REM sleep episodes during the Multple Sleep Latency Test in narcoleptic patients.

Forty narcoleptic patients were given the Multiple Sleep Latency Test, consisting of 20 min opportunities to sleep offered at 10.00, 12.00, 14.00, 16.00 and 18.00 o'clock. Eleven patients had 2 episodes of REM sleep, 5 had 3, 11 had 4, and 13 had 5 before they were awakened. Fourteen control subjects given similar opportunities to sleep (reported in a companion article (Richardson et al. 1978)) had no REM sleep episodes. For the 10.00-18.00 o'clock opportunities respectively, there were 32, 29, 30, 28 and 27 REM sleep episodes. We conclude that this procedure can provide physicians with data useful in the diagnosis of narcolepsy.     

REM latency in neurotic and endogenous depression and the cholinergic REM induction test

Latency of rapid eye movement (REM) sleep was measured in eight healthy volunteers under baseline conditions and after administration of physostigmine. An infusion of 0.5 mg of physostigmine 5 minutes after sleep onset caused a significant shortening of REM latency in comparison with baseline conditions. In 45 patients with major depression, REM latency during baseline nights was significantly shorter than in control subjects. This shortening of the REM latency was found to be similar in endogenous, neurotic, and unclassified depressed patients. In contrast to findings in the controls, the physostigmine infusion provoked no further significant reduction of REM latency in depressed patients, but awakened the majority of patients. The data concerning spontaneous REM latency and REM latency after physostigmine do not allow a differentiation among the endogenous, neurotic, and unclassified depressed subgroups. The results of the cholinergic REM induction test do not conclusively support the hypothesis of a cholinergic hypersensitivity in depression.     

A case of insufficient sleep syndrome

Abstract All night polysomnographic evaluation (PSG) soon after admission and at the late period of admission revealed an atypically high sleep efficiency and a prolonged total sleep time. Sleep onset latency and distribution of REM and NREM sleep stages were like those of normal sleepers. On REM latency, while it was remarkably reduced (25.0 min) soon after admission and sleep onset REM period (SOREMP) was found, at the late period of admission it was prolonged and SOREMP was not found. Giving multiple sleep latency test with polysomnography, soon after admission subjective excessive daytime sleepiness had already improved and mean sleep latency (13.2 min) was within normal range. However, SOREMP appeared twice in five tests. We considered that the appearance at the early period of admission was the result of REM pressure growing.     

Narcolepsy in childhood and adolescence.

The objective of this study was to evaluate clinical, polysomnographic and the multiple sleep latency test (MSLT) features in young narcoleptics. We evaluated 14 patients with mean age of 13.6 years old (ranging from 6 to 18 years); 11 were males and 3 females. Daytime sleepiness was the main complaint in all cases and started at the ages of 6 to 17 years. Cataplexy was described in 10 cases and it was considered mild to moderate in all but one case. Sleep paralysis was present in 6 cases and hypnagogic hallucinations in 7 cases. The main polysomnographic characteristics were the short sleep latency in 9 cases and the sudden onset of REM periods in 7 cases. The MSLT showed short or borderline sleep latencies in 13 cases, with a mean of 4.9 min; 2 or more REM periods were present in 13 cases. Clinical, polysomnographic and MSLT characteristics in the age bracket focused were remarkably similar to those of adult narcoleptics suggesting the stability of these physiopathological markers.     

Early return to REM sleep after nocturnal awakening in depression.

Sixteen male outpatients with major depression and 20 age-equated healthy controls were awakened from rapid eye movement (REM) sleep between 1:30 and 3:30 AM, and the rapidity of return to REM sleep was determined. The time it took to return to REM sleep was reduced in depressives compared with controls: 61.6 (17.9 SD) min versus 80.6 (24.9 SD) min, respectively (p = 0.01). The time elapsed until the return to REM sleep was significantly correlated with baseline REM latency in controls (but not depressives). In contrast, return to REM time was significantly correlated with depression severity scores in depressives (but not controls). There was no evidence to support the hypothesis that the more rapid return to REM sleep in depression was caused by a slow wave sleep deficit. The mechanism underlying the rapid return of REM sleep in depression thus may be related to a severity-linked disturbance, such as a proposed increase in REM "pressure."     

