E-Book, Englisch, 388 Seiten
E-Book, Englisch, 388 Seiten
Reihe: Handbook of Clinical Neurology
ISBN: 978-0-444-63534-1
Verlag: Elsevier Science & Techn.
Format: EPUB
Kopierschutz: 6 - ePub Watermark
Autoren/Hrsg.
Weitere Infos & Material
1;Front Cover;1
2;Traumatic Brain Injury Part II;4
3;Copyright;5
4;Foreword;8
5;Preface;10
6;Contributors;12
7;Contents of Part II;16
8;Contents of Part I;18
9;Section 6: Clinical Sequelae and Long-term Outcome;22
9.1;Chapter 29: Predicting Outcome After Traumatic Brain Injury;24
9.1.1;Introduction;24
9.1.2;Methodology of Prognostic Studies;25
9.1.2.1;Expressing Prognostic Strength;26
9.1.2.2;Choice and Selection of Predictors;26
9.1.2.3;Scoring and Handling of Predictors;26
9.1.2.4;Missing data;27
9.1.3;Outcome Measures for Prognostic Studies in Patients With Traumatic Brain Injury;28
9.1.4;Building Blocks for Prognostic Analysis;29
9.1.4.1;``Traditional´´ Predictors;29
9.1.4.1.1;Demographic Factors;29
9.1.4.1.2;Injury Details;31
9.1.4.1.3;Clinical Severity;31
9.1.4.1.4;Extracranial Injuries;32
9.1.4.1.5;Intracranial Injuries;32
9.1.4.1.6;Second Insults;33
9.1.4.2;Novel and Emerging Predictors;34
9.1.4.2.1;Genetic Constitution;34
9.1.4.2.2;Laboratory Values and Biomarkers;35
9.1.4.2.3;Advanced MR Imaging Techniques;36
9.1.4.3;Clinical Course;36
9.1.4.4;Available models for traumatic brain injury;37
9.1.5;Prognostic Models;37
9.1.5.1;Available Models for Traumatic Brain Injury;37
9.1.5.2;Applications of Prognostic Models;38
9.1.6;Conclusion and Future Directions;39
9.1.7;References;39
9.2;Chapter 30: Movement Disorders Secondary to Craniocerebral Trauma;44
9.2.1;Introduction;44
9.2.2;Movement Disorders in Craniocerebral Trauma;45
9.2.2.1;Epidemiology;45
9.2.2.2;Pathomechanisms;46
9.2.2.3;Treatment Concepts;46
9.2.3;Post-traumatic tremor;47
9.2.3.1;Treatment;48
9.2.3.1.1;Medical Treatment;48
9.2.3.1.2;Surgical Treatment;49
9.2.4;Post-traumatic Dystonia;50
9.2.4.1;Treatment;52
9.2.4.1.1;Medical Treatment;52
9.2.4.1.2;Surgical Treatment;52
9.2.5;Other Hyperkinetic Movement Disorders;54
9.2.5.1;Chorea and Ballism;54
9.2.5.2;Paroxysmal Autonomic Instability With Dystonia;55
9.2.5.3;Paroxysmal Dyskinesias;55
9.2.5.4;Tics and Tourettism;56
9.2.5.5;Unusual post-traumatic Hyperkinesias;56
9.2.6;Post-traumatic Parkinsonism and Parkinson's Disease;56
9.2.6.1;Parkinsonism After Single Head Injury;56
9.2.6.2;Parkinsonism After Repeated Head Injury;57
9.2.6.3;Parkinson's Disease and Head Trauma;58
9.2.6.4;References;59
9.3;Chapter 31: Language Impairments in Traumatic Brain Injury: a Window Into complex Cognitive Performance;66
9.3.1;Introduction;66
9.3.1.1;Overview of the Movie the King's Speech Highlighting the Main Ideas and Themes;66
9.3.2;Language in Traumatic Brain Injury;67
9.3.3;Construct of Gist Reasoning: A complex Language Function;68
9.3.4;Neurobiological Support of Gist Reasoning;69
9.3.5;Theoretical Support of Gist Reasoning;70
9.3.6;Measurement of Gist Reasoning;70
9.3.7;Gist Reasoning and Traumatic Brain Injury;71
9.3.8;Higher-order/complex Language Rehabilitation;72
9.3.9;Gist Reasoning and Cognition;74
9.3.10;Future Directions;75
9.3.11;Conclusions;75
9.3.12;References;76
9.4;Chapter 32: Connecting Clinical and Experimental Investigations Of awareness in Traumatic Brain Injury;80
9.4.1;Impaired Awareness of Deficit After Brain Injury;80
9.4.2;The Online Experience Of awareness;81
9.4.3;Brain Injury and Error Awareness in Routine Action;82
9.4.4;Refining Measurement of Online Awareness;82
9.4.5;Neural Signals and Disruption to the Emergence of Awareness;83
9.4.6;Objects of Insight in Online Experiences;86
9.4.7;Retrospective Confidence and Online Awareness;88
9.4.8;Prospective Judgments and Online Awareness;89
9.4.9;Conclusions;90
9.4.10;References;91
9.5;Chapter 33: Post-traumatic Epilepsy: Clinical Clues to Pathogenesis And paths to Prevention;94
9.5.1;Background;94
