(BQ) Part 1 book Sleepy or sleepless - Clinical approach to the sleep patient presents the following contents: Key history and physical examination findings in the sleepy patient, diagnostic tools and testing in the sleepy patient, central nervous system hypersomnias, sleep deprivation, the sleepy child,...
Sleepy or Sleepless Clinical Approach to the Sleep Patient Raman K Malhotra Editor 123 Sleepy or Sleepless Raman K Malhotra Editor Sleepy or Sleepless Clinical Approach to the Sleep Patient Editor Raman K Malhotra, MD Director, Neurology Residency Program Co-Director, SLUCare Sleep Disorders Center Director, Sleep Medicine Fellowship Assistant Professor of Neurology Saint Louis University School of Medicine St Louis, MO, USA ISBN 978-3-319-18053-3 ISBN 978-3-319-18054-0 DOI 10.1007/978-3-319-18054-0 (eBook) Library of Congress Control Number: 2015942895 Springer Cham Heidelberg New York Dordrecht London © Springer International Publishing Switzerland 2015 This work is subject to copyright All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed The use of general descriptive names, registered names, trademarks, service marks, etc in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use The publisher, the authors and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication Neither the publisher nor the authors or the editors give a warranty, express or implied, with respect to the material contained herein or for any errors or omissions that may have been made Printed on acid-free paper Springer International Publishing AG Switzerland is part of Springer Science+Business Media (www.springer.com) Foreword Dr Raman K Malhotra, an authority in sleep medicine education, has assembled a group of exemplary authors who superbly summarize the major sleep disturbances in an effective, accurate, and efficient manner This book consists of practical and probabilistic approaches to any patient who may present with a sleep complaint It is with this foresight that Dr Malhotra, as book editor, embarks on his uniquely imaginative symptoms-based perspective of sleep medicine Given that the majority of patients who arrive in a sleep disorders clinic often complain of excessive sleepiness and insomnia, the title of the book is very appropriate indeed It is with this in mind that this book is strategically divided into two sections: Part I focuses on “The Sleepy Patient” and is subdivided into seven chapters addressing history and physical findings, diagnostic tools and tests, and then proceeds with a discussion of the two key clinical entities: sleep disordered breathing and central nervous system hypersomnias, which most commonly present with excessive sleepiness The chapter on sleepiness in industry is indispensable given the important contributions of shift work schedule requirements on human sleep Part I concludes with two chapters covering sleep deprivation, a pervasive problem in today’s society as frequently demonstrated by National Sleep Foundation polls, and the sleepy child, which is an often neglected problem but a recent epidemic for any number of reasons Part II “The Sleepless or Restless Patient” mirrors Part I in its organizational approach covering history, physical exam, and tests in addressing these patients This is followed by a discussion of key causes of sleeplessness including insomnia, circadian rhythm disorders, and movement disorders of sleep Separate discussion is later provided covering the sleepless child and problems with sleeplessness during and after pregnancy The authors have done a remarkable job in producing a text that is eloquent, practical, and concise All are authorities on the various topics assigned to them through their intimate knowledge of the subject area, which they have not only researched, but also have contributed to the evidence for diagnostic approaches and management strategies The readership should be aware that the authors’ credibility as writers is derived from their reputable clinical expertise, as well as serving as key opinion leaders and researchers in the field v vi Foreword Every clinician, whether a busy primary care physician, a subspecialist or a trainee needs to ask patients about their sleep quality Having a “road map” within reach to empower clinicians for making appropriate and well-reasoned decision is critical Given that sleep medicine is underrepresented in graduate medical education curriculum, resources such as Sleepy or Sleepless: Approach to the Sleep Patient are indispensible Dr Malhotra and his fellow authors should be congratulated on delivering this masterful textbook and for their commitment and determination in propelling sleep medicine education and clinical care Los Angeles, CA February 25, 2015 Alon Avidan, M.D., M.P.H Preface Sleep disorders are regularly encountered in clinical practice, and when left untreated can lead to significant consequences to patients, their families, and society as a whole Unfortunately, common sleep disorders, such as sleep apnea, insomnia, and insufficient sleep, remain undiagnosed and untreated by clinicians This is partially due to patients not bringing their sleep complaints to their health care providers’ attention; however, this also highlights inadequate exposure and education about sleep disorders during medical school, residency, and fellowship training Though sleep disorders can affect almost all functions and organ systems of the body, very little time is dedicated to sleep disorders in medical education Furthermore, though some medical schools and postgraduate training programs have increased formal teaching and rotations in sleep medicine, there remain limited resources, curricula, or references available for