1 To Grace Zamudio and Zoe Lee-Chiong. 2 Preface Carpe noctem. Teofilo Lee-Chiong MD Professor of Medicine Division of Sleep Medicine National Jewish Health Denver, Colorado University of Colorado Denver School of Medicine Denver, Colorado Chief Medical Liaison Philips Respironics Murrysville, Pennsylvania 3 Abbreviations AHI Apnea-hypopnea index BPAP Bi-level positive airway pressure CPAP Continuous positive airway pressure CSA Central sleep apnea ECG Electrocardiography EEG Electroencephalography EMG Electromyography EOG Electro-oculography FEV1 Forced expiratory volume in 1 second GABA Gamma-aminobutyric acid N1 NREM stage 1 sleep N2 NREM stage 2 sleep N3 NREM stages 3 (and 4) sleep NREM Non-rapid eye movement O2 Oxygen OSA Obstructive sleep apnea PaCO2 Partial pressure of arterial carbon dioxide PaO2 Partial pressure of arterial oxygen REM Rapid eye movement sleep SaO2 Oxygen saturation SOREMP Sleep onset REM period 4 Table of contents Introduction 15 Neurobiology of sleep 16 Neural systems generating wakefulness 16 Neural systems generating NREM sleep 16 Neural systems generating REM sleep 16 Main neurotransmitters 17 Acetylcholine 17 Adenosine 17 Dopamine 17 Gamma-aminobutyric acid 17 Glutamate 17 Glycine 17 Histamine 18 Hypocretin 18 Melatonin 18 Norepinephrine 18 Serotonin 18 Physiology during sleep 19 Autonomic nervous system 19 Respiratory system 19 Respiratory patterns 19 Cardiovascular system 19 Gastrointestinal system 20 Renal and genito-urinary systems 20 Endocrine system 20 Growth hormone 20 Thyroid stimulating hormone 20 Cortisol 20 Melatonin 21 Testosterone 21 Insulin 21 Leptin 21 Ghrelin 21 Musculoskeletal system 21 Pupillary changes 21 5 Immune system 21 Thermoregulation 21 Metabolic rate 22 Dreaming 22 Regulation of sleep and waking 23 Sleep homeostasis 23 Circadian neurosystem 23 Suprachiasmatic nucleus 24 Melatonin 25 Sleep deprivation 26 Consequences 26 Central nervous system 26 Autonomic nervous system 26 Cognition 26 Respiratory system 26 Endocrine system 26 Metabolism 26 Immune system 26 Behavioral and psychiatric effects 26 Polysomnographic features 27 Insomnia 28 General changes in sleep architecture 28 Prevalence 28 Mechanisms 28 Risk factors 28 Consequences 29 Classification 29 Specific causes 29 Adjustment insomnia 29 Altitude insomnia 30 Behavioral insomnia of childhood 30 Limit-setting sleep disorder 30 Sleep-onset association disorder 30 Fatal familial insomnia 30 Idiopathic insomnia 31 Inadequate sleep hygiene 32 Paradoxical insomnia 32 Psychophysiologic insomnia 32 6 Medications 33 Evaluation of insomnia 33 Polysomnographic features 33 Therapy of insomnia 33 Sleep hygiene 33 Cognitive-behavioral treatments for insomnia 34 Cognitive therapy 34 Paradoxical intention 34 Relaxation techniques 35 Sleep restriction 35 Stimulus control 35 Multi-component behavioral therapy 35 Pharmacotherapy of insomnia 35 Benzodiazepines 37 Benzodiazepine receptor agonists 37 Melatonin receptor agonist 37 Antidepressants and antipsychotics 38 Non-prescription hypnotic agents 38 Melatonin 38 Botanical compounds 38 Excessive sleepiness 39 Prevalence 39 Consequences 39 Mechanisms 39 Specific causes of excessive sleepiness 39 Insufficient sleep syndrome 39 Idiopathic hypersomnia 40 Recurrent hypersomnia 40 Medical, neurological or psychiatric 41 Medications 41 Evaluation of excessive sleepiness 41 Subjective tests of sleepiness 41 Polysomnography 41 Multiple sleep latency test 41 Maintenance of wakefulness test 41 Effective countermeasures for sleepiness 42 Narcolepsy 43 Excessive sleepiness 43 Cataplexy 43 7 Status cataplecticus 43 Sleep hallucinations 44 Sleep paralysis 44 Sleep disturbance 44 Other important clinical features 44 Consequences 44 Prevalence 44 Clinical course 44 Pathophysiology 45 Narcolepsy without cataplexy 45 Secondary narcolepsy 45 Evaluation 46 Polysomnographic features 46 Multiple sleep latency test 46 Maintenance of wakefulness test 46 Cerebrospinal fluid hypocretin-1 46 Human leukocyte antigen typing 47 Therapy 47 Excessive sleepiness 47 Sleep disturbance 47 Cataplexy 47 Obstructive sleep apnea 48 Apnea 48 Hypopnea 48 Respiratory effort-related arousal 48 Complex sleep apnea 48 Apnea-hypopnea index 48 Prevalence 48 Pathophysiology 49 Risk factors 49 Clinical features 49 Physical examination 50 Consequences 50 Evaluation 51 Polysomnographic features 51 Multiple sleep latency test 51 Upper airway imaging studies 52 Therapy 52 8 General measures 52 Positional therapy 52 Oxygen therapy 52 Pharmacologic treatments 52 Positive airway pressure therapy 52 Oral devices 55 Upper airway surgery 56 Residual sleepiness 57 Upper airway resistance syndrome 57 Central sleep apnea 59 Polysomnography 59 Classification 59 Primary central sleep apnea 60 Cheyne Stokes respiration 60 High altitude