Hartmut Schulz

A 1-year systematic diary was kept by an anonymous diarist in Hamburg in the year 1755-1756. Sleep, activities, food intake, urine volume, and meteorological data were documented daily. The systematic recording of sleep and naps, with an accuracy of a quarter of an hour allowed analysis of the placement, duration, and consistency of sleep.

Sleep became a subject of scientific research in the second half of the 19th century. Since sleep, unlike other physiological functions, cannot be attributed to a specific organ, there was no distinct method available to study sleep until then. With the development of physiology and psychology, and a rapidly increasing knowledge of the structure and functioning of the nervous system, certain aspects of sleep became
accessible to objective study. A first step was to measure responsiveness to external stimuli systematically, during sleep, allowing a first representation of the course of sleep (Schlaftiefe = sleep depth). A second method was to register continuously the motor activity across the sleep–wake cycle, which allowed the documentation in detail of rest–activity patterns of monophasic and polyphasic sleep–wake rhythms, or between day or night active animals. The central measurement for sleep research,
however, became the electroencephalogram in the 1930s, which allowed observation
of the sleeping brain with high temporal resolution. Beside the development of instruments to measure sleep, prolonged sleep deprivation was applied to study physiological and psychological effects of sleep loss. Another input came from clinical and neuropathological observations of patients with pronounced disorders of the sleep–wake cycle, which for the first time allowed localisation of brain areas that are
essentially involved in the regulation of sleep and wakefulness. Experimental brain stimulation and lesion studies were carried out with the same aim at this time. Many of these activities came to a halt on the eve of World War II. It was only in the early 1950s, when periods with rapid eye movements during sleep were recognised, that sleep became a research topic of itself. Jouvet and his team explored the brain mechanisms and transmitters of paradoxical sleep, and experimental sleep research became established in all European countries. Sleep medicine evolving simultaneously in different countries, with early centres in Italy and France. In the late 1960s sleep research and chronobiology began to merge. In recent decades, sleep research, dream research, and sleep medicine have benefited greatly from new methods in genetic research and brain imaging techniques. Genes were identified that are involved in the regulation of sleep, circadian rhythms, or sleep disorders.
Functional imaging enabled a high spatial resolution of the activity of the sleeping brain, complementing the high temporal resolution of the electroencephalogram.

Geschichte der Schlafmedizin • Überblick über die Bedeutung des Schlafs in der Medizin von der Antike bis zur aktuellen Schlaff orschung • Entdeckung und Klassifi kation der unterschiedlichen Schlafstörungen im Verlauf der Jahrhunderte Kernaussagen 6.1 Einleitung Wissen über den Schlaf gehört seit der Antike zur ärztlichen Kunst. Hippocrates (c. 460-c. 375 v. Chr.) und Galen (c. 129-c. 199 n. Chr.) blieben mit ihrem Wissen und ihren Anschauungen bis in die frühe Neuzeit die verbindlichen Autoritäten auch für das Erkennen und Behandeln von Störungen des Schlafs und des Wachseins. Der große islamische Arzt und Gelehrte Al-Razi (Rhazes, c. 854-925 / 935 n. Chr.) kompilierte und verbreitete dieses Wissen, zusammen mit den ihm bekannten indischen und chinesischen Quellen. Der andere führende Mediziner und Philosoph des Orients war Ibn Sina, latinisiert Avicenna (c. 980-1037 n. Chr.). Sein "Canon Medicinae", der die Anatomie, Physiologie, Krankheits-und Arzneilehre umfasste, galt bis zum Ende des 15. Jahrhunderts als das vollständigste medizinische Lehrbuch. Angaben über den Schlaf und die Schlafstörungen Incubus und Wachsein der Kinder im Schlaf fi ndet sich in den Werken beider Ärzte. Die früheste und größte medizinische Schule des Mittelalters war die von Salerno. Hier wurde eine Gesundheitslehre entwickelt, die bis in die frühe Neuzeit ärztliches Handeln beeinfl usste. Von ganz unmittelbarem Interesse für die Medizin waren dabei die beiden Bücher des Aristoteles (384-322 v. Chr.) über den Schlaf und über die Träume. Das Wachsein (vigilia) ist bei Aristoteles durch die Fähigkeit zur Wahrnehmung gekennzeichnet, der Schlaf (somno) durch dessen Abwesenheit. Das Vermögen der Wahrnehmung hat seinen Sitz im

