Grafman / Salazar Traumatic Brain Injury, Part I

1. Auflage 2015
ISBN: 978-0-444-63498-6
Verlag: Elsevier Science & Techn.
Format: EPUB
Kopierschutz: 6 - ePub Watermark

E-Book, Englisch, 490 Seiten

Reihe: Handbook of Clinical Neurology

The Handbook of Clinical Neurology volume on traumatic brain injury (TBI) provides the reader with an updated review of emerging approaches to traumatic brain injury (TBI) research, clinical management and rehabilitation of the traumatic brain injury patient. Chapters in this volume range from epidemiology and pathological mechanisms of injury, and neuroprotection to long-term outcomes with a strong emphasis on current neurobiological approaches to describing the consequences and mechanisms of recovery from TBI. The book presents contemporary investigations on blast injury and chronic traumatic encephalopathy, making this state-of-the-art volume a must have for clinicians and researchers concerned with the clinical management, or investigation, of TBI. - Internationally renowned scientists describe cutting edge research on the neurobiological response to traumatic brain injury, including descriptions of potential biomarkers and indicators of potential targets for treatments to reduce the impact of the injury - Explores cellular and molecular mechanisms as well as genetic predictors of outcome - Offers coverage of various diagnostic tools - CT, MRI, DDTI, fMRI, EEG, resting functional imaging, and more - State-of-the-art traumatic brain injury management and treatment principles are presented for both civilian and military care

Autoren/Hrsg.

Grafman, Jordan H.

Salazar, Andres M.

Inhaltsverzeichnis

1;Front Cover;1
2;Traumatic Brain Injury Part I;4
3;Copyright ;5
4;Handbook of Clinical Neurology 3rd Series;6
5;Foreword;8
6;Preface;10
7;Contributors;12
8;Contents of Part I;16
9;Contents of Part II;20
10;Section 1: Risk and Predisposition;22
10.1;Chapter 1: Epidemiology of Traumatic Brain Injury;24
10.1.1;Overview: Importance of Injury and Traumatic Brain Injury;24
10.1.2;Overall Traumatic Brain Injury rates;24
10.1.3;Definitions;24
10.1.4;Cost: Burden of Injury;25
10.1.5;Severity Measures;25
10.1.6;Emergency Department rates;26
10.1.6.1;Trends;27
10.1.7;Hospitalizations;27
10.1.7.1;Trends;27
10.1.8;Deaths;28
10.1.8.1;Trends;29
10.1.9;Mechanism (external Causes);29
10.1.10;Peaks Within Age Groups;30
10.1.11;Gender;30
10.1.12;Race;30
10.1.13;Traumatic Brain Injury In the military;30
10.1.14;Disability;31
10.1.15;Alzheimer's Disease and Epilepsy;31
10.1.16;Rehabilitation;31
10.1.17;Conclusions;32
10.1.18;Disclaimer;32
10.1.19;References ;32
10.2;Chapter 2: Classification of Traumatic Brain Injury: Past, Present, and Future;36
10.2.1;Introduction;36
10.2.2;History of and Approaches To disease Classification;36
10.2.3;An Ideal Classification System;37
10.2.4;Classifying Traumatic Brain Injury;37
10.2.4.1;Defining Traumatic Brain Injury;37
10.2.4.2;Challenges in Classifying Traumatic Brain injury;37
10.2.4.3;Classifying Brain Injury By Physical Mechanism;38
10.2.4.4;Classifying Brain Injury By Pathoanatomy;38
10.2.4.5;Classifying Brain Injury By symptoms/severity;39
10.2.4.6;Classifying Brain Injury By Prognosis;40
10.2.5;The Future of Traumatic Brain Injury Classification;40
10.2.6;Conclusion;40
10.2.7;References ;41
10.3;Chapter 3: Genetic Predictors of Outcome Following Traumatic Brain Injury;44
10.3.1;Traumatic Brain Injury is a Chronic Debilitating Condition;44
10.3.2;State of Genomics Research on Traumatic Brain Injury;44
10.3.3;Goals;45
10.3.4;Candidate Gene Approaches;45
10.3.4.1;APOE;45
10.3.4.2;COMT;46
10.3.4.3;BDNF;48
10.3.5;Candidate Gene Targets;51
10.3.5.1;Interleukins;51
10.3.5.2;Circadian rhythm-regulated genes;52
10.3.5.2.1;Melatonin and Its Receptors, MTNR1A and MTNR1B ;52
10.3.6;Going Beyond Candidate Gene Association Studies;53
10.3.6.1;Bioinformatics In GWAS;53
10.3.6.2;Decision Trees and Random Forests;53
10.3.6.3;Multifactor Dimensionality Reduction;54
10.3.6.4;Role of Epigenetics in Complex Diseases;54
10.3.6.5;MicroRNAs in Traumatic Brain Injury;54
10.3.7;Future Directions;55
10.3.7.1;Define and Measure Phenotypes;55
10.3.7.2;The Future Of Gwas;56
10.3.7.3;New Approaches for Testing the Common Disease Rare Variant Hypothesis: Whole Genome Sequencing;56
10.3.8;Conclusions;57
10.3.9;Glossary;57
10.3.10;References ;57
11;Section 2: Pathology and Mechanisms of Traumatic Brain injury;64
11.1;Chapter 4: The Neuropathology of Traumatic Brain Injury;66
11.1.1;Introduction;66
11.1.1.1;Severity of Injury;66
11.1.1.2;Focal Versus Diffuse Injury;67
11.1.1.3;Primary Versus Secondary Injury;67
11.1.2;Acute moderate-severe Traumatic Brain Injury;67
11.1.2.1;Focal Injuries;67
11.1.2.1.1;Skull Fractures ;67
11.1.2.1.2;Contusion and Laceration ;68
11.1.2.1.3;Hemorrhage and Hematoma ;68
11.1.2.2;Diffuse Injuries;68
11.1.2.2.1;Diffuse Vascular Injury ;68
11.1.2.2.2;Diffuse Brain Swelling ;68
11.1.2.2.3;Diffuse Axonal Injury ;68
11.1.2.2.4;Excitotoxicity and Oxidative Stress ;69
11.1.2.3;Secondary Effects of moderate-severe Traumatic Brain Injury;69
11.1.2.3.1;Vascular Injury ;69
11.1.2.3.2;Hypoxic-Ischemic Injury ;69
11.1.2.3.3;Hypometabolism ;69