The effect of naloxone on normal human sleep

Placebo and naloxone (4, 8, and 12 mg) were infused on separate nights in a double-blind fashion over a 20-min period between the 25th and 45th min of sleep in normal volunteers. Naloxone produced a dose-dependent increase in REM latency (the time from onset of sleep until the first REM period), and duration of the first REM period and second NREM period. The number of REM periods was also reduced.     

Repeated nocturnal sleep latencies in narcoleptic, sleepy and alert subjects.

OBJECTIVES: The purpose of this study was to assess nocturnal sleep latencies among narcoleptics. METHODS: Thirteen narcoleptics and matched sleepy and alert controls participated in this study. Subjects were awakened three times on each of two experimental nights. The latencies to sleep and rapid eye movement sleep were evaluated at the beginning of the night and following each experimental awakening. RESULTS: The alert group (AG) had a significantly longer mean nocturnal sleep latency than the narcoleptic (NG) and sleepy groups (SG). The sleep latencies at 23:00 and 01:10 h were significantly longer than the latencies at 03:10 and 05:10 h. The interaction between group and time of night demonstrated longer latencies at 23:00 and 03:10 h for the AG when compared to the SG and the NG. At 01:10 and 05:10 h all groups had comparable latencies. The number of subjects in the NG who had multiple sleep onset REM periods (SOREMPs) was significantly higher than in either the AG or the SG. CONCLUSIONS: Narcoleptics were found to have a heightened propensity to fall asleep and increased number of SOREMPs during nocturnal sleep opportunities. These characteristics are consistent with the daytime polysomnographic findings known in this patient population.     

Occurrence of ‘microsleeps’ during daytime sleep onset in normal subjects

The main aim of this study was to explore whether the multiple sleep latency test (MSLT) could be made more sensitive to low daytime sleepiness in normal, healthy subjects by adopting a shorter period of sleep (microsleep) as a sleep onset criterion. Subjects underwent MSLTs under two conditions: after normal (baseline) nightime sleep, and after nighttime sleep extension (creating a ‘floor effect’ of minimal daytime sleepiness). MSLT sleep onset thresholds of 5 s (microsleeps), 30 s (the norm) and 90 s of sustained sleep gave 3 separate sleep latency scores for 240 MSLT trials derived from 10 subjects. With low daytime sleepiness, whether this be in the morning after baseline sleep or throughout the day after sleep extension, the 5 s sleep onset criterion was a more sensitive measure of sleepiness than the established 30 s criterion. This was the case both for sleep onset latency and for the frequency of sleep onsets. Spectral analyses of the EEG indicated that successive microsleep episodes generally became more substantial, and, depending on the level of sleepiness, culminated in more overt signs of sleep. There was little difference between the 30 s and 90 s criteria for sleep onset latency scores, although there was a small but significant difference between them in the frequency of sleep onsets. As daytime sleepiness increased, particularly in the afternoon and under baseline, the 5 s criterion reached a ceiling, with the 30 s criterion becoming more sensitive.     

Sleep studies on a 90-minute day.

After 2 adaptation and 2 baseline all-night sleep recordings, 5 normal young adult subjects (3 males) were placed on a schedule alternating 60 min of wakefulness and 30 min of sleep for 5 1/3 24-h periods. A 2-day recovery period followed. One male subject (MA15) was later placed on the identical protocol with the exception that he was allotted periods of 75 min of wakefulness and 15 min of sleep during the experimental period. One male narcolepsy-cataplexy patient was placed on the 60-30 schedule for 48 h. All subjects showed REM sleep during the schedule manipulation. REMM sleep occurred within 10 min of sleep onset (SOREMP) on 79 of 110 REM sleep occasions in the normals, on all 29 REM episodes in MA15, and on 16 of 17 REM periods in the narcoleptic. In the normals, REM sleep showed a tendency to recur on alternate 90-min cycles, while in the narcoleptic REM recurred on consecutive periods. Compared to baseline, REM sleep 24 h was decreased in the normals and increased in the narcoleptic. Time spent in slow wave sleep and stage 2 was also reduced in the normal subjects on the 90-min schedule, and stage 1 sleep time was increased. Peak sleep times for the 5 normals occurred between 09.00 and 12.30 and lowest sleep times from 21.00 to 02.00. During the first recovery night, sleep times ranged from 11.5 to 18.5 h, including significant increases of slow wave sleep and REM sleep. Except for SOREMPs, no signs of the narcolepsy-cataplexy syndrome were seen in any of the normal subjects.     