9.5.2;Military Penetrating Head Injury and Clues to post-traumatic Epilepsy Pathogenesis;94
9.5.2.1;Incidence of post-traumatic Epilepsy After Missile Wounds;95
9.5.2.2;Seizure Onset Latency;96
9.5.2.3;Seizure type;96
9.5.2.4;Seizure Frequency and Persistence;97
9.5.2.5;Clinical Correlates of post-traumatic Epilepsy;97
9.5.2.6;Anatomic (CT) Correlates of post-traumatic Epilepsy, the Effects of Lesion Location After Military Penetrating Head Injury...;98
9.5.3;Post-traumatic Epilepsy After Penetrating Head Injury and Clinical Outcome;99
9.5.3.1;Post-traumatic Epilepsy, Cognition, and Behavior;99
9.5.3.2;Relationship of post-traumatic Epilepsy to Overall Outcome;99
9.5.4;Pathogenesis;99
9.5.4.1;Immunologic, Neuroinflammatory Response to Traumatic Brain Injury;100
9.5.4.2;Hemorrhage, Iron, and Oxidative Stress;100
9.5.4.2.1;Traumatic Disruption of the Blood–Brain Barrier;100
9.5.4.2.2;Inflammatory Signaling;100
9.5.4.2.3;Chronic Microglial Activation;101
9.5.4.3;Neuroinflammation, Excitotoxicity, And epileptogenesis;101
9.5.4.4;Brain Plasticity and Misdirected Axon Sprouting; Neural Circuit Reorganization;102
9.5.4.5;Epigenetics, Neuroinflammation, And epilepsy;102
9.5.5;Towards Strategies for Prevention of post-traumatic Epilepsy;102
9.5.5.1;Prophylactic Anticonvulsants;102
9.5.5.2;Neuroprotection and post-traumatic Epilepsy Prevention;104
9.5.5.3;Antioxidants, Lipid Peroxidation Inhibitors;104
9.5.5.4;Towards Rational Design of Clinical Trials for Prevention of post-traumatic Epilepsy;104
9.5.6;Conclusions;105
9.5.7;References;105
9.6;Chapter 34: Autonomic Dysfunction Syndromes After Acute Brain Injury;108
9.6.1;Introduction;108
9.6.2;The Central Autonomic Network;108
9.6.3;Autonomic Dysfunction and Ischemic Stroke Syndromes;110
9.6.3.1;Treatment Implications for Ischemic Stroke patients;111
9.6.4;Subarachnoid hemorrhage-related Hyperadrenergic Crises;111
9.6.4.1;Clinical Descriptions;111
9.6.4.2;Treatment Options;112
9.6.4.3;Acute Brain Injuries and Hyperthermia;113
9.6.4.4;Fever Treatments in Subarachnoid Hemorrhage;113
9.6.5;Paroxysmal Sympathetic Hyperactivity;114
9.6.5.1;Incidence, Risk Factors, and Pathophysiology;114
9.6.5.2;Clinical Descriptions;116
9.6.5.3;Paroxysmal Sympathetic Hyperactivity Management;116
9.6.6;Conclusion;117
9.6.7;References;118
9.7;Chapter 35: Sleep in Traumatic Brain Injury;122
9.7.1;Introduction;122
9.7.2;Normal Sleep;122
9.7.2.1;Sleep Architecture;122
9.7.2.2;Neurophysiology of sleep;123
9.7.2.3;Sleep and the Immune System;124
9.7.3;Sleep Disorders and Their Evaluation;124
9.7.3.1;Dyssomnias;124
9.7.3.2;Parasomnias;127
9.7.4;Assessment of Sleep Disorders;128
9.7.5;Treatment of Insomnia;129
9.7.5.1;Benzodiazepines;130
9.7.5.2;Nonbenzodiazepine-benzodiazepine Agonists;130
9.7.5.3;Antidepressants;131
9.7.5.4;Melatonin and Melatonin Agonists;131
9.7.5.5;Atypical Antipsychotics;131
9.7.5.6;Nonpharmacologic Treatment Options;132
9.7.5.7;On the Horizon;132
9.7.5.8;References;133
9.8;Chapter 36: Post-traumatic Headaches;136
9.8.1;Introduction;136
9.8.2;Epidemiology of Chronic Pain Conditions After Traumatic Brain Injury;136
9.8.3;Pathophysiology of post-traumatic Headaches;138
9.8.4;Clinical Features of post-traumatic Headaches;139
9.8.5;Treatment of post-traumatic Headaches;140
9.8.5.1;Pharmacologic Treatment of post-traumatic Headaches;141
9.8.5.1.1;Episodic Tension or Cervicogenic Headaches;141
9.8.5.1.2;Migrainous Headache;142
9.8.5.1.3;Chronic Daily Headache;144
9.8.5.2;Nonpharmacologic Interventions for post-traumatic Headaches;144
9.8.5.2.1;Tension and Cervicogenic Headaches;144
9.8.5.2.2;Migraine Headaches;145
9.8.5.2.3;Sleep and Post-Traumatic Headaches;145
9.8.6;Prognosis of post-traumatic Headaches;145
9.8.7;Conclusion;146
9.8.8;Acknowledgments;146
9.8.9;References;146
9.9;Chapter 37: Traumatic Brain Injury and Cognition;148
9.9.1;Introduction;148