trainees that fit their needs Most rotators want the most up-to-date information on clinical sleep medicine and the ability to review relevant materials by the end of their short rotation This textbook seeks to fill this gap as a concise textbook that medical students, residents, fellows, or health care providers who are beginners to sleep medicine can review during a rotation This text is one of the first to incorporate new classification systems such as the International Classifications of Sleep Disorders—third Edition that was released in 2014 as well as the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) To further make this text more practical, the content is separated into two sections: (1) The Sleepy Patient and (2) The Sleepless/Restless Patient With a focus first on the patient’s chief complaint, this layout will provide the reader the proper framework to perform a complete clinical evaluation of their patient’s sleep complaint, make the proper diagnosis, and then choose the most effective management for their patient Each of the two sections provides a detailed chapter on proper history-taking and key physical examination findings that will be helpful in the clinical evaluation of sleep patients In addition, I have included a chapter in each section on common screening tools, tests, and “templates” that can be used in the clinical setting to assist in the office visit Much of these tools are validated and used frequently in clinical trials and research Other tools, on the other hand, were vii viii Preface included primarily due to the expert author’s own experience in using these tools successfully when seeing sleep patients in their own clinical practice In addition to chapters on common sleep disorders such as sleep-disordered breathing, insomnia, restless legs syndrome, hypersomnias, parasomnias, and circadian rhythm disorders, there are specialty chapters on sleep in special populations (pregnancy, children, high consequence industries) Sleep deprivation and its effects on the individual and society is highlighted in a separate chapter I hope this book serves useful for learners on the sleep medicine elective or learners on other rotations interested in how patients with sleep disorders present In addition, this book will provide a solid foundation to clinicians who want to better evaluate patients who present to their office with sleepiness or sleeplessness St Louis, MO, USA Raman K Malhotra, M.D Acknowledgments I would like to express my gratitude to all the accomplished authors who took time away from their families and friends to contribute to this book I would also like to thank my colleagues and staff at the SLUCare Sleep Disorders Center and in the Department of Neurology and Psychiatry at Saint Louis University for their support and guidance with this project I would like to give my sincere gratitude to my Chairman, Dr Henry Nasrallah, for his input and advice I would like to thank Dr Ronald Chervin who helped guide me early on in my career and drew me to the exciting field of sleep medicine while I was at the University of Michigan Sleep Disorders Center in Ann Arbor, Michigan I would like to thank Dr Alon Avidan who has provided me invaluable support and guidance throughout this project and throughout my career I would like to thank the publishing team from Springer who made this book possible and were wonderful to work with Lastly, I would like to thank my parents, my wife, Shalini, and my two sons, Yash and Sanjay, for their inspiration and understanding while I worked on this important endeavor St Louis, MO, USA Raman K Malhotra, M.D ix Sleep Deprivation 83 Commercial aviation is not free from the impact of sleep deprivation on pilots and engineers There were instances where pilots were found to be asleep in their cockpits [114] In one study, the maintenance engineers were found to have shifts longer than 12 h with an average of 50 h per week 10 % of the 1,209 engineers in that survey reported falling asleep while driving The National Transportation Safety Board examined accidents between 1978 and 1990 and found that half of the captains involved in accidents had been awake for more than 12 h and half of the first officers had been awake for more than 11 h Drowsiness has been identified as the reason behind many disastrous industrial accidents as well [115] The Exxon Valdez accident was found to be due to the fatigue caused by reduced sleep and extended working hours [116] Similar observations involving sleep deprivation were seen in the Chernobyl nuclear plant meltdown, Three Mile Island reactor accident in Pennsylvania [117], Davis–Besse reactor in Ohio, [118], Rancho Seco nuclear reactor in California [119], Bhopal disaster in India, space shuttle Challenger accident [115, 120], and a nearcatastrophic launch of the shuttle Columbia Many of them were associated with shift work-related sleep deprivation Sleep Deprivation in Medical Profession While residents in medical and surgical training are plagued by a variety of stressors, sleep deprivation has been consistently identified to be associated with a negative impact on their performance and an increased likelihood of committing a serious medical error Despite the recent efforts in cutting down the number of duty hours while on call and other measures to balance education with clinical duties, sleep deprivation continues to be rampant among physicians in training The formal study of the effect of residents’ long duty hours on performance began in 1971 when Friedman et al reported that interns made almost twice as many errors reading electrocardiograms (EKG) after an extended work shift than after a night of sleep [121] The topic on the