Autonomic Nervous System and Sleep. Order and Disorder

Foreword
Preface
Acknowledgments
Contents
Contributors
	Editors
	Contributors
1: Introduction
	References
Part I: Basics
	2: Central Autonomic Network
		Overview
		Neurotransmission and Effector Mechanisms of the Central Autonomic Control
			Inputs and Signaling in the Central Autonomic Network
			Outputs of the Central Autonomic Network
			Segmental Control of Preganglionic Neurons
		Lower Brainstem Areas Controlling Cardiovascular, Respiratory, and Gastrointestinal Functions
			Nucleus of the Solitary Tract
			Rostral Ventrolateral Medulla
			Rostral Ventromedial Medulla and Medullary Raphe
			Medullary Respiratory Circuits
			Parabrachial Nuclear Complex
			Pelvic Organ Stimulating Center
		Upper Brainstem and Behavioral State-Dependent Regulation of Autonomic Output
			Periaqueductal Gray
			Locus Coeruleus
			Pedunculopontine Tegmental Nucleus
		Hypothalamus: Pattern Generator for Basic Survival Functions
			Functional Organization
			Autonomic Output
		Limbic Areas Involved in Emotion, Cognition, and Autonomic Control
			Amygdala
			Insular Cortex
			Anterior and Midcingulate Cortices
		Summary
		References
	3: Functional Neuroanatomy of the Peripheral Autonomic Nervous System
		Introduction
		The Sympathetic Efferent Organization
		The Parasympathetic Efferent Organization
		The Enteric Nervous System
		Autonomic Afferent Fibers
		Pharmacology and Physiology of the ANS (See Also Chap. 5)
			Physiology
		Clinico-Anatomical Correlation
		Comments (Based on Clinico-Anatomo-Physiological Correlation)
		References
	4: Functional Neuroanatomy and Mechanism of Sleep
		Introduction and Historical Note
		General Comments
			Historical Note
		Neuroanatomical Substrates and Control of Wake-Sleep States
			Neuroanatomical Substrates and Control of Wakefulness
			Neuroanatomical Substrates of NREM Sleep
			Neuroanatomical Substrates of REM Sleep
			Animal Models
			Essential Physiological Components of REM Sleep
		Summary of Mechanisms of Sleep
		References
	5: Physiological Changes in the Autonomic Nervous System During Sleep
		Autonomic Function and Behavioral States
		Sleep, Autonomic Function, and Respiratory Regulation
		Sleep, Autonomic Function, and Cardiovascular Regulation
		Sleep, Autonomic Function, and the Regulation of Body Temperature and Energy Expenditure
		Sleep and Autonomic Function Within the Frame of Physiological Regulation
		References
	6: Brain–Heart Interaction: Cardiovascular Reflexes
		Introduction
		Sleep and Cardiovascular Control: A Matter of Time Scales
			The Time Scale of Minutes: Sleep Macrostructure
			The Time Scale of Seconds: Sleep Microstructure
			The Time Scale of Hours: Circadian Sleep Rhythm
		The Role of the ABR in the Hierarchic Organization of Cardiovascular Control
			The ABR and Other Cardiovascular Reflexes Constitute the Intermediate Level of Cardiovascular Control
			The ABR Modulates Tissue-Specific Local Mechanisms That Constitute the Lowest Level of Cardiovascular Control
			Central Autonomic Commands Represent the Highest Level of Cardiovascular Control and Modulate the ABR
		The ABR During Sleep
			Insights from the Relationship Between Controlled and Instrumental Variables of the ABR During Sleep at Different Time Scales
			Sleep Modifies the Integration Between the ABR and Central Autonomic Commands at Different Time Scales
			Central Autonomic Commands Change ABR Properties During Sleep
		The Functional Neuroanatomy of the ABR and Central Autonomic Commands in Different Wake–Sleep States
			Functional Neuroanatomy of the ABR and Central Autonomic Commands During Wakefulness
			Functional Neuroanatomy of the Direct Cardiovascular Effects of Sleep-Related Central Autonomic Commands
			Functional Neuroanatomy of the Modulation of ABR Properties by the Central Autonomic Commands During Sleep
