Primer on the Autonomic Nervous System

4th Edition - December 7, 2022
Imprint: Academic Press
Editors: Italo Biaggioni, Kirsteen Browning, Gregory Fink, Jens Jordan, Phillip A. Low, Julian F.R. Paton
Language: English
Paperback ISBN:
9 7 8 - 0 - 3 2 3 - 8 5 4 9 2 - 4
eBook ISBN:
9 7 8 - 0 - 3 2 3 - 8 5 4 9 3 - 1

Primer on the Autonomic Nervous System, Fourth Edition provides a concise and accessible overview of autonomic neuroscience for students, scientists, and clinic… Read more

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Primer on the Autonomic Nervous System, Fourth Edition provides a concise and accessible overview of autonomic neuroscience for students, scientists, and clinicians. The book's 142 chapters draw on the expertise of more than 215 basic scientists and clinicians who discuss key information on how the autonomic nervous system controls the body, particularly in response to stress. This new edition also focuses on the translational crossover between basic and clinical research. In addition to comprehensively covering all aspects of autonomic physiology and pathology, topics such as psychopharmacology decoding and modulating nerve function are also explored.

Cover image
Title page
Table of Contents
Copyright
Contributors
Preface
Acknowledgments
Section I. Introduction
Chapter 1. Evolution of the cardiovascular autonomic nervous system in vertebrates
The autonomic nervous system in vertebrates
Anatomy of the cardiovascular system in vertebrates
Autonomic regulation of the heart
Innervation of the systemic vasculature
Autonomic regulation of the pulmonary circulation
Cardiorespiratory integration and respiratory sinus arrythmia
The evolution of adrenergic and muscarinic receptors
Cardiovascular responses to altered pressure, exercise, and hypoxia
Chapter 2. Central autonomic control
Central autonomic control: overview
Lower brainstem and autonomic reflexes
Upper brainstem and integration of autonomic with arousal and stress responses
Hypothalamus: central pattern generator for homeostasis and adaptation
Amygdala: tagging of stimulus valence and innate survival responses
Insular cortex: interoception, bodily awareness, and autonomic control
Anterior cingulate cortex, predictive motor commands to autonomic nuclei
Chapter 3. Peripheral autonomic nervous system
Introduction
Sympathetic nervous system (SNS)
Central autonomic network
Organization of SNS
Sympathoadrenal axis and the adrenal gland
Parasympathetic nervous system (PNS)
The concept of plurichemical transmission and chemical coding
Visceral afferent neurons and autonomic nervous system
Functional neuroanatomy and biochemical pharmacology
Psychosocial stress and autonomic dysfunction
Synucleinopathies and autonomic dysfunction
Section II. Biochemical and pharmacological mechanisms
Chapter 4. Noradrenergic neurotransmission
Norepinephrine synthesis
Norepinephrine storage
Norepinephrine release
Norepinephrine disposition and metabolism
Noradrenergic innervation of the cardiovascular system
Chapter 5. Antidepressant-sensitive norepinephrine transporters: structure and regulation
NET structure, localization, and function
Regulation of NET
NET genetic variation and clinical implications
Chapter 6. α1-Adrenergic receptors
α1-Adrenergic receptor (α1-AR) subtypes
Structure of α1-adrenergic receptors
Ligand binding and activation of α1-adrenergic receptors
Signaling of α1-adrenergic receptors
Regulation of α1-adrenergic receptors
Function of α1-adrenergic receptors
Chapter 7. Alpha2-adrenergic receptors
Chapter 8. β-Adrenergic receptors
β-Adrenoreceptor subtypes
Ligand binding and activation
β-Adrenoreceptor desensitization
Biological functions of β-adrenoreceptors
Chapter 9. Dopaminergic neurotransmission
Introduction
Central dopamine systems
Disorders of central dopamine systems
Peripheral dopamine systems
Chapter 10. Dopamine receptors
Introduction
Distribution and expression of dopamine receptors
Dopamine receptor structure
Dopamine receptor function: signal transduction pathways
Chapter 11. Cholinergic neurotransmission
Acetylcholine biosynthesis and metabolism
Acetylcholine receptors
Cholinergic pharmacologic agents
Chapter 12. Acetylcholine and muscarinic receptors
Cholinergic neurotransmission: sites and receptors
Muscarinic agonists
Muscarinic antagonists
Chapter 13. Nicotinic acetylcholine receptors in the autonomic nervous system
Subtype diversity and distribution of nicotinic receptors
Physiologic events associated with receptor activation
Pharmacology of ganglion–type nicotinic receptors
Chapter 14. Neuropeptide Y and the autonomic nervous system
Introduction
NPY structure and receptors
Conclusion
Chapter 15. Serotonin receptors
Serotonin
Synthesis and metabolism
Neurotransmission
Receptors
Pharmacology and role in disease
Role in autonomic processes
Chapter 16. Purinergic neurotransmission and nucleotide receptors
Purinergic neurotransmission
Receptors for purines and pyrimidines
Conclusions
Chapter 17. Nitric oxide and the autonomic nervous system
NO synthesis and actions
Central NO–autonomic nervous system interactions