11.1.2.3.4;Neuroinflammation ;69
11.1.2.3.5;Edema and Herniation ;69
11.1.3;Acute Mild Traumatic Brain Injury;69
11.1.3.1;Concussive Injury;69
11.1.3.2;Blast Injury;70
11.1.3.3;Juvenile Head Trauma Syndrome and Second Impact Syndrome;71
11.1.4;Chronic Effects of Traumatic Brain Injury;72
11.1.4.1;Cognitive Deficits and Mood Disturbances;72
11.1.4.2;Alzheimer's Disease;73
11.1.4.3;Parkinson's Disease;74
11.1.4.4;Amyotrophic Lateral Sclerosis;74
11.1.4.5;Creutzfeldt-Jakob Disease;74
11.1.4.6;Chronic Traumatic Encephalopathy;75
11.1.4.6.1;Neuropathology of Choronic Traumatic Encephalopathy;75
11.1.4.6.1.1;Gross Pathologic Features of Chronic Traumatic Encephalopathy;75
11.1.4.6.1.2;Microscopic Pathology of Chronic Traumatic Encephalopathy;75
11.1.4.6.1.2.1;Hyperphosphorylated tau;75
11.1.4.6.1.2.2;Stages of Chronic Traumatic Encephalopathy: evolution of Tau Pathology;75
11.1.4.6.1.2.3;TDP-43 Pathology;76
11.1.4.6.1.2.4;Axonal Pathology;76
11.1.4.6.1.2.5;Inflammation;77
11.1.4.6.1.2.6;Amyloid-ß Peptide;77
11.1.4.6.1.2.7;Lewy Bodies;77
11.1.4.6.2;Chronic Traumatic Encephalopathy and Comorbid Diaease ;77
11.1.4.6.3;Chronic Traumatic Encephalopathy with Motor Neuron Disease ;78
11.1.4.6.4;Clinical Aspects of Chronic Trumatic Encephalopathy ;79
11.1.4.7;Clinical Progression of Chronic Traumatic Encephalopathy;79
11.1.4.8;Dementia in Chronic Traumatic Encephalopathy;79
11.1.4.9;Chronic Traumatic Encephalopathy and post-traumatic Stress Disorder;79
11.1.4.10;Differential Diagnosis of Chronic Traumatic Encephalopathy;79
11.1.5;Future Areas for Research;80
11.1.5.1;Potential Risk Factors for Chronic Traumatic Encephalopathy;80
11.1.5.1.1;Apolipoprotein E ;80
11.1.5.1.1.1;MAPT ;80
11.1.5.1.2;Gender ;80
11.1.5.1.3;Cognitive Reserve ;80
11.1.5.1.4;Biomarkers ;80
11.1.5.2;Candidate Biomarkers for Chronic Traumatic Encephalopathy;80
11.1.5.3;Blood;81
11.1.5.4;Magnetic Resonance Imaging ;81
11.1.5.5;Functional Magnetic Resonance Imaging;81
11.1.5.6;Diffusion Tensor Imaging;81
11.1.5.7;Magnetic Resonance Spectroscopy;81
11.1.5.8;Susceptibility Weighted Imaging;82
11.1.5.9;Positron Emission Tomography ;82
11.1.6;Conclusions;82
11.1.7;Acknowledgments;82
11.1.8;References ;82
11.2;Chapter 5: Cellular and Molecular Mechanisms of Injury And spontaneous recovery;88
11.2.1;Cellular and Molecular Mechanisms of Injury and Spontaneous Recovery;88
11.2.2;Focal Brain Injury;88
11.2.3;Diffuse/generalized Change;89
11.2.3.1;Diffuse Neuronal Injury;89
11.2.3.2;Diffuse Axonal Injury;89
11.2.3.2.1;Pathogenesis of Diffuse Axonal Injury;90
11.2.3.2.2;The Retrograde Neuronal Consequences Of diffuse Axonal Injury;90
11.2.3.2.3;The Anterograde Consequences of Diffuse Axonal Injury/traumatic Axonal Injury;92
11.2.4;Generalized Injury;92
11.2.4.1;Excitotoxicity;92
11.2.4.2;Metabolic Change;93
11.2.4.3;Cerebrovascular Change;94
11.2.4.4;Electrophysiologic Change;95
11.2.5;Biological Mediators of Traumatic Brain injury-induced Damage;96
11.2.5.1;Inflammatory Response;96
11.2.5.2;Oxidative Stress;97
11.2.6;Long-term Neurodegenerative Change and Its Implications;98
11.2.7;Recovery From Traumatic Brain injury;99
11.2.8;The Relationship Between Nonpenetrating Traumatic Brain Injury and the Pathobiology of Blast Or Missile Wound/penetrating Brai.;100
11.2.9;Perspectives on Therapeutic Interventions for Blunting The damaging Consequences Of nonpenetrating Traumatic Brain Injury...;101
11.2.10;References ;102
11.3;Chapter 6: Chapter Injury Biomechanics, Neuropathology, and Simplified Physics Of explosive Blast and Impact Mild Traumati ...;110
11.3.1;Introduction;110
11.3.2;Human mechano-anatomy of Head Injury;110
11.3.3;Head Impact and Acceleration;111
11.3.3.1;Velocity and Acceleration: Translational And angular;111
11.3.3.2;Static and Dynamic Loading: Contact Or noncontact;113
11.3.3.3;Classical Acceleration Head Injury Criteria;113
11.3.4;Explosive blast;115
11.3.4.1;Static, Dynamic, Incident, and Reflected Pressures and Overpressure;116
11.3.4.2;The Positive and Negative Phases;117
11.3.4.3;Explosive Blast Impulse;117
11.3.4.4;Complex waves;117
11.3.4.5;Shock tubes;118
11.3.4.6;Blast Pressure Dosimeters;118
11.3.5;Neuropathology of Explosive Blast MTbI;119
11.3.5.1;Human Studies;119
11.3.5.1.1;Histopatology ;119
11.3.5.1.2;Neuropathologic Changes Observed Through Brain Imaging Studies ;119
11.3.5.2;Animal Model Studies;120
11.3.5.2.1;Large Animal Studies ;120
11.3.5.2.2;Small Animal Studies ;120
11.3.6;Neurpopathology of Nonblast Impact mTBI;122
11.3.6.1;Human brain;122
11.3.6.2;Animal brain;122
11.3.7;Summary;123
11.3.8;Disclaimer;123
11.3.9;References ;124
11.4;Chapter 7: Cellular Biomechanics of Central Nervous System Injury;126
11.4.1;Introduction;126
11.4.2;Mechanical Loading in the Brain: How It Occurs, and what Influences it;127
11.4.3;Recreating Trauma In vitro;127
11.4.4;What are the Critical Cellular Inputs for Recreating the Mechanical Spectrum?;128
11.4.5;Are there Important Mechanosensors?;129
11.4.6;Do These Mechanosensors Cause Functional Changes?;130
11.4.7;Can We Use In silico Simulations as a Complement to In vitro Systems?;131
11.4.8;Looking Into the Future: Multiscale Questions and the Key for the Future;132
11.4.9;References ;133