		References
	7: Sleep and Circadian Regulation of the Autonomic Nervous System
		Sleep from an Integrated Perspective: Central and Autonomic Nervous System Interactions
		Sleep ANS Control: Sleep Stage Modulation
		Sleep ANS Control: Circadian Modulation
		Sleep ANS Control: The Falling Asleep Period
		Sleep ANS Control: Developmental Maturation and Sex Differences
		Sleep ANS Control: Female-Specific Hormonal Factors
		Potential Advancements in Understanding Sleep ANS Control: Sleep-Tracking Technology
		References
	8: Nocturnal Arousal Phenomenon and the Autonomic Nervous System
		The House of Sleep
		Beyond the Sleep Stages
		Surrogate Markers of Cortical Arousals
		Measuring Heart Rate Variability: The R-R Interval
		R-R
		Cardiopulmonary Coupling and CAP
		Sleep Protection Insurance
		References
Part II: Laboratory Evaluation
	9: Methods of Laboratory Evaluation of the Autonomic Nervous System in Wakefulness and Sleep
		Laboratory Evaluation of the Autonomic Nervous System (ANS) in Wakefulness
			Clinically Validated Methods for Evaluation of Sudomotor Function
				Quantitative Sudomotor Axon Reflex Test (QSART)
				Sympathetic Skin Response
				Heart Rate Response to Deep Breathing (HRDB)
				Valsalva Maneuver (VM)
				Head-Up Tilt (HUT)
			Non-clinically Validated Tests of Autonomic Functioning
				Lower Body Negative Pressure (LBNP)
				Isometric (Static) Handgrip
			Techniques for Measuring Sympathetic Nerve Activity (Autonomic Functioning)
				Microneurography
			Tests of Sympathetic Integrity
				Neuroimaging Tests
				Neuropharmacological Tests
				Neurochemical Tests
			Laboratory Evaluation of the ANS During Sleep (Rationale and Measurement Techniques for Studying ANS Functions During Sleep)
			Respiration (See Also Chap. 11)
				Airflow Sensing
				Blood Gas Measurement
				Respiratory Effort (Movement and Volume)
			Blood Pressure
				24-Hour Ambulatory Blood Pressure
				Methods for Evaluating Asleep Blood Pressures
			Neuroendocrine
				Melatonin
				Cortisol, Norepinephrine, and Epinephrine
			Body Temperature
				Choosing a Site
				Equipment
		References
	10: Interpreting Heart Rate Variability in Sleep: Why, When, and How?
		Introduction
		Is the Autonomic Nervous System Really Autonomous?
		Heart Rate Variability: The Modelling Approach
		Heart Rate Variability: A Synopsis
		Sleep: A Simplified View
		The Close Link Between Sleep and the Autonomic Nervous System
		Heart Rate Variability in Sleep Disorders
		HRV and Sleep in the Clinic
		HRV and the Clinic: Importance of Models
		Conclusion: HRV, Sleep, and Digital Medicine
		References
	11: Laboratory Evaluation of Sleep Disorders: PSG, MSLT, MWT, and Actigraphy
		Introduction
		Techniques to Measure Sleep-Disordered Breathing
			Polysomnography
		Tests for Daytime Hypersomnolence
			Multiple Sleep Latency Testing
			MSLT Guidelines
			MSLT Interpretation, Limitations, and Pitfalls
			Maintenance of Wakefulness Testing
		Techniques to Measure Body Movements/Sleep-Wake Cycles
			Actigraphy
			Consumer-Oriented Sleep Technology
		Brief Review of Sleep Laboratory Findings in Selected Cases of Autonomic Failure
			Multiple System Atrophy (Formerly Known as the Shy-Drager Syndrome)
			Postural Tachycardia Syndrome (POTS)
			Familial Dysautonomia (FD, Riley-Day Syndrome)
			Diabetic and Amyloidotic Polyneuropathies and Guillain-Barre Syndrome
			Neurodegenerative Diseases (Synucleopathies, e.g., PD and DLBD)
			Fatal Familial Insomnia (FFI)
		References
Part III: Clinical Aspects
	12: An Approach to a Patient with Suspected Autonomic and Sleep Dysfunction
		Introduction
		Classification of Dysautonomia
		General and Specific Clinical Manifestations of Autonomic Dysfunction and Physiology of Orthostatic Blood Pressure Control
