Sleep disorders: disorders of arousal? Enuresis, somnambulism, and nightmares occur in confusional states of arousal, not in "dreaming sleep".

In summary, the classical sleep disorders of nocturnal enuresis, somnambulism, the nightmare, and the sleep terror occur preferentially during arousal from slow-wave sleep and are virtually never associated with the rapid-eye-movement dreaming state. Original data are reported here which indicate that physiological differences from normal subjects, of a type predisposing the individual to a particular attack pattern, are present throughout the night. The episode, at least in the case of enuresis, appears to be simply a reinforcement of these differences to a clinically overt level. A number of features are common to all four sleep disorders. These had been shown previously to be attributable to the arousal itself. New data obtained by means of evoked potential techniques suggest that these common symptoms of the confusional period that follows non-REM sleep are related to alterations of cerebral reactivity, at least of the visual system. The symptoms which distinguish the individual attack types (that is, micturition, prolonged confusional fugues, overt terror) appear to be based upon physiological changes present throughout sleep which are markedly accentuated during arousal from slow-wave sleep. These changes may in some way be related to diurnal psychic conflicts. But, to date, it has proved impossible to demonstrate potentially causal psychological activity, dreaming or other forms of mental activity, or even a psychological void in sleep just preceding the attacks. The presence of all-night or even daytime predisposing physiological changes and the difficulty in obtaining any solid evidence of a preceding psychological cause explain, no doubt, why the results of efforts to cure the disorders at the moment of their occurrence (for example, by conditioning procedures in nocturnal enuresis) have been far from satisfactory. I stress the points that the attacks are best considered disorders of arousal and that the slow-wave sleep arousal episode which sets the stage for these attacks is a normal cyclic event. Indeed it is the most intense recurrent arousal that an individual regularly experiences. The most fruitful possibilities for future research would appear to be more detailed studies of those physiological changes that predispose individuals to certain types of attacks when they undergo intense arousal or stress; the reversal of these changes by psychological or pharmacological means; and more refined investigations of the physiological and psychological characteristics of the process of cyclic arousal from non-REM sleep.

Good sleep, bad sleep: a meta-analysis of polysomnographic measures in insomnia, depression, and narcolepsy.

Primary insomnia, major depression, and narcolepsy are usually considered to be separate disorders, distinguished by different polysomnographic profiles. But do polysomnographic data provide adequate evidence to segregate the three disorders, or might they display fundamentally the same sleep disturbance, differing only in degree? To test the viability of these two alternate hypotheses, the authors performed a meta-analysis of controlled polysomnographic studies of these disorders. A summary measure of degree of sleep disturbance was constructed from five variables: wakefulness after sleep onset, percentage of stage 1 sleep, percentage of stage 3 + 4 sleep, rapid eye movement (REM) latency, and REM density. The results of available studies for each variable were combined using a weighted average of effect sizes. An overall "sleep disturbance index" was then calculated by combining the estimates for the five above listed variables. On both the individual measures and especially on the summary index, insomnia, depression, and narcolepsy were arrayed on a simple continuum of progressively more severe sleep disturbance--congruent with the clinical observation that these disorders display progressively more disturbed sleep. These findings suggest that sleep can be disturbed in only a limited number of ways: in evaluating sleep architecture, it may not be possible to elaborate much beyond a single axis of good-to-bad sleep. Thus, polysomnographic measures may not provide adequate evidence to classify insomnia, depression, and narcolepsy as separate entities.

Randomized, double-blind, placebo-controlled crossover trial of modafinil in the treatment of excessive daytime sleepiness in narcolepsy.