NO–autonomic nervous system interactions in the periphery
NO–autonomic nervous system interactions in heart rate control
Conclusions
Chapter 18. Glutamatergic neurotransmission
Synthesis and vesicular release
Receptors
Clearance of glutamate
Glutamate metabolism
Glutamate in the autonomic nervous system
Glutamatergic drugs and the autonomic nervous system
Summary
Chapter 19. Pharmacology: GABAergic neurotransmission
Overview of GABA mediated signaling
GABA responses are mediated by both ionotropic and metabotropic receptors
GABAA receptors mediate multiple modes of neuronal signaling
Neurotransmission is mediated by a diverse set of GABAA receptor subtypes
Subtype-preferring drugs allow for selective components of GABA signaling
Chapter 20. Renin-angiotensin
Introduction
Components and features of the RAS
RAS: autonomic interactions for cardiovascular control
RAS in clinical populations
Summary and gaps in knowledge
Chapter 21. Aldosterone, the mineralocorticoid receptor, and sympathetic nervous system
The sympathetic nervous system and RAAS interact to maintain hemodynamic homeostasis
Chapter 22. Vasopressin in central autonomic regulation
VP structure, brain synthesis and release
Modes of VP neurotransmission
Vasopressin receptors in the brain—structure, distribution, and function
VP in central autonomic regulation of circulation
Hyperadrenergic conditions and central VP
Central VP in regulation of respiration
Central VP in regulation of body temperature
Central VP in regulation of gastrointestinal tract, nausea, and vomiting
Central VP in pain modulation
Perspectives
Chapter 23. Calcitonin gene-related peptide and adrenomedullin
Introduction
α-CGRP peptide structure
CGRP synthesis, localization, and release
CGRP receptor
CGRP-mediated cell signaling
CGRP and CGRP agonists in the treatment of cardiovascular disease
CGRP-antagonists for treatment of migraine
Adrenomedullin and its role in the cardiovascular system
Conclusion
Chapter 24. Leptin signaling and energy homeostasis
Introduction
Leptin: from discovery to utility in understanding energy balance dysfunction
Leptin receptor activation drives a variety of second messenger responses in the central nervous system
Neuropeptide Y (NPY)/agouti-related peptide and anorexic pro-opiomelancortin cells are important mediators of leptin action in the brain
Hypothalamic leptin and the regulation of metabolic homeostasis through actions at AGRP and POMC neurons
Leptin acts as an important regulator of metabolism during fasting conditions
Leptin influences autonomic outflow via POMC and NPY/AgRP neurons
Leptin action outside of NPY/AgRP and POMC neurons also contributes to metabolic homeostasis
Leptin regulation outside of NPY/AgRP and POMC action on autonomic sensory neuron activity in the periphery
Questions for future study
Chapter 25. The endothelin system
Introduction: endothelin system components
Effects of preproET-1 or ET receptor gene deletion
Mechanism of action of ET
Pathophysiology of the endothelin system in experimental models
Renal effects of ET-1
Cardiac effects of ET-1
ET-1 in essential hypertension
Molecular genetics of the endothelin system
Endothelins and the nervous system
Role of endothelins (ETs) in the brain and sympathetic nervous system
Conclusion
Chapter 26. Pharmacology of the neurotransmission of the baro- and chemoreflex in the Nucleus Tractus Solitarius
Introduction
Major neurotransmitters in the NTS
Section III. Autonomic physiology
Chapter 27. Rhythms in sympathetic nerve activity
Ubiquitous nature of biological rhythms
The diversity of rhythms in SNA
Functions of rhythms in SNA
Chapter 28. Circadian rhythms and autonomic function
The master clock
SCN output and autonomic control
Circadian and sleep control of the autonomic nervous system
Circadian autonomic regulation: cardiovascular variables and metabolic control
Conclusion
Chapter 29. Cardiorespiratory interactions in health and disease
Introduction
Cardiorespiratory interactions under resting conditions and physiological challenges
The origin of cardiorespiratory coupling: the duet between the autonomic nervous system and respiratory central pattern generator
Chapter 30. Baroreceptor reflexes
Neural pathways and effector mechanisms
Determinants of afferent baroreceptor activity
Baroreflex resetting and sensitivity in hypertension and other diseases
BRS: a determinant of cardiovascular risk and therapeutic target
Chapter 31. Cardiac and other visceral afferents
Introduction
Reflex control of the cardiovascular and viscera
Structural and functional organization of visceral afferent signaling
Afferents as central drivers of adverse remodeling of ANS in cardiovascular diseases
Summary and conclusions
Chapter 32. Sympathetic control of the heart
Introduction
A brief history
Future perspectives and therapeutic opportunities
Chapter 33. Cardiac vagal ganglia
Extrinsic and intrinsic cardiac innervation
Physiology of intracardiac neurons
Anatomy and heterogeneity of intrinsic cardiac ganglia
Pathophysiology in the intracardiac ganglia and therapeutic strategies