		History and Physical Examination
			Step 1. History
			Step 2. Physical Examination
			Step 3. General Physical Examination
			Step 4. Special Examination of Each System
		Clinical Scales and Questionnaires
		Autonomic Function and Other Laboratory Tests
		Brief Description of Some Important and Unusual Dysautonomic Entities
			Summary of ANS Dysfunction in Narcolepsy–Cataplexy
		Fits and Faints, Including Syncope and Other Mimics of Autonomic Dysfunction
			Types of Syncope (see Box 12.9) [15, 124, 125, 127]
			Drop Attacks
			Carotid Sinus Supersensivity Syncope
			Mastocytosis-Related Syncope
			Breath-holding Spells
			Other rare types in infants and children
		Clinical–Anatomical–Laboratory Correlations with Case Examples
		Principles of Therapy
		References
	13: Obstructive Sleep Apnea in Adults and the Autonomic Nervous System
		Introduction
		Comorbidities Associated with OSA
		The Autonomic Nervous System in OSA
			Intrathoracic Pressure Changes
			Additional Mechanisms
		Treatment of OSA
			Cardiovascular Autonomic Consequences of Treating OSA
			Other Clinical Outcomes of Treating OSA
		Conclusions
		References
	14: Primary Insomnia and Dysautonomia
		Introduction
		Primary Insomnia and Cardiovascular Disease: The State of the Science
			Primary Insomnia and Cardiovascular Autonomic Control: The Neurophysiological Basis
				Blood Pressure and Heart Rate
				Sympathoadrenal Activity and Imbalance Between the Sympathetic and Parasympathetic Activities
			Primary Insomnia and Cardiovascular Risk: The Experimental Data
		Insomnia Phenotypes and Cardiovascular Disease Risk
			Insomnia with Short Sleep Duration
			Insomnia in Menopausal Transition State
			Insomnia and Cardiovascular Diseases: The Link with Hypertension
		Conclusion and Future Directions
		References
	15: Restless Legs Syndrome, Periodic Limb Movements, and Dysautonomia
		Restless Legs Syndrome: Description, Diagnosis, and Prevalence
			Description
			Diagnosis
			Prevalence
		Periodic Limb Movements During Sleep and Wakefulness
		Association Between RLS and Cardiovascular Disease
			Epidemiological Cross-Sectional Studies
			Longitudinal Epidemiological Studies
		Association Between PLMS and Cardiovascular Disease
		Possible Mechanisms Linking RLS and PLMS with CVD
			Sleep Disruptions
			PLMS-Related Cardiovascular Changes
			Increased Sympathetic Activity
		Conclusion
		References
	16: NREM-Related Parasomnias and Dysautonomia
		Introduction
		The Role of Arousal
		Autonomic Activity
		Autonomic Activation in the Differential Diagnosis Between NREM Parasomnias and Epilepsy
		Conclusion
		References
	17: Narcolepsy, Idiopathic Hypersomnia, and Dysautonomia
		Introduction
		Dysautonomia in Narcolepsy Type I
			Pathophysiological Aspects: Orexin and Autonomic Nervous System
				Neuroanatomy
				Pharmacological and Animal Studies
			Human Studies
				Autonomic Symptoms
				Arterial Blood Pressure
				Heart Rate and Its Variability
				Muscle Sympathetic Nerve Activity
				Other Measures of Autonomic Disturbances
				Comorbid Disorders
				Dysautonomia During Cataplexy
		Dysautonomia in Other Central Disorders of Hypersomnolence
		Conclusion and Perspectives
		References
	18: Fatal Familial Insomnia
		Introduction
		Fatal Familial Insomnia
			Historical Notes
			Demographics
			Features
			Dysfunction of the Autonomic Nervous System: Unbalanced Autonomic Control and Sympathetic Hyperactivation
				Cardiovascular
					Blood Pressure and Heart Rate
					Hormonal and Catecholamine Circadian Rhythms
					Pharmacological Tests Evaluating Autonomic Function
				Breathing
				Body Temperature
				Gastrointestinal
				Genitourinary
				Salivation, Lacrimation, and Pupillary Tone
				Sporadic Familial Insomnia
		Agrypnia Excitata in Other Neurological Disorders
			Morvan Syndrome
			Delirium Tremens
