Goswami / Pandi-Perumal / Thorpy Narcolepsy

A Clinical Guide
1. Auflage 2009
ISBN: 978-1-4419-0854-4
Verlag: Springer
Format: PDF
Kopierschutz: 1 - PDF Watermark

E-Book, Englisch, 330 Seiten

Narcolepsy serves as a prototype of how the interaction of high quality clinical research and groundbreaking basic science can collaborate to defne the cause of a disease and change forever how we evaluate and treat it. There is scarcely a topic in this book that would have been covered in the same way 10 years ago as it is d- cussed today. We are also fortunate that many of the players in this dramatic tu- around have contributed to this volume, so that the result is a tapestry of the events that have transformed the feld over the last decade that is both authentic and detailed. The frst section of the book provides much of the basic science background. As described in the frst two chapters, the dramatic convergence of lines of evidence from two different laboratories frst demonstrated in 1999 that narcolepsy is a disease of loss of neurotransmission by lateral hypothalamic neurons making the peptides that have been called orexins or hypocretins. These fndings did much to clarify and unify a feld that had puzzled for decades over the fundamental nature of this puzzling disease, as refected in the chapters that review its epidemiology and neuroanatomical and imaging fndings.

Meeta Goswami, BDS, PhD, MPH, has been the director of the Narcolepsy Institute since its inception in 1985 and serves as an Assistant Professor of Neurology, Albert Einstein College of Medicine. Her general area of research interest includes narcolepsy and psychosocial issues. S.R. Pandi-Perumal, M.Sc, is the President and Chief Executive Officer of Somnogen Inc, a New York Corporation. He is a well-recognized sleep researcher both nationally and internationally, and has authored many publications. His general area of research interest includes sleep and biological rhythms. He is a well-known editor in the field of sleep medicine and has edited over 15 volumes dealing with various sleep-related topics. Michael J Thorpy, MD, has won many awards for his research including one of the sleep field's highest honors: the Nathaniel Kleitman Award. He is a well-published researcher and a board-certified sleep physician. He serves as a Professor of Neurology at Albert Einstein College of Medicine and the Director of the Sleep-Wake Disorders Center at Montefiore Medical Center, Bronx, New York.

Autoren/Hrsg.

Goswami, Meeta

Pandi-Perumal, S. R.

Thorpy, Michael J.

Inhaltsverzeichnis

1;Foreword;5
2;Credits and Acknowledgments;7
3;Preface;8
4;Contents;11
5;Contributors;14
6;Biographies;18
7;Section I Etiology;20
8;Chapter 1;21
8.1;Narcolepsy: Genetic Predisposition and Pathophysiology;21
8.1.1;Prevalence Studies;21
8.1.2;Animal Models;22
8.1.3;Twin Studies and Environmental Factors in Narcolepsy;24
8.1.4;Familial Aspects of Human Narcolepsy;25
8.1.5;Hypocretin (Orexin) Deficiency and Human Narcolepsy–Cataplexy;26
8.1.6;HLA-DR2, Narcolepsy and Autoimmunity;26
8.1.7;DQB1*0602 and DQA1*0102 Are the Main HLA Narcolepsy Susceptibility Genes;27