11.5;Chapter 8: Animal Models of Traumatic Brain Injury;136
11.5.1;Introduction;136
11.5.2;Biomechanics of Traumatic Brain injury;137
11.5.3;Contusion Models of Traumatic Brain Injury;138
11.5.4;Models of Traumatic Axonal Injury;140
11.5.4.1;Gyrencephalic Models of Diffuse Axonal injury;141
11.5.4.2;Rodent Models of Traumatic Axonal Injury;143
11.5.5;Animal Model of blast-induced Traumatic Brain Injury;143
11.5.6;Models of Acute Hematoma;144
11.5.7;Genetic Manipulation and Models of Traumatic Brain Injury;144
11.5.8;Conclusion;144
11.5.9;References ;144
12;Section 3: Special Considerations;150
12.1;Chapter 9: Mild Traumatic Brain Injury;152
12.1.1;Definitions and Diagnostic Criteria;152
12.1.1.1;Mild Traumatic Brain Injury;152
12.1.1.2;"Complicated" Mild TBI;153
12.1.1.3;Concussion;154
12.1.1.4;Postconcussive Syndrome;155
12.1.2;Epidemiology;156
12.1.3;Pathophysiology;157
12.1.4;Neuroimaging;157
12.1.4.1;Computed Tomography;157
12.1.4.2;Magnetic Resonance Imaging;157
12.1.4.3;Diffusion Tensor Imaging;158
12.1.4.4;Functional Magnetic Resonance Imaging;158
12.1.4.5;Magnetic Resonance Spectroscopy;158
12.1.5;Serum Biomarkers;159
12.1.6;Clinical Markers: Eye Motility;159
12.1.7;Clinical Problems, Natural History, and Outcome;159
12.1.8;The Domains of Symptomatology After Mild TBI;159
12.1.8.1;Cognitive Symptoms;160
12.1.8.2;Somatic Symptoms;160
12.1.8.2.1;Headache;160
12.1.8.2.2;Dizziness;160
12.1.8.2.3;Fatigue;161
12.1.8.3;Emotional Symptoms;161
12.1.8.3.1;Depression;161
12.1.8.3.2;Post-traumatic Stress Disorder;161
12.1.9;Natural History and Outcome;161
12.1.9.1;Early and Late Phases;161
12.1.9.2;Persistent Symptoms: Extending the Late phase;163
12.1.9.3;Factors Causing Persistent Symptoms;163
12.1.9.3.1;The Brain Injury;163
12.1.9.3.2;Other Injuries;164
12.1.9.3.3;Genetics;164
12.1.9.3.4;Preinjury Psychiatric Problems;164
12.1.9.3.5;Mental Stress;164
12.1.9.3.6;Personality Factors;164
12.1.9.3.7;Litigation;164
12.1.9.3.8;Bias in Belief and Attitude;165
12.1.9.3.9;Prognosis of Persistent Symptoms;165
12.1.9.4;Assessment and Treatment;165
12.1.9.5;Treatment of Somatic Symptoms;167
12.1.9.5.1;Headache;167
12.1.9.5.2;Dizziness;167
12.1.9.5.3;Fatigue and Sleep Disturbance;168
12.1.9.6;Treatment of Psychological Symptoms;168
12.1.9.7;Treatment of Cognitive Symptoms;169
12.1.9.8;Exercise;170
12.1.10;Conclusions;170
12.1.11;References ;171
12.2;Chapter 10: Acute sports-related Traumatic Brain Injury and Repetitive Concussion;178
12.2.1;Introduction;178
12.2.2;Pathophysiology of sports-related Traumatic Brain Injury;179
12.2.3;Evaluation of Acute sports-related Traumatic Brain Injury;180
12.2.3.1;Emergency Action Planning and Establishing a Concussion Policy;181
12.2.3.2;On-field Evaluation: the Primary Survey;183
12.2.3.3;On-field Evaluation: the Secondary Survey;184
12.2.4;Long-term Neurologic Sequelae of Repetitive Concussion;190
12.2.5;Conclusion;190
12.2.6;References ;191
12.3;Chapter 11: Brain Injury From Explosive Blast: Description and Clinical Management;194
12.3.1;Introduction;194
12.3.2;Explosive Blast Versus Penetrating and Conventional Traumatic Brain Injury;194
12.3.3;Severity Levels of Explosive Blast Traumatic Brain Injury;195
12.3.4;Clinical Management;195
12.3.4.1;Mild Traumatic Brain Injury Or Concussive Explosive Blast Injury;195
12.3.4.2;Moderate to Severe Traumatic Brain Injury;196
12.3.5;Conclusion;200
12.3.6;Disclaimer;200
12.3.7;References ;200
12.4;Chapter 12: Surgical Management of Civilian Gunshot Wounds to The head;202
12.4.1;Introduction;202
12.4.2;Epidemiology;202
12.4.3;Pathogenesis;202
12.4.4;Pathology;203
12.4.5;Clinical Presentation;205
12.4.6;Prehospital Triage;206
12.4.7;Emergency Department Management;206
12.4.8;Imaging Studies;206
12.4.9;Intracranial Pressure Monitoring;207
12.4.10;Surgical Management;208
12.4.10.1;Selection of Surgical Technique;208
12.4.10.1.1;Uncomplicated, Small Entry Wound in a Conscious Patient ;208
12.4.10.1.2;Extensive Wounds with Extensive Damage to the Scalp, Skull, Dura, and Brain ;208
12.4.10.1.3;Presence of Mass Effect ;208
12.4.10.1.4;Involvement of Paranasal Sinuses or Mastoid Air Cells ;208
12.4.10.1.5;Removal of Rsetained Fragments ;208
12.4.10.1.6;Craniectomy Versus Craniotomy ;209
12.4.10.1.7;Decompressive Craniectomy ;209
12.4.10.1.8;Case Report;209
12.4.10.2;Prophylactic Antibiotics;209
12.4.11;Complications;210
12.4.11.1;Infection;210
12.4.11.2;Post-traumatic Epilepsy;210
12.4.11.3;Traumatic Intracranial Aneurysms;211
12.4.12;Summary;211
12.4.13;References ;211
12.5;Chapter 13: Acute Loss of Consciousness;216
12.5.1;Introduction;216
12.5.2;Etiology of Acute Loss of Consciousness: Natural, Induced, and Acquired Models;216
12.5.3;Classification of the Disorders of Consciousness;218
12.5.4;The Acute Phase Following Traumatic Brain Injury;218
12.5.5;Defining the Level of Consciousness;219
12.5.5.1;Semiology;219
12.5.5.2;EEG;220
12.5.5.3;Somatosensory Evoked Potentials;220
12.5.5.4;Neuroimaging;221
12.5.6;Post-traumatic Amnesia;222
12.5.7;Conclusions;223
12.5.8;References ;223
12.6;Chapter 14: Systemic Manifestations of Traumatic Brain Injury;226
12.6.1;Introduction;226
12.6.2;Primary Systemic Manifestations;226
12.6.2.1;Endocrine Manifestations;226
