly used neuroscience jargon. The chapters address controversial issues in current day neuroscience research including translational research, drug discovery, ethical issues, and the promises of personalized medicine. This book provides an introduction for course adoption and an introductory tutorial for students, scholars, researchers and medical professionals interested in learning the state of the art concerning our understanding and treatment of diseases of the nervous system. 2016 PROSE Award winner of the Best Textbook Award in Biological & Life Sciences Provides a focused tutorial introduction to the core diseases of the nervous system Includes comprehensive introductions to Stroke, Epilepsy, Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, ALS, Head and Spinal Cord Trauma, Multiple Sclerosis, Brain Tumors, Depression, Schizophrenia and many other diseases of the nervous system Covers more than 40 diseases from the foundational science to the best treatment protocols Includes discussions of translational research, drug discovery, personalized medicine, ethics, and neuroscience

Front Cover 1
IFC 3
DISEASES OF THE NERVOUS SYSTEM 4
Copyright 5
Dedication 6
Contents 8
Acknowledgments 12
Introduction 14
Part I - STATIC NERVOUS SYSTEMDISEASES 20
Chapter 1 - Cerebrovascular Infarct: Stroke 22
1. CASE STORY 22
2. HISTORY 23
3. Clinical Presentation/Diagnosis/Epidemiology 24
4. DISEASE MECHANISM/CAUSE/BASIC SCIENCE 27
5. TREATMENT/STANDARD OF CARE/CLINICAL MANAGEMENT 40
6. EXPERIMENTAL APPROACHES/CLINICAL TRIALS 41
7. CHALLENGES AND OPPORTUNITIES 45
Acknowledgments 46
References 46
General Readings Used as Source 47
Suggested Papers or Journal Club.Assignments 47
Chapter 2 - Central Nervous System Trauma 48
1. CASE STORY 49
2. HISTORY 49
3. Clinical Presentation/Diagnosis/Epidemiology 52
4. Disease Mechanism/Cause/Basic Science 60
5. TREATMENT/STANDARD OF CARE/CLINICAL MANAGEMENT 73
6. EXPERIMENTAL APPROACHES/CLINICAL TRIALS 74
7. CHALLENGES AND OPPORTUNITIES 76
Acknowledgments 77
References 77
General Readings Used as Source 78
Suggested Papers or Journal Club.Assignments 78
Chapter 3 - Seizure Disorders and Epilepsy 80
1. CASE STORY 81
2. HISTORY 81
3. Clinical Presentation/Diagnosis/Epidemiology 82
4. DISEASE MECHANISM/CAUSE/BASIC SCIENCE 89
5. TREATMENT/STANDARD OF CARE/CLINICAL MANAGEMENT 105
6. EXPERIMENTAL APPROACHES/CLINICAL TRIALS 111
7. CHALLENGES AND OPPORTUNITIES 112
Acknowledgments 112
References 113
General Readings Used as Source 113
Suggested Papers or Journal Club.Assignments 114
Part II - PROGRESSIVE NEURODEGENERATIVE DISEASES 116
Chapter 4 - Aging, Dementia, and Alzheimer Disease 118
1. CASE STORY 119
2. HISTORY 119
3. Clinical Presentation/Diagnosis/Epidemiology 121
4. DISEASE MECHANISM/CAUSE/BASIC SCIENCE 126