9.9.2;Spectrum of Traumatic Brain Injury Severity;148
9.9.3;Spectrum of Physical Mechanisms Causing Traumatic Brain Injury;150
9.9.4;Spectrum of Chronicity in Relation to Cognitive Functions;150
9.9.4.1;Recovery Course;151
9.9.5;Cognitive Sequelae of Traumatic Brain Injury;151
9.9.5.1;Cognitive Functioning Across Traumatic Brain Injury Subtypes;152
9.9.5.1.1;Closed Traumatic Brain Injury;152
9.9.5.2;Mild Closed Traumatic Brain Injury;152
9.9.5.3;Moderate to Severe Closed Traumatic Brain Injury;152
9.9.5.3.1;Penetrating Traumatic Brain Injury;153
9.9.5.3.2;Blast Traumatic Brain Injury;154
9.9.5.3.3;Concussion Traumatic Brain Injury;155
9.9.5.4;Memory Functioning After Traumatic Brain injury;155
9.9.5.4.1;Declarative Memory;156
9.9.5.4.2;Episodic Memory;156
9.9.5.4.3;Semantic Memory;156
9.9.5.4.4;Autobiographical Memory;156
9.9.5.4.5;Ecologically Valid Studies of Memory;156
9.9.5.5;Executive Functions After Traumatic Brain injury;157
9.9.5.5.1;Working Memory;158
9.9.5.5.2;Inhibition;158
9.9.5.5.3;Shifting;158
9.9.5.5.4;Planning;159
9.9.5.5.5;Ecologically Valid Studies of Executive Functions;159
9.9.5.6;Attention After Traumatic Brain Injury;159
9.9.5.6.1;Selective Attention;159
9.9.5.6.2;Sustained Attention;160
9.9.5.6.3;Divided Attention;160
9.9.5.6.4;Ecologically Valid Studies of Attention;161
9.9.5.7;Lack of Awareness;161
9.9.6;Pediatric Traumatic Brain Injury;162
9.9.7;Ninds Common Data Elements;163
9.9.8;Neuroimaging After Traumatic Brain Injury;164
9.9.8.1;Computed Tomography and Magnetic Resonance Imaging;164
9.9.8.2;Perfusion With single-photon Emission Computed Tomography and Positron Emission Tomography;164
9.9.8.3;Functional Magnetic Resonance Imaging;165
9.9.8.3.1;Resting State Brain Connectivity;165
9.9.8.4;Diffusion Tensor Imaging;165
9.9.9;Rehabilitation of Cognitive Functioning After Traumatic Brain Injury;166
9.9.9.1;Memory Rehabilitation;166
9.9.9.2;Executive Function Rehabilitation;167
9.9.9.3;Comprehensive Rehabilitation;168
9.9.10;Genetics as Predictor Of cognitive Outcomes;169
9.9.10.1;Working Memory;169
9.9.10.2;Executive Functions;169
9.9.11;Summary;170
9.9.12;Acknowledgments;170
9.9.13;References;170
9.10;Chapter 38: Mood Disorders;182
9.10.1;Introduction;182
9.10.2;Diagnosis of Mood Disorders;183
9.10.3;Differential Diagnosis of Mood Disorders Due to Traumatic Brain Injury;183
9.10.3.1;Mood Disorders With Depressive Features;183
9.10.3.2;Mood Disorders With Manic, Hypomanic, Or mixed Features;184
9.10.4;Frequency of Mood Disorders;185
9.10.4.1;Depressive Disorders;185
9.10.4.2;Mood Disorders With Manic, Hypomanic, Or mixed Features;187
9.10.4.3;Mood Disorders Associated With combat-related Traumatic Brain Injury;187
9.10.5;Risk Factors for Mood Disorders Due to Traumatic Brain Injury;188
9.10.6;Pathophysiologic Aspects of Mood Disorders Due to Traumatic Brain Injury;189
9.10.7;Effect of Mood Disorders on the Outcome of Traumatic Brain Injury Patients;192
9.10.8;Treatment of Mood Disorders;193
9.10.9;Conclusion;194
9.10.10;References;195
9.11;Chapter 39: Post-traumatic Stress Disorder and Traumatic Brain Injury;202
9.11.1;Introduction;202
9.11.2;Definition Of terms;202
9.11.2.1;Post-traumatic Stress Disorder;202
9.11.2.2;Acute Stress Disorder;203
9.11.2.3;Changes to post-traumatic Stress Disorder and Acute Stress Disorder in the DSM-5;203
9.11.2.4;Traumatic Brain Injury;203
9.11.2.5;Postconcussive Syndrome;204
9.11.3;Diagnostic Challenges: Symptom Overlap;204
9.11.4;Evidence for the Dual Diagnosis;205
9.11.4.1;Theoretical Background;205
9.11.4.2;Epidemiology of post-traumatic Stress Disorder and Traumatic Brain Injury;206
9.11.5;Link Between Traumatic Brain Injury Severity and post-traumatic Stress Disorder;206
9.11.6;Trajectory of post-traumatic Stress Disorder Following Traumatic Brain Injury;207
9.11.7;Models of post-traumatic Stress Disorder;207
9.11.7.1;Neurocircuitry Models of Anxiety/post-traumatic Stress Disorder;207