12.6.2.1.1;Pituitary-adrenal axis;227
12.6.2.1.2;Growth Hormone;228
12.6.2.1.3;Thyroid Hormone;228
12.6.2.1.4;Antidiuretic Hormone;229
12.6.2.1.5;Other Hormones;229
12.6.2.1.6;Current Status;229
12.6.2.2;Immune System;229
12.6.2.2.1;Immune Response in Brain Following Traumatic Brain Injury;229
12.6.2.2.2;Effect of Traumatic Brain Injury on Systemic Immune Response;230
12.6.2.2.3;Current Status;231
12.6.2.3;Respiratory System;231
12.6.2.3.1;Current Status;231
12.6.2.4;Cardiovascular System;231
12.6.2.4.1;Current Status;232
12.6.2.5;Hematologic Manifestations;232
12.6.2.5.1;Current Status;232
12.6.2.6;Other Systems;232
12.6.2.6.1;Gastrointestinal System;232
12.6.2.6.2;Musculoskeletal System;233
12.6.2.6.3;Autonomic Nervous System;233
12.6.2.6.4;Sexual Function After Traumatic Brain Injury;233
12.6.2.6.5;Metabolism;233
12.6.2.6.6;Electrolyte Imbalance;234
12.6.3;Secondary Systemic Manifestations;234
12.6.3.1;Cerebral Perfusion pressure-guided Therapy;234
12.6.3.2;Barbiturate coma;234
12.6.3.3;Hypothermia;234
12.6.3.4;Sedation and Analgesia;234
12.6.3.5;Ventilation and Pneumonia;235
12.6.4;Conclusion;235
12.6.5;References ;235
12.7;Chapter 15: Special Considerations in Infants and Children;240
12.7.1;Introduction;240
12.7.2;Epidemiology of Pediatric Head Injury;240
12.7.3;Injury Classification Schemes: Special Considerations in Children;241
12.7.4;Pathophysiologic Differences Relevant to Injury;242
12.7.4.1;Baseline Systemic Physiologic norms;242
12.7.4.2;Blood Volume And shock;242
12.7.4.3;Brain Physiology and age-dependent Vulnerability;242
12.7.5;Clinical Assessment Tools for Infants and Children;243
12.7.5.1;General Considerations;243
12.7.5.2;Neuroassessment Scales;244
12.7.6;Imaging Considerations in Pediatric Traumatic Brain Injury;245
12.7.7;Management of Pediatric Head Injury: General Principles;246
12.7.7.1;Initial Triage and Management of Pediatric Head Injury;246
12.7.7.2;Basic Minimum Acute data;246
12.7.7.3;Swelling-prone and nonswelling-prone Injuries;246
12.7.8;Acute Phase Management Of pediatric Head Injury;247
12.7.8.1;Evidence-based Guidelines Documents for Pediatric Head Injury;247
12.7.8.2;Evacuation of Mass Lesions, Surgical Decompression, and Cerebrospinal Fluid Drainage;248
12.7.8.3;Seizure Prophylaxis;249
12.7.8.4;Intracranial Pressure Monitoring;250
12.7.8.5;Osmotherapy;250
12.7.8.6;Analgesia, Sedation, and Pharmacologic Paralysis;250
12.7.8.7;Additional Treatment Methods;251
12.7.9;Specific Injury Patterns in Children;251
12.7.9.1;"Ping-pong" Fractures;251
12.7.9.2;"Growing" Skull Fractures;251
12.7.9.3;Crush Injuries;251
12.7.9.4;Subdural Hematomas in Infants and Young Children;251
12.7.9.5;Cervicomedullary Distraction Injuries;252
12.7.9.6;Skull Penetration Injuries;254
12.7.9.7;Arterial Dissections;254
12.7.9.8;Concussion;254
12.7.10;Profound Injuries and Brain Death in Children;254
12.7.11;Outcomes and Rehabilitation;254
12.7.12;Follow-up Considerations for Children;256
12.7.13;Summary;257
12.7.14;References ;257
13;Section 4: Current and Emerging Diagnostic Tools;264
13.1;Chapter 16: Biomarkers;266
13.1.1;Introduction;266
13.1.2;Currently Available Biomarkers Accessible in Biofluids;267
13.1.2.1;Blood Biomarkers of Acute Brain Injury;267
13.1.2.1.1;Inflammatory Cytokines and Markers Of metabolic/oxidative Stress;267
13.1.2.1.2;S-100B;267
13.1.2.1.3;Glial Fibrillary Acidic Protein;268
13.1.2.1.4;Myelin Basic Protein;268
13.1.2.1.5;Neuron-specific Enolase;269
13.1.2.1.6;Ubiquitin C-terminal Hydrolase L-1;269
13.1.2.1.7;Microtubule-associated Protein 2;269
13.1.2.1.8;Neurofilament;269
13.1.2.1.9;t and amyloid-related Proteins;270
13.1.2.1.10;aII-Spectrin;270
13.1.2.2;CSF Biomarkers of Acute Brain Injury;270
13.1.2.2.1;Albumin;270
13.1.2.2.2;Inflammatory Cytokines and Markers of Metabolic, Oxidative Stress and Cell death;270
13.1.2.2.3;S-100B;271
13.1.2.2.4;Glial Fibrillary Acidic Protein;272
13.1.2.2.5;Neuron-specific Enolase;272
13.1.2.2.6;UCH-L1;272
13.1.2.2.7;Neurofilament-light (NF-L) and Phosphorylated tau t
(pTAU );272
13.1.2.2.8;Amyloid-related Proteins;273
13.1.2.2.9;a-Synuclein;273
13.1.2.2.10;aII-spectrin Breakdown Products;273
13.1.3;Brain Markers and Clinical Practice;273
13.1.3.1;Diagnostic Biomarkers: Assess the Disease;273
13.1.3.2;Monitoring Biomarkers: Track the Course of disease;275
13.1.3.3;Predictive Biomarkers: Forecast the Likely Response to Treatment;276
13.1.3.4;Limitations;277
13.1.4;Future Directions: Multimarker Strategies;277
13.1.5;Conclusions;277
13.1.6;References ;278
13.2;Chapter 17: Current and Future Diagnostic Tools for Traumatic Brain Injury: CT, Conventional MRI, and Diffusion Tensor Imag ...;288
13.2.1;Introduction;288
13.2.2;Assessment goal;288
13.2.2.1;Determine Whether there is an Immediately life-threatening Intracranial Lesion;288
13.2.2.2;Assess for Delayed Progression of an Intracranial Lesion in Stabilized Patients;288
13.2.2.3;Documentation of the Presence of Intracranial Abnormalities for Medicolegal Reasons;289
13.2.2.4;Presurgical Epilepsy Planning;290
13.2.2.5;Early Prognostic Decision Making;290
13.2.2.6;Prognostic Assessment for Rehabilitative Planning;292
13.2.2.7;Stratification of Subjects for Pathophysiologically Targeted Therapies;292