Comparative analysis of multiple sleep latency tests (MSLT) parameters and occurrence of dreaming in patients with daytime sleepiness of narcoleptic and non-narcoleptic origin

OBJECTIVE: To compare MSLT parameters in two groups of patients with daytime sleepiness, correlated to the occurrence and onset of dreams. METHOD: Patients were submitted to the MSLT between January/1999 and June/2002. Sleep onset latency, REM sleep latency and total sleep time were determined. The occurrence of dreams was inquired following each MSLT series. Patients were classified as narcoleptic (N) or non-narcoleptic (NN). RESULTS: Thirty patients were studied, 12 were classified as narcoleptics (N group; 40%), while the remaining 18 as non-narcoleptic (NN group; 60%). Thirty MSLT were performed, resulting in 146 series. Sleep was detected in 126 series (86%) and dreams in 56 series (44.44%). Mean sleep time in the N group was 16.0+/-6.3 min, while 10.5+/-7.5 min in the NN group (p<0.0001). Mean sleep latency was 2.0+/-2.2 min and 7.2+/-6.0 min in the N and NN group, respectively (p<0.001). Mean REM sleep latency in the N group was 3.2+/-3.1min and 6.9+/-3.7 min in the NN group (p=0.021). Dreams occurred in 56.9% of the N group series and 28.4% in that of the NN group (p=0.0009). Dream frequency was detected in 29.8% and 75% of the NREM series of the N and NN groups, respectively (p=0.0001). CONCLUSION: Patients from the N group, compared to the NN group, slept longer and earlier, demonstrated a shorter REM sleep onset and greater dream frequency. NN patients had a greater dream frequency in NREM series. Thus, the occurrence of dreams during NREM in the MSLT may contribute to differentially diagnose narcolepsy and daytime sleepiness.     

Hypersomnia in bipolar depression: a comparison with narcolepsy using the multiple sleep latency test

OBJECTIVE: This study characterized objectively the hypersomnia frequently seen in the depressed phase of bipolar affective disorder. On the basis of previous work in sleep and affective disorders, it has been hypothesized that the hypersomnia is related to greater REM sleep. This hypothesis was tested by using a multiple sleep latency test to compare bipolar affective disorder with narcolepsy, a well-defined primary sleep disorder associated with known REM sleep dysfunction. METHOD: Twenty-five bipolar depressed patients were selected on the basis of complaints of hypersomnia. They underwent 2 nights of polysomnography followed by a multiple sleep latency test. Data on their nocturnal sleep and daytime naps were compared with similar data on 23 nondepressed narcoleptic patients referred for sleep evaluation. RESULTS: Despite their complaints of hypersomnia, no abnormalities were noted for the bipolar group in the results from the multiple sleep latency test. Contrary to the working hypothesis, REM sleep was notably absent during daytime naps in the depressed patients, in marked contrast to the findings for the narcoleptic group. CONCLUSIONS: The complaint of sleepiness in the hypersomnic bipolar depressed patient appears to be related to the lack of interest, withdrawal, decreased energy, or psychomotor retardation inherent in the anergic depressed condition, rather than an increase in true sleep propensity or REM sleep propensity.     

Sleep propensity at daytime as assessed by Multiple Sleep Latency Tests (MSLT) in patients with schizophrenia increases with clozapine and olanzapine

Sleep propensity at daytime has not been investigated in untreated patients with schizophrenia. Furthermore, while the antipsychotics clozapine and olanzapine are considered to frequently cause 'sleepiness' or 'sedation', this has not been objectified yet. Therefore, 30 patients with schizophrenia were included in this randomized, double-blind study. Sleep propensity was assessed before and after 2, 4 and 6 weeks of treatment with either clozapine or olanzapine using a Multiple Sleep Latency Test (MSLT); in the MSLT, sleep latencies of 5 nap opportunities of 20 min during daytime are averaged. In addition, the number of sleep onsets was recorded. Mean sleep latency in untreated schizophrenic patients was 16.2 ± 0.8 min at baseline. Both antipsychotics induced an increase of sleep propensity as indicated by a shortened sleep latency and more sleep onsets during the treatment period as compared to baseline. These effects were strongest in the morning. Four patients receiving clozapine and 3 patients receiving olanzapine reported subjective sleepiness, in all but one commencing in the first treatment week and persisting until study end. While the mean sleep latency during treatment was significantly shorter in these patients (12.3 ± 0.8 min) than in those without subjective sleepiness (14.9 ± 0.7 min), a short sleep latency was not necessarily associated with subjective sleepiness. In conclusion, mean sleep latency was >36% longer (i.e. sleep propensity was lower) in untreated patients with schizophrenia than in healthy subjects previously consistently reported. Furthermore, clozapine and olanzapine increased sleep propensity in schizophrenic patients. A minority of patients reported subjective sleepiness.     