resident duty hours gained more attention when a college freshman by the name Libby Zion died within h of her emergency admission in a New York teaching hospital [122] The cause of death is thought to be serotonin syndrome and a grand jury investigation found that the death was related to 36 h duty periods of the residents involved in the patient care along with inadequate supervision by the attending physicians [123] In another recent study, surgical residents made up to twice the number of technical errors in performing simulated laparoscopic surgical skills after an overnight work call than after a night of sleep [124] The “Intern Sleep and Patient Safety Study” which studied the performance of medical residents found that interns made more serious medical errors when they worked frequent shifts of 24 h or more than when they worked shorter shifts [125] Lockley et al found that eliminating the extended work shifts in the intensive care unit significantly increased sleep and reduced the number of attention failures during the night work hours [126] 84 P.C Bollu et al Management of Sleep Deprivation Non-pharmacological Treatments To put in simple terms, sleep is the treatment for sleepiness due to sleep deprivation People typically nap when they are sleepy secondary to a restricted sleep routine Naps tend to improve alertness and performance [127] In a study, the nap rate in adult population is as high as 74 % [128] If a nap happens after a period of prolonged wakefulness, it is called a “recuperative nap,” but if it happens prior to a prolonged wakeful period, it is a “prophylactic nap.” Longer naps, though always not feasible, are more efficient in improving alertness, reaction times, and shortterm memory [129–131] Naps shorter than 10 however are not very restorative and are associated with only limited improvement [132] Naps in the midafternoon (1–4 pm) were found to be more restorative than those in the early afternoon [133] Other than naps, some behavioral measures like walking while reading, reading out loudly, bright lighting, increasing the sound of music, etc are all adopted by people when they sleep However, their effect is limited and short lasting at best Pharmacological Therapies Various different medications have been used over the years to counteract sleepiness Coffee is one of the widely used stimulants worldwide Other medications that are used in routine clinical practice include amphetamines, methylphenidate, modafinil, and armodafinil They are discussed later in this book Conclusion With the advent of electricity, creation of shift work, and poor sleep hygiene, sleep deprivation is a rampant and under-recognized problem of the twenty-first century Increasing evidence ties sleep deprivation to multiple physiological maladaptations in the body leading to changes in immune, cardiovascular, endocrine, and metabolic functions and adversely affecting the health outcomes and quality of life References Bonnet MH, Arand DL We are chronically sleep deprived Sleep 1995;18:908–11 Bliwise DL Historical change in the report of daytime fatigue Sleep 1996;19(6):462 Johnson EO Sleep in America: 1999 Results from the National Sleep foundations Washington: National Sleep Foundation; 1999 Sleep Deprivation 85 Zhang J, et al Extended wakefulness: compromised metabolics in and degeneration of locus ceruleus neurons J Neurosci 2014;34(12):4418–31 Hublin C, et al Sleep and mortality: a population-based 22-year follow-up study Sleep 2007;30(10):1245 Wehr TA, et al Conservation of photoperiod-responsive mechanisms in humans Am J Physiol 1993;265(4):R846–57 Bliwise DL, et al Prevalence of self-reported poor sleep in a healthy population aged 50-65 Soc Sci Med 1992;34(1):49–55 Carmona R Frontiers of knowledge in sleep and sleep disorders: opportunities for improving health and quality of life J Clin Sleep Med 2005;1(1):83 de Manaceine M Quelques observations experimentales sur l’influence de l’insomnie absolue Arch Ital Biol 1894;21:322–5 10 Daddi L Sulle alterazioni degli elementi del sistema nervoso centrale nell’insonnia sperimentale Riv Pat Nerv Ment 1898;3:1–12 11 Tarozzi G Sulle’influenza dell’insonnio sperimentale sul ricambio materiale Riv Pat Nerv Ment 1899;4:1–23 12 Patrick G, Gilbert JA Studies from the psychological laboratory of the University of Iowa: on the effects of loss of sleep Psychol Rev 1896;3(5):469 13 Legendre R, Pieron H Le probleme des facteurs du sommeil Resultats d’ injections vasculaires et intracerebrales de liquides insomniques C R Soc Biol (Paris) 1910;68:1077–9 14 Johnson LC, Slye ES, Dement W Electroencephalographic and autonomic activity during and after prolonged sleep deprivation Psychosom Med 1965;27(5):415–23 15 Webb W Partial and differential sleep deprivation In: Kales A, editor Sleep, physiology and pathology: a symposium Philadelphia: J.B Lippincott; 1969 p 221–31 16 Kleitman N Sleep and wakefulness Chicago: University of Chicago Press; 1963 17 Banks S, Dinges DF Behavioral and physiological consequences of sleep restriction J Clin Sleep Med 2007;3(5):519 18 Stepanski EJ The effect of sleep fragmentation on daytime function Sleep 2002;25(3):268–78 19 Dinges D, Rogers N, Baynard M Chronic sleep deprivation In: Kryger MH, Roth T, Dement WC, editors Principles and practice of sleep medicine 4th ed Philadelphia: Elsevier/ Saunders; 2005 p 67–76 20 Lubin A, et al Effects of exercise, bedrest and napping on performance decrement during 40 hours Psychophysiology 1976;13(4):334–9 21 Haslam BD Sleep loss, recovery sleep, and military performance Ergonomics 1982;25(2): 163–78 22 Rosa RR, Bonnet MH, Warm JS Recovery of performance during sleep following sleep deprivation Psychophysiology 