Chapter 34. Physiology of the upright posture
Introduction
Regulatory mechanisms involved in the adjustments of the human body to orthostatic stress
Arterial baroreceptors
Local vasoconstrictor mechanisms
Role of capacitance vessels in orthostatic reflex adjustments
Role of skeletal muscle pump
Humoral mechanisms
Chapter 35. Cerebral circulation
Basic considerations
Neurovascular coupling
Regulation of cerebral circulation
Cerebral autoregulation
Role of autonomic innervation
Cerebrovascular reactivity (CVR)
Conclusion
Chapter 36. Autonomic control of the pupil
Parasympatholytic (anticholinergic) drugs
Parasympathomimetic (cholinergic) drugs
Sympathomimetic (adrenergic) drugs
Sympatholytic drugs (adrenergic blockers)
Other agents
Iris pigment and pupillary response to drugs
Pupil sympathetic defects
Pupil parasympathetic defects
Pupil combined sympathetic and parasympathetic defects
Chapter 37. Gastrointestinal function
Introduction
Gastrointestinal secretory functions
Components controlling gastrointestinal motor functions
Chapter 38. Extrinsic control of gastrointestinal function
Parasympathetic control of the gastrointestinal tract
Sympathetic control of the gastrointestinal tract
Chapter 39. The splanchnic circulation
Overview
Sympathetic control of the splanchnic circulation—general features
Sympathetic control of the splanchnic circulation in special circumstances
Sympathetic control of the splanchnic circulation in disease
Neuromodulation therapy targeting the splanchnic sympathetic nerves
Chapter 40. Autonomic control of the kidney
Introduction
Innervation of the kidney
Autonomic receptors in the kidney
Reflex regulation of blood volume
The inhibitory reno-renal reflex
Autonomic control of the kidney in pathophysiological states
Chapter 41. Autonomic control of the lower urinary tract
Introduction
Neural circuits involved in reflex micturition control
Central neural control
Neural circuits involved in voluntary micturition control
Chapter 42. Bladder function in health and disease
Structure of the lower urinary tract
Properties of the healthy lower urinary tract
Clinical evaluation
Clinical conditions
Conclusions
Chapter 43. Physiology and pathophysiology of female sexual function
Physiology of the female sexual response cycle
Sexual arousal
Afferent and central pathways
Neurotransmitters
Innervation of female sexual function
Hormones influencing female sexual function
Common etiologies of female sexual dysfunction
Neurogenic etiologies
Assessment of female sexual dysfunction
Laboratory investigation
Common therapeutic approaches in female sexual dysfunction
Chapter 44. Regulation of sweating
Anatomy and function of the sweat gland
Innervation of sweat gland
Chapter 45. Autonomic innervation of the skeleton
Bone sympathetic innervation: anatomy and ontogeny
Sympathetic nerves and bone remodeling
Sympathetic nerves, hematopoietic and cancer cell trafficking in the skeleton
Sympathetic nerves and the endocrine function of the skeleton
Conclusion
Chapter 46. Regulation of metabolism by the autonomic nervous system
Basic considerations
Contribution of the parasympathetic nervous system to satiety
Contribution of the sympathoadrenal system to components of total daily energy expenditure
Contribution of sympathetically stimulated organs/tissues to resting metabolic rate
Mobilization/utilization of specific macronutrients: carbohydrate
Mobilization/utilization of specific macronutrients: lipid
Mobilization/utilization of specific macronutrients: protein
Sympathetic regulation of Brown fat
Role of the sympathoadrenal system in the dysregulation of metabolism
Chapter 47. Sex differences in autonomic function
Introduction
Physiological conditions
Pathophysiological conditions
Conclusions
Chapter 48. Autonomic control during pregnancy
Pregnancy activates the sympathetic nervous system
Pregnancy impairs the baroreceptor reflex
Mechanisms of pregnancy-induced baroreflex impairment
Preeclampsia
Summary and conclusions
Chapter 49. Aging and the autonomic nervous system
Age-related changes in sympathetic activity
Age-related changes in parasympathetic function
Central autonomic pathways
End-organ responsiveness
Autonomic integration and baroreflex function
Volume regulation
Cerebral autoregulation
Clinical consequences of age-related changes in autonomic function: hypertension and orthostatic hypotension
Chapter 50. Autonomic function in sleep and sleep deprivation
Stages of sleep
Autonomic function during sleep
Autonomic responses to sleep deprivation
Conclusion
Chapter 51. Telemetric autonomic monitoring
Introduction—why assess autonomic function using telemetry?
Designing your experiment to maximize success and minimize stress
Implantation for long-term nerve recordings
Validating your nerve signal
Quantifying your nerve signal
Summary
Section IV. Autonomic response to environmental challenges
Chapter 52. Exercise
Introduction
Acute exercise
Exercise training
Conclusion
Chapter 53. Psychological stress and the autonomic nervous system
Introduction
Psychological stress and autonomic activity
Normal psychological stresses and autonomic activity
