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Postgraduate Education Corner: CONTEMPORARY REVIEWS IN SLEEP MEDICINE |

There and Back Again: A Current History of Sleep Medicine FREE TO VIEW

Douglas Benjamin Kirsch, MD; American Association for the Advancement of Science
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From the Division of Sleep Medicine, Harvard Medical School, Brighton, MA.

Correspondence to: Douglas Benjamin Kirsch, MD, Sleep HealthCenters, 1505 Commonwealth Ave, 5th Floor, Brighton, MA 02135; e-mail: Doug_Kirsch@sleephealth.com


Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/site/misc/reprints.xhtml).


© 2011 American College of Chest Physicians


Chest. 2011;139(4):939-946. doi:10.1378/chest.10-1235
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Sleep science has been a vigorously evolving field over the past 60 years, and the practice of sleep medicine has become increasingly complex with a growing number of tests and treatments. This article briefly traces the history of the field of sleep science over the past three millennia. The foundations of sleep medicine can be traced back to ancient civilizations around the globe. Many philosophers, scientists, and researchers have espoused theories about the causes of sleep throughout the centuries, theories that have become more intricate as our understanding of medicine and neurobiology has continued to advance.

As the field of sleep medicine matures and evolves on the basis of a changing medical and scientific research landscape, an understanding of the underpinnings of our field may have significance. The story of our progenitor sleep theoreticians, researchers, and physicians educates us about the ongoing struggles to sleep throughout the centuries as well as the effort of science to understand why and how we sleep.

It is worthwhile to consider our current confidence in our clinical practice of sleep medicine and our satisfaction in the depth of our biologic understanding of sleep. Looking back at the practice of leeching in medicine centuries ago, we might have laughed at its folly, yet medical science now recognizes that the functions of the leech again has value in certain medical conditions.1 Perhaps, we can still learn from our past. As our field looks forward toward continued growth and deeper understanding, a quick glance in the rearview mirror might prove worthwhile, remembering our field in its infancy and adolescence.

Allan Hobson2 wrote in his book Sleep, “More has been learned about sleep in the last 60 years than in the past 6000.” That being said, many ancient cultures attempted to understand the phenomenon of sleep. The history of sleep medicine begins in the distant human past, in multiple civilizations. The knowledge of the science of sleep in ancient days is limited, partially due to the limited surviving writings and partially to our ability to decipher them.

Egypt

Information about Egyptian medicine has been decoded through available papyri; only a few of the scrolls have revealed information that might pertain to sleep disorders. The Edwin-Smith papyrus and the Ebers papyrus are the keystone texts of our current understanding of historical Egyptian surgery as well as of assessment and treatment of numerous ailments.3 The poppy seed, a source of opium, was described in the Ebers papyrus to be a treatment of pain; it has been suggested that poppy may also have been used as a treatment of insomnia.4 Nightshade (scopolamine) and alcohol, also available in Egypt, may have had similar uses.5 The mere existence of the Chester Beatty papyrus, with a strong focus on dream interpretation, conveys the importance of dreams in the Egyptian culture.6

Greece

Medicine of the ancient Greek civilization has survived more thoroughly due to the larger volume of surviving and interpretable texts. Alcmaeon, in approximately 500 bce, wrote that “sleep is produced by the withdrawal of the blood away from the surface of the body to the larger (‘blood-flowing’) vessels and that we awake when the blood diffuses throughout the body again.”7 Around 300 bce, Aristotle, who had a similar interest in sleep, wrote an entire opus (translated as On Sleep and Sleeplessness) devoted to sleep and waking.8 Aristotle theorized that sleep was the converse of wake: “waking and sleep appertain to the same part of the animal, inasmuch as they are opposites, and sleep is evidently a privation of waking.”9 Aristotle further explained the relationship between sleep and food, describing the manner in which ingesting food causes sleepiness through “fumes” that are carried through the blood vessels into the brain.10 In 300 bce, Hippocrates, considered by some to be the father of Greek medicine, wrote about sleep and its relationship to health11:

With regard to sleep—as is usual with us in health, the patient should wake during the day and sleep during the night. If this rule be anywise altered it is so far worse: but there will be little harm provided he sleep in the morning for the third part of the day; such sleep as takes place after this time is more unfavorable; but the worst of all is to get no sleep either night or day; for it follows from this symptom that the insomnolency is connected with sorrow and pains, or that he is about to become delirious.