1983;20(2):152–9 23 Bonnet MH, Rosa R Sleep and performance in young adults and older normals and insomniacs during acute sleep loss and recovery Biol Psychol 1987;25(2):153–72 24 Carskadon MA, Dement WC Sleep loss in elderly volunteers Sleep 1985;8(3):207–21 25 Carskadon MA, Dement WC Effects of total sleep loss on sleep tendency Percept Mot Skills 1979;48(2):495–506 26 Bonnet MH Effect of 64 hours of sleep deprivation upon sleep in geriatric normals and insomniacs Neurobiol Aging 1986;7(2):89–96 27 Reynolds III CF, et al Sleep deprivation as a probe in the elderly Arch Gen Psychiatry 1987;44(11):982 28 Borb AA, Achermann P Sleep homeostasis and models of sleep regulation J Biol Rhythms 1999;14(6):559–70 29 Spiegel K, Leproult R, Van Cauter E Impact of sleep debt on metabolic and endocrine function Lancet 1999;354(9188):1435–9 30 Goichot B, et al Nocturnal plasma thyrotropin variations are related to slow‐wave sleep J Sleep Res 1992;1(3):186–90 31 Weibel L, et al Comparative effect of night and daytime sleep on the 24-hour cortisol secretory profile Sleep 1995;18(7):549–56 86 P.C Bollu et al 32 Follenius M, et al Nocturnal cortisol release in relation to sleep structure Sleep 1992;15(1):21 33 Späth-Schwalbe E, et al Sleep disruption alters nocturnal ACTH and cortisol secretory patterns Biol Psychiatry 1991;29(6):575–84 34 Omisade A, Buxton OM, Rusak B Impact of acute sleep restriction on cortisol and leptin levels in young women Physiol Behav 2010;99(5):651–6 35 Takahashi Y, Kipnis D, Daughaday W Growth hormone secretion during sleep J Clin Investig 1968;47(9):2079 36 Sassin J, et al Human growth hormone release: relation to slow-wave sleep and sleep-waking cycles Science 1969;165(3892):513–5 37 Van Cauter E, Plat L, Copinschi G Interrelations between sleep and the somatotropic axis Sleep 1998;21(6):553–66 38 Brandenberger G, et al Effect of sleep deprivation on overall 24 h growth-hormone secretion Lancet 2000;356(9239):1408 39 Holl RW, et al Thirty-second sampling of plasma growth hormone in man: correlation with sleep stages J Clin Endocrinol Metab 1991;72(4):854–61 40 Satinoff E Neural organization and evolution of thermal regulation in mammals Science 1978;201(4350):16–22 41 Schmidek WR, Zachariassen KE, Hammel HT Total calorimetric measurements in the rat: influences of the sleep-wakefulness cycle and of the environmental temperature Brain Res 1983;288(1):261–71 42 Kleitman N, Ramsaroop A, Englmann T Variations in skin temperatures of the feet and hands and the onset of sleep In: Federation proceedings 1948 43 Kräuchi K, et al Physiology: warm feet promote the rapid onset of sleep Nature 1999;401(6748):36–7 44 Murray EJ, Williams HL, Lubin A Body temperature and psychological ratings during sleep deprivation J Exp Psychol 1958;56(3):271 45 Bergmann B, et al Sleep deprivation in the rat: V Energy use and mediation Sleep 1989;12(1):31–41 46 Vaara J, et al The effect of 60-h sleep deprivation on cardiovascular regulation and body temperature Eur J Appl Physiol 2009;105(3):439–44 47 Fiorica V, et al Physiological responses of men during sleep deprivation Washington: Department of Transportation, Federal Aviation Administration, Office of Aviation Medicine; 1970 48 Young AJ, et al Exertional fatigue, sleep loss, and negative energy balance increase susceptibility to hypothermia J Appl Physiol 1998;85(4):1210–7 49 Redwine L, et al Disordered sleep, nocturnal cytokines, and immunity in alcoholics Psychosom Med 2003;65(1):75–85 50 Redwine L, et al Effects of sleep and sleep deprivation on interleukin-6, growth hormone, cortisol, and melatonin levels in humans J Clin Endocrinol Metab 2000;85(10):3597–603 51 Born J, et al Effects of sleep and circadian rhythm on human circulating immune cells J Immunol 1997;158(9):4454–64 52 Petrovsky N, Harrison LC Diurnal rhythmicity of human cytokine production: a dynamic disequilibrium in T helper cell type 1/T helper cell type balance? J Immunol 1997;158(11):5163–8 53 Everson CA, Toth LA Systemic bacterial invasion induced by sleep deprivation Am J Physiol 2000;278(4):R905–16 54 Gangwisch JE, et al Inadequate sleep as a risk factor for obesity: analyses of the NHANES I Sleep 2005;28(10):1289 55 Spiegel K, et al Sleep loss: a novel risk factor for insulin resistance and type diabetes J Appl Physiol 2005;99(5):2008–19 56 Gangwisch JE, et al Short sleep duration as a risk factor for hypertension analyses of the First National Health and Nutrition Examination Survey Hypertension 2006;47(5):833–9 Sleep Deprivation 87 57 Palagini L, et al Sleep loss and hypertension: a systematic review Curr Pharm Des 2013;19(13):2409–19 58 Dean E, et al Association between habitual sleep duration and blood pressure and clinical implications: a systematic review Blood Press 2012;21(1):45–57 59 Ruiter M, et al Short sleep predicts stroke symptoms in persons of normal weight Sleep 2012;35:A279–A279 60 Sauvet F, et al Effect of acute sleep deprivation on vascular function in healthy subjects J Appl Physiol 2010;108(1):68–75 61 Zhong X, et al Increased sympathetic and decreased parasympathetic cardiovascular modulation in normal humans with acute sleep deprivation J Appl Physiol 2005;98(6):2024–32 62 Scheen AJ, et al Relationships between sleep quality and glucose regulation in normal humans Am J Physiol Endocrinol Metab 1996;271(2):E261–70 63 Spiegel K, et al Leptin levels are dependent on sleep duration: relationships with sympathovagal balance, carbohydrate regulation, cortisol, and thyrotropin J Clin Endocrinol Metab 2004;89(11):5762–71 64 Spiegel K, et al Adaptation of the 24-h growth hormone profile to a state of sleep debt Am J Physiol 2000;279(3):R874–83 65 Vgontzas A, et al Adverse effects of modest sleep