Measured and rated sleep differ in normal sleepers and even more in patients with sleep disorders. The study aimed to asses sleep/wake perception in electrophysiologically defined sleep in patients with sleep disorders. 117 consecutively referred patients (75 females), median age 50.3 years, range 20–73 years) with various sleep disorders were randomized for one induced waking, either out of stage 2 (S2) or REM sleep, as part of a clinical routine polysomnography. Patients were classified as either nonsleepy (Epworth Sleepiness Scale score ESS ≤ 10) or sleepy (ESS ≥ 11). The most frequent diagnoses of non-sleepy patients were insomnia and RLS, while sleepy patients suffered predominantly from OSAS, hypersomnia and insufficient sleep syndrome. Subjects were deliberately aroused once, either out of consolidated stage 2 sleep (n = 66) or REM sleep (n = 51) and asked for sleep/wake perception (sleep/wake and related questions). While 81 (69.2%) of the subjects estimated that they had been sleeping or dozing before they were aroused, 36 (30.8%) reported that they had been awake. Awake ratings were significantly more frequent for S 2 (45.5%) than for REM sleep (11.8%). The difference between sleep states was most pronounced for insomniacs (58.1% awake ratings in S2 vs. 5.3% in REM sleep). Mismatches between measured sleep and perceived state are quite frequent, with a greater disparity for S2 than for REM sleep, especially in insomniac patients. We suggest that state judgement is contingent not only on the state of the sleep regulating system but also on cognitive processes associated with processing of external and internal stimuli, and dreaming.

Hossain et al. (2005) have recently suggested that fatigue and sleepiness can be independent consequences of sleep disorders. They found that a majority (64%) of referred patients with sleep disorders had pathological fatigue scores without overlap of sleepiness, while only 4% had pathological sleepiness without overlapping fatigue. To clarify the relationship between fatigue and sleepiness is of general interest since fatigue is a frequently encountered symptom also in other diseases such as multiple sclerosis (MS), where fatigue is one of the most disabling symptoms. Here we present data on the relationship of fatigue and sleepiness in a sample of 53 patients (39 females, 14 males) with relapsing-remitting or secondary progressive MS from an ongoing study on fatigue and actimetry in MS patients. Patients had a mean age of 42 ± 11 years. Mean duration of the disease was 7.3 ± 6.7 years and the mean score on the Expanded Disability Status Scale (EDSS) was 2.8 ± 1.5. All patients were under treatment with Interferon-beta 1b (Beta-feron). Exclusion criteria were psychoactive medication or treatment with corticosteroids during the last 3 months. The patients completed different questionnaires, two of them addressing fatigue and sleepiness. As in the study by Hossain et al. (2005) fatigue was assessed by the Fatigue Severity Scale (FSS; Krupp et al., 1989) and sleepiness by the Epworth Sleepiness Scale (ESS; Johns, 1991). Mean (±SD) scores were 4.2 ± 1.6 for the FSS, and 8.3 ± 3.7 for the ESS. We adopted from Hossain et al. an FSS cutoff scores >3 for increased fatigue and an ESS cutoff score >10 for pathological sleepiness. As in the Hossain et al. analysis we classified the MS patients into four groups according to their FSS and ESS scores. Twenty-five patients (47.2%) were fatigued but not sleepy, 12 patients (22.6%) were both fatigued and sleepy while only three patients (5.7%) were not fatigued but sleepy. The remaining 13 patients (24.5%) were neither fatigued nor sleepy (Fig. 1). The observed proportions are close to those reported by Hossain et al. for patients with sleep disorders, 63.9% scored high on fatigue only, 19.1% on fatigue and sleepiness, 3.9% on sleepiness only and 13.1% neither on fatigue nor on sleepiness. The data from both samples suggest that self-rated fatigue and sleepiness are two dimensions, which vary independently to a large degree. However, while Hossain et al. reported a low correlation (r ¼ 0.18) between FSS and ESS total scores, this correlation was higher and significant (r ¼ 0.52, P < 0.001) for our sample of MS patients. To further explore the relationship between the two scales, we have performed a single-item analysis (chi-squared tests). Taking multiple testing into account, only P-values £ 0.01 were accepted as statistically significant. Four of eight ESS items were significantly related to one or more FSS items, namely the items ESS 1 (sitting and reading), ESS 2 (watching TV), ESS 3 (sitting, inactive in a public place, e.g. a theatre or a meeting) and ESS 4 (as a passenger in a car for an hour without a break). From the nine FSS items, only three (FSS 1, FSS 3 and FSS 4) were significantly related to single ESS items. The single-item analysis showed that there is limited overlap between both scales, and that the correlation between the FSS and ESS total scores depends essentially on a subset of items. The four ESS items, which were significantly related to FSS items describe situations where patients tend to fall asleep unintentionally while sitting more or less inactive. The four remaining ESS items, which did not correlate significantly with FSS items, describe situations where sleepiness is either intended or at least not clearly avoided, as in item 5 (ÔLying down to rest in the afternoon when circumstances permitÕ) and item 7 (ÔSitting quietly after a lunch without alcoholÕ), or situations, where sleepiness would be absolutely inappropriate as in items 6 (ÔSitting and talking to someoneÕ) and 8 (ÔIn a car, while stopped for a few minutes in trafficÕ). It would be of interest to see whether patients with sleep disorders show a