Followers of Asclepius, the Greek god of healing, made pilgrimages to his temples when they or their family members were ill. After cleansing rituals, they were admitted to the sanctuary where a visit from the god might occur during dreams and guide them to a cure. If this did not occur, the priests of Asclepius often were able to interpret the dreams and prescribe a therapy.12 One example of cure through dreaming was as follows13:

Arata, a woman of Lacedaemon (Sparta), was dropsical. While she remained in Lacedaemon, her mother slept in the temple on her behalf and saw a dream. It seemed to her that the god cut off her daughter’s head and hung up her body in such a way that her throat was turned downwards. Out of it came a huge amount of fluid. He then took down the body and fitted her head back onto her neck. After she had seen this dream she went back to Lacedaemon where she found her daughter in good health; she had seen the same dream (Inscriptiones Graecae, IV, 1, 121-2, Stele I: Cures of Apollo and Asclepius).

Homer, the Greek poet, scribed that Hypnos and Thanatos (the god of sleep and god of death, respectively) were brothers, demonstrating the believed link in Greek thought between the two states of repose, one temporary and one more permanent: “What else is sleep but the image of chill death?”14 He also wrote astutely in The Odyssey, “There is a time for many words, and there is a time for sleep.”15

China

China has a long history of medical innovation, predating the time frame of Greek and Roman medical thought. The Huangdi Neijing, or Canon of Medicine, was perhaps written as early as 2900 bce, but the surviving text dates to the third century bce. This manuscript introduced the theory of yin and yang, a symbol that also has been used to represent sleep and wake.16 Acupuncture and herbal/natural treatments were emphasized in the Huangdi Neijing for many disorders; sleep disorders, although not referenced specifically, may have been treated similarly. Other options available for treatment of sleep disorders included ephedra (or ma huang), a stimulant medication, and ginseng, potentially used for the purposes of activation or relaxation.5

Religious Writings

Western religious texts also reveal beliefs around the importance of sleep. Ecclesiastes 5:12 from the Bible states, “Sweet is the sleep of a laborer”; one interpretation of this statement is that hard work can lead to better sleep.17 Dreams were a method of prophecy frequently referenced in the Bible; for example, Joseph’s dreams remain a fixture in the book of Genesis.18 The Talmud, one of the core treatises of Judaic faith, remarks that “sleep is one-sixtieth death,” again linking the temporary loss of consciousness with a more permanent state, similar to the thoughts of the Greek philosophers.19 Maimonides, a Jewish philosopher in the late 1100s, wrote the following about appropriate sleeping hours in the Mishneh Torah, a compendium of laws20:

The day and night consist of 24 hours. It is sufficient for a person to sleep one third thereof which is eight hours. These should be at the end of the night so that from the beginning of sleep until the rising of the sun will be eight hours. Thus he will arise from his bed before the sun rises.

Western medical schools and hospitals began to prosper at the end of the Middle Ages in France and Italy. Although mysticism and astrology held a strong foothold in common thought, in some locations, ancient Greek medical theories resurfaced with the emergence of the medical schools.

The 17th century is commonly referred to as the Scientific Revolution; this was the time of Descartes. He espoused a new model of sleep, one of hydraulics, in which the pineal gland played the gatekeeper role between sleep and alertness. Descartes focused on the pineal gland because of his beliefs regarding its function in sensation, memory, and bodily movements, although this viewpoint correlated with neither ancient understanding nor 17th-century knowledge about its function.21 During sleep, he theorized that the pineal gland would only produce a small amount of “animal spirits,” causing the ventricles of the brain to collapse and the nerves (which act as pipes carrying fluid) to become limp. During wakefulness, the pineal gland would be much more active, keeping the ventricles open.5

Thomas Willis, one of the fathers of neurology, had ground-breaking opinions on sleep, sleepwalking, and insomnia.22 His book, The Practice of Physick, published in 1692, has several references related to sleepiness and insomnia; he also recognized coffee’s effect on sleep.23 Willis’s writings regarding “animal spirits” in the cerebellum and their derangement in dreams fit within the context of Descartes’s hydraulic model, and his descriptions of narcolepsy and restless legs syndrome still ring true today:

…a sleepy disposition—[when] they eat and drink well, go abroad, take care well enough of their domestick affairs, yet whilst talking, or walking, or eating, yea their mouths being full of meat, they shall nod, and unless rouzed up by others, fall fast asleep.23

…so great a restlessness and tossing of their [limbs] ensue, that the diseased are no more able to sleep than if they were in a place of greatest torture.24

Biologic rhythms began to be more prominently studied by Jean Jacques d’Ortous de Mairan and Carl von Linné (Linnaeus) in the mid-18th century. De Mairan reported in 1729 that a heliotrope plant kept a stable pattern of opening its blooms for the day, even when kept in a dark environment without the sun for a cue. Linnaeus’s flower clock demonstrated that one could use the pattern of blooming times for certain flower species to tell what time of day it was, revealing that even lowly plants had entrained clocks.25 Around the same time, Albrecht von Haller wrote his Elementa physiologiae corporis humani. Von Haller’s book included pages on the physiology of sleep, many of them supporting his theory that blood flow to the brain caused increased pressure, which led to sleep.5