restriction on sleepiness, performance, and inflammatory cytokines J Clin Endocrinol Metab 2004;89(5):2119–26 66 Vgontzas AN, et al Circadian interleukin-6 secretion and quantity and depth of sleep J Clin Endocrinol Metab 1999;84(8):2603–7 67 Modirrousta M, Mainville L, Jones BE Orexin and MCH neurons express c‐Fos differently after sleep deprivation vs recovery and bear different adrenergic receptors Eur J Neurosci 2005;21(10):2807–16 68 White P, et al Electroencephalographic abnormalities during sleep as related to the temporal distribution of seizures Epilepsia 1962;3(2):167–74 69 Frucht MM, et al Distribution of seizure precipitants among epilepsy syndromes Epilepsia 2000;41(12):1534–9 70 Kreuzer P, et al Reduced intra-cortical inhibition after sleep deprivation: a transcranial magnetic stimulation study Neurosci Lett 2011;493(3):63–6 71 Haque B, et al Precipitating and relieving factors of migraine versus tension type headache BMC Neurol 2012;12(1):82 72 Singh NN, Sahota P Sleep-related headache and its management Curr Treat Options Neurol 2013;15(6):704–22 73 Sahota RK, Dexter J Sleep and headache syndromes: a clinical review Headache 1990;30(2):80–4 74 Kelman L, Rains JC Headache and sleep: examination of sleep patterns and complaints in a large clinical sample of migraineurs Headache 2005;45(7):904–10 75 Spierings EL, Ranke AH, Honkoop PC Precipitating and aggravating factors of migraine versus tension‐type headache Headache 2001;41(6):554–8 76 Ong JC, Park M Chronic headaches and insomnia: working toward a biobehavioral model Cephalalgia 2012;32(14):1059–70 77 Hedström AK, et al Shift work at young age is associated with increased risk for multiple sclerosis Ann Neurol 2011;70(5):733–41 78 van Mark A, et al The impact of shift work induced chronic circadian disruption on IL-6 and TNF-a immune responses J Occup Med Toxicol 2010;5:18 79 Chen H, et al A prospective study of night shift work, sleep duration, and risk of Parkinson’s disease Am J Epidemiol 2006;163(8):726–30 80 Gao J, et al Daytime napping, nighttime sleeping, and Parkinson disease Am J Epidemiol 2011;173(9):1032–8 81 Gerner RH, et al Biological and behavioral effects of one night’s sleep deprivation in depressed patients and normals J Psychiatr Res 1979;15(1):21–40 82 Johnson L Psychological and physiological changes following total sleep deprivation In: Kales A, editor Sleep psychology and pathology—a symposium Philadelphia: JB Lippincott; 1969 88 P.C Bollu et al 83 Aubrey J, et al Total sleep deprivation affects memory for a previously learned route Sleep 1999;22:S246 84 Norton R The effects of acute sleep deprivation on selective attention Br J Psychol 1970;61(2):157–61 85 Brendel DH, et al Sleep stage physiology, mood, and vigilance responses to total sleep deprivation in healthy 80‐year‐olds and 20‐year‐olds Psychophysiology 1990;27(6):677–85 86 Lautenbacher S, Kundermann B, Krieg J-C Sleep deprivation and pain perception Sleep Med Rev 2006;10(5):357–69 87 Sivertsen B, et al The epidemiology of insomnia: associations with physical and mental health: the HUNT-2 study J Psychosom Res 2009;67(2):109–16 88 Theadom A, Cropley M, Humphrey K-L Exploring the role of sleep and coping in quality of life in fibromyalgia J Psychosom Res 2007;62(2):145–51 89 Taylor DJ, et al Comorbidity of chronic insomnia with medical problems Sleep 2007;30(2):213 90 Haack M, Mullington JM Sustained sleep restriction reduces emotional and physical wellbeing Pain 2005;119(1):56–64 91 Edwards RR, et al Duration of sleep contributes to next-day pain report in the general population Pain 2008;137(1):202–7 92 Lewandowski AS, et al Temporal daily associations between pain and sleep in adolescents with chronic pain versus healthy adolescents Pain 2010;151(1):220–5 93 Volkow ND, et al Hyperstimulation of striatal D2 receptors with sleep deprivation: implications for cognitive impairment Neuroimage 2009;45(4):1232–40 94 Nascimento DC, et al Pain hypersensitivity induced by paradoxical sleep deprivation is not due to altered binding to brain μ-opioid receptors Behav Brain Res 2007;178(2):216–20 95 Blanco-Centurion CA, Salin-Pascual RJ Extracellular serotonin levels in the medullary reticular formation during normal sleep and after REM sleep deprivation Brain Res 2001;923(1):128–36 96 Pflug B, Tolle R Therapy for endogenous depression by means of sleep deprivation Der Nervenarzt 1971;42:117–24 97 Benedetti F, Colombo C Sleep deprivation in mood disorders Neuropsychobiology 2011;64(3):141–51 98 Giedke H, Wormstall H, Haffner H-T Therapeutic sleep deprivation in depressives, restricted to the two nocturnal hours between 3: 00 and 5: 00 Prog Neuropsychopharmacol Biol Psychiatry 1990;14(1):37–47 99 Giedke H, Schwärzler F Therapeutic use of sleep deprivation in depression Sleep Med Rev 2002;6(5):361–77 100 Gardner JP, Fornal CA, Jacobs BL Effects of sleep deprivation on serotonergic neuronal activity in the dorsal raphe nucleus of the freely moving cat Neuropsychopharmacology 1997;17(2):72–81 101 Amin M, Khalid R, Khan P Relationship between sleep deprivation and urinary MHPG levels Int Pharmacopsychiatry 1979;15(2):81–5 102 Ebert D, Berger M Neurobiological similarities in antidepressant sleep deprivation and psychostimulant use: a psychostimulant theory of antidepressant sleep deprivation Psychopharmacology (Berl) 1998;140(1):1–10 103 Gillin JC, et al Sleep deprivation as a model experimental antidepressant treatment: findings from functional brain imaging Depress Anxiety 2001;14(1):37–49 104 Webb WB, Agnew H Sleep: effects of a restricted regime Science 1965;150(3704): 1745–7 105 Joncas S, et al The value of sleep deprivation as a diagnostic tool in adult sleepwalkers Neurology 2002;58(6):936–40 