Fatigue is a frequent and disabling symptom in patients with multiple sclerosis (MS). The objective of the study was to compare fatigue and sleepiness in MS, and their relationship to physical activity. Eighty patients with MS rated the extent of experienced fatigue (Fatigue Severity Scale, FSS) and sleepiness (Epworth Sleepiness Scale, ESS). The relationship between the scales was analysed for the scales as a whole and for single items. The clinical status of the patients was measured with the Extended Disability Status Scale (EDSS). In addition, physical activity was recorded continuously for 1 week by wrist actigraphy. The mean scores of fatigue and sleepiness were significantly correlated (FSS vs. ESS r = 0.42). Single item analysis suggests that fatigue and sleepiness converge for situations that demand self-paced activation, while they differ for situations in which external cues contribute to the level of activation. While fatigue correlated significantly with age (r = 0.40), disease severity (EDSS, r = 0.38), and disease duration (r = 0.25), this was not the case for sleepiness. Single patient analysis showed a larger scatter of sleepiness scores in fatigued patients (FSS [ 4) than in non-fatigued patients. Probably, there is a subgroup of MS patients with sleep disturbances that rate high on ESS and FSS. The amount of physical activity, which was measured actigraphically, decreased with disease severity (EDSS) while it did not correlate with fatigue or sleepiness.

SUMMARY While electrophysiologically measured sleep and perception of sleep generally concur, various studies have shown this is not always the case. The objective of the present study was to assess the perception of actual state during sleep by the technique of planned awakenings and interviewing subjects on the preawakening state. Sixty-eight (43 females, 25 males) young (mean age: 24.1, SD 5.1 years) normal sleeping subjects were deliberately awakened out of consolidated sleep, either stage 2 (S2), or REM sleep, during the first night in a non-clinical sleep laboratory. While the preawakening state was experienced as sleep in 48 cases (70.6%), it was experienced as wakefulness in 20 cases (29.4%). The percentage of awake judgements was somewhat, but not significantly, higher for awakenings out of S2 (38.2%), to REM sleep (20.6%). The proportion of mismatches between electrophysiologically defined sleep and state judgements was time-dependent with more awake judgements for REM sleep in the second half of the sleep period (41.7%) than in the first one (17.4%). Those subjects who made an awake judgement more frequently had a feeling of being aware of the situation and their surroundings than those who made a sleep judgement (80% versus 33%). Awareness during sleep may be a cognitive style, which favours mismatches between state perception and electrophysiologically defined sleep. Sleep periods with concordant or discordant state judgements did not differ in electrophysiologically defined sleep onset latency, sleep efficiency, or sleep state distribution. k e y w o r d s awakening, awareness, cognitive activity, sleep perception