Scientists in the beginning of the 19th century demonstrated a keen interest in brain function. Luigi Rolando was able to induce a “sleep-like state” in birds in 1809 by the removal of the cerebral hemisphere.5 This experiment was replicated in pigeons by Marie Jean Pierre Flourens in 1822: “Just imagine [an] animal which has been condemned to be permanently asleep, one that has been devoid even of the ability to dream during sleep.”5

Four primary theories of sleep were postulated in this time period: vascular, chemical, neural, and behavioral. The vascular theory had its roots in ancient Greek medicine based on Alcmaeon’s supposition that blood filling the brain was the cause of sleep. Von Haller’s theories went a step further, suggesting that blood flow caused brain swelling, cutting off animal spirits. One of the first books devoted entirely to sleep and its disorders was written by a Scottish physician, Robert MacNish, in the 1830s. This book, The Philosophy of Sleep, supported the congestive theory of blood flow but also advocated the duality of sleep: the active state of the brain during the wake state and the passive condition of the brain during sleep at which time sensory input was reduced to allow for recuperation.26

The theory of increasing blood flow being causative of sleep conflicted with Johann Friedrich Blumenbach’s ideas. He observed a pale brain surface through a skull window in a sleeping subject compared with when awake, signifying perhaps that low blood flow was the cause of sleep.27 Through a variety of methods of observing blood flow (retinal arteries, direct observation of the brain), several other physicians championed this alternative vascular theory.

Camillo Golgi first demonstrated the nerve cell in 1873, and several neural theories of sleep were based on his study of neurohistology.28 Hermann Rabl-Ruckhard posited the theory of “neurospongium” in 1890, which involved blockage of information transfer between neurons, allowing for sleep.5 Other scientists suggested alternate models of axonal and dendritic changes of the neurons relating to sleep, but it was not until the 1900s that neurotransmitters became the dominant model for brain information transfer.9

Sleep being caused by a chemical process harkened back to Aristotle and his sleep-inducing, food-related “fumes.” Hypotheses abounded regarding the primary “toxin,” including decreased oxygen, increased lactic acid, and other products. A particularly prominent theory came from Leo Errera of Brussels, who suggested that leucomaines were substances that accumulated during wake and were broken down during sleep.29 Other suggestions for chemical compounds related to sleep induction included carbon dioxide and “urotoxins.”9

The final major theory type appeared as behavioral explanations at the end of the 1800s. These theories tended to describe the activity rather than to provide an underlying explanation. In 1889, Charles-Édouard Brown-Séquard, a prominent neurologist, wrote that sleep was an inhibitory reflex.9 Marie de Manaceine wrote in 1897 that sleep was the “resting state of consciousness.”5 Pavlov and others continued to expand on this theory well into the 20th century.

During the 1800s, the study of circadian rhythms began on the human body. James George Davey evaluated his own core body temperature in 1845. Several years later (1866), William Ogle described a similar pattern5:

There is a rise in the early morning while we are still asleep, and a fall in the evening while we are still awake, which cannot be explained by reference to any of the hitherto mentioned influences. They are not due to variations in light; they are probably produced by periodic vacations in the activity of the organic functions.

The 19th century was the time of advances in the more practical aspects of sleep medicine. The first medication produced specifically to induce sleep was bromide in 1853. Several other options followed in the latter half of the century, including paraldehyde, urethane, and sulfonal.5 William Hammond, a physician during the Civil War, wrote Sleep and Its Derangements in 1869, primarily discussing insomnia.30 In 1880, Jean-Baptiste-Édouard Gélineau described the clinical manifestations of narcolepsy.31 Although mostly scientists and philosophers have described sleep disorders, Charles Dickens, British novelist of the 19th century, described the character (or perhaps caricature) of Joe, the fat boy, who represented a severe case of sleep apnea or obesity hypoventilation32:

“Damn that boy,” said the old gentleman, “he’s gone to sleep again.”

“Very extraordinary boy, that,” said Mr. Pickwick; “does he always sleep in this way?”

“Sleep!” said the old gentleman, “he’s always asleep. Goes on errands fast asleep, and snores as he waits at table.”

“How very odd!” said Mr. Pickwick.

“Ah! odd indeed,” returned the old gentleman; “I’m proud of that boy—wouldn’t part with him on any account—he’s a natural curiosity! Here, Joe—Joe—take these things away, and open another bottle—d’ye hear?”