8.1.8;HLA Typing in Clinical Practice;28
8.1.9;Genetic Factors Other Than HLA;29
8.1.10;CSF Hypocretin-1 as a Diagnostic Tool for Narcolepsy;30
8.1.11;Secondary Narcolepsy Cases;31
8.1.12;Pharmacological Studies: Monoaminergic and Cholinergic Interactions in Hypocretin Deficiency;32
8.1.13;Hypocretin Compounds as Therapeutic Targets;34
8.1.14;Conclusion and Perspectives;34
8.2;References;35
9;Chapter 2;40
9.1;Animal Models of Narcolepsy: Development, Findings and Perspectives;40
9.1.1;Introduction;40
9.1.2;Narcolepsy for the Veterinarian;41
9.1.3;Canine Narcolepsy;41
9.1.3.1;The Canine Narcoleptic Phenotype;42
9.1.3.2;Neurotransmitter Differences and Imbalances in the Canine Narcoleptic;43
9.1.3.3;The Genetics of Canine Narcolepsy;44
9.1.4;Rodent Narcolepsy;45
9.1.4.1;Vigilance State Characterization of Orexin- and Orexin-Receptor Deficient Rodents;46
9.1.4.1.1;The Orexin / Mouse;46
9.1.4.1.2;Orexin/Ataxin-3 Transgenic Mice and Rats;48
9.1.4.1.3;The Orexin Receptor Null Mice: OX1R-/-, OX2R.-/- and OX1R.-/-; OX2R-/-;49
9.1.4.1.4;Summary;49
9.1.5;Current Research Issues;50
9.1.5.1;Etiology;50
9.1.5.2;Cataplexy;50
9.2;References;51
10;Chapter 3;55
10.1;Neuroimaging of Narcolepsy;55
10.1.1;Introduction;55
10.1.2;Functional Neuroimaging Studies of Healthy Human Sleep;55
10.1.3;Narcolepsy;56
10.1.4;Narcolepsy Pharmacotherapy and Neuroimaging;57
10.1.4.1;Receptor Ligand Studies;58
10.1.5;Summary;58
10.2;References;58
11;Section II Clinical Considerations;60
12;Chapter 4;61
12.1;Epidemiology of Narcolepsy;61
12.1.1;Introduction;61
12.1.2;Narcolepsy Has a Variable Phenotype;61
12.1.3;Difficulties with Diagnosis Complicate Epidemiological Estimates;61
12.1.4;Prevalence and Incidence Estimates Vary by Methods and Populations;62
12.1.5;Age of Onset Generally Begins in the First Two Decades;63
12.1.6;Narcolepsy Without Cataplexy Is More Common Among Men than Women;63
12.1.7;Narcolepsy Has Few Links to Lifestyle Characteristics;64
12.1.8;Narcolepsy Impairs Quality of Life and Increases Accident Risks;64
12.1.9;Narcolepsy Overlaps with a Variety of Co-morbidities;64
12.1.10;Narcolepsy Has Both a Genetic and Environmental Link;64
12.1.11;Seasonality of Birth Gives Clues to Environmental Origins of Narcolepsy;65
12.1.12;Treatment Options Are Developing Rapidly;65
12.1.13;Looking Ahead: The Future of Epidemiology of Narcolepsy;65
12.2;References;66
13;Chapter 5;68
13.1;Narcolepsy in Childhood;68
13.1.1;Historical Notes;68
13.1.2;Introduction;68
13.1.3;Prevalence;68
13.1.4;Clinical Presentation;69
13.1.4.1;Pre-School-Age Children;69
13.1.4.2;School-Age Children;69
13.1.4.3;Histocompatibility Antigens and Human Narcolepsy;71
13.1.4.4;Hypocretin Deficiency;71
13.1.4.5;Two Threshold Hypothesis;71
13.1.4.6;Secondary Narcolepsy;72
13.1.5;Physical Examination;72
13.1.6;Diagnosis;72
13.1.6.1;Evaluating Sleepiness;72
13.1.6.2;Sleep Laboratory Testing;72
13.1.7;Differential Diagnoses;73
13.1.8;Management;75
13.1.8.1;Immunotherapy;77
13.1.9;Conclusions;77
13.2;References;77
14;Chapter 6;81
14.1;Narcolepsy in the Older Adult;81
14.1.1;Introduction;81
14.1.2;Narcolepsy Onset After Age 35;81
14.1.3;Delayed Diagnosis;82
14.1.4;Secondary or Symptomatic Narcolepsy;83