SUMMAR Y Daytime tiredness or sleepiness and deficits in cognitive performance are common complaints in sleep disordered patients. Till now there are few studies comparing patients from different diagnostic groups of sleep disorders in the same experimental protocol. We studied the time course of cognitive functions and subjective alertness in a parallel group design with four groups of patients [narcolepsy, untreated or treated obstructive sleep apnea (OSA), or psychophysiological insomnia] and a control group of subjects without sleep complaints. Each group consisted of 10 subjects, matched for age and gender. After a night with polysomnography, subjects were studied for 10 h from 08:00 hours to 18:00 hours at 20 min intervals under standardized environmental conditions. Four psychological tests were applied, (1) a critical flicker fusion (CFF) test to measure optical fusion threshold (alertness); (2) a paper-and-pencil visual line tracking test (selective attention); (3) a visual analog scale (VAS) for tiredness/ sleepiness; and (4) the Tiredness Symptoms Scale (TSS), a 14 items check list. Each test session lasted for 8 min, followed by a 12 min pause. The level and time course of cognitive performance and self-rating data were analysed with hierarchical linear mixed effects models. Cognitive tests showed decrements in alertness and selective attention in untreated patients with insomnia, narcolepsy, and sleep apnea. Narcoleptic patients and untreated OSA had a lower CFF threshold than controls, and for narcoleptic patients the time course differed from that of all other groups. In the visual tracking test the performance of all groups of patients was worse compared with normal controls. Self-rated tiredness/sleepiness was significantly more pronounced in the three groups of untreated patients than in control subjects. k e y w o r d s alertness, cognitive performance, critical flicker fusion, insomnia, narcolepsy, obstructive sleep apnea, selective attention, sleepiness, tiredness

Spontaneous awakenings from sleep were studied in a group of 20 infants whose sleep-waking patterns were recorded polygraphically for 24 h. While 10 infants were orally fed the other 10 underwent continuous feeding for various gastrointestinal diseases. Spontaneous awakening from sleep was analysed with regard to the prior sleep state, age and feeding condition. Infants awoke preferentially out of REM sleep and less often out of non-REM sleep. The feeding condition had no significant influence on the distribution of awakenings. The propensity for REM awakenings was significantly greater than would have been expected according to the REM sleep amount. This tendency was more pronounced for younger (__< 3 months) than for older (> 4 months) infants. REM sleep episodes which were interrupted by awakenings were significantly shorter than uninterrupted ones, since awakenings occurred predominantly shortly after REM sleep onset. It is proposed that the specific pattern of brain activity during REM sleep facilitates the transition from sleep into the waking state, particularly in the youngest infants.

For centuries the scope of sleep disorders in medical writings was limited to those disturbances which were either perceived by the sleeper him-or herself as troublesome, such as insomnia, or which were recognized by an observer as strange behavioral acts during sleep, such as sleepwalking or sleep terrors. Awareness of other sleep disorders, which are caused by malfunction of a physiological system during sleep, such as sleep-related respiratory disorders, were widely unknown or ignored before sleep monitoring techniques became available, mainly in the second half of the 20 th century. Finally, circadian sleep-wake disorders were recognized as a group of disturbances by its own only when chronobiology and sleep research began to interact extensively in the last two decades of the 20 th century. Sleep medicine as a medical specialty with its own diagnostic procedures and therapeutic strategies could be established only when key findings in neurophysiology and basic sleep research allowed a breakthrough in the understanding of the sleeping brain, mainly since the second half of the last century.