Patterns of autonomic response to stress
Heart rate variability and cardiac disease
Gastrointestinal (GI) control
Psychosomatic disorders and the autonomic nervous system
Posttraumatic stress disorder, panic, and anxiety
Chapter 54. Hypoglycemia
Normal mechanisms of glucose regulation
Impaired counterregulatory responses to hypoglycemia in diabetes (DM)
Impaired counterregulatory responses to hypoglycemia in autonomic failure (AF)
Hypoglycemia-associated autonomic failure (HAAF)
Chapter 55. Autonomic response to hypovolemic shock
Introduction
Mechanisms of autonomic compensation
Other factors that influence compensatory responses to hypovolemia
Conclusion
Chapter 56. Physiology of thermoregulation: central and peripheral mechanisms
Introduction
Peripheral (outside the brain) physiological mechanisms of thermoregulation
Central neural control of thermoregulation
Overall summary
Chapter 57. Effects of high altitude
Introduction
Hyperacute altitude exposure
Acute altitude exposure
Acute mountain sickness (AMS) and high altitude cerebral edema (HACE)
High altitude pulmonary edema (HAPE)
Chronic altitude exposure and chronic mountain sickness (CMS)
Summary and key unanswered questions
Chapter 58. Space physiology
Introduction
Space motion sickness
Orthostatic intolerance
Clinical interactions
Chapter 59. Noise, air pollution, and the autonomic nervous system
Background
Health risks
Epidemiological evidence suggesting autonomic involvement
Animal studies
Human investigations
Underlying mechanisms
Areas of uncertainty
Section V. Pathophysiological mechanisms
Chapter 60. The autonomic inflammatory reflex
The autonomic inflammatory reflex
Chapter 61. Reactive oxygen species and oxidative stress
Introduction
Biochemistry of reactive oxygen species
Production of reactive oxygen species in the ANS
Protecting against oxidative stress—antioxidant defenses
ROS and the autonomic nervous system
Conclusions
Chapter 62. Insulin resistance and the autonomic nervous system
Introduction
Obesity and insulin resistance
Obesity and sympathetic activity
Contribution of sympathetic activity to insulin resistance in obesity
Contribution of sympathetic activity to insulin resistance in PCOS
Conclusions
Chapter 63. Salt sensitivity of blood pressure
Prognosis of SSBP
Mechanisms of SSBP
Interstitial Na+ and SSBP
Immunity and SSBP
Genetics of SSBP
Environmental factors
Diagnosis of SSBP
Treatment of SSBP
Chapter 64. Airway afferent nerves
Introduction
Extrinsic innervation of airway afferents
Characterization of airway afferent subtypes
Mechanisms of activation
Physiological consequence of airway afferent activation
Summary
Section VI. Evaluation of autonomic function
Chapter 65. Clinical evaluation of autonomic disorders
Approach in history taking
Assessment: bedside and laboratory testing
Final thoughts
Chapter 66. Autonomic function testing
Introduction
Aims of and clinical indications for autonomic testing
The autonomic reflex screen
Evaluation of cardiovagal function
Tests of cardiovascular adrenergic function
Chapter 67. Tilt table testing
Head-up tilt table (HUTT) test: background
Indications for HUTT testing
Utility and clinical applications of HUTT testing
Conclusions
Chapter 68. Patient symptom and rating scales: OHQ, COMPASS, UMSARS
Introduction
The orthostatic hypotension questionnaire (OHQ)
The composite autonomic symptom score (COMPASS)
The unified multiple system atrophy rating scale (UMSARS)
Chapter 69. Sympathetic microneurography and clinical applications
Microelectrode recordings of sympathetic nerve activity in humans
Analysis of multiunit sympathetic nerve activity
Muscle sympathetic nerve activity in health and disease
Cardiovascular, respiratory, and renal disease
Neurological and psychiatric disorders
Skin sympathetic nerve activity in health and disease
Disorders of thermoregulation
Conclusions
Chapter 70. Assessment of the autonomic control of the cardiovascular system by a frequency domain approach
Introduction
The frequency domain approach for exploring cardiovascular and sympathetic discharge variability and their relationship with respiration
The frequency domain approach for exploring baroreceptor function during carotid baroreceptor rhythmic stimulation
The frequency domain approach for exploring autonomic and baroreceptor abnormalities during orthostatic presyncope
Conclusions
Chapter 71. Evaluation of sudomotor function
Introduction
Quantitative sudomotor axon reflex test
Quantitative direct and indirect test of sudomotor function
Silicone imprint
Neuropad
Sympathetic skin response
Electrochemical skin conductance
Thermoregulatory sweat test
Summary
Chapter 72. Plasma catechols
Primer on the autonomic nervous system
DHPG
DA
DOPAC
EPI
DOPA
Cys-DOPA
Cys-DA
Diagnostic abnormal patterns of plasma catechols
DBH deficiency
LAAAD deficiency
Menkes disease
Supportive abnormal patterns of plasma catechols
Evoked changes in plasma catechol levels
Conclusions
Chapter 73. Imaging cortical and subcortical sites involved in cardiovascular control
Functional identification of the medullary circuitry subserving the arterial baroreflex in humans