14.1.5;Implications of Narcolepsy in the Older Adult and Therapeutic Challenges;84
14.1.6;Conclusion;85
14.1.7;Case Example;86
14.2;References;87
15;Chapter 7;89
15.1;Diurnal and Nocturnal Sleep in Narcolepsy with Cataplexy;89
15.1.1;Introduction;89
15.1.2;Clinical Characteristics;89
15.1.3;Laboratory Characteristics;92
15.1.3.1;Daytime MSLT;92
15.1.3.2;Polysomnographical Findings;92
15.1.3.2.1;Sleep Structure;92
15.1.3.2.2;Sleep Microstructure;93
15.1.3.2.3;Periodic Limb Movements;93
15.1.3.2.4;Dissociated Sleep;93
15.1.3.2.5;Sleep Apnea/Hypopnea Syndrome;94
15.1.4;Conclusion;95
15.1.5;Diagn ostic criteria for narcolepsy with cataplexy [24];95
15.2;References;96
16;Chapter 8;98
16.1;Hypnagogic Hallucinations and Sleep Paralysis;98
16.1.1;Introduction;98
16.1.2;Hypnagogic Hallucinations;99
16.1.2.1;Clinical Features;99
16.1.2.2;Hypnagogic Hallucinations and Dreams;99
16.1.2.3;Hypnagogic Hallucinations and Schizophrenia;100
16.1.2.4;Hypnagogic Hallucinations and other Neurological Disorders;100
16.1.3;Sleep Paralysis;101
16.1.3.1;Clinical Features;101
16.1.3.2;Isolated Sleep Paralysis and Culturally Determined Interpretations;101
16.1.4;Neurobiology of Hypnagogic Hallucinations and Sleep Paralysis;102
16.1.4.1;General View;102
16.1.4.2;Neurobiology of Hallucinations;102
16.1.4.3;Neurobiology of Sleep Paralysis;103
16.1.5;Dissociated REM Phenomena in the AIM State Space Model;103
16.1.6;Hypnagogic Hallucinations in the AIM Model;104
16.1.7;Sleep Paralysis in the AIM Model;104
16.1.8;Treatment of Hypnagogic Hallucinations and Sleep Paralysis;105
16.1.8.1;Sodium Oxybate;105
16.1.8.2;Antidepressant Medications;106
16.1.9;Conclusive Remarks;106
16.2;References;107
17;Chapter 9;109
17.1;REM Sleep Behavior Disorder in Narcolepsy with Cataplexy;109
17.1.1;Introduction;109
17.1.2;Diagnostic Criteria for RBD;110
17.1.3;RBD in Narcoleptic Patients;111
17.2;References;112
18;Chapter 10;114
18.1;Narcolepsy and Other Comorbid Medical Illnesses;114
18.1.1;Introduction;114
18.1.2;Comorbid Eating Disorders and Obesity;114
18.1.3;Diabetes Mellitus;116
18.1.4;Psychiatric Disorders;117
18.1.5;Fibromyalgia;118
18.1.6;Migraines and Other Headaches;118
18.1.7;Cognitive Dysfunction;119
18.1.8;Psychosocial Comorbidities;120
18.1.9;Conclusion;120
18.2;References;121
19;Chapter 11;123
19.1;Humor Processing in Human Narcolepsy with Cataplexy;123
19.1.1;Introduction;123
19.1.2;Emotional Triggers of Cataplexy;123
19.1.2.1;Weak with Laughter;124
19.1.3;Anatomical Findings in Human Narcolepsy;125
19.1.4;Functional Abnormalities in Narcolepsy;126
19.1.5;Neural Correlates of Humor and Laughter;126
19.1.6;Neuroimaging of Humor Processing in Narcolepsy–Cataplexy;127
19.1.6.1;Abnormal Hypothalamic and Amygdala Activity;127
19.1.6.2;Implications for Models of Cataplexy;129
19.1.7;Conclusions;130
19.2;References;130
20;Chapter 12;133
20.1;Dreams in Patients with Narcolepsy;133
20.2;References;134
21;Chapter 13;136
21.1;Psychoanalysis and Narcolepsy;136
21.1.1;Psychoanalytic Approaches to Narcolepsy;136
21.1.2;Narcolepsy – The Rems Model;138
21.1.3;Narcolepsy and Neuroscientific Theory;139
21.1.4;Discussion;140
21.2;References;140