periodic breathing 60 Medication use 61 Congestive heart failure 61 Sleep-onset central apneas 61 During positive airway pressure titration 61 Therapy of central sleep apnea 61 Hypoventilation syndromes 63 Mechanisms 63 Medical and neurological disorders 63 Idiopathic alveolar hypoventilation 63 Congenital central alveolar hypoventilation 63 Polysomnography 64 Therapy 64 Parasomnias 65 Disorders of arousal 65 Parasomnias occurring during REM sleep 65 Catathrenia 65 Confusional arousals 66 Exploding head syndrome 66 Isolated sleep paralysis 66 Nightmare disorder 67 REM sleep behavior disorder 67 Sleep enuresis 69 9 Sleep-related eating disorder 69 Sleep terrors 70 Sleepwalking 70 Restless legs syndrome and Periodic limb movement disorder 71 Prevalence 71 Classification 71 Risk factors 71 Consequences 72 Evaluation 72 Suggested immobilization test 72 Polysomnography 72 Differential diagnosis 72 Pathophysiology 72 Therapy 73 Dopaminergic agents 73 Benzodiazepines 73 Opioid agents 73 Anticonvulsant agents 73 Periodic limb movements during sleep 73 Periodic limb movement disorder 74 Circadian rhythm sleep disorders 75 Advanced sleep phase syndrome 75 Delayed sleep phase syndrome 75 Free-running circadian rhythm syndrome 76 Irregular sleep-wake rhythm syndrome 77 Jet lag 77 Shift work sleep disorder 78 Medical disorders 79 Asthma 79 Chronic obstructive pulmonary disease 79 Cardiac arrhythmias 80 Chronic pain syndromes 80 Congestive heart failure 80 Coronary artery disease 81 Diaphragm paralysis 81 End-stage renal disease 81 Fibromyalgia 81 10 Gastroesophageal reflux 81 Human immunodeficiency virus infection 82 Hypertension 82 Restrictive pulmonary diseases 83 Sleeping sickness 83 Neurological disorders 84 Alzheimer’s dementia 84 Amyotrophic lateral sclerosis 84 Attention deficit hyperactivity disorder 84 Blindness 84 Cerebral degenerative disorders 84 Down syndrome 85 Headache syndromes 85 Multiple system atrophy 86 Neuromuscular disorders 86 Parkinson disease 86 Seizure disorders 87 Stroke 88 Psychiatric disorders 89 Anxiety disorders 89 Acute stress disorder 89 Generalized anxiety disorder 89 Post-traumatic stress disorder 90 Panic disorder 90 Eating disorders 90 Mood disorders 90 Major depressive episode 90 Manic episode 90 Hypomanic episode 91 Mixed episode 91 Major depressive disorder 91 Bipolar disorder 91 Seasonal affective disorder 91 Atypical depression 92 Schizophrenia 92 Miscellaneous sleep disorders 93 Alcohol-dependent sleep disorder 93 Alternating leg muscle activation 93 11 Benign sleep myoclonus of infancy 93 Environmental sleep disorder 93 Fragmentary myoclonus 94 Hypnagogic foot tremor 94 Hypnotic-dependent sleep disorder 94 Long sleeper 94 Propriospinal myoclonus at sleep onset 95 Rhythmic movement disorder 95 Short sleeper 95 Sleep hyperhidrosis 96 Sleep-related abnormal swallowing 96 Sleep-related bruxism 96 Sleep-related choking syndrome 97 Sleep-related laryngospasm 97 Sleep-related neurogenic tachypnea 97 Sleep-related painful erections 97 Sleep-related leg cramps 98 Sleep start 98 Sleep talking 98 Snoring 98 Stimulant-dependent sleep disorder 99 Sudden infant death syndrome 99 Sudden unexplained nocturnal death 99 Infants and children 100 Milestones in sleep architecture 100 Sleep stages in the first 6 months of age 100 Sleep stages after 6 months of age 101 Milestones in sleep-related behaviors 101 Aggregate hours of sleep per day 101 Insomnia in children 102 Excessive daytime sleepiness 103 Childhood obstructive sleep apnea 104 Apnea of prematurity 104 Infant sleep apnea 105 Apparent life-threatening event 105 Snoring 105 Aging 106 Physiologic changes with aging 106 12 Changes in sleep architecture 106 Insomnia 106 Sleep in women 107 Obstructive sleep apnea 107 Central sleep apnea 107 Menstruation 107 Polycystic ovarian syndrome 108 Pregnancy 108 Postpartum period 108 Menopause 108 Medications and their effects on sleep 110 Alcohol 110 Antidepressants 110 Antipsychotics 111 Drugs of abuse 111 Hypnotic agents 111 Opioids 111 Stimulants 112 Agents that can cause insomnia 112 Agents that can cause sedation 112 Agents causing restless legs syndrome 112 Agents causing REM behavior disorder 112 Polysomnography and other sleep tests 113 Indications 113 Polygraph 113 Derivation 113 Electroencephalography 114 Electroencephalographic waveforms 114 Electro-oculography 115 Chin electromyography 115 Electrocardiography 115 Measuring airflow 116 Measuring respiratory effort 116 Measuring oxygenation and ventilation 116 Identifying snoring 117 Electromyography of the anterior tibialis 117 Scoring sleep stages 117 Adult sleep stages 117 13 Stage wake 117 Stage N1 sleep 118 Stage N2 sleep 119 Stage N3 sleep 120 Stage REM sleep 121 Major body movements 121 Pediatric sleep stage scoring rules 122 Sleep scoring