The level and course of attention was measured hourly in 9 drug intoxicated patients after a suicide attempt over periods which varied between 12 and 72 hrs. Attention was measured by the use of two additive 5 step scales for susceptibility to stimulation and reactivity, which were developed by the authors in earlier investigations and proven to be very reliable. Although, the original data set of attention measures was different among the patients, some common features could be elaborated: 1. The level of attention varies very little within 1 hr. Differences greater than one step on the scales were rarely observed between two measurements. 2. The mean course of recovery from attention deficit is linear throughout the scales while the variance is substantial at each step of the scales. For quantification of attention deficit a measure was defined which gives the relation between the actual deficit and full attention. Since the correlation between both scales is high over the whole observation period, it was concluded that the intoxication alters the level but not the structure of attention.

In a previous report two additive scales were developed for measuring susceptibility to stimulation (with 4 experimental stimuli) and reactivity (with 4 types of reactions). The degree of loss of attention in neurological patients as determined by the position of a patient correlates with the frequencies of his reactions. Thus the measurement of frequencies does not add any further information. There is no patterning of reactions due to the different etiology of the disorder of attention. These results support the suggested one-factor theory of attention.

Shortened latency of rapid eye movement (REM) sleep is a feature frequently observed in depressed patients. Three hypotheses on the origin of early REM sleep episodes propose that short REM latency is due to (1) a phase-shift of one subset of the circadian rhythms relative to other circadian rhythms, (2) a loss of inhibition of REM sleep due to a slow wave sleep deficit, or (3) a reduction in amplitude of a putative circadian arousal cycle. From an analysis of experimental data, it is concluded that the hypothesis of a reduced circadian amplitude best explains the early occurrence of REM sleep.

The periodic alternation between REM and NREM sleep was analyzed. Usually, sleep records of consecutive nights of a subject are regarded to be independent events. However, it may be that consecutive nights are realizations of a continuously ongoing rhythm. This was tested in the present study. The temporal patterns of REM and NREM sleep in sequences of about 30 consecutive nights for 3 subjects were analyzed. The results show that only the onset of the first REM sleep phase during any one night may be predicted from the sleep onset time, whereas a systematic phase shift between consecutive nights was observed in the later REM sleep phases. Thus, the onset of later REM sleep phases is better predicted by assuming a rhythm with stable period length which controls the appearance of REM sleep phases in successive nights. Under the experimental conditions the phase shift was between 5 and 10 min per 24 hrs for the 3 subjects. The result is accordance with Kleitman&amp;#39;s basic rest activity cycle (BRAC) hypothesis.

... M. Teschemacher und Frau J. Dinkel. Literatur Brinkmann, R., v. Cramon, D., Schulz, H.: Skalierung von Aufmerksamkeitsst6rungen bei neurologischen Patienten. J. Neurol. 209, 1--8 (1975) Cramon, D. v., Brinkmann, R., Schulz, H.: Entwicklung eincs Mel]instrumentes zur ...

58 patients with various underlying neurological diseases, who had an impairment of attention, were examined. 12 patients without clinically evident disorders of attention were examined as a control group. The aim of the study was the development of a standardized procedure for the assessment of impaired attention. An additive, 4 step scale of the “susceptibility to stimulation” (Guttman scale) was

Visual sleep scoring is the obligatory reference for sleep analysis. An essential step in sleep scoring is sleep staging. This technique was first described in 1937 and later adapted 3 times: first, in 1957, after the detection of rapid eye movement (REM) sleep, when electrooculography (EOG) was added; second, in 1968, when sleep staging was standardized and electromyography (EMG) was added; and third, in 2007, to integrate accumulated knowledge from sleep science, adding arousals and respiratory, cardiac, and movement events. In spite of the dramatic changes that have taken place in recording and storing techniques, sleep staging has undergone surprisingly few changes. The argument of the present comment is that sleep staging was appropriate as long as sleep biosignals were recorded in the analog mode as curves on paper, whereas this staging may be insufficient for digitally recorded and stored sleep data. Limitations of sleep staging are critically discussed and alternative strategies of sleep analysis are emphasized.