9.11.7.1.1;Amygdala;208
9.11.7.1.2;Prefrontal Cortex;209
9.11.7.1.3;Hippocampus;209
9.11.7.2;Cognitive Models of post-traumatic Stress Disorder;210
9.11.8;Neuropathology of Traumatic Brain Injury;210
9.11.8.1;Brain Structure;210
9.11.8.1.1;Gray Matter/Cortex;210
9.11.8.1.2;White Matter;211
9.11.8.2;Brain Function;211
9.11.9;Overlap in Neurobiological Substrates;211
9.11.9.1;Neurologic Risk Factors for post-traumatic Stress Disorder;211
9.11.10;Future Directions and Implications for Treatment;213
9.11.11;Conclusions;213
9.11.12;References;214
9.12;Chapter 40: Long-term Functional Outcomes of Traumatic Brain Injury;218
9.12.1;Introduction;218
9.12.2;Selecting Outcome Measures;219
9.12.3;Defining the Injury;219
9.12.3.1;Tbi;219
9.12.3.2;Tbi Severity;219
9.12.4;Methodology;220
9.12.5;Long-term Work Outcomes Following Traumatic Brain Injury;220
9.12.6;Prognosis for Work Following Traumatic Brain Injury;222
9.12.6.1;Studies of the Efficacy of Treatments for Return to Work (randomized Controlled Trials);222
9.12.6.2;Long-term Return to Driving;224
9.12.7;Summary;224
9.12.8;Disclaimer;226
9.12.9;Acknowledgments;226
9.12.10;References;227
9.13;Chapter 41: Sequelae in Children: Developmental Consequences;230
9.13.1;Epidemiology of Traumatic Brain Injury in Children and Adolescents;230
9.13.2;Understanding the Developmental Context of Childhood Traumatic Brain Injury;230
9.13.2.1;Recovery From Traumatic Brain Injury in Very Early Childhood (birth to 5 years);231
9.13.2.2;Recovery From Traumatic Brain Injury In school-aged Children (6-12 years);231
9.13.2.3;Recovery From Traumatic Brain Injury In adolescents (13-18 years);232
9.13.3;Neurologic Impacts of Traumatic Brain Injury in Children: Imaging Findings;232
9.13.4;Sequelae After Traumatic Brain Injury in Children;232
9.13.4.1;Intellectual Functioning;232
9.13.4.2;Attention and Processing speed;233
9.13.4.3;Executive Functions;234
9.13.4.4;Memory;235
9.13.4.5;Language;235
9.13.4.6;Academic Performance;236
9.13.4.7;Behavior;236
9.13.4.8;Social Competence;237
9.13.5;Predictors of Outcome;238
9.13.5.1;Injury Severity;238
9.13.5.2;Age At Injury;238
9.13.5.3;Preinjury Function;238
9.13.5.4;Environmental Factors;239
9.13.6;Rehabilitation and Intervention;240
9.13.7;Summary;240
9.13.8;Future Directions;241
9.13.9;References;241
10;Section 7: Brain Plasticity and Long-term Risks;248
10.1;Chapter 42: Cellular and Molecular Neuronal Plasticity;250
10.1.1;Introduction;250
10.1.2;Pathophysiology of Traumatic Brain Injury and Neuroplasticity;250
10.1.3;Neuroplasticity After Traumatic Brain Injury is Dependent on Tissue Health;251
10.1.4;Environmental Influences on post-traumatic Brain Injury Neuroplasticity;252
10.1.5;Experience-dependent Plasticity is Influenced By Postinjury time;253
10.1.6;Neuroplasticity After Traumatic Brain Injury in the Developing brain;253
10.1.7;Concluding Remarks;255
10.1.8;References;255
10.2;Chapter 43: Traumatic Brain Injury and Reserve;260
10.2.1;General Concepts of Reserve;260
10.2.2;Measures of Reserve;261
10.2.3;Epidemiologic Evidence for Cognitive Reserve;262
10.2.4;Imaging Studies of Cognitive Reserve;263
10.2.5;Traumatic Brain Injury and Reserve;263
10.2.6;Recovery and Traumatic Brain Injury Severity;264
10.2.7;Injury Severity and Overall Lesion Burden;264
10.2.8;Size-function Rule and Neural Connectivity;266
10.2.9;Brain Atrophy;268
10.2.9.1;Brain Reserve, Brain Size, and Traumatic Brain injury;269
10.2.9.2;Hippocampal Atrophy;269
10.2.10;Premorbid Intellectual and Academic Ability and Cognitive Outcome From Traumatic Brain Injury;269
10.2.11;Premorbid Neurologic and Neuropsychiatric Burden and Cognitive Outcome From Traumatic Brain Injury;270
10.2.12;Age;270
10.2.13;Traumatic Brain Injury and Dementia;271
10.2.14;Summary;273
10.2.15;References;273
10.3;Chapter 44: Traumatic Brain Injury and late-life Dementia;280