The fat boy rose, opened his eyes, swallowed the huge piece of pie he had been in the act of masticating when he last fell asleep, and slowly obeyed his master’s orders….

Ivan Pavlov’s behavioral theory of sleep appeared to become more prominent as the chemical and vascular theories of sleep faded. Pavlov wrote, “Sleep…is an inhibition which has spread over the great section of the cerebrum, over the entire hemispheres and even into the lower lying mid-brain.”5 His dog studies demonstrated that a monotonous stimulus would be followed by drowsiness and sleep, but the underlying physiology of this process was less well described.

Steps Toward the Polysomnogram

Although the electrical activity of the nervous system was demonstrated by Luigi Galvani in the 18th century and action potentials in the brain were discovered by Richard Caton in 1875, it was not until 1925 that Hans Berger measured the electrical activity of the human brain.33 He described α and β waves from his “Elektrenkephalogramm” in his publications in 1929. Alfred Loomis took this device, using it to evaluate brain wave changes during sleep in 1937.34 Two groups performed the majority of sleep-related research in the late 1930s: E. Newton Harvey, Garret Hobart, Alfred Loomis, Pauline Davis, and Hallowell Davis at Harvard University and Helen Blake, Ralph Gerard, and Nathaniel Kleitman at the University of Chicago. Loomis’s group listed sleep stages A to E, from the rhythm of wakefulness to stages of deep non-rapid eye movement (NREM) sleep, in order of resistance to change by disturbance.35 Sleep staging advanced a step further with the discovery of rapid eye movement (REM) sleep by Kleitman and his student Eugene Aserinsky in 1953 after observation of episodic eye movements during sleep in infants. They developed the electrooculogram to help better characterize the eye movements, noting both rapid and slow eye motions. Then, when questioning subjects about dreaming, vivid visual dreams were more commonly reported during the REM phase.36 Kleitman and William Dement then applied this knowledge and the new technology to demonstrate the recurring pattern of REM and NREM sleep; sleep was no longer a purely homogenous state with low frequency EEG, much to the surprise of many others working in the field. Kleitman37 wrote:

It is very difficult today [circa 1990] to understand and appreciate the exceedingly controversial nature of these findings. I wrote them up, but the paper was nearly impossible to publish because it was completely contradictory to the dominant neurophysiological theory of the time. The assertion by me that an activated EEG could be associated with unambiguous sleep was considered to be absurd.

In the 1960s, the Association for the Psychophysiological Study of Sleep met to discuss research findings and to create a consistent system for sleep staging. In 1967, Allan Rechtschaffen and Anthony Kales became cochairs of an expert committee from the association’s membership, including several luminaries in the sleep field, tasked to develop a scoring manual for human sleep. A Manual of Standardized Terminology, Techniques, and Scoring System for Sleep Stages of Human Subjects was published in 1968 with the hope that it would “markedly increase the comparability of results reported by different investigators.”38 With this publication, a formal definition of the polysomnogram was now in place, defining a sleep epoch as 30 s and clarifying the stages of sleep (wakefulness, movement time, stages 1-4 [NREM sleep], and REM sleep).38 The polysomnographic technology could be used to evaluate not only nighttime sleep but also daytime sleepiness. The Mean Sleep Latency Test was developed in the early 1980s and used to evaluate daytime sleep propensity, particularly in persons with narcolepsy.39 Formal guidelines of this test were published a few years later in 1986.40 The original reports of the Maintenance of Wakefulness Test being used to examine the ability of subjects to remain awake in sleep-inducing circumstances came in 1982.41 Yet, normative data for this test were not published until many years later in 1997.42

Neurophysiology of Sleep

The neurophysiology of sleep in the 20th century developed from Constantin von Economo’s work based on viral encephalitis in Europe in the 1910s (encephalitis lethargica). He linked posterior hypothalamic pathology with symptoms of hypersomnia and was able to correlate lesions in the preoptic area and anterior hypothalamus with the clinical complaint of insomnia.43 Meanwhile, in 1913, the first book evaluating sleep from a physiological perspective, Le Probleme Physiologique Du Sommeil, was written by Henri Pieron in France.44 The relationship of the thalamus to sleep was confirmed by Walter Hess in an experiment showing that stimulation of the central gray matter of the thalamus induced sleep.45 Further experimentation by Frédéric Bremer at the University of Brussels in 1935 was able to demonstrate through transaction of the midbrain that sleep and wake continued in the brain on EEG.46 Giuseppe Moruzzi and Horace Magoun47 located the ascending reticular activating system in 1949, later demonstrated to be the center of wakefulness. Following the discovery of REM sleep on the EEG, Michel Jouvet’s work focused on the localization and neurobiology of REM sleep, demonstrating that stimulating the caudal mesencephalic region or pontine tegmentum led to an REM-like state.48 The anatomy of sleep has continued to be defined in several laboratories across the world, though discussion continues about how the neuroanatomical and neurochemical transitions between wake and sleep, as well as the converse, occur.