22;Chapter 14;142
22.1;Symptomatic Narcolepsy or Hypersomnia, with and Without Hypocretin (Orexin) Deficiency;142
22.1.1;Introduction;142
22.1.2;Definition of Symptomatic Narcolepsy and Its Overview;143
22.1.3;Anatomical Substrate for the Symptoms of Narcolepsy;150
22.1.4;Hypocretin Status in Various Neurological Conditions;151
22.1.4.1;Hypocretin Status in Symptomatic Narcolepsy–Cataplexy Associated with Distinct CNS Lesions;151
22.1.4.2;Status in Symptomatic Narcolepsy–Cataplexy and/or EDS Associated with Inherited Disorders;152
22.1.4.2.1;Prader-Willi Syndrome;152
22.1.4.2.2;Niemann-Pick Type C Disease;153
22.1.4.2.3;Myotonic Dystrophy;153
22.1.4.3;Status in Hypersomnia in Various Neurological Conditions: Focal/Generalized CNS Invasion;154
22.1.4.3.1;Cerebral Tumors;154
22.1.4.3.2;Infarctions;155
22.1.4.3.3;Encephalopathies;156
22.1.4.3.3.1;Wernicke’s Encephalopathy;156
22.1.4.3.3.2;Limbic Encephalopathy;156
22.1.4.3.3.3;Rasmussen’s Syndrome;157
22.1.4.3.3.4;Brain Stem Encephalitis;157
22.1.4.3.4;Neurodegenerative Disorders;158
22.1.4.3.4.1;Parkinson’s Disease;158
22.1.4.3.4.2;Dementia with Lewy Bodies;158
22.1.4.3.4.3;Progressive Supranuclear Palsy;158
22.1.4.3.4.4;Alzheimer’s Disease;159
22.1.4.3.4.5;Hungtington’s Disease;159
22.1.4.3.5;Head Trauma;159
22.1.5;CNS Diseases Mediated with Neuroimmune Mechanisms;161
22.1.5.1;Demyelinating Diseases;161
22.1.5.1.1;Multiple Sclerosis;161
22.1.5.1.1.1;Pathophysiological Considerations of MS Cases;162
22.1.5.1.2;Neuromyelitis Optica and Anti-AQP4 Antibody;163
22.1.5.1.2.1;Pathophysiological Considerations of MS Cases and NMO Cases;164
22.1.5.1.3;Acute Disseminated Encephalomyelitis;164
22.1.5.1.3.1;Pathophysiological Considerations of MS Cases and ADEM Cases;165
22.1.5.1.3.2;Conclusions of Demyelinating Disease;165
22.1.5.1.4;Guillain-Barre’s Syndrome;165
22.1.5.1.5;Paraneoplastic Syndrome;166
22.1.6;Conclusion;166
22.2;References;168
23;Chapter 15;173
23.1;Hypersomnias Other than Narcolepsy: Differential Diagnosis;173
23.1.1;Introduction;173
23.1.2;Positive Diagnosis of Hypersomnia;173
23.1.3;Differential Diagnosis of Hypersomnia;173
23.1.3.1;Clinical Approach;173
23.1.3.2;Laboratory Tests;174
23.1.3.2.1;Neurophysiological Tests;174
23.1.3.2.1.1;Multiple Sleep Latency Test;174
23.1.3.2.1.2;Maintenance of Wakefulness Test;174
23.1.3.2.2;Prolonged Polysomnographic Recording;175
23.1.3.2.3;Brain Imaging;175
23.1.3.2.4;Psychometric/Psychiatric Evaluation;175
23.1.4;Various Causes of Hypersomnia;175
23.1.4.1;Hypersomnia as a Direct Consequence of a Behaviour or of the Use of a Drug or Substance;175
23.1.4.1.1;Behaviorally Induced Insufficient Sleep Syndrome;175
23.1.4.2;Hypersomnia Due to Drug or Substance;175
23.1.4.3;Psychotropic Drugs;175
23.1.4.3.1;Anxiolytics and Hypnotics;175
23.1.4.3.2;Antidepressants;176
23.1.4.3.3;Neuroleptics;176
23.1.4.3.4;Stimulants;176
23.1.4.4;Cardiovascular Drugs;176
23.1.4.4.1;Antihypertensive Drugs;176
23.1.4.5;Drugs Used in Neurology;176
23.1.4.5.1;Antiparkinsonian Drugs;176
23.1.4.5.2;Antiepileptic Agents;176
23.1.4.6;Analgesics;176
23.1.4.6.1;Opioïds;176
23.1.4.6.2;Substances;176
23.1.5;Hypersomnias in the Context of Sleep-Related Breathing Disorders;176