10.3.1;Introduction;280
10.3.2;Epidemiologic Evidence of Association Between Traumatic Brain Injury and Dementia;280
10.3.2.1;Traumatic Brain Injury in Later life;283
10.3.3;Traumatic Brain Injury and APOE 4;283
10.3.4;Traumatic Brain Injury and Age of Onset of Dementia;284
10.3.5;Sports-related Traumatic Brain Injury and Cognitive Problems;284
10.3.6;Penetrating Head Injuries and Cognitive Decline;285
10.3.7;Chronic Traumatic Encephalopathy and Repetitive Brain Injury;286
10.3.8;Limitations of the Studies Linking Traumatic Brain Injury to late-life Dementia;286
10.3.9;Biological Evidence Connecting Head Injury and Alzheimer's Disease;288
10.3.10;Summary;288
10.3.11;References;289
10.4;Chapter 45: Genetic Factors in Traumatic Brain Injury;292
10.4.1;Introduction;292
10.4.2;Genetic Response to Neurotrauma;292
10.4.3;Genetic Influence on Extent Of injury;292
10.4.3.1;TP53;293
10.4.3.2;B-cell Lymphoma 2 (BCL-2);294
10.4.3.3;Nitric Oxide Synthase (NOS3);294
10.4.3.4;Poly(Adp-ribose) polymerase-1 (PARP-1);294
10.4.3.5;Angiotensin-converting Enzyme (ACE);294
10.4.3.6;Calcium Channel Subunit Gene (CACA1A);294
10.4.3.7;Neuroglobin Gene (NGB);295
10.4.3.8;Inflammation;295
10.4.3.8.1;Il-1 Family;295
10.4.3.8.2;Il-6;295
10.4.4;Alleles Impacting on Repair And recovery;295
10.4.4.1;Neurogenesis;295
10.4.4.2;Serotonin Transporter;296
10.4.4.3;Synaptic Organization and Adaptation (neurotrophins);296
10.4.4.3.1;Brain-derived Neurotrophic Factor (BDNF);296
10.4.4.4;Repair;297
10.4.4.4.1;Apolipoprotein E (ApoE);297
10.4.4.4.2;Apoe Promotor Polymorphisms;298
10.4.5;Neurobehavioral Function And cognitive Capacity/reserve;298
10.4.5.1;Dopamine (DA) Receptor Gene Polymorphisms;298
10.4.5.2;Dopamine D2Receptor (DRD2);298
10.4.5.3;Polymorphisms of Monoamine Transporters;299
10.4.5.3.1;Dopamine Transporter (Dat);299
10.4.5.3.2;Serotonin (5-hydroxytryptamine) Transporter (5-HTT);299
10.4.5.3.3;Norepinephrine Transporter Gene (NET);299
10.4.5.4;Polymorphisms of Enzymes Involved In catecholamine Synthesis and Metabolism;299
10.4.5.4.1;Dopamine beta-hydroxylase (DBH);299
10.4.5.4.2;Catechol-O-methyltransferase (COMT);300
10.4.5.4.3;Monoamine oxidase-A (MAO-A);300
10.4.5.5;Polymorphisms Relevant to the Cholinergic System;300
10.4.5.6;Cholinergic Receptors;300
10.4.6;Implications for Treatment;301
10.4.7;Conclusions;304
10.4.8;Acknowledgments;304
10.4.9;References;304
11;Section 8: Conducting Clinical Trials in Traumatic Brain injury;310
11.1;Chapter 46: Ethical and Regulatory Considerations in the Design of Traumatic Brain Injury Clinical Studies;312
11.1.1;Introduction;312
11.1.2;Research Conducted in Emergency Settings;312
11.1.2.1;The Need for Informed Consent;312
11.1.2.2;Exception From Informed Consent and Traumatic Brain Injury Research;314
11.1.3;Maintaining Equipoise in Traumatic Brain Injury Clinical Trials;316
11.1.3.1;Delays in Obtaining Institutional Review Board Approvals for Multicenter Clinical Trials;316
11.1.3.2;The Effect of Time on Clinical Equipoise;317
11.1.3.3;Equipoise and the Potential for Beneficence;318
11.1.3.4;Strategies for Accelerating Study Completion;318
11.1.4;Traumatic Brain Injury Research on Vulnerable Populations;319
11.1.4.1;Children and Adolescents;319
11.1.4.2;Older Adults;320
11.1.4.3;Military Personnel;320
11.1.4.4;Prisoners;321
11.1.4.5;Neuroethics: Tinkering With The brain;321
11.1.4.6;Global Health and Traumatic Brain Injury Research;322
11.1.5;Ethical Considerations for Data Sharing;323
11.1.6;Conclusions;324
11.1.7;Author Disclosure Statement;324
11.1.8;Acknowledgments;324
11.1.9;References;324
11.2;Chapter 47: Design of Acute Neuroprotection Studies;330
11.2.1;Introduction;330
11.2.2;Targets for Intervention;331
11.2.2.1;Excitotoxicity;331
11.2.2.2;Intracellular Calcium;333
11.2.2.3;Ischemia and Mitochondrial Dysfunction;333
11.2.2.4;Free radical-mediated Injury;334
