Hector Warnes: Historical Overview of Sleep Medicine
1.    Introduction
Historical discoveries in the field


          There are three distinct modes of being or states of consciousness clearly distinguished for their neural activity, chemical and physiological regulation: wakefulness, NREM and REM sleep. The boundaries between them may overlap in pathological states. A brief historical survey of the principal discoveries in the field follows. I do not pretend to improve upon the already excellent survey by William Dement's 2008 “History of Sleep Medicine”; Kryger, Roth and Dement’s 2010 “Principles and Practice of Sleep Medicine” is really an encyclopedia on the subject and most of my historical notes are listed in that book. I did not follow a chronological but a thematic order in my list of breakthroughs in the field of sleep medicine. Further summaries in this series shall deal with the circadian pacemaker, chronopharmacotherapeutics, REM and NREM sleep pathophysiology and functions, seasonal affective disorders and pharmacology of sleep disorders.


1836- Charles Dickens described what came to be known as the Pickwick syndrome consisting of hypersomnolence, obesity, snoring and facial erythema (suggesting polycythemia) along with sleep apnea.

1913- Henri Piéron suggested that a hypnotoxin is built up in the dogs deprived of sleep which if inoculated to non-deprived dogs induced them to sleep.

1929- Constantin von Economo found lethargic lesions in the dorsal hypothalamus in patients who died of encephalitis; in those who had severe organic insomnia, he found lesions in the anterior hypothalamus and preoptic area.

1932- Walter Rudolf Hess, using electrical stimulation in animals, confirmed von Economo’s observations. Hess also found that the rhythmic stimulation of the thalamus provoked slow waves and induced sleep.

1929- Hans Berger, using scalp electrodes, described different cerebral electrical activity (EEG) associated to states of consciousness. He observed that when the subject opened his eyes the alpha rhythm of the EEG was inhibited and during deep sleep slow wave activity predominated (delta wave). In 1933 his observations were confirmed by Edgar Adrian and Brian Matthews.

1939- Nathaniel Kleitman’s monumental treatise, “Sleep and Wakefulness,” was published by the University of Chicago Press, Ill.; it was reprinted in 1963.

1937- A.L. Loomis, E.N. Harvey and G.A. Hobart described five stages of sleep (from A to E) each with its characteristic EEG pattern, not including REM sleep which was discovered in 1953 by E. Aserinsky and N. Kleitman.

1939- Loomis A.L., Harvey E.N. and Hobart G.A. observed that an auditory stimulus during sleep evoked slow waves of large amplitude (K complexes) which also occurred normally during the stage 2 of NREM sleep.

1962- M. Critchley observed cases of periodic hypersomnia lasting up to 20 hours and megafagia in male adolescents (Kleine-Levin syndrome).

1957- W. Dement and N. Kleitman published in the Journal of EEG and Clinical Neurophysiology the standard classification of sleep in five stages.

1955-1958- William C. Dement described the cycles of REM and NREM sleep and confirmed the relation of REM sleep with oniric content. He also studied REM sleep in mammals.

1959- Michel Jouvet studied paradoxical sleep (REM) as a different state of consciousness and by stimulating the pons was able to induce muscular atonia.

1965-1966- E. Lugaresi et al.  observed nocturnal mioclonus of the limbs and its relationship with the restless leg syndrome (Ekbom syndrome).

1975- W.B. Webb and H.W. Agnew showed a relation between the duration of sleep privation and the amount of compensatory delta sleep.

1975- R. McCarley and J.A. Hobson proposed a model of neurons which were capable of kindling REM sleep (REM “on,” cholinergic neurons) and other neurons (REM “off,” aminergic neurons) capable of terminating REM sleep. They had a reciprocal interaction.

1990- M.H. Chase and F.R. Morales noticed that REM atonia was related to glycinergic activity and a cholinoceptive cascade which resulted in motor neuron inhibition and muscle atonia during active sleep.

1982- A.A. Borbély described an oscillating model of two processes: S, homeostatic, during NREM sleep the brain restores its supply of adenosine triphosphate (ATP); and the other C (circadian).

1987- R.E. Kronauer proposed the existence of two oscillators: one was called the strong “X” oscillator associated with temperature, REM sleep, cortisol secretion and short-term memory; and the other was called the weak “Y” oscillator associated to the basic cycle of rest-activity (BRAC), delta sleep and the release of somatropin.

1972-  R.Y. Moore and associates discovered the suprachiasmatic nucleus, the biological clock which regulates critical functions such as behavior, hormone levels, sleep, blood pressure, body temperature and metabolism and was later confirmed in far-reaching investigations on the Drosophila melanogaster by M. Rosbash, M.W. Young and their team which merited their award of the Nobel Prize. 

1978- Elliot Weitzman and his team described the hormonal cycles of temperature and sleep-awakening and further studied the circadian rhythm of melatonin secretion in man.

1880- J. Gelineau described the narcolepsy; in 1957 R.E. Yoss and D.D. Daly confirmed it in the known tetrad: sleep attacks, cataplexia, sleep paralysis and hypnagogic hallucinations.

1962- B. Roth distinguished narcolepsy from idiopathic or symptomatic hypersomnia.

1960- Gerald Vogel discovered that the narcoleptic subjects showed a REM latency of less than 40 minutes (normal 90 min.)

1979- Colin Sullivan discovered Continuous positive airway pressure (CPAP) which was a breakthrough in the treatment of sleep apnea.

1982- D.J. Kupfer and F. Reynolds confirmed the findings of Vogel and found that endogenous depressive had a short REM latency.

1965-  Charles Fisher et al. observed nocturnal and recurrent penal erection during REM sleep.

1969- A. Kales, E.J. Malmstrom and H.K. Kee et al. described the effects of hypnotics on sleep architecture.

1978- Mary Carskadon, G.S. Richarson and W. Dement introduced the Multiple Sleep Latency Test to objectively measure the degree of hypersomnolence.

1968- R. Broughton studied somnambulism and pavor nocturnus occurring during NREM sleep as Arousal Disorders because of their characteristics: sudden onset, confusion, disorientation, automatism, non-reactivity to waking stimulus, retrograde amnesia and occasional self-injuries.

1968- Allan Rechtschaffen and Anthony Kales published a standard method for scoring the Polysomnogram.

1986- C.H. Schenck, M.W. Mahowald and others identify the REM behavioral disorder or REM without atonia based on Michel Jouvet’s animal experiments.

1973- P. Hauri and D.R. Hawkins identified a type of sleep which was called alpha-delta because of manifest intrusion of delta waves during alpha periods and was associated with fibromialgias and chronic fatigue

1983- Y.  Honda, A. Asaka, Y. Tanaka and T. Juji discovered the association of narcolepsy with the complex of histocompatibility located in chromosome 6.

1935- M. Prinzmetal and W. Blomberg used amphetamines for the treatment of narcolepsy

1956- D. Daly and R.E. Yoss introduced methylphenidate (Ritalin) for similar purpose

1958- Imipramine (Tofranil) was found useful in the control of cataplexia. Later clomipramine and other antidepressant compounds were found equally useful.

1986- E. Lugaresi et al. described a prion disease of sleep as “the fatal familiar insomnia” with dysautonomia and degeneration of the thalamic nucleus.

1992-  J. Montpaisir, O. Lapierre, H. Warnes et al. presented clinical material to treat the restless leg syndrome and the periodic movement of the limbs during sleep.



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April 19, 2018