5. TREATMENT/STANDARD OF CARE/CLINICAL MANAGEMENT 139
6. EXPERIMENTAL APPROACHES/CLINICAL TRIALS 143
7. CHALLENGES AND OPPORTUNITIES 147
Acknowledgments 149
References 149
General Readings Used as Source 149
Suggested Papers or Journal Club.Assignments 150
Chapter 5 - Parkinson Disease 152
1. CASE STORY 152
2. HISTORY 153
3. CLINICAL PRESENTATION, DIAGNOSIS AND EPIDEMIOLOGY 155
4. DISEASE MECHANISM/CAUSE/BASIC SCIENCE 160
5. TREATMENT/STANDARD OF CARE/CLINICAL MANAGEMENT 175
6. EXPERIMENTAL APPROACHES/CLINICAL TRIALS 179
7. CHALLENGES AND OPPORTUNITIES 181
Acknowledgments 181
References 182
General Readings Used as Source 183
Suggested Papers or Journal Club.Assignments 183
Chapter 6 - Diseases of Motor Neurons and Neuromuscular Junctions 184
1. CASE STORY 185
2. HISTORY 185
3. Clinical Presentation/Diagnosis/Epidemiology 187
4. DISEASE MECHANISM/CAUSE/BASIC SCIENCE 194
5. TREATMENT/STANDARD OF CARE/CLINICAL MANAGEMENT 210
6. EXPERIMENTAL APPROACHES/CLINICAL TRIALS 211
7. CHALLENGES AND OPPORTUNITIES 213
Acknowledgments 214
References 215
General Readings Used as Source 216
Suggested Papers or Journal Club.Assignments 216
Chapter 7 - Huntington Disease 218
1. CASE STORY 219
2. HISTORY 220
3. Clinical Presentation/Diagnosis/Epidemiology 221
4. DISEASE MECHANISM/CAUSE/BASIC SCIENCE 223
5. TREATMENT/STANDARD OF CARE/CLINICAL MANAGEMENT 238
6. EXPERIMENTAL APPROACHES/CLINICAL TRIALS 239
7. CHALLENGES AND OPPORTUNITIES 242
Acknowledgments 242
References 243
General Readings Used as Source 244
Suggested Papers or Journal Club.Assignments 244
Part III - SECONDARY PROGRESSIVE NEURODEGENERATIVE DISEASES 246
Chapter 8 - Multiple Sclerosis 248
1. CASE STORY 248
2. HISTORY 249
3. Clinical Presentation/Diagnosis/Epidemiology 252
4. DISEASE MECHANISM/CAUSE/BASIC SCIENCE 256
5. TREATMENT/STANDARD OF CARE/CLINICAL MANAGEMENT 268
6. EXPERIMENTAL APPROACHES/CLINICAL TRIALS 271
7. CHALLENGES AND OPPORTUNITIES 274
Acknowledgments 275
References 275
General Readings Used as Source 276
Suggested Papers or Journal Club.Assignments 276
Chapter 9 - Brain Tumors 278
1. CASE STORY 278
2. HISTORY 280
3. Clinical Presentation/Diagnosis/Epidemiology 282
4. DISEASE MECHANISM/CAUSE/BASIC SCIENCE 286
5. TREATMENT/STANDARD OF CARE/CLINICAL MANAGEMENT 300
6. EXPERIMENTAL APPROACHES/CLINICAL TRIALS 303
7. CHALLENGES AND OPPORTUNITIES 304
Acknowledgments 306
References 306
General Readings Used as Source 307
Suggested Papers or Journal.Club Assignments 307
Chapter 10 - Infectious Diseases of the Nervous System 308
1. CASE STORY 308
2. HISTORY 309
3. CLINICAL PRESENTATION/DIAGNOSIS/EPIDEMIOLOGY/DISEASE MECHANISM 311
4. BEYOND THE INFECTION: BONA FIDE BRAIN DISORDERS INVOLVING PATHOGENS 328
5. EXPERIMENTAL APPROACHES/CLINICAL.TRIALS 330