Sleep disturbances, which are a prominent symptom of depressive illness, were analyzed in endogenously depressed patients during depression and during full remission. These disturbances may be described at the level of sleep stages, at the level of the sleep profile, and at the level of consecutive sleep records. The scoring of sleep stages in sleep records of depressive patients provides difficulties, because the temporal coherence of different electrophysiological descriptors of sleep is weakened during depression. The sleep profile of depressed patients is characterized by alterations in the normal sequence of sleep stages and frequent stage changes. The disturbances in the sleep profile are unstable in that they show marked day to day fluctuations. It could be shown in some patients that there is a correlation between parameters of the first REM sleep and urinary free cortisol excretion in corresponding nights.

We investigated the characteristics of periodic leg movements (PLM) during nocturnal sleep and wakefulness in 13 drug-free patients presenting with the restless legs syndrome (RLS, n = 9) or with isolated PLM (n = 4). Eight-hour polygraphic sleep recordings included the electromyogram (EMG) of both tibialis anterior muscles. Scoring of leg movements was done according to established criteria for periodic movements in sleep, but movements occurring during episodes of wakefulness were scored as well. Twelve out of 13 patients had PLM during wakefulness, including three subjects not affected by RLS. The frequency of periodic movements in sleep (PMS) per hour of total sleep time was significantly lower than the frequency of PLM (including movements during wakefulness) per hour of polygraphic recording. Movement indices based on PMS alone underestimated the relative frequency of PLM particularly in patients with high amounts of wakefulness (> 20%). All features of PLM clearly differed between sleep stages. Relative frequency of movements, their duration and their arousing effect decreased along the nonrapid eye movement (NREM) sleep stages, whereas the intermovement interval increased. During rapid eye movement (REM) sleep the duration of movements was shortest and the intermovement interval was longest. The results presented suggest that the processes underlying PLM are most active at the transition from wakefulness to sleep and considerably attenuated during deep NREM sleep and even more during REM sleep. We suggest including movements during wakefulness in routine PLM scoring to get a more complete picture of the disturbance.

When sleep was recognized as an active process which is regulated by the interaction of homeostatic and circadian systems a new understanding of sleep disturbances set in, and sleep medicine developed as a new medical speciality. An internationally recognized classification system was developed which allows to diagnose the different sleep disturbances reliably. Sleep disorders comprise (a) dysregulations of the sleep-wake system (insomnias, hypersomnias, narcolepsy, parasomnias), (b) sleep associated disturbances of functional systems (for example sleep apnea, restless legs syndrome), (c) disturbances of the circadian sleep-wake rhythm, and (d) sleep disturbances in association with other organic or psychiatric illnesses. The present contribution shows the diagnostic procedures for four main sleep disorders, namely insomnia, obstructive sleep apnea (OSAS), restless legs syndrome (RLS), and narcolepsy.

Der zirkadiane Schlaf-Wach-Rhythmus ist durch die regelhafte Abfolge einer langen Schlaf- und einer langen Wachphase innerhalb von 24 Stunden gekennzeichnet. Der Schlaf-Wach-Zyklus steht in enger Beziehung mit metabolischen Veränderungen und als deren Ausdruck mit dem zirkadianen Rhythmus der Körperkerntemperatur. Ein weiterer Marker für die zirkadiane Phasenlage ist die Sekretion von Melatonin aus dem Pinealorgan mit einem Maximum in der Dunkelphase, die beim Menschen üblicherweise der Schlafphase entspricht.

For centuries the scope of sleep disorders in medical writings was limited to those disturbances which were either perceived by the sleeper him-or herself as troublesome, such as insomnia, or which were recognized by an observer as strange behavioral acts during sleep, such as sleepwalking or sleep terror. Awareness of other sleep disorders, which are caused by malfunction of a physiological system during sleep, such as sleep-related respiratory disorders, were widely unknown or ignored before sleep monitoring techniques became available, mainly in the second half of the 20 th century. Finally, circadian sleep-wake disorders were recognized as a group of disturbances by its own only when chronobiology and sleep research began to interact extensively in the last two decades of the 20 th century. Sleep medicine as a medical specialty with its own diagnostic procedures and therapeutic strategies could be established only when key findings in neurophysiology and basic sleep research allowed a breakthrough in the understanding of the sleeping brain, mainly since the second half of the last century.