13.2.2.8;Providing Pharmacodynamic Biomarkers for Candidate Therapeutics;294
13.2.3;Future Directions;294
13.2.4;Conclusions;296
13.2.5;References ;296
13.3;Chapter 18: Using Functional Magnetic Resonance Imaging and Electroencephalography to Detect Consciousness After Severe Br ...;298
13.3.1;Introduction;298
13.3.2;Differential Diagnosis in Disorders of Consciousness;298
13.3.3;Functional Magnetic Resonance Imaging Studies;299
13.3.3.1;Decoding Thoughts in Healthy Participants;299
13.3.3.2;Using Mental Imagery to Detect Consciousness in Nonresponsive Patients;299
13.3.3.3;Using Anesthesia to Induce Behavioral Nonresponsiveness in Healthy Participants;301
13.3.3.4;Other Functional Magnetic Resonance Imaging Approaches to Detecting Consciousness in Nonresponsive Patients;302
13.3.3.5;Using Functional Magnetic Resonance Imaging to Communicate With Behaviorally Nonresponsive Patients;302
13.3.4;Electroencephalographic Studies;304
13.3.4.1;Using Electroencephalography to Detect Consciousness in Nonresponsive Patients;304
13.3.4.2;Using Electroencephalography to Communicate With Behaviorally Nonresponsive Patients;307
13.3.5;Implications;307
13.3.5.1;Diagnosis;307
13.3.5.2;Prognosis;308
13.3.5.3;Legal Issues;309
13.3.6;Conclusions;310
13.3.7;Acknowledgments;311
13.3.8;References ;311
13.4;Chapter 19: Resting Functional Imaging Tools (MRS, SPECT, PET and PCT);316
13.4.1;Magnetic Resonance Spectroscopy;316
13.4.1.1;Technique;316
13.4.1.2;Mild Traumatic Brain Injury;316
13.4.1.3;Severe Traumatic Brain Injury;317
13.4.1.4;Summary;318
13.4.2;Single Photon Emission Computed Tomography;318
13.4.2.1;Technique;318
13.4.2.2;Mild Traumatic Brain Injury;319
13.4.2.3;Severe Traumatic Brain Injury;320
13.4.2.4;Summary;320
13.4.3;Positron Emission Tomography;320
13.4.3.1;Technique;320
13.4.3.2;Mild Traumatic Brain Injury;321
13.4.3.3;Severe Traumatic Brain Injury;321
13.4.3.4;Summary;322
13.4.4;Perfusion Computed Tomography;322
13.4.4.1;Technique;322
13.4.4.2;Mild Traumatic Brain Injury;322
13.4.4.3;Severe Traumatic Brain Injury;322
13.4.4.4;Summary;323
13.4.5;Functional Resting State Imaging in Children;323
13.4.6;Comparison of Clinical Applicability of Spect, Pet, And mrs;324
13.4.7;References ;326
13.5;Chapter 20: Advances in Imaging Explosive Blast Mild Traumatic Brain Injury;330
13.5.1;Introduction;330
13.5.2;Diffusion Tensor Imaging;330
13.5.3;Functional Imaging;332
13.5.4;Metabolic Imaging;333
13.5.4.1;Positron Emission Tomography;333
13.5.4.2;Magnetic Resonance Spectroscopy Imaging;334
13.5.5;Summary;337
13.5.6;Disclaimer;337
13.5.7;Referenes ;337
13.6;Chapter 21: Electrophysiologic Recordings in Traumatic Brain Injury;340
13.6.1;Introduction;340
13.6.2;Background;340
13.6.3;Historical Background and Early Experimental Studies;341
13.6.4;Experimental Models of Seizures in Traumatic Brain Injury;342
13.6.5;Clinical Eeg in Acute Mild Traumatic Brain Injury;342
13.6.6;Quantitative Eeg and Mild Traumatic Brain Injury;344
13.6.7;Clinical Eeg and Seizures Following Moderate and Severe Traumatic Brain Injury;345
13.6.8;Clinical Eeg and Prognosis Following Moderate to Severe Traumatic Brain Injury;346
13.6.9;Eeg in Traumatic Brain Injury, post-traumatic Epilepsy, and Epileptogenesis;346
13.6.10;Intracranial EEG and Limitations of Scalp EEG;350
13.6.11;Intracranial EEG and Cortical Spreading Depression;350
13.6.12;EEG in the Evaluation of post-traumatic Epilepsy;351
13.6.13;Evoked Potentials and Traumatic Brain Injury;352
13.6.14;Event-related Potentials and Traumatic Brain Injury;354
13.6.15;Bispectral Index and Traumatic Brain Injury;354
13.6.16;Magnetoencephalography and Traumatic Brain Injury;355
13.6.17;References ;355
14;Section 5: Management and Treatment;362
14.1;Chapter 22: Neuroprotection for Traumatic Brain Injury;364
14.1.1;Introduction;364
14.1.2;Neuronal Cell Death: Morphology Versus Mechanism;365
14.1.2.1;Intrinsic Apoptosis;366
14.1.2.2;Extrinsic Apoptosis;366
14.1.2.3;Regulated Necrosis;366
14.1.2.4;Autophagy;367
14.1.3;Cell Death Mechanisms in Traumatic Brain Injury;367
14.1.3.1;Caspase-dependent Neuronal Cell Death Pathways;367
14.1.3.2;Caspase-independent Neuronal Cell Death Pathways;368
14.1.3.2.1;Apoptosis-inducing factor;368
14.1.3.3;Parthanatos;369
14.1.3.4;Necroptosis;369
14.1.3.5;Autophagic Cell death;369
14.1.3.6;Crosstalk Between Cell Death Programs;369
14.1.3.7;Neuroinflammation After Traumatic Brain injury;370
14.1.3.8;Microglia: Mediators of the Innate Immune Response to Central Nervous System Injury;371
14.1.3.9;Involvement of pro- and anti-inflammatory Cytokines in Traumatic Brain Injury;372
14.1.3.10;Chronic Microglial Activation and Neurodegeneration After Traumatic Brain injury;372
14.1.3.11;Neuroprotection: Challenges for Clinical Translation;373
14.1.3.12;Multipotential Drug Treatment Strategies For traumatic Brain Injury;375
14.1.3.13;Statins;375
14.1.3.14;Progesterone;376
14.1.3.15;Ciclosporin;377
14.1.3.16;Diketopiperazines;378
14.1.3.17;SUR1-regulated NCca-ATP Channel Inhibitors;378
14.1.3.18;Cell Cycle Inhibitors;378
14.1.4;Conclusion;379
14.1.5;References ;379
14.2;Chapter 23: The Prehospital Management of Traumatic Brain Injury;388