			Whipple Disease
		FFI and Agrypnia: The Role of the Thalamus Not Only in Sleep–Wake Organization, But Also in Autonomic Control
		Conclusion: From Homeostasis to Allostatic Overload
		References
	19: Sleep-Related Epilepsy, Dysautonomia, and Sudden Nocturnal Death
		Sleep-Related Epilepsy
		Seizures Occurring Predominantly or Exclusively During Sleep Associated with ANS Dysfunction
			Sleep-Related Hypermotor Epilepsy
				Epidemiology
				Genetic Forms of Sleep-Related Hypermotor Epilepsy
				Symptomatic Forms
				Clinical Features
				Sleep-Related Hypermotor Epilepsy: Always a Frontal Onset?
				Electroencephalographic Features
				Treatment
				SHE and Autonomic System
			Benign Epilepsy with Centrotemporal Spikes (BECTS)
			Panayiotopoulos Syndrome
			Juvenile Myoclonus Epilepsy
			West Syndrome
			Lennox–Gastaut Syndrome
			Electrical Status Epilepticus During Slow Sleep (ESES)
			Sudden Unexpected Death in Epilepsy (SUDEP)
				Definitions
				Epidemiology
				Risk Factors for SUDEP
				Genetics of SUDEP
				SUDEP and Sleep
				Longstanding Effects of Sleep and Epilepsy Interaction: Implications for SUDEP
				Seizures During Sleep: Precipitating Factors for SUDEP
				Sleep Disorders Comorbidities in Epileptic Patients: Implications for SUDEP
				Prevention of SUDEP
		References
	20: The Postural Tachycardia Syndrome (PoTS)
		Introduction
		Clinical Features
		Diagnosis
			Autonomic Investigations
			Differential Diagnosis
			Non-autonomic Investigations
		Pathophysiology
		Overlapping Features
		Treatment
		Conclusion
		References
	21: Congenital Central Hypoventilation Syndrome
		Introduction and History
		Epidemiology and Genetics
			Genotype–Phenotype Relationship
		Clinical Manifestations and Natural History
			Hypoventilation and Central Apnea in CCHS
			Dysautonomia in CCHS
			Neurocristopathy in CCHS
			Late-Onset Congenital Central Hypoventilation Syndrome
			Other Genetic Hypoventilation Syndromes Associated with Autonomic Dysfunction
			Sudden Infant Death Syndrome
		Hypothesized Pathophysiology of PHOX2B Mutation
			Disordered Sleep and General Dysautonomia
		Diagnosis
			Polysomnography
			Other Diagnostic Considerations
			Differential Diagnosis
		Current Management Strategies
			Ventilatory Management
			Other Ventilatory Options
			Management of Autonomic Nervous System Dysfunction
			Other Management Considerations
			Management Considerations in a Thriving CCHS Cohort
			Annual Surveillance in CCHS
			Outcomes
		Future Directions in Research and Therapeutics
		Conclusions
		References
			Further Reading
	22: Autonomic Dysfunction in Parasomnias of REM Sleep
		Introduction
		Anatomy of REM Sleep and the Central Autonomic Network
		Rapid Eye Movement Sleep Behavior Disorder
		Autonomic Symptoms in Patients with RBD
		Objective Markers of Autonomic Impairment in RBD
			Heart Rate Variability
			Cardiac Scintigraphy
			Cardiovascular Reflex Testing and Blood Pressure Analysis
			Gastrointestinal Motility
			Biopsy and Tissue Analysis
			Nightmare Disorder and Trauma-Associated Sleep Disorder
		Conclusions
		References
	23: Multiple System Atrophy
		Introduction
		Epidemiology and Natural History
		Clinical Features
		Clinical Assessment of MSA
		Diagnosis
		Current Therapies
		References
	24: Pure Autonomic Failure
		Introduction
		Clinical Features
			Symptoms
			Signs
		Pathology
			Antemortem Pathology
		Diagnosis
			Orthostatic Hypotension due to Adrenergic Failure
			Additional Visceral Involvement
			Exclusion of Other Causes of Autonomic Dysfunction
			Distinguishing Postganglionic (e.g., PAF) from Preganglionic/Central Autonomic Failure (e.g., MSA)
			Phenoconversion and Predictors
		Treatment
			Pharmacologic Interventions
		Conclusion
		References
	25: Acute Autonomic Neuropathy
		What Is an Acute Autonomic Neuropathy?