23.1.5.1;Obstructive Sleep Apnoea Syndrome;176
23.1.5.2;Central Sleep Apnoea Syndrome;177
23.1.6;Hypersomnias of Central Origin;177
23.1.6.1;Idiopathic Hypersomnia;178
23.1.6.2;Recurrent Hypersomnias;179
23.1.7;Hypersomnias Associated with Various Medical Disorders;180
23.1.7.1;Hypersomnia Associated with Neurological Diseases;180
23.1.7.1.1;Brain Tumours;180
23.1.7.1.2;Stroke;180
23.1.7.2;Neurodegenerative Diseases;180
23.1.7.3;Neuromuscular Diseases;180
23.1.7.4;Multiple Sclerosis;181
23.1.7.5;Epilepsy;181
23.1.7.6;Chiari Malformation;181
23.1.7.7;Rare Inherited Disorders;181
23.1.7.8;Hypersomnia Associated with Infectious Disease;181
23.1.7.9;Hypersomnia Associated with Metabolic and Endocrine Diseases;181
23.1.7.10;Post-traumatic Hypersomnia;181
23.1.7.11;Hypersomnia not due to Substance or Known Physiological Condition (Psychiatric Hypersomnia);182
23.1.7.12;The Issue of Periodic Limb Movements in Sleep (PLMS) and Excessive Daytime Sleepiness;182
23.1.8;Conclusion;182
23.2;References;182
24;Section III Psychosocial Considerations;185
25;Chapter 16;186
25.1;Psychosocial Impact of Narcolepsy in Children and Adolescents;186
25.1.1;Preamble;186
25.1.2;Introduction;186
25.1.3;Review of the Literature;187
25.1.3.1;General Accounts;187
25.1.3.2;Childhood;188
25.1.3.2.1;Problems Related to Sense of Self and Others;188
25.1.3.2.2;Problems with Social Functioning;188
25.1.3.2.3;Problems with Mood and Family;188
25.1.3.2.4;Problems at School;188
25.1.3.3;Adolescence;188
25.1.3.4;Empirical Research Studies;188
25.1.4;Issues Arising;189
25.1.4.1;What Do We Know About the Psychosocial Problems of Children with Narcolepsy in General?;189
25.1.4.2;What Aspects Need to Be Considered in Describing Narcoleptic Children’s Psychosocial Problems and How Should They Be Assessed?;190
25.1.4.3;Which Aspects of Narcolepsy Determine the Likelihood, Nature and Extent of Psychosocial Difficulties?;190
25.1.4.4;What Resources Are Needed to Prevent or Offset the Psychosocial Difficulties to Which Children and Adolescents Are Apparently P;191
25.1.4.5;Are Preventive or Intervention Measures Effective in Reducing Psychosocial Complications to the Lives of Young People with Na;191
25.1.5;Conclusion;191
25.2;References;192
26;Chapter 17;193
26.1;Quality of Life and Psychosocial Issues in Narcolepsy;193
26.1.1;Introduction;193
26.1.2;QOL, Health-Related Quality of Life, and Health Status;193
26.1.3;Measuring Health-Related Quality of Life in Narcolepsy;195
26.1.3.1;The Short Form 36;195
26.1.3.2;Sickness Impact Profile;196
26.1.3.3;Functional Outcomes of Sleep Questionnaire;196
26.1.4;Points to Consider in Critical Appraisal of Research on HRQOL in Narcolepsy;196
26.1.5;Quality of Life in Narcolepsy;196
26.1.6;Health-Related Quality of Life;198
26.1.7;Narcolepsy and Support Groups;201
26.1.7.1;Why Do Some Members Not Attend Support Group Meetings?;202
26.1.7.2;What Characteristics Differentiate Those Who Attend Support Groups from Those Who Don’t?;203
26.1.7.3;Implications for Management of Narcolepsy;203
26.1.8;Social Support and Counseling;203
26.1.9;Transportation;204
26.1.10;Employment;204
26.1.11;Research Implications;205