Seventy-five patients meeting international diagnostic criteria for narcolepsy enrolled in a 6-week, three-period, randomized, crossover, placebo-controlled trial. Patients received placebo, modafinil 200 mg, or modafinil 400 mg in divided doses (morning and noon). Evaluations occurred at baseline and at the end of each 2-week period. Compared with placebo, modafinil 200 and 400 mg significantly increased the mean sleep latency on the Maintenance of Wakefulness Test by 40% and 54%, with no significant difference between the two doses. Modafinil, 200 and 400 mg, also reduced the combined number of daytime sleep episodes and periods of severe sleepiness noted in sleep logs. The likelihood of falling asleep as measured by the Epworth Sleepiness Scale was equally reduced by both modafinil dose levels. There were no effects on nocturnal sleep initiation, maintenance, or architecture, nor were there any effects on sleep apnea or periodic leg movements. Neither dose interfered with the patients' ability to nap voluntarily during the day nor with their quantity or quality of nocturnal sleep. Modafinil produced no changes in blood pressure or heart rate in either normotensive or hypertensive patients. The only significant adverse effects were seen at the 400-mg dose, which was associated with more nausea and more nervousness than either placebo or the 200-mg dose. As little as a 200-mg daily dose of modafinil is therefore an effective and well-tolerated treatment of excessive daytime somnolence in narcoleptic persons.

Psychosocial impact of narcolepsy.

Despite remarkable progress in our understanding of narcolepsy, the disease continues to cause the sufferer severe negative life effects. Before and after diagnosis, narcoleptics often experience unrelenting severe psychosocial stress. Child and adolescent narcoleptics report embarrassment, academic decline and feelings of loss of self-worth related to the symptoms of their disease. Personality characteristics may be adapted in order to avoid social situations that would precipitate cataplexy or draw attention to the patient's degree of somnolence. Misdiagnosis of these illnesses may result in inappropriate treatment and underestimation of an individual's potential. Adult narcoleptics also face the concerns of the workplace. Worry about loss of job and income are a source of anxiety and are often based in reality. Accidents at home, while driving and in the workplace are increased, creating safety concerns for both the patient and the community. Marital difficulties are common and psychopathology is known to occur more frequently. Narcolepsy's marked impact on quality of life has been found to be similar across cultural lines and these effects appear to be an inherent part of the disease. The socioeconomic impact in general is even more severe than those of comparable forms of epilepsy. Successful diagnosis and treatment do not end the narcoleptic's difficulties. The need for stimulants often creates problems with pharmacists and family. Somnolence, which responds the most poorly of all narcoleptic symptoms, leads to continued problems in the workplace. Side effects related to stimulant use may be a further source of difficulty. Finally, families may be unwilling to accept the illness and thereby alienate the patient.(ABSTRACT TRUNCATED AT 250 WORDS)

Rapid decline in body temperature before sleep: fluffing the physiological pillow?

A novel approach to the analysis of body core temperature was employed in an effort to further clarify the temporal relationship between the nightly decline in body temperature and the timing of the onset of nocturnal sleep. Core body temperature and EEG sleep recordings were obtained from 10 healthy elderly subjects while they lived in the laboratory and self-selected bedtimes and wake-up times. A rate-of-change curve was then generated for each temperature data set, showing the relative magnitude by which body core temperature declined (or increased) from minute to minute across the recording period. The time at which the maximum rate of decline (MROD) occurred was determined, and this time was compared with subjects' self-selected bedtimes and with subsequent EEG-defined sleep onsets. Eight of the 10 subjects' body temperature curves showed a maximum rate of decline well before (mean 41 min) the decision was made to retire. There was a significant positive correlation between the amount of wakefulness within the first hour after initial sleep onset and MROD relative to both bedtime and sleep onset (rs = 0.70; p < 0.04). That is, the closer MROD occurred to either bedtime or sleep onset, the less wakefulness there was within the first hour after sleep onset. The findings indicate that the process of sleep initiation is most likely to occur when body temperature is declining at its maximum rate and is most successfully accomplished at this phase of the temperature cycle.

Waking ultradian rhythms of performance and motility in hyperkinetic and normal children.

Waking ultradian rhythms in a visual performance task (detections and false positives) and in motility (global body movements and segmental limb movements during the task, and segmental limb movements during off-task periods) were examined in groups of nonmedicated hyperkinetic (HK) children (N = 11) and matched normal controls (N = 11). Testing was conducted for 5 minutes every 15 minutes (with 10-minute "rest periods") over a 6-hour period on 2 consecutive days. Increased limb movement (p less than .01) during off-task periods on both days. Increased limb movement in HK subjects during the task was marginally significant (p less than .06) on one day. False positives and global body movements failed to differentiate the groups. With regard to ultradian rhythmicity, some subjects in both groups showed evident ultradian peaks, which were present across a wide range of frequencies in one or more variables. There were no significant differences in the incidence of the period of evident ultradian peaks between the two groups.