Circadian Rhythms

Over the early portion of the 20th century, studies of animal models of circadian rhythms were conducted, looking at bees and rodents. Initial studies in 1965 by Curt Richter suggested that the anterior-ventral hypothalamus was the home of the biologic clock.49 Closer evaluation in the early 1970s by multiple groups revealed the biologic location of the clock to be a portion of the anterior hypothalamus known as the suprachiasmatic nucleus.50 In the same time frame, multiple researchers began to assess human circadian rhythms without the effects of sunlight, moving to specialized laboratories or lightless caves and demonstrating a biologic rhythm of slightly > 24 h. The circadian rhythmicity of cortisol secretion was demonstrated by Elliot Weitzman in the late 1960s, and he, along with Charles Czeisler, established the relationship among temperature, the endocrine system, and the sleep-wake cycle.51 Czeisler went on to further establish the effects of light and dark in entrainment of the circadian cycle.52

Evaluation and Treatment of Sleep Disorders

Although insomnia was viewed as treatable with the advent of many sleep-induction medications, particularly the benzodiazepines developed in the 1970s, other areas of sleep disorders were in their infancy. Nonmedication treatments for insomnia, such as stimulus control (Richard Bootzin in 1972) and sleep restriction (Arthur Spielman in 1987), were later found to be at least as effective as medications when applied as a program of cognitive-behavioral therapy.53-55 Obstructive sleep apnea (OSA), though recognized by William Osler in the 19th century, was not demonstrated on a polysomnogram until 1965 by Henri Gastaut. Tracheostomy was the sole treatment option for OSA until the uvulopalatopharyngoplasty was developed for snoring in 1964 by Takenosuke Ikematsu, a surgery that was later applied to sleep apnea.56 Continuous positive airway pressure was developed in 1980 by Colin Sullivan and has become the gold standard for treatment of OSA.57 Although an early description of restless legs was written by Thomas Willis in the late 1600s, the syndrome was not named “restless legs” and described in detail until Karl-Axel Ekbom published his report of eight patients in 1944 and his doctoral thesis “Restless legs: a clinical study of a hitherto overlooked disease in the legs characterized by peculiar paraesthesia (‘Anxietas tibiarum’), pain and weakness and occurring in two main forms, asthenia crurum paraesthetica and asthenia crurum dolorosa” in 1945.58 Narcolepsy was described initially in the late 19th century, but stimulants were not applied until the 1930s.59 The well-described REM sleep onsets were first observed in persons with narcolepsy in 1960 by Gerald Vogel.60 Although many books were devoted to sleep, it was not until the Association of Sleep Disorders Centers produced the Diagnostic Classification of Sleep and Arousal Disorders in 1989 that the disorders were organized and defined in one widely used book. This book evolved into what is now the International Classification of Sleep Disorders, currently in its second edition.

The late 20th and early 21st century have seen the advent of new medications for treatment of sleep disorders. The most influential medication was zolpidem; approved for the treatment of insomnia by the US Food and Drug Administration (FDA) in 1993.61 This medication, a “nonbenzodiazepine” receptor agonist, was marketed as being more specific to sleep initiation than the original benzodiazepines. Several medications followed zolpidem to the market, many with similar modes of action, including zopiclone, zaleplon, and eszopiclone. Others had different neurochemical functions, such as ramelteon, which acts as a melatonin receptor agonist. Restless legs syndrome was treated with dopamine agonists, with ropinirole being the first agent approved by the FDA in 2005, followed by pramipexole in 2006.62 Although amphetamine-based stimulants had been the treatment gold standard to improve alertness for many years and continue to be frequently used, a new stimulant, modafinil, was granted orphan drug status by the FDA in 1998.63 Although modafinil’s mode of action remains somewhat unclear, it has been commonly used for narcolepsy, sleepiness post-OSA treatment, and shift-work disorder.64 Another orphan drug, sodium oxybate, a sleep-induction drug, was approved by the FDA in 2002 for use in narcolepsy for symptoms of daytime sleepiness and cataplexy.65