Functional identification of areas above the brainstem involved in blood pressure control
Functional significance of the sympathetic connectome
Conclusions
Chapter 74. Clinical sympathetic neuroimaging
Sympathetic imaging and methods
Sympathetic neuroimaging in clinical autonomic disorders
Sympathetic neuroimaging in the diagnosis of LBDs
Sympathetic neuroimaging as a biomarker of catecholaminergic dysfunction in LBDs
Chapter 75. Cutaneous autonomic innervation: assessment by skin biopsy
Introduction
Cutaneous neuroanatomy
Skin biopsies to evaluate specific autonomic disorders
Recent advances in skin biopsies
Summary
Chapter 76. Sympatho-effector transduction
Sympatho-effector transduction
Assessment of sympatho-effector transduction
Sympatho-effector transduction in health and disease
Conclusions
Section VII. Cardiovascular disorders
Chapter 77. Neurally mediated syncope (Autonomically mediated syncope)
Background
Pathophysiology of vasovagal syncope
Natural history of VVS
Diagnosis of VVS
Role of head-up tilt table testing
Management strategies
Other specific NMS/AMS entities
Conclusions
Chapter 78. Orthostatic hypotension
Autonomic mechanisms that maintain upright blood pressure
Definition, epidemiology, and clinical relevance
Evaluation of the patient with orthostatic hypotension
Conclusions
Chapter 79. Spectrum of orthostatic hypotension
Introduction
Initial OH
Delayed OH
Hyperadrenergic OH
Management of orthostatic hypotension
Conclusions
Chapter 80. Baroreflex failure
Introduction
Causes of baroreflex failure
Clinical presentation
Diagnosing baroreflex failure
Treatment
Chapter 81. Essential hypertension
Guidelines' recommendation
Consequences of differences between recommendations
Sympathetic overdrive
Hypertension-related target organ damage
Therapeutic implications
Chapter 82. Obesity-associated hypertension
Epidemiology and significance
Chapter 83. Pheochromocytoma and paraganglioma
Introduction
Clinical presentation
Genetics
Biochemical diagnosis
Tumor localization
Pre to postoperative patient management
Pathology and metastatic disease
Chapter 84. Autonomic dysfunction in heart failure
Heart failure
Autonomic disturbances in heart failure with reduced ejection fraction
Autonomic disturbances in heart failure with preserved ejection fraction
Clinical considerations and future directions
Chapter 85. Myocardial stunning and takotsubo cardiomyopathy
Introduction
Pathophysiology
Triggers
Cardiology findings
Autonomic studies in the acute phase
Autonomic studies after recovery
Predisposition and susceptibility
Chapter 86. The autonomic nervous system and cardiac arrhythmias
Introduction
Anatomy of the cardiac autonomic nervous system
Neural remodeling and autonomic dysregulation in arrhythmias
Neuromodulatory interventions for arrhythmia management
Conclusion
Section VIII. Congenital autonomic disorders
Chapter 87. Deficiencies of tetrahydrobiopterin, tyrosine hydroxylase, and aromatic L-amino acid decarboxylase
Biochemistry
Presentation and neurological symptoms
Diagnosis
Treatment
Chapter 88. Congenital disorders of noradrenergic neurotransmission
Familial autonomic ganglionopathy
Dopamine-β-hydroxylase (DBH) deficiency
Cytochrome b561 deficiency
Norepinephrine transporter deficiency
Chapter 89. Monoamine oxidase deficiency
Chapter 90. Congenital central hypoventilation syndrome (CCHS) and PHOX2B pathogenic variants
Paired-like homeobox 2B (PHOX2B) gene
PHOX2B genotype and CCHS phenotype association
Comprehensive clinical evaluation
Chapter 91. Hereditary autonomic neuropathies
Hereditary sensory and autonomic neuropathies
Fabry disease
Porphyria
Multiple endocrine neoplasia type 2B
Chapter 92. Familial dysautonomia (Riley–Day syndrome)
Introduction
Clinical features
Autonomic features
Genetics
Pathological studies
Long-term consequences of baroreflex deafferentation
Treatment
Section IX. Autonomic synucleinopathies
Chapter 93. α-Synuclein and neurodegeneration
α-Synuclein—physiological function and association with disease
α-Synuclein toxicity and prion properties
Animal models of α-synucleinopathy
Anti-α-synuclein therapeutics
Conclusion
Chapter 94. Multiple system atrophy
Background
Epidemiology
Pathophysiology
Clinical presentation
Survival
Differential diagnosis
Autonomic testing in multiple system atrophy
Treatment
Chapter 95. Parkinson disease
Summary
Chapter 96. Dementia with Lewy bodies
Clinical aspects and differential diagnosis
Practical management
Therapy
Chapter 97. Pure autonomic failure
Clinical manifestations
Diagnosis
Prognosis
The phenotype of nOH predicts prognosis in PAF
Is PAF “pure”?
Clinical laboratory separation of Lewy body versus non-Lewy body PAF
Lewy body PAF versus premotor MSA
Treatment
Summary
Section X. Peripheral autonomic disorders
Chapter 98. Small fiber neuropathy
Systemic disorders associated with SFN
Treatment
Conclusions
Chapter 99. Diabetic autonomic dysfunction
Iris
Upper GI dysmotility
Gallbladder
Colon
Bladder
Penis
Vagina
Adrenal medulla
Sudomotor
Cardiovascular
Chapter 100. Amyloidosis and autonomic failure