106 Nielsen T, et al Changes in cardiac variability after REM sleep deprivation in recurrent nightmares Sleep 2010;33(1):113 107 Maycock G Sleepiness and driving: the experience of UK car drivers Accid Anal Prev 1997;29(4):453–62 Sleep Deprivation 89 108 Horne JA, Reyner LA Sleep related vehicle accidents BMJ 1995;310:565–7 109 Wang J-S, Knipling RR, Goodman MJ The role of driver inattention in crashes: new statistics from the 1995 crashworthiness data system In: 40th annual proceedings of the Association for the Advancement of Automotive Medicine 1996 110 Maycock G Sleepiness and driving: the experience of UK car drivers J Sleep Res 1996;5(4):229–31 111 Harris W Fatigue, circadian rhythm, and truck accidents In: Vigilance Heidelberg: Springer; 1977 p 133–46 112 Van Dongen H, Kerkhof G Sleep loss and accidents—work hours, life style, and sleep pathology In: Human sleep and cognition, Part II: clinical and applied research, vol 2; 2011, p 169 113 Philip P, Åkerstedt T Transport and industrial safety, how are they affected by sleepiness and sleep restriction? Sleep Med Rev 2006;10(5):347–56 114 Graeber RC Aircrew fatigue and circadian rhythmicity Chichester: Wiley; 1988 115 Mitler MM, et al Catastrophes, sleep, and public policy: consensus report Sleep 1988;11(1):100 116 Ross WA, RA Pyrology, and microscopical chemistry Science 1880;1(16):193–5 117 Boles K Writing a policies and procedures manual for the dietary department Hospitals 1968;42(21):86–90 118 Herzog JH Proprioceptive cues and their influence on operator performance in manual control NASA CR-1248 NASA Contract Rep NASA CR 1968:1–160 119 Partridge RE, Duthie JJ Rheumatism in dockers and civil servants A comparison of heavy manual and sedentary workers Ann Rheum Dis 1968;27(6):559–68 120 Vaughan JA, Higgins EA, Funkhouser GE Effects of body thermal state on manual performance Aerosp Med 1968;39(12):1310–5 121 Friedman RC, Bigger JT, Kornfeld DS The intern and sleep loss N Engl J Med 1971;285:201–3 122 Saratschev TM [Degenerative articular and extraarticular changes of the elbow as an occupational disease of manual brakemen in railroad traffic] Beitr Orthop Traumatol 1968;15(8):478–81 123 Reinhold H, Tillmann R [Scheuermann’s disease as a social problem in heavy manual labor occupations] Dtsch Gesundheitsw 1968;23(31):1469–72 124 Grantcharov TP, et al Laparoscopic performance after one night on call in a surgical department: prospective study BMJ 2001;323:1222–3 125 Landrigan CP, et al Effect of reducing interns’ work hours on serious medical errors in intensive care units N Engl J Med 2004;351(18):1838–48 126 Lockley SW, et al Effect of reducing interns’ weekly work hours on sleep and attentional failures N Engl J Med 2004;351(18):1829–37 127 Dinges DF Adult napping and its effects on ability to function In: Stampi C, editor Why we nap Boston: Birkhauser; 1992 p 118–34 128 Pilcher JJ, Michalowski KR, Carrigan RD The prevalence of daytime napping and its relationship to nighttime sleep Behav Med 2001;27(2):71–6 129 Taub JM, Tanguay PE, Clarkson D Effects of daytime naps on performance and mood in a college student population J Abnorm Psychol 1976;85(2):210 130 Evans FJ, et al Appetitive and replacement naps: EEG and behavior Science 1977;197(4304):687–9 131 Lumley M, et al The alerting effects of naps in sleep‐deprived subjects Psychophysiology 1986;23(4):403–8 132 Bonnet MH Performance and sleepiness as a function of frequency and placement of sleep disruption Psychophysiology 1986;23(3):263–71 133 Hayashi M, Watanabe M, Hori T The effects of a 20 nap in the mid-afternoon on mood, performance and EEG activity Clin Neurophysiol 1999;110(2):272–9 Chapter The Sleepy Child Suresh Kotagal Excessive daytime sleepiness in childhood is a common but frequently underrecognized health problem It affects both boys and girls The exact prevalence is difficult to determine, but, based upon questionnaire surveys, it seems to vary between and 20 % [1, 2] Sleepiness is important to recognize because many of the underlying conditions are potentially treatable Excessive sleepiness can also become a major public health hazard In a survey of 339 students of 18–21 years of age, Pizza et al found that when subjects with a history of automobile crashes were compared with ones who had not sustained crashes, they found that the former group was significantly more likely to have experienced daytime sleepiness while driving [3] This chapter will provide an overview of excessive sleepiness in childhood What Factors Make Children and Adolescents More Prone to Sleepiness? Physiological changes around adolescence make teenagers more prone to sleepiness These include a physiological delay in onset of the secretion of melatonin, which is the key sleep-inducing hormone Consequently, teens find themselves unable to fall asleep prior to 10:30 or 11:00 p.m Further, the use of electronic media such as cell phones, computers, and television in the 1–2 h prior to bedtime may also in interfere with timely sleep onset Their morning wake-up time on school mornings remains unaltered however at around 5:30 or 6:00 am Consequently, most teens receive only between and h of sleep on most school nights This is further substantiated by the longitudinal study of Iglowstein et al who found that S Kotagal, M.D (*) Division of Child Neurology and Center for Sleep Medicine, Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA e-mail: Kotagal.Suresh@mayo.edu © Springer International Publishing Switzerland 2015 R.K Malhotra (ed.), Sleepy or Sleepless, DOI 10.1007/978-3-319-18054-0_7 91 S Kotagal 92 the mean sleep duration in 10-year-olds was 9.9 ± 0.6 h whereas the mean sleep duration in 16-year-olds had diminished