14.2.1;Introduction;388
14.2.1.1;Prehospital Systems;388
14.2.2;Prehospital Patient Assessment;389
14.2.2.1;Initial Evaluation and Examination;389
14.2.2.2;The Pupil Examination;389
14.2.2.3;Vital signs;390
14.2.2.4;The Glasgow Coma Scale;390
14.2.3;Patient Management;391
14.2.3.1;Airway, Ventilation, and Oxygenation;391
14.2.3.2;Fluid Resuscitation;392
14.2.3.3;Additional Management Principles;392
14.2.4;Special Considerations for Suspected Herniation;393
14.2.4.1;Hyperventilation;393
14.2.4.2;Brain-directed Hyperosmolar Fluid Therapy;393
14.2.5;Patient Transport Decisions;393
14.2.6;Future Directions;394
14.2.7;Conclusions;395
14.2.8;References ;396
14.3;Chapter 24: Acute Management of military-related Injury;400
14.3.1;Introduction;400
14.3.2;Historical Experience;401
14.3.2.1;Ancient/premodern;401
14.3.2.2;World War I;401
14.3.2.3;World War II;402
14.3.2.4;Korea;403
14.3.2.5;Vietnam;403
14.3.2.6;Iraq/Afghanistan;404
14.3.3;Type of Wounds;405
14.3.4;Penetrating Brain Injury;406
14.3.4.1;Debridement;406
14.3.4.2;Antibiotics;407
14.3.4.3;Seizures;407
14.3.4.4;CSF leak;407
14.3.4.5;Vascular Considerations;407
14.3.4.6;Intracranial Pressure Monitoring;408
14.3.4.7;Radiographic Imaging;408
14.3.5;Closed Head Injury;408
14.3.6;Blast-related Traumatic Brain Injury;410
14.3.7;Echelons of care;411
14.3.8;Conclusion;411
14.3.9;Disclaimer;411
14.3.10;Referenes ;411
14.4;Chapter 25: Clinical Management of the Minimally Conscious state;416
14.4.1;Assessment of the Minimally Conscious state;416
14.4.1.1;Diagnostic Criteria for the Minimally Conscious state;416
14.4.1.2;Approaches to the Assessment and Diagnosis of the Minimally Conscious state;417
14.4.1.3;Standardized Behavioral Approaches to Assessment;417
14.4.1.4;Individualized Quantitative Behavioral Assessment;419
14.4.1.5;Neuroimaging and Electrophysiological Techniques;419
14.4.1.6;Functional Neuroimaging;420
14.4.1.7;Electrophysiologic Studies;421
14.4.1.8;Factors That Confound Assessment of Patients With Disorders of Consciousness;421
14.4.2;Clinical Management of the Minimally Conscious state;422
14.4.2.1;Pharmacologic Interventions;423
14.4.2.1.1;Amantadine ;423
14.4.2.1.2;Methylphenidate ;424
14.4.2.1.3;Zolpidem ;424
14.4.2.2;Invasive and Noninvasive Brain Stimulation;424
14.4.2.3;Deep Brain Stimulation ;424
14.4.2.4;Repetitive Transcranial Magnetic Stimulation ;425
14.4.2.5;Hyperbaric Oxygen Treatment;425
14.4.2.6;Physical and Environmental Management Strategies;425
14.4.3;A Systematic Approach to Clinical Management of Patients in the Minimally Conscious state;426
14.4.3.1;Diagnostic Assessment;426
14.4.3.2;Prognostic Assessment;426
14.4.3.3;Treatment;426
14.4.3.4;Family and Caretakers;426
14.4.4;Conclusions and Future Directions;427
14.4.5;Acknowledgment;427
14.4.6;References ;427
14.5;Chapter 26: Rehabilitation After Traumatic Brain Injury;432
14.5.1;Epidemiology;432
14.5.2;Early Rehabilitation After Traumatic Brain Injury;432
14.5.3;Prognosis and Recovery;433
14.5.4;Rehabilitation and Disorders of Consciousness;434
14.5.5;Rehabilitation Strategies for Cognitive Dysfunction;434
14.5.6;Motor Recovery After Traumatic Brain Injury;435
14.5.7;Post-traumatic Agitation;436
14.5.7.1;ß-Blockers;436
14.5.7.2;Neuroleptics;436
14.5.7.3;Antiepileptics;437
14.5.7.4;Neurostimulants;437
14.5.7.5;Benzodiazepines;437
14.5.7.6;Amantadine;437
14.5.7.7;Other Medications;437
14.5.8;Spasticity;437
14.5.9;Dysautonomia;438
14.5.10;Heterotopic Ossification;439
14.5.11;Other Traumatic Brain Injury Complications That Impact Rehabilitation;440
14.5.12;Rehabilitation of Mild Traumatic Brain Injury and Concussion;440
14.5.13;Health Systems Change;440
14.5.14;Future Developments in Traumatic Brain Injury Rehabilitation;440
14.5.15;References ;441
14.6;Chapter 27: Long-term Social Integration and Community Support;444
14.6.1;Introduction;444
14.6.2;Factors Related to Social Functioning Following Traumatic Brain Injury;445
14.6.2.1;The Role of Executive Functions in Social Functioning;445
14.6.2.2;The Role of self-regulation in Social Functioning;446
14.6.3;Interventions to Improve Social Functioning;446
14.6.3.1;Social Skills and Social Communications Training;446
14.6.3.2;Treatment of Emotional Disorders;447
14.6.3.3;Social Peer Mentoring;447
14.6.3.4;Self-regulation Training;447
14.6.4;Using Existing Technology to Increase Social Functioning;447
14.6.5;Conclusions;449
14.6.6;Acknowledgment;449
14.6.7;References ;449
14.7;Chapter 28: Recent Developments in Clinical Trials for the Treatment Of traumatic Brain Injury;454
14.7.1;Introduction and Background;454
14.7.1.1;What are the Numbers?;454
14.7.1.2;Is "mild" Brain Injury Ever Really mild?;454
14.7.1.3;Functional Deficits May Appear Long After the Initial Injury;455
14.7.1.4;Traumatic Brain Injury has Also Become a Major Problem for the Us Military;455
14.7.1.5;No Neuroprotective Agents are Clinically Available;455
14.7.1.6;Why has the Development of an Effective Treatment Been so Elusive?;456
14.7.1.7;Postinjury Structural and Functional Reorganization May Not Always Be Adaptive;456
14.7.1.8;What is the Most Appropriate Molecular Or Biomarker assay?;456
14.7.1.9;Behavioral Pharmacology Also has Issues;457