Growth of a Field

One of the earliest meetings of sleep researchers occurred in Italy in 1967, the findings of which were published under the title Abnormalities of Sleep in Man. Clinical assessment of sleep disorders in a formal clinic began in the United States at the Stanford University Narcolepsy clinic in the 1960s under the direction of Dr William Dement. Although the model did not prove to be financially sustainable initially, persistence proved worthwhile, as the Stanford University Sleep Disorders Clinic opened in 1970. As other clinics began to open across the United States, they began to meet as the Association of Sleep Disorders Centers, which eventually merged with other groups to form what is now known as the American Academy of Sleep Medicine.66 The American Medical Association recognized sleep medicine as a specialty in 1995.66 The number of sleep laboratories or centers has grown steadily since the mid-1990s, and today, there are an estimated 3,000 to 3,500 of them operating in the United States.67

This article has reviewed sleep medicine from several hundred years bce and forward; however, for more indepth and personal accounts of the growth of this field in the 20th and 21st centuries, I recommend articles from Drs Shepard66 and Dement.37

Public interest in sleep and sleep medicine has increased over the past decade, particularly as researchers have gained a better understanding of sleep disorders and the effects of sleep on daytime functioning. However, sleep medicine continues to face challenges in an environment of medical cost containment and relatively limited treatment options. The goals of the field should be to continue to expand our understanding of the science of sleep, to increase the specificity of sleep testing, and to improve sleep disorders treatment options. Human fascination with sleep has persisted from ancient times to current days. While we continue to unravel the mysteries of sleep, we can hope that our theories stand up to future generations looking back.

Financial/nonfinancial disclosures: The author has reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Other contributions: I would like to indicate my appreciation for two particular texts in my research: Dr Michael Thorpy’s chapter “History of Sleep and Man” in his book The Encyclopedia of Sleep and Sleep Disorders and Dr Nathaniel Kleitman’s book Sleep and Wakefulness were essential sources in writing this article.

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Dement WC. History of sleep medicine. Neurol Clin. 2005;234:945-965. [CrossRef] [PubMed]
 
Rechtschaffen A, Kales A. A Manual of Standardized Terminology, Techniques and Scoring System for Sleep Stages of Human Subjects. 1968; Washington, DC Public Health Service, US Government Printing Office
 
Richardson GS, Carskadon MA, Flagg W, Van den Hoed J, Dement WC, Mitler MM. Excessive daytime sleepiness in man: multiple sleep latency measurement in narcoleptic and control subjects. Electroencephalogr Clin Neurophysiol. 1978;455:621-627. [CrossRef] [PubMed]
 
Carskadon MA, Dement WC, Mitler MM, Roth T, Westbrook PR, Keenan S. Guidelines for the multiple sleep latency test (MSLT): a standard measure of sleepiness. Sleep. 1986;94:519-524. [PubMed]
 
Mitler MM, Gujavarty KS, Browman CP. Maintenance of wakefulness test: a polysomnographic technique for evaluation treatment efficacy in patients with excessive somnolence. Electroencephalogr Clin Neurophysiol. 1982;536:658-661. [CrossRef] [PubMed]
 
Doghramji K, Mitler MM, Sangal RB, et al. A normative study of the maintenance of wakefulness test (MWT). Electroencephalogr Clin Neurophysiol. 1997;1035:554-562. [CrossRef] [PubMed]
 
Triarhou LC. The percipient observations of Constantin von Economo on encephalitis lethargica and sleep disruption and their lasting impact on contemporary sleep research. Brain Res Bull. 2006;693:244-258. [CrossRef] [PubMed]
 
A brief history of sleep research. The Stanford Sleep Well Web site.http://www.stanford.edu/~dement/history.htmlAccessed October 24, 2010.
 
Hess CW, Walter R. Hess (17.3.1881–12.8.1973). Schweiz Arch Neurol Psychiatry. 2008;1594:255-261
 
Kerkhofs M, Lavie P. Frédéric Bremer 1892-1982: a pioneer in sleep research. Sleep Med Rev. 2000;45:505-514. [CrossRef] [PubMed]
 
Moruzzi G, Magoun HW. Brain stem reticular formation and activation of the EEG. Electroencephalogr Clin Neurophysiol. 1949;14:455-473. [PubMed]
 
Fuller PM, Saper CB, Lu J. The pontine REM switch: past and present. J Physiol. 2007;584pt 3:735-741. [CrossRef] [PubMed]
 
Schulkin J, Rozin P, Stellar E. Curt P. Richter 1894–1988. 1994; Washington, DC National Academy of Sciences
 
Weaver DR. The suprachiasmatic nucleus: a 25-year retrospective. J Biol Rhythms. 1998;132:100-112. [CrossRef] [PubMed]
 
Czeisler CA, Weitzman E, Moore-Ede MC, Zimmerman JC, Knauer RS. Human sleep: its duration and organization depend on its circadian phase. Science. 1980;2104475:1264-1267. [CrossRef] [PubMed]
 