11.2.2.5;Drugs Acting on Neuroinflammation;334
11.2.3;Methodological Shortcomings Of trials to Date and the Failure to Translate;334
11.2.3.1;Limitations of Animal Models;335
11.2.3.2;Heterogeneity of the Traumatic Brain Injury Population;336
11.2.3.3;Insufficient Sample size;336
11.2.3.4;Questionable Experimentation/result Reporting;337
11.2.4;Designing Better Clinical Trials;337
11.2.4.1;Dealing With Heterogeneity;337
11.2.4.2;Choosing Agents to Explore in Human Trials;337
11.2.4.3;Combination of Agents;337
11.2.4.4;Randomization;338
11.2.4.5;Inclusion/exclusion Criteria;339
11.2.4.6;Sample size;339
11.2.4.7;Blinding;339
11.2.4.8;Ethics;340
11.2.4.9;Placebos And shams;340
11.2.4.10;Alternate Trial Designs;340
11.2.4.11;Trial Monitoring;341
11.2.4.12;Outcome Measures;341
11.2.4.13;Cost Containment;341
11.2.5;Lessons From Impact;342
11.2.6;Conclusion;343
11.2.7;References;343
11.3;Chapter 48: Design of Brain Injury Rehabilitation Treatment Research;348
11.3.1;Introduction;348
11.3.1.1;Severity;348
11.3.1.2;Neuropathology;348
11.3.1.3;Clinical Aims/treatment Methods;349
11.3.1.4;Time frame;349
11.3.2;The Trajectory of Functional Improvement After Traumatic Brain Injury;349
11.3.3;The Trajectory of Treatment Research;350
11.3.4;Dimensions Relevant to Rehabilitation Treatment Study designs;352
11.3.4.1;Restorative Versus Compensatory Treatments;352
11.3.4.2;Focused Versus Comprehensive Treatments;352
11.3.5;Issues in Study Design;353
11.3.5.1;Subject Selection;353
11.3.5.2;Defining the Treatment and Comparison Treatments;353
11.3.5.3;Measuring Treatment Outcomes;354
11.3.5.4;Selecting the Study Design;355
11.3.5.5;A Case Example;355
11.3.5.6;A Hypothetical Restorative Treatment for Traumatic Brain injury-related Attention Deficits;355
11.3.6;Research on Existing Treatments;360
11.3.7;Research Funding and Training;361
11.3.8;Conclusion;362
11.3.9;References;362
11.4;Chapter 49: The Ebb and Flow of Traumatic Brain Injury Research;364
11.4.1;Recent Trends in Traumatic Brain Injury Research;364
11.4.2;Research Stability;365
11.4.3;Timeline for Intervention;365
11.4.4;Primary and Secondary Neuroprotection;365
11.4.4.1;Preinjury Prevention Strategies;365
11.4.4.2;Acute Care and Traumatic Brain Injury;365
11.4.5;Medical Neuroprotection Strategies and Pitfalls in Clinical Traumatic Brain Injury Research;366
11.4.6;Traumatic Brain Injury Rehabilitation;366
11.4.7;Long-term Effects of a Traumatic Brain Injury;367
11.4.8;Neuroplasticity;368
11.4.9;Genetic Predisposition and Epigenetics;369
11.4.10;Concluding Remarks;369
11.4.11;References;371
12;Index;372
Chapter 29 Predicting outcome after traumatic brain injury
Andrew I.R. Maas1,*; Hester F. Lingsma2; Bob Roozenbeek3 1 Department of Neurosurgery, Antwerp University Hospital and University of Antwerp, Edegem, Belgium
2 Department of Public Health, Erasmus Medical Center, Rotterdam, The Netherlands
3 Department of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands
* Correspondence to: Andrew I.R. Maas, M.D., Ph.D., Department of Neurosurgery, Antwerp University Hospital/University of Antwerp, Wilrijkstraat 10, 2650 Edegem, Belgium. Tel: +32-3-821-46-32 email address: andrew.maas@uza.be Abstract
Developing insight into which factors determine prognosis after traumatic brain injury (TBI) is useful for clinical practice, research, and policy making. Several steps can be identified in prediction research: univariate analysis, multivariable analysis, and the development of prediction models. For each step, several methodological issues should be considered, such as selection/coding of predictors and dealing with missing data. “Traditional” predictors include demographic factors (age), type of injury, clinical severity, second insults, and the presence of structural abnormalities on neuroimaging. In combination, these predictors can explain approximately 35% of the