6. CHALLENGES AND OPPORTUNITIES 333
Acknowledgments 333
References 333
General Readings Used as Source 334
Suggested Papers or Journal Club.Assignments 334
Part IV - DEVELOPMENTALNEUROLOGICALCONDITIONS 336
Chapter 11 - Neurodevelopmental Disorders 338
1. CASE STUDY 338
2. HISTORY 339
3. DEVELOPMENT OF SYNAPSES IN THE HUMAN CORTEX AND DISEASES THEREOF 341
4. DOWN SYNDROME 343
5. FRAGILE X SYNDROME 349
6. RETT SYNDROME 353
7. AUTISM SPECTRUM DISORDER 356
8. COMMON DISEASE MECHANISM 363
9. CHALLENGES AND OPPORTUNITIES 363
Acknowledgments 364
References 364
General Readings Used as Source 365
Suggested Papers or Journal Club.Assignments 365
Part V - NEUROPSYCHIATRIC ILLNESSES 368
Chapter 12 - Mood Disorders and Depression 370
1. CASE STORY 370
2. HISTORY 371
3. CLINICAL PRESENTATION/DIAGNOSIS/EPIDEMIOLOGY 373
4. DISEASE MECHANISM/CAUSE/BASIC SCIENCE 375
5. TREATMENT/STANDARD OF CARE/CLINICAL MANAGEMENT 383
6. EXPERIMENTAL APPROACHES/CLINICAL TRIALS 388
7. CHALLENGES AND OPPORTUNITIES 390
Acknowledgments 391
References 391
General Readings Used as Source 392
Suggested Papers or Journal Club Assignments 392
Chapter 13 - Schizophrenia 394
1. CASE STORY 394
2. HISTORY 395
3. Clinical Presentation/Diagnosis/Epidemiology 396
4. DISEASE MECHANISM/CAUSE/BASIC SCIENCE 398
5. TREATMENT/STANDARD OF CARE/CLINICAL MANAGEMENT 413
6. EXPERIMENTAL APPROACHES/CLINICAL TRIALS 415
7. CHALLENGES AND OPPORTUNITIES 420
Acknowledgments 420
References 420
General Readings Used as Source 421
Suggested Papers or Journal Club.Assignments 422
Part VI - COMMON CONCEPTS IN NEUROLOGICAL AND NEUROPSYCHIATRIC ILLNESSES 424
Chapter 14 - Shared Mechanisms of Disease 426
1. INTRODUCTION 427
2. NEURONAL DEATH 427
3. GLUTAMATE TOXICITY 429
4. PROTEIN AGGREGATES AND PRION-LIKE.SPREAD OF DISEASE 434
5. MITOCHONDRIAL DYSFUNCTION 437
6. IN SPITE OF OBVIOUS DISEASE HERITABILITY, GENETIC CAUSES OFTEN REMAIN ELUSIVE 439
7. EPIGENETICS 442
8. NON-CELL-AUTONOMOUS MECHANISMS 447
9. INFLAMMATION 449
10. VASCULAR ABNORMALITIES 453
11. BRAIN-DERIVED NEUROTROPHIC FACTOR 455
12. CHALLENGES AND OPPORTUNITIES 460
References 461
General Readings Used as Source 462
Suggested Papers or Journal Club.Assignments 462
Part VII - BENCH-TO-BEDSIDE TRANSLATION 464
Chapter 15 - Drug Discovery and Personalized Medicine 466
1. INTRODUCTION 467
2. HOW DID WE GET TO THIS POINT?.A BRIEF HISTORY 467
3. DRUG DISCOVERY: HOW ARE CANDIDATE.DRUGS IDENTIFIED? 468
4. WHAT ARE CLINICAL TRIALS AND.WHY DO THEM? 471
5. THE PLACEBO EFFECT 476
TRIALS FAIL? 477
7. PERSONALIZED MEDICINE 480
8. CHALLENGES AND OPPORTUNITIES 481
References 482
General Readings Used as Source 482
Suggested Papers or Journal Club.Assignments 482
Part VIII - NEUROSCIENCE JARGON 484
Chapter 16 - “Neuro”-dictionary 486
Index 520