Czeisler CA, Richardson GS, Zimmerman JC, Moore-Ede MC, Weitzman ED. Entrainment of human circadian rhythms by light-dark cycles: a reassessment. Photochem Photobiol. 1981;342:239-247. [PubMed]
 
Bootzin RR, Nicassio PM.Hersen M, Eissler R, Miller P. Behavioral treatments for insomnia. Progress in Behavior Modification. 1978;Vol 6 New York, NY Academic Press:1-45
 
Spielman AJ, Saskin P, Thorpy MJ. Treatment of chronic insomnia by restriction of time in bed. Sleep. 1987;101:45-56. [PubMed]
 
Jacobs GD, Pace-Schott EF, Stickgold R, Otto MW. Cognitive behavior therapy and pharmacotherapy for insomnia: a randomized controlled trial and direct comparison. Arch Intern Med. 2004;16417:1888-1896. [CrossRef] [PubMed]
 
Ikematsu T. Study of snoring, 4th report: therapy. J Jpn Otorhinolaryngology. 1964;64:434-435
 
Sullivan C. Past, present and future of CPAP. National Sleep Foundation Web site. http://www.sleepfoundation.org/article/ask-the-expert/past-present-and-future-cpap. Accessed May 1, 2010.
 
Ekbom K, Ulfberg J. Restless legs syndrome. J Intern Med. 2009;2665:419-431. [CrossRef] [PubMed]
 
Prinzmetal M, Bloomberg W. The use of benzedrine for the treatment of narcolepsy. J Am Med Assoc. 1935;10525:2051-2054. [CrossRef]
 
Vogel G. Studies in psychophysiology of dreams. III. The dream of narcolepsy. Arch Gen Psychiatry. 1960;3:421-428. [CrossRef] [PubMed]
 
Downs MF. To sleep, perchance to…walk: reports raise questions about sleeping pill side effect. Is Ambien sleepwalking understated? Washington Post. March 14, 2006; http://www.washingtonpost.com/wp-dyn/content/article/2006/03/13/AR2006031301317.html. Accessed April 25, 2010.
 
Medical and scientific info. The RLS Foundation Web site.http://www.rls.org/Page.aspx?pid=523. Accessed October 24, 2010.
 
Provigil Web site.http://www.provigil.com/index.php?t=hcp&p=homeAccessed October 24, 2010.
 
History of Xyrem®: what is an orphan drug? Xyrem Web site. http://www.xyrem.com/learn/. Accessed May 5, 2010.
 
Shepard JW Jr, Buysse DJ, Chesson AL Jr, et al. History of the development of sleep medicine in the United States. J Clin Sleep Med. 2005;11:61-82. [PubMed]
 
Sleep centers, sleep labs. SleepWeb Web site. http://www.sleepweb.com/SleepLabs/SleepLabs.aspx. Accessed May 1, 2010.
 

Figures

Tables

References

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Haas LF. Hans Berger (1873-1941), Richard Caton (1842-1926), and electroencephalography. J Neurol Neurosurg Psychiatry. 2003;741:9. [CrossRef] [PubMed]
 
Deak M, Epstein LJ. The history of polysomnography. Sleep Med Clin. 2009;43:313-321. [CrossRef]
 
Aserinsky E, Kleitman N. Regularly occurring periods of eye motility, and concomitant phenomena, during sleep. Science. 1953;1183062:273-274. [CrossRef] [PubMed]
 
Dement WC. History of sleep medicine. Neurol Clin. 2005;234:945-965. [CrossRef] [PubMed]
 
Rechtschaffen A, Kales A. A Manual of Standardized Terminology, Techniques and Scoring System for Sleep Stages of Human Subjects. 1968; Washington, DC Public Health Service, US Government Printing Office
 
Richardson GS, Carskadon MA, Flagg W, Van den Hoed J, Dement WC, Mitler MM. Excessive daytime sleepiness in man: multiple sleep latency measurement in narcoleptic and control subjects. Electroencephalogr Clin Neurophysiol. 1978;455:621-627. [CrossRef] [PubMed]
 
Carskadon MA, Dement WC, Mitler MM, Roth T, Westbrook PR, Keenan S. Guidelines for the multiple sleep latency test (MSLT): a standard measure of sleepiness. Sleep. 1986;94:519-524. [PubMed]
 
Mitler MM, Gujavarty KS, Browman CP. Maintenance of wakefulness test: a polysomnographic technique for evaluation treatment efficacy in patients with excessive somnolence. Electroencephalogr Clin Neurophysiol. 1982;536:658-661. [CrossRef] [PubMed]
 
Doghramji K, Mitler MM, Sangal RB, et al. A normative study of the maintenance of wakefulness test (MWT). Electroencephalogr Clin Neurophysiol. 1997;1035:554-562. [CrossRef] [PubMed]
 
Triarhou LC. The percipient observations of Constantin von Economo on encephalitis lethargica and sleep disruption and their lasting impact on contemporary sleep research. Brain Res Bull. 2006;693:244-258. [CrossRef] [PubMed]
 
A brief history of sleep research. The Stanford Sleep Well Web site.http://www.stanford.edu/~dement/history.htmlAccessed October 24, 2010.
 