Overview of amyloidosis
Amyloidosis subtypes
Neuropathy patterns
Autonomic manifestations
Case 1
Case 2
Treatment
Prognosis
Conclusion
Chapter 101. Autoimmune autonomic syndromes
Autoimmune autonomic ganglionopathy
Paraneoplastic autonomic neuropathy
Immune-mediated sensory and autonomic neuropathy
Autoimmunity in postural orthostatic tachycardia syndrome
Other autoimmune conditions with associated autonomic dysfunction
Summary
Chapter 102. Paraneoplastic autonomic dysfunction
Introduction
Immunobiology and immunopathology
Clinical disorders and their course
Testing
Management
Conclusion
Chapter 103. Autonomic disturbances following spinal cord injury
Classification of spinal cord injury
Spinal shock
Cardiovascular system
Cutaneous circulation
Thermoregulation and sudomotor function
Gastrointestinal system
Urinary system
Respiratory system
Reproductive system
Functional recovery strategies
Chapter 104. Drug-induced autonomic dysfunction
Introduction
Drug-induced hypertension
Drug-induced hypotension
Section XI. Autonomic syndromes
Chapter 105. Postural tachycardia syndrome. Pathophysiological mechanisms
Diagnostic challenges
Etiology and pathophysiology
“Primary” POTS
“Secondary” POTS
Hypovolemia
Autoimmune mechanisms
Deconditioning
The mosaic theory of POTS?
Implications for therapy
Chapter 106. Postural tachycardia syndrome (POTS)
Introduction
Clinical features and phenotypes
Phenotypes of POTS
Neuropathic POTS
Hyperadrenergic POTS
POTS associated with poor conditioning
Role of hypovolemia, genetic mutations, connective tissue disorders, and autoimmunity
Follow-up
Management
Conclusions
Chapter 107. Joint hypermobility and dysautonomia
Introduction
Epidemiology and pathophysiology
Clinical manifestation and diagnosis
Autonomic dysfunction in JHS
Mechanism of dysautonomia and orthostatic intolerance in JHS
Management
Chapter 108. Mast cell activation and autonomic disorders
Introduction
MCAD and POTS: mechanistic insights
Diagnosis
Conclusion
Chapter 109. Chronic fatigue syndrome and the autonomic nervous system
Chronic fatigue syndrome and the autonomic nervous system
Chronic fatigue syndrome and autonomic dysfunction
Chronic fatigue syndrome and orthostatic intolerance
Postural orthostatic tachycardia syndrome
Neurally mediated hypotension
Pathophysiology
Conclusions
Section XII. Special clinical conditions
Chapter 110. Neuroleptic malignant syndrome
Introduction
Clinical features
Medications and risk factors
Differential diagnosis
Pathogenesis
Treatment
Chapter 111. Migraine and autonomic nervous system
Functional anatomy of migraine
Autonomic symptoms during the migraine attack
Interictal autonomic dysfunction in migraine
The pain of migraine
Migraine as a biobehavioral disorder
Migraine as a reflection of genetically determined adaptive Darwinian behavioral responses
Conclusion
Chapter 112. Autonomic regulation in epilepsy
Introduction
Ictal autonomic dysfunction
Interictal autonomic dysfunction
Chapter 113. Autonomic complications of acute brain injury and stroke
Introduction
Pathophysiology
Clinical manifestations
Differential diagnosis
Specific clinical scenarios
Management considerations
Chapter 114. Sleep apnea
Critical need for understanding the interactions between sleep apnea, the autonomic nervous system, and cardiovascular disease
Autonomic function during physiologic sleep
Obstructive sleep apnea
OSA and the autonomic nervous system
Central sleep apnea
Traditional and novel treatment modalities for sleep apnea
Chapter 115. Panic disorder: Autonomic nervous mechanisms of risk
Resting sympathetic nervous system function in panic disorder
Autonomic nervous changes during a panic attack
Brain monoamine turnover in panic disorder
Abnormal sympathetic nerve biology in panic disorder
Cardiac risk: clinical management
Chapter 116. Disorders of sweating
Introduction
Hyperhidrosis
Hypohidrosis and anhidrosis
Distal anhidrosis
Global anhidrosis
Dermatomal, focal, or multifocal anhidrosis
Segmental anhidrosis
Regional anhidrosis
Hemianhidrosis
Chapter 117. Complex regional pain syndrome
CRPS I is a neuronal disorder involving the central nervous system (CNS)
Sympathetic systems supplying skin
Sympathetic neurons and edema, inflammation, and trophic changes
Sensory systems of the skin
Somatomotor changes
Initiating events
CRPS and sympathetically maintained pain (SMP)
Conclusions
Chapter 118. Abdominal pain and cyclic vomiting
Cyclic vomiting syndrome (CVS)
Chronic abdominal pain
Chapter 119. Male erectile dysfunction
Mechanism of erection
Etiology of erectile dysfunction
Neuromuscular junction disorders
Neurogenic erectile dysfunction
Endocrine disorders
Medical and surgical treatment
Section XIII. Management of neurogenic orthostatic hypotension
Chapter 120. Management of orthostatic hypotension. Introduction
Goal of treatment and overall strategy
Pathophysiological concepts relevant to orthostatic hypotension
Nonpharmacologic approaches
Pressor agents (Fig. 120.3)
Chapter 121. Physical measures
Physical measures
Counterpressure maneuvers
External support
Respiratory maneuvers
Conclusion