Introduction

The study of nervous tissue and its role in learning and behavior, which we often call neuroscience, is a very young discipline. Johannes Purkinje first described nerve cells in the early 1800s, and by 1900, the pathologist Ramón y Cajal generated beautifully detailed histological drawings illustrating all major cell types in the brain and spinal cord and their interactions. Cajal also described many neuron specific structures including synaptic contacts between nerve cells, yet how these structures informed the brain to function like a biological computer remained obscure until recently. Although Luigi Galvani’s pioneering experiments in the late-1700s had already introduced the world to concept of biological electricity, ion channels and synaptic neurotransmitter receptors were only recognized as “molecular batteries” in the late-1970s and early 1980s. The first structural image of an ion channel was generated even more recently in 1998, and for many ion channels and transmitter receptors such information still eludes us.

Surprisingly, however, long before neuroscience became a freestanding life science discipline, doctors and scientists had been fascinated with diseases of the nervous system. Absent any understanding of cellular mechanisms of signaling, many neurological disorders were quite accurately described and diagnosed in the early to mid-1800s, including Epilepsy, Parkinson disease, Schizophrenia, Multiple Sclerosis, and Duchenne’s muscular dystrophy. During this period and still today, the discovery process has been largely driven by a curiosity about disease processes. What happens when things go wrong? Indeed, much of the early mapping of brain function was only possible because things went very wrong. Had it not been for brain tumors and intractable epilepsy, surgeons such as Harvey Cushing and Wilder Penfield would have had no justification to open the human skull of awake persons to establish functional maps of the cortex. Absent unexpected consequences of surgery, such as the bilateral removal of the hippocampi in H.M. that left him unable to form new memories, or unfortunate accidents exemplified by the railroad worker, Phineas Gage, who destroyed his frontal lobe in a blast accident, we would not have had the opportunity to learn about the role of these brain structures in forming new memories or executive function, respectively. Such fascination with nervous system disease and injury continues to date, and it is probably fair to say that neuroscience is as much a study of health as that of disease.

For the past 15 years, I have been teaching a graduate course entitled “Diseases of the Nervous System” and more recently I added an undergraduate course on the same topic as well. Every year, almost without fail, students would ask me whether I could recommend a book that they could use to accompany the course. I would usually point them to my bookshelf, filled with countless neuroscience and neurology textbooks ranging from Principles in Neuroscience to Merritt’s Neurology. I concluded that there was no such book and there really should be one. For the next year I kept my eyes peeled for this textbook to appear. Surely, sooner or later some brave neuroscientist would venture to write a book about neurological illnesses. Surprisingly, as of this writing, this has not happened so two years ago I decided to fill this void. My initial inclination was to produce a multiauthor edited book. By calling on many friends and colleagues to each write a chapter on their favorite disease this should be a quick affair. However from own experience I know that book chapters are always the lowest priority on my “to do” list, and I really was eager to pester my colleagues monthly to deliver their goods. Ultimately they would surely ask a senior postdoc to take the lead and in the end, the chapters would be heterogeneous and not necessarily at a level appropriate for a college audience. For my target audience this book needed to be a monograph. While I did not know at the time what I was getting into, roughly 18 months later, having read over 2500 scientific papers and reviews and after writing for about 7–10 h daily, I feel exhausted but also quite a bit more educated than before.

The target audience for this book is any student interested in neurological and neuropsychiatric illnesses. This includes undergraduates, early graduate students, and medical students taking a medical neuroscience course. I also expect the material to be of benefit to many health professionals who are not experts in the field. The book may even appeal to science writers or simply a science minded layperson, possibly including persons affected by one of the illnesses. Purposefully, the book lacks a basic introduction to neuroscience and I would expect the reader to have a basic understanding of neurobiology. Many excellent textbooks have been written, each of which would prepare one well to comprehend this text. I feel that I could not have done justice to this rapidly expanding field had I attempted to write a short introduction. However, to at least partially make up for this, I include an extensive final chapter that is called “Neuroscience Jargon.” I consider this more than just a dictionary. It has a succinct summary of approximately 500 of the most important terms and is written as nontechnically as possible. I hope that this will assist the reader to get his/her bearings as needed.