Sleepiness in sleepwalking and sleep terrors: a higher sleep pressure?

ObjectiveTo identify the determinants of excessive daytime sleepiness in adults with sleepwalking or sleep terrors (SW/ST).MethodsWe collected the charts of all consecutive adult patients admitted from 2012 to 2014 for SW/ST. They had completed the Paris Arousal Disorders Severity Scale and the Epworth Sleepiness Scale, and had undergone one (n = 34) or two consecutive (n = 124) nocturnal videopolysomnographies. The demographic, clinical, and sleep determinants of excessive daytime sleepiness (defined as an Epworth Sleepiness Scale score of greater than 10) were analyzed.ResultsAlmost half (46.8%) of the 158 adult patients with SW/ST reported excessive daytime sleepiness. They had shorter sleep onset latencies (in night 1 and night 2), shorter REM sleep latencies, longer total sleep time, and higher REM sleep percentages in night 2, but no greater clinical severity of the parasomnia than patients without sleepiness. The level of sleepiness correlated with the same measures (sleep onset latency on both nights, REM sleep onset latency, and total sleep time in night 2), plus the latency to N3. In the regression model, higher sleepiness was determined by shorter sleep onset latency on night 1, lower number of awakenings in N3 on night 1, and higher total sleep time on night 2.ConclusionDaytime sleepiness in patients with SW/ST is not the consequence of disturbed sleep but is associated with a specific polygraphic phenotype (rapid sleep onset, long sleep time, lower numbers of awakenings on N3) that is suggestive of a higher sleep pressure that may contribute to incomplete arousal from N3.     

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.     

Sleep disorders in temporal lobe epilepsy

The objective of this study was to evaluate sleep macrostructure and sleep disturbance in a group of 39 patients with temporal lobe epilepsy (TLE). Patients completed questionnaires to evaluate their sleep and subjective daytime sleepiness (Epworth Sleepiness Scale [ESS]) and undergone Polysomnography and Multiple Sleep Latency Test (MSLT). Daytime sleepiness was the most frequent complaint (85%), followed by wakefulness during sleep, history of seizures during sleep (75%) and initial insomnia (26%). Parasomnias (67%), obstructive sleep apneas (13%), restless legs syndrome (15%) and periodic limb movements (5%) were the most frequent sleep disorders. The most frequent changes of sleep patterns were: sleep architecture fragmentation (100%), decreased amount of REM sleep (92%) and increase in time awake after sleep onset (77%). There were significative correlations between the ESS and the MSLT (p<0,05). In conclusion, TLE patients have fragmented sleep with increased sleep stages shifts, increased number of awakenings and in time awake after sleep onset. REM sleep was decreased. Daytime sleepiness was the most frequent complaint in TLE patients.     

Sleep EEG effects of 3,4-methylenedioxyethamphetamine (MDE; "eve") in healthy volunteers.

3,4-methylenedioxyethamphetamine (MDE; "Eve") exerts similar psychotropic effects in humans as 3,4-methylenedioxymethamphetamine (MDMA; "Ecstasy") and is less toxic in animal studies. We conducted a double-blind, placebo-controlled, cross-over sleep electroencephalogram (EEG) study with healthy volunteers. One hundred forty milligrams of MDE or placebo were administered PO in six subjects at 11 PM. Sleep EEG was registered from 11 PM-7 AM the next morning. All subjects had a normal sleep onset latency. They all awoke 60 to 120 min after administration of MDE and stayed awake for at least 150 min (total sleep time, TST MDE < placebo and intermittent time awake MDE > placebo: p < 0.001). After again falling asleep rapid eye movement (REM) sleep was totally suppressed (REM during time in bed, TIB MDE < placebo: p < 0.001). A cyclic alternation of relatively long periods of slow wave sleep (SWS) with periods of light sleep occurred in three subjects during the second part of the night (stage 4 in second part of night MDE > placebo: p = 0.16). The effects of MDE on sleep variables largely demonstrate the stimulant, amphetamine-like properties of MDE.     