Chapter 122. Dietary sodium and fludrocortisone
Dietary sodium
Fludrocortisone
Chapter 123. Water and the osmopressor response
Introduction
The water-induced pressor response
Evidence for water-induced sympathetic activation
A spinal sympathetic reflex?
Evidence for an osmosensitive mechanism involving Trpv4 in the liver
Therapeutic utility of water drinking
Speculation on the purpose of the osmopressor response
Chapter 124. Midodrine
Introduction
Clinical development of midodrine
Use of midodrine in clinical practice
Chapter 125. Droxidopa
Introduction
Historical background
Clinical studies
Droxidopa dose selection
Other therapeutic considerations
Chapter 126. Pyridostigmine in autonomic disorders
Introduction
Pyridostigmine in the treatment of neurogenic orthostatic hypotension
Pyridostigmine in the treatment of orthostatic intolerance associated with postural tachycardia syndrome
Other indications of pyridostigmine in autonomic disorders
Chapter 127. Norepinephrine transporter inhibitors in autonomic disorders
Introduction
Selective NET inhibition for the treatment of neurogenic orthostatic hypotension
NET inhibition as an adjuvant for the treatment of refractory neurogenic orthostatic hypotension
NET inhibition in neurally mediated syncope
Conclusion
Chapter 128. Acarbose and octreotide for the treatment of postprandial hypotension
Introduction
Acarbose
Octreotide
Chapter 129. Management of supine hypertension in patients with autonomic failure
Considerations for the management of supine hypertension
Management of supine hypertension
Novel approaches
Conclusions
Chapter 130. Anesthetic considerations in patients with autonomic dysfunction
Responses to surgery and anesthesia in a patient with intact autonomic function
Anticipated responses to surgery and anesthesia in a patient with autonomic failure
PAF versus MSA
Parkinson disease
Diabetes
Anesthetic approach to a patient with AF
Regional anesthesia
Preoperative screening
Conclusion
Chapter 131. Chronic constitutional hypotension
Introduction
Perspective
Section XIV. Autonomic neuromodulation as a treatment strategy
Chapter 132. Renal denervation as therapeutic intervention
Origins of catheter-based renal denervation therapy for cardiovascular disease
The Symplicity HTN-3 renal denervation trial
Improved RDN devices and RDN procedures
The modern era of RDN (post-2016): proof of efficacy and safety
Patient selection for RDN
Further optimization of the RDN procedure
Reinnervation of the kidneys after catheter-based denervation?
Other clinical applications of renal denervation
Summary
Chapter 133. Baroreflex amplification by carotid sinus stimulation
Background
Electrical carotid sinus stimulation
Mechanical carotid sinus stimulation
Perspectives
Chapter 134. Targeting carotid body chemoreceptors as a therapeutic intervention
Introduction
Carotid body: a multimodal receptor
The chemoreflex
Transduction mechanisms within the carotid body
Carotid body transmission during hypoxia
Blood flow to the carotid body
Pathophysiology of the carotid body
Identifying pathological carotid bodies
Preclinical carotid body modulation
First-in-human studies
Beyond resection—the next vista of carotid body therapy
Chapter 135. Bionic baroreflex
Introduction
Implementation of algorithm of artificial vasomotor center in BBS
Epidural catheter approach for human BBS
Feasibility study of BBS in patients with high cervical spinal cord injury
Implantable BBS
Chapter 136. Therapeutic targeting of splanchnic nerves
Role of the splanchnic vascular compartment and splanchnic nerves in the regulation of vascular tone and blood volume shifts
Targeting the splanchnic compartment and splanchnic nerves for the treatment of cardiovascular disease
Splanchnic nerve blockade as a treatment for cardiovascular disease
Conclusion
Section XV. Novel approaches in autonomic neuroscience
Chapter 137. Modeling the autonomic nervous system
Hodgkin–Huxley type models
Activity-based models
Integrate and fire models
Boolean models
Phenomenological models
Black box models
Conclusions
Chapter 138. Optogenetics: application to central autonomic regulatory pathways
Introduction
Optically activated molecules
Excitation
Inhibition
The genetics of optogenetics
How does optogenetics benefit central autonomic neuroscience research?
Conclusion
Chapter 139. Mapping the autonomic nervous system: the SPARC project
Introduction
2D flatmaps
3D organ scaffolds
3D body scaffolds
Conclusions and future work
Chapter 140. Autonomic nervous system-gut-microbiome axis in chronic diseases
Gut microbiota in health and disease
Autonomic regulation of the GI tract
Links between autonomic dysfunction and gut dysbiosis
Future directions and potential of probiotic and bioelectronic medicine
Chapter 141. Novel fluid biomarkers in synucleinopathies
Introduction
Catecholamines and catechols
Neurofilament light chain
Alpha-synuclein and alpha-synuclein subspecies
Conclusion
Chapter 142. Novel disease-modifying treatments for synucleinopathies
Introduction
Pathophysiology of synucleinopathies
Disease-modifying therapeutic approaches
Conclusion
Index

