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PubMed1990

The effects of gamma-hydroxybutyrate on the sleep of narcolepsy patients: a double-blind study.

The effects of gamma-hydroxybutyrate (GHB: 25 mg/kg h.s. and 3 h later) vs. placebo on objectively evaluated nighttime sleep and daytime sleepiness in narcolepsy were evaluated in a double-blind, counterbalanced crossover design. Twenty narcolepsy patients were given an overnight polysomnogram (PSG), followed by a daytime multiple sleep latency test (MSLT) at baseline and on the 1st and 29th days of GHB and placebo treatment. The overnight PSGs indicated that the narcolepsy patients had the following significant results during GHB versus placebo treatment: decreased stage 1 (p = 0.012), increased stage 3 (p = 0.008), increased delta (stage 3 and 4 combined) sleep (p = 0.049), fewer stage shifts (p = 0.002), and fewer awakenings (p = 0.006). Minutes of wakefulness were significantly increased only for the last 2 h of the 8 h sleep period on GHB versus placebo (p = 0.019), which is beyond the time of GHB's direct influence. The MSLTs indicated that the narcolepsy patients had a marginally increased sleep latency mean during GHB versus placebo treatment (p = 0.074) and significantly increased total stage 0 (wakefulness) on day 29 of GHB versus day 29 of placebo treatment (p = 0.038). Female narcolepsy patients had significantly fewer naps with REM sleep (REM naps) on day 29 of GHB vs. day 29 of placebo treatment (p = 0.020). The therapeutic effect of GHB in narcolepsy patients, i.e., decreases cataplexy, appears to be due to its improving nocturnal sleep quality, since its half-life is only 1.5 to 2 h. It is conjectured that GHB, an endogenous neurochemical, may be a sleep neurotransmitter or neuromodulator, since GHB rapidly induces sleep, and increases sleep continuity and delta sleep without suppressing REM sleep in both normals and narcolepsy patients.

Adult↗

PubMed1981

Nocturnal electrographic features of frequently changing-irregular sleep-wakefulness rhythms.

Polygraphic characteristics of nocturnal sleep associated with frequently changing-irregular rest-activity schedules were investigated in healthy young adults. Two groups each of 12 male university students were classified according to a priori criteria as either: (a) controls who slept regularly for 7--8 hr at night or (b) whose retiring and arising times combined varied chronically +/- 1.5 hr. Sleep was recorded during three consecutive 8-hr nocturnal periods at fixed clock times. Polygraphic indices generally reflected greater discontinuity and fragmentation associated with the nocturnal sleep in the young adults whose 24-hr rest-activity cycle tended to be frequently changing-irregular. The significantly: (a) larger absolute quantities of (i) transitional stage 1 sleep, (ii) intermittent wakefulness and (b) increases stage shifts provided some indication that the intrasleep cycle becomes disturbed when rest-activity schedules follow no predictable pattern in the everyday environment. Despite, or because of, the enforced hour (11:30 p.m +/- 30 min) for retiring, it is possible that the capacity to fall asleep had become phase-delayed among subjects with irregular rest-activity schedules who experienced more initial wakefulness (on average) before sleep onset stage 1. Finally, the recorded sleep perturbations associated with frequently changing-irregular schedules were extremely variable across nights and among individuals. This was especially pronounced on a nightly basis as reflected by significantly larger variability (SDs): (a) in the latency to sleep onset, for (b) total time asleep, (c) intermittent wakefulness, and (d) the ultradian (90-min) REM cycle. Variability (the SD) between individuals was also more substantial for these same polygraphic measures at statistically significant levels.

Adult↗

PubMed1989

The intrasleep relationship between wake and stage 4 examined by transition probability analysis.

The relationship between wake and stage 4 of slow-wave sleep (SWS), in particular the previously observed deficiency in SWS accompanying sleep containing long-wake periods, is examined in this study of 147 health subjects. Stage shift comportment is compared between those NREM/REM cycles with wake periods greater than 3 minutes and those with less, using the method of transition probabilities. It is shown that these long wake interruptions occur preferentially in light sleep, and systematically disrupt the regular normal descent towards SWS, but do not significantly reduce the number of SWS episodes. There is at the same time, however, a reduction in the average duration of stage 4 periods of SWS which accounts for the observed reduction in the total amount of SWS.

Adolescent↗

PubMed1991

Sleep EEG and amitryptiline treatment in depressed inpatients.