variance in outcome in populations with severe and moderate TBI. Novel and emerging predictors include genetic constitution, biomarkers, and advanced magnetic resonance (MR) imaging. To estimate prognosis for individual patients reliably, multiple predictors need to be considered jointly in prognostic models. Two prognostic models for use in TBI, developed upon large patient numbers, have been extensively validated externally: the IMPACT and CRASH prediction models. Both models showed good performance in validations across a wide range of settings. Importantly, these models were developed not only for mortality but also for functional outcome. Prognostic models can be used for providing information to relatives of individual patients, for resource allocation, and to support decisions on treatment. At the group level, prognostic models aid in the characterization of patient populations, are important to clinical trial design and analysis, and importantly, can serve as benchmarks for assessing quality of care. Continued development, refinement, and validation of prognostic models for TBI is required and this should become an ongoing process. Key words Traumatic brain injury prognosis prediction model discrimination validation biomarkers advanced MR imaging No head injury is too severe to be despaired of, nor too trivial to be ignored. Hippocrates Introduction
Interest in prognosis after traumatic brain injury (TBI) dates back to classical times. In Ancient Greece, the quality of care was judged not so much by the actual result of treatment, but rather by the accuracy of the physician's prediction of outcome. Estimates of prognosis – often subconsciously applied – are an important component in clinical decision making. However, as captured in the Hippocratic aphorism quoted above, it has always been considered difficult to predict the likely outcome in patients with TBI. For many years estimates of prognosis after TBI were little more than prophecies based upon clinical experience of physicians. The science of clinical decision making and advances in statistical modeling allow us now to consider prognosis in terms of probabilities rather than vague prophecies. Standardization of the assessment of initial severity following the introduction of the Glasgow Coma Scale (GCS) (Teasdale and Jennett, 1974) and standardized approaches to outcome assessment based upon the Glasgow Outcome Scale (GOS) (Jennett and Bond, 1975) have facilitated prognostic analysis in TBI. Furthermore, the availability of large databases has offered new opportunities for an evidence-based approach. Quantification of prognostic risk and predictive statements can be useful in a number of ways. Concern about the most likely outcome is of paramount importance to relatives, and prognostic estimates facilitate realistic counseling. The role of quantification of prognostic risk in influencing decisions about the management in individual patients is more controversial. Although many physicians acknowledge that prognostic estimates have an important role in decision making, others attribute only a minor or even nonexistent role to prognosis. This difference reflects a range of attitudes influenced by both ethical and cultural differences as well as by clinical convictions. Nevertheless, some form of prognostic estimate is consciously or subconsciously used by physicians when allocating resources and prioritizing treatment – particularly in situations where resources may be more limited. Caution in the interpretation of prognostic risk estimates is appropriate: a prognostic estimate in an individual patient concerns a probabilistic equation with a range of uncertainties reflected in the confidence interval (CI). We should further recognize that predictive equations can never include all items relevant to an individual patient. Estimates derived