SCN controlled circadian arousal and the afternoon "nap zone".

This paper outlines a conceptual model for the regulation of the circasemidian sleep propensity process with emphasis on a possible mechanism of the afternoon "nap zone". It is proposed that the afternoon nap zone is due to increasing sleep propensity after morning wakening (Borb ly's Process-S) being overwhelmed by a light-sensitive SCN-dependent circadian arousal process of the type discovered by Edgar et al., (1993) and currently being identified in its pathways and neurochemistry by Jouvet and colleagues. It is maintained that this arousal process is reflected in the circadian core body temperature pattern, and that under normal entrained conditions the latter does not resemble a sine-wave or skewed sine-wave. Rather it is very asymmetrical in time and somewhat asymmetrical in amplitude. Cosinor type analyses which enforce symmetry in time and amplitude are therefore ill suited to adequately curve-fit the empirical data. The shape of the circadian arousal system was clarified by meta-analyses of data from three laboratories for three conditions: the normal entrained state, the constant routine, and temporal isolation. Under normal entrained conditions for about one-third of the circadian day core body temperature, and therefore the assumed intensity of the circadian arousal system, is below the mesor with the nadir being at about 0500h; and for about two-thirds of the circadian day it is above the mesor with the acrophase on average being at about 2100h. For modeling purposes, the homeostatic process (Process-S) employed the actual data of the Zurich laboratories for night sleep, but altered the equation for the daytime period to ensure an exponential increase after wake-up. Combining these modified processes indicated that the nap zone could be explained, as predicted, by an increasing homeostatic pressure for sleep across the daytime being reversed by the circadian arousal process. This 2-process combination predicted quite well the shape of the entire circasemidian sleep/wake propensity process and can explain the presence of morning sleep inertia without requiring a third process. It would appear that the circadian arousal process can be modified in phase and in amplitude by a number of normal and pathological conditions.

Diagnostic ambiguities in a case of post-traumatic narcolepsy with cataplexy.

Narcolepsy arising from trauma can present particular problems of differential diagnosis. In this case study presentation the patient suffered a head trauma, without unconsciousness, and began to experience unusual episodic behaviours. Symptom presentation differed from the typical clinical manifestations of idiopathic narcolepsy leading to an 8-year search for a definitive diagnosis. Key relevant aspects that led to diagnostic ambiguities were the order of symptom development, negative for the antigen HLA DR2, significance of the Multiple Sleep Latency Test (MSLT) mean sleep latency versus number of sleep onset rapid eye movement periods, the somewhat atypical features of cataplexy, the coexistence of sleep apnoea, and the mildness of the original head injury. It is argued that cases of post-traumatic narcolepsy should be considered in the context of their clinical development over time and that practitioners should be aware that this form of narcolepsy can differ from the typical clinical history of idiopathic narcolepsy.

Complex event-related potentials (P300 and CNV) and MSLT in the assessment of excessive daytime sleepiness in narcolepsy-cataplexy.

The P300 and contingent negative variation (CNV) evoked potential (EP) paradigms were performed by 12 untreated narcoleptics and controls immediately prior to each nap of the Multiple Sleep Latency Test (MSLT) in order to assess whether they might hold promise as rapid quantitative techniques to assess excessive daytime sleepiness. The Stanford Sleepiness Scale (SSS) was also completed across test days and immediately before and after both the evoked potential recordings and MSLT naps. MSLT findings confirmed shorter sleep latencies and frequent SOREMPs in narcoleptics and a strong mid-afternoon increase in sleepiness based upon pressure for NREM sleep in both groups. On SSS narcoleptics were sleepier and they showed greater increase in sleepiness induced by the EP tests and greater sleepiness reduction by the MSLT naps. In the P300 paradigm, narcoleptics showed smaller component P3 amplitudes and larger P1 amplitudes. In the CNV paradigm, N1 latencies were greater in narcoleptics to both S1 and S2 and the post-CNV negative component was larger: but no significant differences were seen for the main CNV measures of negativity amplitude in the first or second halves of the response. The P300 paradigm but not the CNV, therefore, appeared to be a sensitive EP measure of sleepiness. Finally, EP components in both the P300 and CNV paradigms showed time-of-day (circadian) differences between narcoleptics and controls.