We studied the baseline sleep electroencephalogram (EEG) variables and treatment-related sleep changes after 35-46 days of amitryptiline treatment (AMI) in a group of 18 depressed inpatients, mostly suffering from a major depressive disorder endogenous subtype (according to the Research Diagnostic Criteria, RDC), with a short rapid eye movement (REM) latency. The aim of the study was to identify potential sleep "predictors" of clinical response to AMI as well as short-term sleep changes associated with alleviation of depression. Clinical response to the drug was defined as a reduction of more than 50% of the Hamilton Rating Score for Depression (HRSD). Eleven men and 7 women, 25-68 years old, were included in the study. Their sleep was recorded at baseline and after an average of 39 +/- 4 days of AMI treatment, at a mean daily dose of 165 +/- 35 mg. The comparison of responders (n = 9) and nonresponders (n = 9) with Wilcoxon's test showed that responders (1) were more severely depressed at baseline, and (2) had less stage 4 sleep. A discriminant function using baseline HRSD, stage 4 and the number of stage shifts allowed for discrimination between responders and nonresponders with a 100% hit rate. Antidepressant treatment had, however, no differential effect on sleep parameters in the two response groups.

Adult↗

PubMedDate not supplied

Sleep EEG recordings in generalized anxiety disorder with significant depression.

After one accommodation night, sleep EEG recordings were performed during three consecutive nights in ten drug-free inpatients presenting generalized anxiety disorder (GAD) with significant depression, compared with a age- and sex-matched group of patients with GAD and a group of primary major depressive disorder (MDD) patients. GAD patients with depression did not differ from GAD patients in any sleep variable. Patients with MDD showed more stage shifts and a greater number of awakenings than patients with GAD. REM latency was significantly shorter in MDD patients than in the other groups, and may thus help to differentiate anxious from depressed patients.

Adult↗

PubMed2004

[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.

Adolescent↗

PubMed1984

Distribution of REM latencies and other sleep phenomena in depression as explained by a single ultradian rhythm disturbance.

The McCarley-Hobson model, describing the alternation of NREM and REM sleep in the cat, was applied to human electroencephalographic data. The influence of initial conditions on oscillatory behavior was especially emphasized. It appears that the distribution of REM latency in depression, the abnormal accumulation of REM sleep, the variability of NREM-REM cycle duration, the frequent stage shifts, and frequent awakenings can be explained in this model by means of a decrease in the initial value of a single variable, which may be regarded as representing the strength of REM inhibition. The observation of slow wave sleep deficiency in depression may well be another reflection of this parameter.

Biological Clocks↗

PubMed2005

Altered sleep regulation in leptin-deficient mice.

Recent epidemiological, clinical, and experimental studies have demonstrated important links between sleep duration and architecture, circadian rhythms, and metabolism, although the genetic pathways that interconnect these processes are not well understood. Leptin is a circulating hormone and major adiposity signal involved in long-term energy homeostasis. In this study, we tested the hypothesis that leptin deficiency leads to impairments in sleep-wake regulation. Male ob/ob mice, a genetic model of leptin deficiency, had significantly disrupted sleep architecture with an elevated number of arousals from sleep [wild-type (WT) mice, 108.2 +/- 7.2 vs. ob/ob mice, 148.4 +/- 4.5, P < 0.001] and increased stage shifts (WT, 519.1 +/- 25.2 vs. ob/ob, 748.0 +/- 38.8, P < 0.001) compared with WT mice. Ob/ob mice also had more frequent, but shorter-lasting sleep bouts compared with WT mice, indicating impaired sleep consolidation. Interestingly, ob/ob mice showed changes in sleep time, with increased amounts of 24-h non-rapid eye movement (NREM) sleep (WT, 601.5 +/- 10.8 vs. ob/ob, 669.2 +/- 13.4 min, P < 0.001). Ob/ob mice had overall lower body temperature (WT, 35.1 +/- 0.2 vs. ob/ob, 33.4 +/- 0.2 degrees C, P < 0.001) and locomotor activity counts (WT, 25125 +/- 2137 vs. ob/ob, 5219 +/- 1759, P < 0.001). Ob/ob mice displayed an attenuated diurnal rhythm of sleep-wake stages, NREM delta power, and locomotor activity. Following sleep deprivation, ob/ob mice had smaller amounts of NREM and REM recovery sleep, both in terms of the magnitude and the duration of the recovery response. In combination, these results indicate that leptin deficiency disrupts the regulation of sleep architecture and diurnal rhythmicity.

Animals↗

PubMed1991

Sleep organization and epilepsy.

Sleep is known to facilitate epileptic manifestations but can also protect the sleeper against the recurrence of seizures. This has been demonstrated in studies on sleep deprivation, and is particularly evident in alcoholic epilepsy and matutinal myoclonus epilepsy. Sleep organization in the epileptic patient is permanently altered by frequent awakenings and stage shifts. Nocturnal grand mal and repetitive partial seizures worsen the sleep disorder by reducing total sleep time and decreasing REM percentage by half. The cumulative effect of these sleep disorders may act on day-time vigilance in epileptics, and may even exert an influence on the recurrence of seizures.