Vagus nerve stimulation reduces daytime sleepiness in epilepsy patients

BACKGROUND: Given that vagal afferents project to brainstem regions that promote alertness, the authors tested the hypothesis that vagus nerve stimulation (VNS) would improve daytime sleepiness in patients with epilepsy. METHODS: Sixteen subjects with medically refractory seizures underwent polysomnography and multiple sleep latency tests (MSLT) and completed the Epworth Sleepiness Scale (ESS), a measure of subjective daytime sleepiness, before and after 3 months of VNS. Most subjects (>80%) were maintained on constant doses of antiepileptic medications. RESULTS: In the 15 subjects who completed baseline and treatment MSLT, the mean sleep latency (MSL) improved from 6.4 +/- 4.1 minutes to 9.8 +/- 5.8 minutes (+/- SD; p = 0.033), indicating reduced daytime sleepiness. All subjects with stimulus intensities of < or =1.5 mA showed improved MSL. In the 16 subjects who completed baseline and treatment ESS, the mean ESS score decreased from 7.2 +/- 4.4 to 5.6 +/- 4.5 points (p = 0.049). Improvements in MSLT and ESS were not correlated with reduction in seizure frequency. Sleep-onset REM periods occurred more frequently in treatment naps as compared to baseline naps (p < 0.008; Cochran-Mantel-Haenszel test). The amount of REM sleep or other sleep stages recorded on overnight polysomnography did not change with VNS treatment. CONCLUSIONS: Treatment with VNS at low stimulus intensities improves daytime sleepiness, even in subjects without reductions in seizure frequency. Daytime REM sleep is enhanced with VNS. These findings support the role of VNS in activating cholinergic and other brain regions that promote alertness.     

Lithium carbonate: effects on sleep patterns of normal and depressed subjects and its use in sleep-wake pathology

The effects of lithium carbonate on sleep patterns have been investigated both acutely in normal and depressed subjects and chronically in depressed subjects. In normal subjects receiving lithium for two weeks total sleep time did not vary, REM sleep decreased and REM sleep latency increased. In depressed subjects, either on short therm therapy or on long term therapy stages 3 and 4 increased, REM sleep decreased, REM latency increased and REM activity/time spent asleep (an index of REM intensity per minute of sleep) decreased. Plasma lithium levels were negatively correlated with REM sleep percentage and positively correlated with REM sleep latency. Besides, it has been shown in one paper that short term therapy with lithium caused small but significant delays in the sleep-wake circadian rhythm. These effects are of interest in view of polygraphic sleep abnormalities found in affective disorders and possible circadian disturbances accounting for these abnormalities. Indeed lithium might act in correcting spezial sleep abnormalities and/or circadian disturbances. In addition to its predominant use for the prophylaxis of recurrent mania and depression, lithium carbonate has been proposed and tried in the prophylactic treatment of abnormally prolonged sleep episodes featuring the Kleine-Levin syndrome.     

The effects of a 20 min nap in the mid-afternoon on mood, performance and EEG activity.

OBJECTIVE: The aim of the study is to examine the effects of a 20 min nap in the mid-afternoon on mood, performance and EEG activities. METHODS: Seven young adults who had normal sleep-wake habits without habitual daytime napping participated in the study. They underwent Nap and No-nap conditions at intervals of 1 week. After a nocturnal sleep recording (00:00-08:00 h), their EEG recordings during relaxed wakefulness, and their mood, performance and self-ratings of performance level were measured every 20 min from 10:00 to 18:00 h. For the nap condition, they went to bed at 14:00 h and were awakened when 20 min had elapsed from the onset of sleep stage 1. For the No-nap condition, they took a rest without sleep by sitting on a semi-reclining chair. RESULTS: All of the subjects were awakened from sleep stage 2 during the nap. The 20 min nap improved the subjective sleepiness, performance level and self-confidence of their task performance. The nap also suppressed EEG alpha activity during eyes-open wakefulness. CONCLUSIONS: The results suggest that a short 20 min nap in the mid-afternoon had positive effects upon the maintenance of the daytime vigilance level.