Differences between REM and NREM sleepiness measured by event-related potentials (P300, CNV), MSLT and subjective estimate in narcolepsy-cataplexy.

Differences between 'REM sleepiness' and 'NREM sleepiness' states in wakefulness studied respectively prior to REM-containing and NREM-only multiple sleep latency test (MSLT) naps were compared by complex evoked potentials (P300, CNV), subjective estimate (Stanford Sleepiness Scale, SSS) and MSLT measures in 12 untreated patients with narcolepsy-cataplexy. The EP paradigms lasted about 7 min each and were done during the 10 min immediately before MSLT naps at 10.00, 12.00, 14.00, 16.00 and 18.00 h. SSS forms were completed immediately before and after the EP studies and MSLT naps. Patients were studied on 2 days and performed either the P300 or CNV paradigm on each day. 'REM sleepiness' was found to be subjectively and objectively (shorter mean sleep latency on MSLT) greater. Although subjects were sleepier in REM sleepiness, the subsequent REM nap was relatively more refreshing and reduced SSS estimates to levels equivalent to those after NREM-only naps. EP measures also showed differences between the 2 sleepiness states. REM sleepiness was associated with a significantly larger P2 component (in both the P300 paradigm and the CNV paradigm), a strong but not significant trend towards reduced amplitude of the P3 component, and almost total suppression of the slow negative components of the CNV. REM sleepiness and NREM sleepiness therefore appear to be district and differentiable cerebral states.

Comparison of the psychosocial effects of epilepsy and narcolepsy/cataplexy: a controlled study.

A questionnaire survey compared the psychosocial effects of epilepsy in 60 patients without major organic pathology (selected cases with temporal lobe epilepsy or primary generalized epilepsy) with those of matched (duration of illness, sex) patients with narcolepsy/cataplexy and with those of age- and sex-matched controls. Comparing epileptic patients with controls, we confirmed the well-documented marked deleterious effects of epilepsy upon work, education, occupational and household accidents, recreation, personality, interpersonal relations, and other parameters. Comparisons of epileptic and narcoleptic patients, however, showed that, in general, persons with narcolepsy are even more psychosocially impaired. The narcoleptic patients showed greater frequencies of disease-attributed reduced performance at work, poorer driving records, higher accident rates from smoking, greater problems in planning recreation, and other significant differences. Rather dissimilar profiles of psychosocial impairment were found to characterize the two conditions, and these were largely understandable as a function of their symptoms. The only areas in which epileptic patients showed greater problems than those with narcolepsy were in educational achievement and in ability to maintain a driving license. Most of the intergroup differences remained significant even for smaller groups matched also for age. The somewhat greater psychosocial impact of narcolepsy appears to be due to the continuous excessive daytime sleepiness that persists between the diagnostic attacks, whereas persons with epilepsy are relatively alert between seizures.

Guidelines for the recording and quantitative analysis of electroencephalographic activity in research contexts.

Developments in technologic and analytical procedures applied to the study of brain electrical activity have intensified interest in this modality as a means of examining brain function. The impact of these new developments on traditional methods of acquiring and analyzing electroencephalographic activity requires evaluation. Ultimately, the integration of the old with the new must result in an accepted standardized methodology to be used in these investigations. In this paper, basic procedures and recent developments involved in the recording and analysis of brain electrical activity are discussed and recommendations are made, with emphasis on psychophysiological applications of these procedures.

Muscle sympathetic nerve activity during central, mixed and obstructive apnea: are there any differences?

We recorded muscle sympathetic nerve activity (MSNA) from the peroneal nerve during sleep in three OSAS patients who showed three kinds of apnea. During central apneas and central component of mixed apnea, bursts of MSNA appeared in high probability with almost each heart beat. During obstructive apneas and the obstructive component of mixed apneas, bursts of MSNA appeared in a cluster after the end of each inspiratory effort. Burst rate of MSNA during apnea were higher in cental apneas and the central component of mixed apnea than in obstructive apneas and the obstructive component of mixed apneas. These findings indicate that activity in the sympathetic nervous system is enhanced not only in obstructive apnea but also in central and mixed apnea.