to 8.1 ± 0.7 h [4] The need for optimum sleep however remains at 9–9.5 h Most teens are therefore chronically sleep deprived When specific sleep disorders are superimposed on the above increased propensity for sleepiness, clinically significant sleepiness is likely to emerge Sleep-wake function is driven centrally by dynamic interaction between two opposing processes—process C or the circadian drive for sleep and process S or the homeostatic drive for sleep The circadian drive for sleep is highest at the end of the night’s sleep, which is the time at which the homeostatic drive is at the lowest The homeostatic drive for sleep builds up gradually during wakefulness and dissipates progressively during sleep [5, 6] The timing of sleep and wakefulness is regulated by the circadian system, which is composed of the retinohypothalamic pathway, which transmits lightdependent impulses to the suprachiasmatic nucleus (SCN) of the hypothalamus The SCN serves as our biological clock At the cellular level, the activities of the biological clock are based upon a series of transcription–translation feedback loops that are regulated by a series of genes, including Clock, Bmal1, Period, and Cryptochrome [6] Some of the neurons located in the dorsolateral hypothalamus and the rostral midbrain are wake promoting Cells of the dorsolateral hypothalamus secrete hypocretin (orexin), which has widespread projections to the forebrain as well as the brain stem and plays a major role in enhancing alertness and motor activity [5] Narcolepsy is associated with loss of hypocretin-secreting neurons Histaminergic neurons located in the tuberomammillary nucleus and noradrenergic neurons of the locus ceruleus also play a role in enhancing alertness On the other hand, sleeppromoting structures include the anterior hypothalamus, which contains gamma amino butyric acid, a major inhibitory neurotransmitter What Are Some Common Disorders Leading to Hypersomnia in Childhood and Adolescence? Table 7.1 lists sleep disorders that are commonly associated with excessive daytime sleepiness The relative frequency of these disorders will likely vary from a community practice to a pediatric sleep clinic, with conditions like inadequate sleep Table 7.1 Disorders associated with excessive daytime sleepiness in childhood Health condition Inadequate sleep hygiene Sedation from drugs (prescription or over the counter) Depression Sleep apnea–hypopnea syndrome Narcolepsy Neoplastic, traumatic, and inflammatory brain lesions Kleine–Levin syndrome Idiopathic hypersomnia a Authors opinion based upon clinical practice Relative frequencya ++++ +++ ++ ++ ++ ++ + + The Sleepy Child 93 hygiene being more prevalent in the former setting and indolent problems like narcolepsy, idiopathic hypersomnia, and Kleine–Levin syndrome presenting more often in the sleep clinic environment What Are the Clinical Features of Childhood Excessive Daytime Sleepiness? Excessive sleepiness may be difficult to establish in preschool-age children as physiological daytime napping may still occur at this age Usually, however, most 3–4-year-olds take one nap per day that lasts about 1–2 h Sleepiness in excess of this is generally abnormal Sometimes daytime hyperactivity can be a manifestation of sleepiness at this age as sleepiness can lead to loss of affect control that is mediated by the ventrolateral prefrontal cortex In children of school-going age, mood swings, inattentiveness, and executive dysfunction may occur on a similar basis There may be a decline in school grades as a consequence of impaired attention span due to hypersomnolence In children of school-going age, there may be reappearance of the tendency to take daytime naps The child may be subjected to bullying by peers Patients with depression may have a flat affect or admit to feelings of sadness or anhedonia Obesity and precocious puberty may accompany daytime sleepiness of narcolepsy–cataplexy [7] Cataplexy, a condition characterized by abrupt muscle weakness in response to emotional stimuli like laughter or surprise, is seen in patients with narcolepsy–cataplexy (for details, please refer to the section dealing with narcolepsy) Sleepiness can be documented using questionnaires Some of the questionnaires that are available to the practitioner include the Pediatric Daytime Sleepiness Scale, the modified Epworth Sleepiness Scale, the Sleep Disturbance Scale for Children, the Cleveland Adolescent Sleepiness Scale, the Pediatric Sleep Questionnaire, and the Children’s Sleep Wake Scale [8] The clinician is advised to utilize the questionnaire that best meets the demands of the individual practice The author utilizes the Pediatric Daytime Sleepiness Scale because of its ease of use and numeric representation of the results The sleep history should also inquire into the bed-onset time and sleep-onset time, whether there is significant departure in the sleep time from school nights to non-school nights, feelings of restlessness in the legs prior to sleep onset, hypnagogic hallucinations and sleep paralysis, habitual snoring, periods of observed apnea, restless sleep, and the morning awakening time and whether the patient feels tired or refreshed upon awakening Patients with delayed sleep-phase syndrome generally indicate an inability to fall asleep prior to midnight or early morning and find it hard to awaken prior to the mid-morning hours Elements of the general medical history that are relevant include changes in weight and appetite over the preceding year, thyroid dysfunction, and use of medications that might impact weight such as corticosteroids The history should explore the possibility of alcohol or substance abuse If there have been previous