26.2;References;205
27;Chapter 18;209
27.1;Narcolepsy, Intimacy and Sexuality;209
27.1.1;Symptoms;209
27.1.2;Impact of Symptoms as a Function of Developmental Stage;210
27.1.3;Case History: MAG;211
27.1.4;Case History: RIL;212
27.1.5;Case History: PR;213
27.1.6;Case History: Mrs. L.;215
27.1.7;Case History: Mr. B.;215
27.2;References;218
28;Chapter 19;220
28.1;Narcolepsy, Driving and Traffic Safety;220
28.1.1;Introduction;220
28.1.2;Narcolepsy and Accident Risk;220
28.1.3;Driving Performance of Untreated Narcolepsy Patients;220
28.1.4;Treatment Effects on Driving Performance;221
28.1.5;Interpretation of Driving Simulator Results;222
28.1.6;Decisions on Fitness to Drive;222
28.2;References;223
29;Chapter 20;225
29.1;Memory and Cognition in Narcolepsy;225
29.1.1;Main Symptoms of Narcolepsy;225
29.1.2;Dysfunction of the Hypocretin System in Narcolepsy;225
29.1.3;Neurotransmitter Dysfunction;225
29.1.4;Cognitive Deficits in Narcolepsy;226
29.1.4.1;Memory;226
29.1.4.2;Attention;227
29.1.4.3;Executive Functions;228
29.1.5;Summary and Discussion;229
29.2;References;230
30;Chapter 21;232
30.1;Medico-Legal Aspects of Disability in Narcolepsy;232
30.1.1;Introduction;232
30.1.2;Disability and Work Disability;232
30.1.3;Work Limitations in Narcolepsy;233
30.1.4;Impairment Variability;234
30.1.5;The Lack of a Clinical Severity Scale;234
30.1.6;The Contribution of Sleep Disorder Experts to Work Disability Determination;235
30.1.7;Conclusions;236
30.2;References;237
31;Chapter 22;239
31.1;Narcolepsy and Mental Health;239
31.1.1;Introduction;239
31.1.2;Cognitive Function;239
31.1.2.1;Methodological Issues;239
31.1.2.2;Attention;239
31.1.2.3;Memory;240
31.1.2.4;Executive Function;240
31.1.3;Mood Disorders;240
31.1.3.1;Anxiety and Depression;240
31.1.3.2;Psychosis;241
31.1.4;Other Psychological Aspects;241
31.1.4.1;Dreams and Hallucinations;241
31.1.4.2;Pain;241
31.1.4.3;Food Cravings;241
31.1.5;Functional Impairment;242
31.1.5.1;Age;242
31.1.5.2;Gender;243
31.1.5.3;Social Activities;243
31.1.5.4;Recreational Activities;243
31.1.5.5;Accidents;243
31.1.5.6;Education;243
31.1.5.7;Employment;243
31.1.6;Treatment;243
31.1.6.1;Explanation;243
31.1.6.2;Lifestyle Aspects;244
31.1.7;Drugs;244
31.1.7.1;Amphetamines;244
31.1.7.2;Modafinil;244
31.1.7.3;Sodium Oxybate;245
31.2;References;246
32;Section IV Management;248
33;Chapter 23;249
33.1;Overview of Management of Narcolepsy;249
33.1.1;Introduction;249
33.1.2;Symptoms of Narcolepsy;249
33.1.2.1;Sleepiness or Excessive Daytime Sleepiness (EDS);250
33.1.2.2;Cataplexy;250
33.1.2.3;Hypnagogic or Hypnopompic Hallucinations;250
33.1.2.4;Sleep Paralysis;251
33.1.3;Treatments of Narcolepsy;251
33.1.3.1;Pharmacological Treatment of Daytime Sleepiness with Amphetamine-Like Compounds;251
33.1.3.2;Modafinil and Armodafinil;254
33.1.3.3;Other Wake Promoting Agents;255
33.1.3.4;Sodium Oxybate and Treatment of Disturbed Nocturnal Sleep;255
33.1.3.5;Antidepressants and the Pharmacological Treatment of Cataplexy;256
33.1.3.6;Treatment of Sleep Paralysis and Hypnagogic Hallucinations;258
33.1.4;Future Treatment Options;258
33.1.5;Conclusion;260
33.2;References;260
34;Chapter 24;264