Hess CW, Walter R. Hess (17.3.1881–12.8.1973). Schweiz Arch Neurol Psychiatry. 2008;1594:255-261
 
Kerkhofs M, Lavie P. Frédéric Bremer 1892-1982: a pioneer in sleep research. Sleep Med Rev. 2000;45:505-514. [CrossRef] [PubMed]
 
Moruzzi G, Magoun HW. Brain stem reticular formation and activation of the EEG. Electroencephalogr Clin Neurophysiol. 1949;14:455-473. [PubMed]
 
Fuller PM, Saper CB, Lu J. The pontine REM switch: past and present. J Physiol. 2007;584pt 3:735-741. [CrossRef] [PubMed]
 
Schulkin J, Rozin P, Stellar E. Curt P. Richter 1894–1988. 1994; Washington, DC National Academy of Sciences
 
Weaver DR. The suprachiasmatic nucleus: a 25-year retrospective. J Biol Rhythms. 1998;132:100-112. [CrossRef] [PubMed]
 
Czeisler CA, Weitzman E, Moore-Ede MC, Zimmerman JC, Knauer RS. Human sleep: its duration and organization depend on its circadian phase. Science. 1980;2104475:1264-1267. [CrossRef] [PubMed]
 
Czeisler CA, Richardson GS, Zimmerman JC, Moore-Ede MC, Weitzman ED. Entrainment of human circadian rhythms by light-dark cycles: a reassessment. Photochem Photobiol. 1981;342:239-247. [PubMed]
 
Bootzin RR, Nicassio PM.Hersen M, Eissler R, Miller P. Behavioral treatments for insomnia. Progress in Behavior Modification. 1978;Vol 6 New York, NY Academic Press:1-45
 
Spielman AJ, Saskin P, Thorpy MJ. Treatment of chronic insomnia by restriction of time in bed. Sleep. 1987;101:45-56. [PubMed]
 
Jacobs GD, Pace-Schott EF, Stickgold R, Otto MW. Cognitive behavior therapy and pharmacotherapy for insomnia: a randomized controlled trial and direct comparison. Arch Intern Med. 2004;16417:1888-1896. [CrossRef] [PubMed]
 
Ikematsu T. Study of snoring, 4th report: therapy. J Jpn Otorhinolaryngology. 1964;64:434-435
 
Sullivan C. Past, present and future of CPAP. National Sleep Foundation Web site. http://www.sleepfoundation.org/article/ask-the-expert/past-present-and-future-cpap. Accessed May 1, 2010.
 
Ekbom K, Ulfberg J. Restless legs syndrome. J Intern Med. 2009;2665:419-431. [CrossRef] [PubMed]
 
Prinzmetal M, Bloomberg W. The use of benzedrine for the treatment of narcolepsy. J Am Med Assoc. 1935;10525:2051-2054. [CrossRef]
 
Vogel G. Studies in psychophysiology of dreams. III. The dream of narcolepsy. Arch Gen Psychiatry. 1960;3:421-428. [CrossRef] [PubMed]
 
Downs MF. To sleep, perchance to…walk: reports raise questions about sleeping pill side effect. Is Ambien sleepwalking understated? Washington Post. March 14, 2006; http://www.washingtonpost.com/wp-dyn/content/article/2006/03/13/AR2006031301317.html. Accessed April 25, 2010.
 
Medical and scientific info. The RLS Foundation Web site.http://www.rls.org/Page.aspx?pid=523. Accessed October 24, 2010.
 
Provigil Web site.http://www.provigil.com/index.php?t=hcp&p=homeAccessed October 24, 2010.
 
History of Xyrem®: what is an orphan drug? Xyrem Web site. http://www.xyrem.com/learn/. Accessed May 5, 2010.
 
Shepard JW Jr, Buysse DJ, Chesson AL Jr, et al. History of the development of sleep medicine in the United States. J Clin Sleep Med. 2005;11:61-82. [PubMed]
 
Sleep centers, sleep labs. SleepWeb Web site. http://www.sleepweb.com/SleepLabs/SleepLabs.aspx. Accessed May 1, 2010.
 
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