sleep evaluations, their date and result should be documented Medications previously used for treating sleepiness and response to them should be recorded 94 S Kotagal Laboratory Investigations Wrist actigraphy and sleep diary maintained for 2–3 weeks are useful in the case of suspected circadian rhythm sleep disorders like delayed sleep-phase syndrome The wrist actigraph in delayed sleep-phase syndrome will demonstrate delayed sleep onset, relative absence of sleep fragmentation, but persistence of sleep into the midmorning hours A urine drug screen should be used in adolescents whenever there is a suspicion of drug-seeking behavior Nocturnal polysomnography is indicated in patients with hypersomnia suspected to be related to sleep disordered breathing, narcolepsy, or Idiopathic hypersomnia or sleepiness related to conditions like head injury or encephalitis Polysomnographic findings are discussed under specific sleep disorders The multiple sleep latency test (MSLT) is generally conducted on the morning after a nocturnal polysomnogram The test helps to quantify the degree of daytime sleepiness and the nature of the transitions from wakefulness to sleep, i.e., whether into REM or NREM sleep Normal values for the MSLT in children and adolescents vary with age and Tanner stage of sexual development (Table 7.2) Inadequate Sleep Hygiene This entity can occur along with other sleep disorders or may be the sole clinical disturbance It is usually encountered in adolescents There may be relatively late bed-onset time on school nights or non-school nights, with consequent late onset of sleep If the morning wake time, especially for school days remains unaltered around 6:00 a.m., there is a likelihood of daytime sleepiness simply due to insufficient sleep at night The history may reveal other factors that predispose to late sleep onset such as excessive consumption of caffeinated beverages; heavy use of electronic media such as cell phones, computers, and television in the 2–3 h prior to bed time; or exercising late in the evening A warm bath in the 2–3 h prior to bedtime might also postpone sleep by artificially raising body temperature The diagnosis can be facilitated by wrist actigraphy for 2–3 weeks and concurrent sleep logs Table 7.2 Medications commonly used for treating daytime sleepiness Medication Modafinil (Provigil) Armodafinil (Nuvigil) Methylphenidate hydrochloride (Ritalin, Concerta) Methylphenidate hydrochloride sustained release (SR) Methylphenidate hydrochloride (Concerta) Methylphenidate skin patch (Daytrana) Dextroamphetamine (Dexedrine, Dextrostat) Amphetamine/dextroamphetamine mixture (Adderall) Lisdexamfetamine (Vyvanse) Dose 50–200 mg/day 50–250 mg/day 5–60 mg/day in 2–3 divided doses 20–60 mg once a day 18–54 mg once a day 10–30 mg skin patch 5–40 mg once a day 10–40 mg/day 30–70 mg once a day The Sleepy Child 95 There may be a discrepancy between the patient’s record of bed-onset time and the actigraphically derived sleep-onset time The management consists of a frank discussion with the adolescent patient and his or her parents during which the importance of receiving adequate sleep and the adverse effects of sleep deprivation are discussed It is sometimes a good idea to build a buffer of 30–45 of “quiet time” for reflection prior to entering bed in which the use of electronic media is avoided The importance of avoiding nicotine, alcohol, and excessive caffeine should be also stressed Narcolepsy This is a chronic, lifelong disorder characterized by irresistible daytime sleepiness, hypnagogic hallucinations, cataplexy, and sleep paralysis Approximately % of narcolepsy has onset prior to age years Overall, about a third of all patients with narcolepsy have onset of their symptoms prior to the age of 15–16 years Two distinct forms can occur: narcolepsy (type 1) with cataplexy and narcolepsy (type 2) without cataplexy Some patients may initially present only with hypersomnia In these instances, cataplexy may appear 5–10 years after onset of the sleepiness The subtype of narcolepsy type is being increasingly recognized as the more common form in childhood In these cases, cataplexy is often present right at the very onset of symptoms Cataplexy is characterized by abrupt episodes of muscle weakness in response to emotional stimuli like laughter or surprise It is the most reliable manifestation of narcolepsy and is found in approximately 70 % of subjects Younger children with narcolepsy may sometimes manifest transient episodes of facial weakness which can almost appear choreiform There may not be a clear emotional trigger in some patients Precocious puberty and obesity may also accompany narcolepsy–cataplexy Mood swings and feelings of sadness may also accompany childhood narcolepsy The pathophysiology of narcolepsy–cataplexy is characterized by a genetic predisposition (HLA DQB1*0602 positivity), which is present in over 95 % of cases When the patient is subjected to an immunological challenge, such as influenza, influenza immunization, or Streptococcus pyogenes infection, there is an immunemediated degeneration of the hypocretin-secreting neurons of the dorsolateral hypothalamus [9] This region is the major site for the synthesis of hypocretin (orexin), a peptide that enhances alertness and motor activity The deficiency of hypocretin can be determined by assessing cerebrospinal fluid levels of hypocretin, which is below 110 pg/mL in narcolepsy–cataplexy The diagnosis of narcolepsy has traditionally been made on the basis of a combined battery of nocturnal polysomnogram and the MSLT The nocturnal polysomnogram may show a sleep-onset REM period (onset within 15 of sleep onset), a reduced latency to REM sleep of