		When to Think of an Acute Autonomic Neuropathy
		How to Diagnose Acute Autonomic Neuropathies
		Additional Tests
		Antibody Testing
		How to Differentiate Among a Variety of Acute Autonomic Neuropathies?
			Autoimmune Autonomic Ganglionopathy (AAG)
		Seronegative Autoimmune Autonomic Ganglionopathy
		Acute Autonomic and Sensory Neuropathy
		Limited Autonomic Neuropathy
		Paraneoplastic Autonomic Neuropathy
		Other Important Conditions Causing Autonomic Neuropathies
			Lambert–Eaton Myasthenic Syndrome (LEMS)
			Immune Encephalitides
			Anti-NMDA Receptor Encephalitis
			Dipeptidyl-Peptidase-Like Protein-6 (DPPX)
			Guillain–Barré Syndrome (GBS)
			Sjögren Syndrome
		Summary
		References
	26: Familial Dysautonomia
		Introduction
		Phenotype of Familial Dysautonomia
			Chemoreflex Failure
			Sleep-Disordered Breathing
			Sudden Unexpected Death During Sleep (SUDS)
		Therapeutic Implications
			Noninvasive Ventilation
			Role of Potassium
		Conclusions
		References
	27: Diabetic Autonomic Neuropathy
		Diabetic Autonomic Neuropathy
		Cardiac Autonomic Neuropathy
		Gastrointestinal Neuropathy
		Urogenital Autonomic Neuropathy
		Sudomotor Dysfunction
		Ocular Manifestations
		References
	28: Spinal Cord Lesion and Dysautonomia
		Introduction
			Autonomic Features in Patients with Spinal Cord Lesions
		Cardiovascular Dysfunction
		Complication and Management of Autonomic Dysreflexia
		Thermodysregulation
		Gastrointestinal Dysfunction
		Genito-urinary Dysfunction
		Sleep Disorders in SCI
		Assessing Cardiovascular Autonomic Function in Patients with Spinal Cord Lesion
			Autonomic Screening Tests
			Liquid Meal Challenge Tests
			Exercise Testing
			Ambulatory 24 BP and HR Monitoring
			Plasma Catecholamines
		Conclusion
		References
	29: Dysautonomia and Sleep Dysfunction in Pediatric Practice
		Introduction
		Physiological Changes in Cardiorespiratory Control
		Sudden Infant Death Syndrome (SIDS)
		Brief Resolved Unexplained Events (BRUE)
		Congenital Central Hypoventilation Syndrome (CCHS)
		Central Hypoventilation Secondary to Other Brainstem Lesions
		Rapid-Onset Obesity with Hypoventilation, Hypothalamic, Autonomic Dysregulation (ROHHAD)
		Autonomic Dysfunction in Pediatric Primary Hypersomnia Syndromes
		Conclusion
		References
	30: Autonomic Regulation of Sleep-Related Gastrointestinal Function
		Introduction
		Gastroesophageal Reflux Disease (GERD)
		Irritable Bowel Syndrome
		Sleep and Irritable Bowel Syndrome
		Conclusions and Comments on Inflammatory Bowel Disease
		References
Index