34.1;Modes of Action of Drugs Related to Narcolepsy: Pharmacology of Wake-Promoting Compounds and Anticataplectics;264
34.1.1;Introduction;264
34.1.2;Neurobiology of Wakefulness and Modes of Action of Amphetamines and Modafinil on EDS;264
34.1.2.1;Neurobiology of Wakefulness;265
34.1.2.2;Modes of Action of Amphetamines;266
34.1.2.2.1;Molecular Targets of Amphetamine Action;266
34.1.2.2.2;Dopaminergic Neurotransmission and EEG Arousal;269
34.1.2.2.3;Anatomical Substrates of Dopaminergic Effects;271
34.1.3;Modes of Action of Modafinil/Armodafinil;271
34.1.3.1;Other Wake-Promoting Compounds;274
34.1.3.2;Mechanisms of Action of Tricyclic anti-Cataplectics;275
34.1.3.3;Preferential Involvement of Adrenergic Neurotransmission in the Control of Canine Cataplexy;275
34.1.3.4;Receptor Subtypes Involved in the Control of Cataplexy;277
34.1.3.5;MAOIs;277
34.1.3.6;GHB;278
34.1.4;Conclusion;280
34.2;References;280
35;Chapter 25;284
35.1;Modafinil/Armodafinil in the Treatment of Narcolepsy;284
35.1.1;The Introduction of Modafinil/Armodafinil;284
35.1.2;Treatment of Narcolepsy by Modafinil;284
35.1.3;Armodafinil;286
35.1.4;Efficacy of Armodafinil in Narcolepsy;286
35.1.5;Mode of Action of Modafinil/Armodafinil;287
35.1.6;Safety and Adverse Event Data with Modafinil/Armodafinil;287
35.1.7;Summary;289
35.2;References;289
36;Chapter 26;292
36.1;Sodium Oxybate in the Treatment of Narcolepsy;292
36.1.1;Conservative Treatment of Narcoleptic Symptoms;292
36.1.2;Gammahydroxybutyrate (GHB)/Sodium Oxybate (SO);292
36.1.2.1;Pharmacology;292
36.1.2.2;Pharmacokinetics;293
36.1.3;Efficacy of SO in Treating Symptoms of Narcolepsy;293
36.1.3.1;Cataplexy;293
36.1.3.2;Excessive Daytime Sleepiness;293
36.1.3.3;Sleep;294
36.1.4;Quality of Life;294
36.1.5;Adverse Events;294
36.1.6;Contraindications;295
36.1.7;Treatment Recommendations;295
36.1.8;Conclusion;296
36.2;References;296
37;Chapter 27;297
37.1;Emerging Treatments for Narcolepsy;297
37.1.1;Introduction;297
37.1.2;Hypocretin-Based Treatments;297
37.1.3;Hypocretin Gene Therapy;299
37.1.4;Hypocretin Cell Transplants;299
37.1.5;Stem Cell Transplantation;300
37.1.6;Hypocretin-Receptor Agonists;300
37.1.7;Immunotherapy;300
37.1.8;Thyrotrophin Releasing Hormone Agonists;301
37.1.9;Histamine 3 Receptor (H3) Antagonists;302
37.1.10;Modified Current Medical Therapies;303
37.1.11;Combination Therapies;303
37.1.12;Others;304
37.1.13;Conclusions;305
37.2;References;305
38;Chapter 28;308
38.1;Non-pharmacologic Treatments of Narcolepsy;308
38.1.1;Introduction;308
38.1.2;Excessive Daytime Somnolence and Involuntary Sleep Episodes;308
38.1.2.1;Scheduled Naps and EDS;309
38.1.2.2;Dietary Manipulation in Managing Excessive Daytime Sleepiness;310
38.1.2.3;Exercise;311
38.1.3;Disrupted Nighttime Sleep;311
38.1.4;Cataplexy;312
38.1.5;Sleep Paralysis;312
38.1.6;Hypnagogic Hallucinations and Nightmares;312
38.1.7;Cognitive Complaints;312
38.1.8;Psychiatric Co-morbidities and Management;313
38.1.9;Interpersonal Difficulties and Limited Psychosocial Support;314
38.1.10;Work and Education Difficulties;314
38.1.11;Difficulties with Driving and Home Chores;315
38.1.12;Conclusion;315
38.2;References;315
39;Index;318