14.7.1.10;What Works and what Does not;457
14.7.2;Hormonal Agents;457
14.7.2.1;Progesterone;457
14.7.2.2;Estrogen;459
14.7.2.3;Erythropoietin;460
14.7.2.4;Growth-promoting Hormone Therapies;460
14.7.2.5;Synthetic insulin-like Growth Factors;460
14.7.2.6;Glyburide;461
14.7.3;Glutamate Antagonists;461
14.7.3.1;Magnesium Sulfate;461
14.7.3.2;Cannabinoids and Their Analogs;461
14.7.4;Immunomodulators;462
14.7.4.1;Statins as a Treatment for Traumatic Brain injury;462
14.7.4.2;Immunosuppressant Drugs Such as Ciclosporin;463
14.7.5;Antioxidants;463
14.7.5.1;Lipid Peroxidation Inhibitors, NOS Inhibitors, and PEG-SOD;464
14.7.5.2;Endogenous Superoxide Dismutases;464
14.7.5.3;Drugs That Increase Brain Oxygen Levels;464
14.7.5.4;Ros, Free Radical Scavengers, and Combination Therapies;464
14.7.6;Coagulation (DIC) Modulator Therapies;465
14.7.6.1;Hypertonic Saline;465
14.7.6.2;Heparin;466
14.7.6.3;Prostacyclin;466
14.7.6.4;Recombinant Activated Human Factor VII and Protein C (APC);466
14.7.6.5;Reversing Hyperfibrinolysis;466
14.7.7;Conclusions;467
14.7.8;Disclosures;467
14.7.9;References ;467
15;Index ;474

Leseproben

Chapter 1 Epidemiology of traumatic brain injury
Mark Faul*; Victor Coronado    Centers for Disease Control and Prevention, Atlanta, GA, USA
* Correspondence to: Mark Faul, PhD, MA, Centers for Disease Control and Prevention, 4770 Buford Highway, Atlanta, GA, USA. Tel: + 1-770-488-1276 email address: [e-mail] Abstract
Traumatic brain injury (TBI) is a leading cause of death, and in a recent analysis it was found that nearly one-third of all injury-related deaths in the US have at least one diagnosis of TBI (CDC-Quickstats, 2010). This chapter presents the burden of TBI as regards age group, gender, costs, race, emergency department (ED) visits, hospitalizations, and deaths. Injury trends over a 15 year period are examined. Rehabilitation estimates and disability estimates are also available. Through good epidemiology we can better understand the causes of TBI and design more effective intervention programs to reduce injury. Important sources of evidence for this chapter include mostly studies from the US because of their leading work in the epidemiology of this important injury. Key words Traumatic Brain Injury costs mechanism race emergency department hospitalizations deaths Alzheimer rehabilitation disability trends Overview: importance of injury and traumatic brain injury
In 2009, injury was the leading cause of death in the US for persons aged 1–44 years (CDC, 2009). Because the burden of injury is concentrated among these younger and middle age groups, the impact on disability-adjusted life years lost for injury is approximately 15% in the US. Meanwhile, the impact of injury on mortality for all age groups is approximately 10% (Murray and Lopez, 1997). Injuries are classified into the two categories of unintentional and intentional injuries, or violence-related injuries. For all age groups, unintentional injury is the fifth leading cause of death, after heart disease, malignant neoplasms, chronic respiratory disease, and cerebrovascular disease (CDC-WISQARS, 2009). After combining unintentional injury and violence-related injury, there were 177,154 total injury deaths in the US during 2009 (CDC-WISQARS, 2009). The most commonly injured body region associated with death was the head (Barell et al., 2002), and in a recent analysis it was found that nearly one-third of all injury-related deaths in the US have at least one diagnosis of traumatic brain injury (TBI) (CDC-Quickstats, 2010). Overall traumatic brain injury rates
The overall incidence rate of TBI in the US for 2002–2006 was 579 per 100 000 persons, or approximately 1.7 million cases per year (Faul et al., 2010). This estimate includes all levels of TBI severity. The TBI-related hospitalization rate in the US was 93.8 per 100 000 persons. In a meta-analysis that included data from the 1990s and the 2000s, the TBI hospitalization rate in Europe was calculated to be 235 per 100 000 persons (Tagliaferri et al., 2005). However, methodological differences and variations in healthcare systems make comparisons of TBI rates across other countries challenging. Large variations of TBI rates are found among European countries (Berga et al., 2005). Most of the differences in rates were due to a broader admission criteria for mild TBI based on different case definitions and patient inclusion rules in Europe compared to the US (Berga et al., 2005). Meanwhile, TBI hospitalizations in Ontario, Canada, have been calculated as 22 per 100 000 persons for females and 52 per 100 000 persons for males during 2006–2007 (Colantonio et al., 2010). These differences are based mostly on a different definition of TBI (see more detailed information below). Because many developing countries experience a rapid surge during urbanization, which is associated with a rise in motor vehicle use, there is an increase in TBI-related motor vehicle crashes in those developing countries (WHO, 2006). The TBI incidence rate in developing nations is generally higher (e.g., India 160 per 100 000 persons and Asia 344 per 100 000, cited in Tagliaferri et al., 2005) than more developed nations and is predicted to surpass many diseases as a main cause of death and disability by the year 2030 (WHO, 2006). Definitions