Italo Biaggioni

Dr. Biaggioni has almost 40 years’ experience investigating the interaction between neural (autonomic) metabolic (renin- angiotensin, insulin) and local (adenosine, nitric oxide) factors involved in cardiovascular regulation. He has had continued NIH funding that has resulted in over 330 peer-reviewed publications. Dr. Biaggioni directs the Vanderbilt Autonomic Dysfunction Center, a multidisciplinary program dedicated to applying clinical research to development novel treatment strategies. His group has discovered 4 novel congenital autonomic disorders and has participated in the development of new medications, have repurposed many approved drugs, and developed novel devices.

Affiliations and expertise

Director, Vanderbilt Autonomic Dysfunction Center; David Robertson Professor of Autonomic Disorders, Professor of Medicine and Pharmacology, Vanderbilt University Medical Center, Nashville, TN, United States

Kirsteen Browning

Dr. Kirsteen Browning is a Professor of Neural and Behavioral Science at Penn State University. She is also Associate Director of the MD/PhD Medical Scientist Training Program. Her research interest is in the regulation of gastrointestinal vagal neurocircuits and vagally mediated peripheral sensation and signaling.

Affiliations and expertise

Professor of Neural and Behavioral Science and Associate Director, MD/PhD Medical Scientist Training Program, Penn State University College of Medicine, Hershey, PA, United States

Gregory Fink

Dr. Gregory Fink is a Professor in Pharmacology and Toxicology at Michigan State University. His research continues to concern central and peripheral mechanisms of blood pressure regulation in hypertension, but other important interests are the renin-angiotensin system, endothelin and the role of venous function and body fluid volume distribution in control of blood pressure. Fink has served on the executive committee and as treasurer for the Inter-American Society of Hypertension, as chairman of the National Institutes of Health, or NIH , Experimental Cardiovascular Sciences Study Section and he just recently finished a two-year term as chair of the American Heart Association Council on Hypertension.

Affiliations and expertise

Professor in Pharmacology and Toxicology, Michigan State University, East Lansing, MI, United States

Jens Jordan

Jens Jordan is Head of the Institute of Aerospace Medicine at the German Aerospace Center and the University of Cologne in Germany. Previously, he directed the Institute for Clinical pharmacology at Hannover Medical School. His group pursues cardiovascular control mechanisms and molecular mechanisms responsible for premature cardiovascular and metabolic disease in human beings. The overall goal is to find ways of extending the healthy lifespan on earth and in space.

Affiliations and expertise

Head of the Institute of Aerospace Medicine, German Aerospace Center and University of Cologne, Cologne, Germany

Phillip A. Low

Dr. Phillip Low is a Neurologist at the Mayo Clinic focusing on Autonomic Disorders. Phillip A. Low, M.D. has a long-standing research focus on clinical and laboratory research into the cause and treatment of autonomic disorders. Efforts have been concentrated on following major areas: multiple system atrophy; development of novel biomarkers and tests and instruments to study autonomic disorders; diagnosis and treatment of autonomic neuropathies; conducting randomized clinical trials. Dr. Low's research has been continuously funded by the National Institutes of Health (NIH) for over the past 30 years.

Affiliations and expertise

Neurologist at the Mayo Clinic focusing on Autonomic Neuropathy

Julian F.R. Paton

Professor Paton is the Director of Manaaki Manawa – the Centre for Heart Research in Auckland. Through modulation of the autonomic nervous system, his research aims to inform new potential ways to control blood pressure in the condition of hypertension and to alleviate heart failure and sleep apnoea. He uses an inter-disciplinary approach involving mathematical modelling, pre-clinical and first-in-human studies incorporating novel drugs and device based therapeutic strategies.

Affiliations and expertise

Professor of Translational Physiology, Manaaki Manawa – The Centre for Heart Research, Department of Physiology, University of Auckland, Auckland, New Zealand

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Primer on the Autonomic Nervous System

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Italo Biaggioni

Kirsteen Browning

Gregory Fink

Jens Jordan

Phillip A. Low

Julian F.R. Paton

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