from evidence-based analysis of large datasets remain preferable to a clinical prophecy, as estimates performed by physicians are often unduly optimistic, or, on the other hand, sometimes even unnecessarily pessimistic or inappropriately ambiguous (Barlow and Teasdale, 1986; Chang et al., 1989; Dawes et al., 1989; Kaufmann et al., 1992). No single clinician's experience can ever match the wealth of data available in databases consisting of thousands of patients. The most important application of prognostic analysis in TBI is perhaps not so much at the level of the individual patient, but more at the group level. Patient populations can be characterized by baseline prognostic risk, thus facilitating more accurate and valid comparisons between different studies. Moreover, estimation of the baseline prognostic risk can be used as a benchmark for evaluating quality of care. Finally, prognostic analysis and identification of covariates are important for stratification and covariate adjustment in clinical trials. In this chapter, we focus on the prediction of outcome in terms of mortality and functional outcome in adult patients with moderate and severe TBI. Cognitive and psychosocial outcomes are addressed in more detail in Chapters 31, 40, and 44. Specific pediatric considerations are described in Chapters 15 and 41. We aim to describe the basics of prognostic analysis and to review current knowledge about traditional and newly recognized predictors for outcome. We will also discuss prognostic modeling as an important instrument in clinical practice and research and critically review existing models. Finally, we will discuss the potential of prognostic analysis in the field of TBI. Methodology of prognostic studies
Prognostic studies are inherently longitudinal and most commonly performed in cohorts of patients with outcome determined at a fixed time point. The cohort is defined by the presence of one or more particular characteristics such as hospital admission for TBI. It is important to define the cohort as accurately as possible in order to prevent a bias in the selection of patients for participation. Several steps can be identified in prediction research (Table 29.1): univariate analysis, multivariable analysis, and the development of prediction models. Table 29.1 Steps in prognostic analysis in traumatic brain injury Univariate analysis To estimate the relation between a single predictor and outcome Does not take into account the role of confounding factors that may explain (part of) the observed association Sensitivity, specificity, positive predictive value, negative predictive value, odds ratio Multivariable analysis To determine the prognostic value of a predictor, adjusting for confounding effects of other predictors In individual patients, predictors may influence outcome in opposite directions; does not take into account interactions or differential effects for specific subpopulations Odds ratio
Risk ratio
Nagelkerkers R2 Prediction models To combine predictors into a model to estimate the risk of an outcome for individual patients External validation essential to prove generalizability outside the development setting Discrimination: area under the receiver operating characteristic curve
Calibration: graphical representation
Hosmer-Lemeshow goodness of fit test (Adapted from Lingsma et al., 2010.) Sensitivity, proportion of patients with the outcome that have the predictor (true positive); specificity, proportion of patients without the outcome that do not have the predictor (true negative); positive predictive value, proportion of patients with the predictor that have the outcome; negative predictive value, proportion of patients without the predictor that do not have the outcome; odds ratio, ratio of the odds for better versus poorer outcome in the presence of the variable, compared...