The book makes every effort to cover all the major neurological illnesses that affect the central nervous system though it is far from complete. My intention was to go fairly deep into disease mechanisms and this precluded a broader coverage of small and less well-known conditions. I found it useful to group the diseases into five broad categories that provided some logical flow and progression. Specifically, I begin with static illnesses, where an acute onset causes immediate disability that typically does not worsen over time. This group is best exemplified by stroke and CNS trauma but also includes genetic or acquired epilepsy (Chapters 1–3). I next covered the classical primary progressive neurodegenerative diseases including Alzheimer, Parkinson, Huntington, and ALS (Chapters 4–7). For each of these chapters I added some important related disorders. For example, the chapter on Alzheimer includes frontal temporal dementia; for Parkinson I included essential tremors and dystonia, and for Huntington I touch on related “repeat disorders” such as spinocerebellar ataxia. The chapter that covers ALS includes a variety of disease along the motor pathway essentially moving from diseases affecting the motor neurons themselves (ALS), their axons (Guillain–Barre Syndrome), to the presynaptic (Lambert Eaton Myotonia), and postsynaptic (myasthenia gravis) neuromuscular junction.

Next, I progressed to neurodegenerative diseases that are secondary to an insult yet still cause progressive neuronal death. I call these secondary progressive neurodegenerative diseases and the examples I am covering include Multiple sclerosis, Brain tumors, and infections (Chapters 8–10). It may be unconventional to call these secondary neurodegenerative diseases yet in multiple sclerosis the loss of myelin causes progressive axonal degeneration, brain tumors cause neurological symptoms by gradually killing neurons, and infection causes progressive illnesses again by progressively killing neurons. Nervous system infection could have quickly become an unmanageable topic since far too many pathogens exist that could affect the nervous system. I therefore elected to discuss important examples for each class of pathogen (prion proteins, bacteria, fungi, viruses, single- and multicellular parasites). While none of these pathogens are brain specific, I chose examples in which the nervous system is primarily affected including meningitis, botulism, tetanus, poliomyelitis, neurosyphilis, brain-eating ameba, neurosistercosis, neuroaids, and prion diseases. I also used this chapter as an opportunity to highlight the tropism displayed by some viruses for the nervous system and how this can be harnessed to deliver genes to the nervous system for therapeutic purposes.

For the section on neurodevelopmental disorders I similarly chose four important examples including Down syndrome, Fragile X, Autism, and Rett syndrome. These disorders have so many commonalities that it made sense to cover them in a single chapter (Chapter 11).

No contemporary book of nervous system disease would be complete without coverage of neuropsychiatric illnesses and I elected to devote one chapter each to depression (Chapter 12) and Schizophrenia (Chapter 13).

Taken together, I believe the material covers the “big” brain disorders that any neuroscientist or medical student should know. However, anyone looking for more detailed information on rare disorders or disorders primarily affecting the peripheral nervous system or sensory organs is referred to some of the excellent neurology textbooks that I cite as my major sources throughout the book.

To assure that the material is presented in an accessible, yet comprehensive format, the book was developed in a uniquely student-centered way, using my target audience as a focus group. To do so, I wrote the book as accompanying text to an undergraduate course, writing each chapter as I was teaching it to a class of neuroscience majors. Rather than embarking on this project on my home turf, I elected to enter a self-imposed exile, free from the distraction of family and friends, which would allow for...

Erscheint lt. Verlag	6.3.2015
Sprache	englisch
Themenwelt	Medizin / Pharmazie ► Medizinische Fachgebiete ► Neurologie
	Studium ► 1. Studienabschnitt (Vorklinik) ► Physiologie
	Naturwissenschaften ► Biologie ► Humanbiologie
	Naturwissenschaften ► Biologie ► Zoologie
ISBN-10	0-12-800403-7 / 0128004037
ISBN-13	978-0-12-800403-6 / 9780128004036

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