According to the US Centers for Disease Control and Prevention (CDC), a TBI is caused by a bump, blow, or jolt to the head or a penetrating head injury that disrupts the normal function of the brain. Not all blows or jolts to the head result in a TBI. Exposures to blasts, and the accompanying overpressure wave, are a leading cause of TBI for active duty military personnel in war zones (Champion et al., 2009). The severity of a TBI may range from mild to severe. Signs and symptoms vary by severity, ranging from loss of consciousness (LOC) lasting a few seconds to seizures, to coma, or even death. Much interest, however, has been placed on the lower severity spectrum of TBI, especially in cases who present with mild TBI (National Center for Injury Prevention and Control, 2003). The majority of reported TBIs in the US are classified as mild TBI (National Center for Injury Prevention and Control, 2003). Research suggests that up to 10% of persons with mild TBI may present persistent symptoms 1 year after the injury and in some cases even lifelong disability (National Center for Injury Prevention and Control, 2003). Patients with mild TBI may present with one or more of the following signs or symptoms: any period of observed or self-reported transient confusion, disorientation, or impaired consciousness; any period of observed or self-reported dysfunction of memory (amnesia) around the time of injury; observed signs of other neurologic or neuropsychological dysfunction, such as seizures acutely following head injury; infants and very young children may exhibit irritability, lethargy, or vomiting following head injury; symptoms among older children and adults such as headache, dizziness, irritability, fatigue, or poor concentration, when identified soon after injury, can be used to support the diagnosis of mild TBI, but cannot be used to make the diagnosis in the absence of LOC or altered consciousness (National Center for Injury Prevention and Control, 2003). Further research may provide additional guidance in this area. Any period of observed or self-reported LOC lasting 30 minutes or less can also be a symptom of TBI (National Center for Injury Prevention and Control, 2003). Based on a clinical definition, the CDC has developed a standard TBI definition for surveillance purposes. This CDC definition is based on diagnostic codes from the International Classification of Disease (ICD) (Marr and Coronado, 2004). TBI is an outcome of an energy force transferred to the head according to the CDC definition. Forms of organic brain degeneration, such as those from congenital sources, stroke or anoxia, are not classified as a TBI (Traumatic Brain Injury Act, 1996). Although widely used, using administrative or billing ICD coded databases may not capture all cases of a particular condition, in this case TBI. The clinical diagnosis of a disease or injury is not always accurately reflected in administrative billing codes. The data used in the diagnosis of a TBI is more detailed and tends to be more accurate than the data used in a surveillance system. While a very specific diagnosis is of prime importance for treatment purposes, surveillance data systems tend to use multiple proxies as the goal is to get an estimate of disease burden. For example, in TBI, Bazarian et al. (2006) compared data obtained from emergency department (ED) medical records of patients with mild TBI to the corresponding data obtained from ICD coded billing records for services rendered in the ED; and found that the sensitivity, specificity, and positive predictive value of the ICD coded CDC definition for TBI was 45.9%, 97.8%, and 23%, respectively. These findings suggest that estimates based on these ICD codes do not completely capture mild TBI in an ED setting and that summary estimates should be viewed with caution. Cost: burden of injury
The economic cost of TBI in the US is measured by combining the costs of two major cost categories (Finkelstein et al., 2006). The first is direct cost and includes the cost of deaths within and outside of the medical system and the costs of medical treatments of hospitalized and nonhospitalized TBI patients. The second category of cost is called productivity costs. Parts of these costs are lost wages and fringe benefits due to the incapacity to work and the absence from the workplace or disability from the injury. Simply stated, these costs represent a loss in value of what is being produced after a TBI. Using year 2000 data, the total annual cost of TBI was estimated to be 60.43 billion US dollars (Finkelstein et al., 2006). The direct cost of TBI was estimated to be 9.22 billion US dollars and the productivity losses were 51.21 US dollars. The productivity losses associated with TBI were higher than those associated with any other injured body region (e.g., other head/neck, spinal cord injury, vertical column injury, torso, upper extremity, lower extremity, other/unspecific and system-wide) (Fig. 1.1). Fig. 1.1 The cost of injury by body region. (Data from Finkelstein et al.,...