Adult↗

PubMed2002

Gabapentin increases slow-wave sleep in normal adults.

PURPOSE: The older antiepileptic drugs (AEDs) have a variety of effects on sleep, including marked reduction in rapid-eye-movement (REM) sleep, slow-wave sleep (SWS), and sleep latency, and an increase in light sleep. The effects of the newer AEDs on sleep are unknown. Our purpose was to study the effect of gabapentin (GBP) on sleep. METHODS: Ten healthy adults and nine controls were the subjects of this study. All underwent baseline and follow-up polysomnography (PSG) and completed sleep questionnaires. After baseline, the treated group received GBP titrated to 1,800 mg daily. Polygraphic variables and Epworth Sleepiness Scale (ESS) scores, a subjective measure of sleep propensity, were compared by using the Wilcoxon signed rank test. RESULTS: Nine of the treated subjects achieved the target dose; one was studied with 1,500 mg daily because of dizziness experienced at the higher dose. GBP-treated subjects had an increase in SWS compared with baseline. No difference in the ESS or other polygraphic variables was observed. However, a minor reduction in arousals, awakenings, and stage shifts was observed in treated subjects. CONCLUSIONS: GBP appears to be less disruptive to sleep than are some of the older AEDs. These findings may underlie the drug's therapeutic effect in the treatment of disorders associated with sleep disruption.

Acetates↗

PubMed2000

Altered sleep and behavioral patterns of arthritic rats.

The present study sought to evaluate concomitant alterations of behavioral and sleep patterns of arthritic rats. Rats were implanted with electrodes for polysomnographic recordings and submitted to the model of arthritis by a subcutaneous (s.c.) administration of Freund adjuvant in the posterior right paw and saline in the posterior left paw. The SHAM group was injected with saline in both paws, whereas the control group (CTL) was not submitted to any manipulation. Behavioral tests were carried out twice before induction of arthritis, on the second day of arthritis, and once a week afterwards until the eighth week. Body weight, colonic temperature, and measurements of the injured paw were carried out on the same days. Arthritic rats presented a reduction of total sleep time, increased latency to synchronized sleep, augmented number of episodes of synchronized sleep, reduction of sleep efficiency, more stage shifts, and increased total alert time. Moreover, these animals presented a lower pain threshold than control and SHAM animals. This reduction was observed on the second day of arthritis and remained so reduced until the end of the study. The data appear to indicate a relationship between altered sleep pattern and increased pain sensitivity in arthritic rats.

Analysis of Variance↗

PubMed1996

Structured psychiatric interview and ambulatory sleep monitoring in young psychophysiological insomniacs.

BACKGROUND: The presence of psychiatric disorders (according to DSM-III-R), the discriminating power of a psychiatric structured interview, and sleep monitoring were investigated in psychophysiological insomnia. METHOD: Forty young (20-40 years old) patients, selected for putative psychophysiological insomnia, underwent a psychiatric structured interview and home ambulatory sleep monitoring for 2 nights. The results were compared with those of a group of nine young normal sleepers. RESULTS: 48% of the insomniacs showed some psychiatric disorders, while 52% did not meet DSM-III-R criteria for a psychiatric diagnosis. Both groups, but not the controls, showed a slight first-night effect in the sleep analysis. The sleep structure of all insomniacs was found to be disturbed, mainly in sleep continuity, but essentially the two groups showed no significant differences. When we used a stepwise logistic regression analysis, the number of sleep stage shifts (indicating sleep instability) was the best variable in discriminating the insomniacs from controls, but not the patients with psychiatric disturbances from those without psychopathologies. CONCLUSION: The evaluation of young insomniacs with a structured psychiatric interview rather than with ambulatory sleep monitoring seems to be most useful in discriminating between patients with only psychophysiological insomnia and patients with both insomnia and an associated diagnosis of another mental disorder.

Adult↗

PubMedDate not supplied

Treatment of prostate cancer: watchful waiting, radical prostatectomy, and cryoablation.

Current advances in diagnostic modalities and screening has lead to diagnosis of prostate cancer at an earlier stage (the so-called "stage shift" phenomenon), making primary treatments of localized disease of extreme importance in management. Therapeutic modalities include conservative management, radical prostatectomy, external beam radiotherapy, and newer techniques such as cryoablation surgery and brachytherapy. This review will focus on the non-radiation, non-hormonal primary treatment of localized prostate cancer and discuss the popularity and success of "watchful waiting," radical surgery, and cryoablation along with their advantages and disadvantages. These treatments will be compared to the qualities of an ideal treatment, which include cost effectiveness, efficacy, convenience of administration, tolerance by patients, low morbidity and mortality, and minimal impact on quality of life.

Brachytherapy↗

PubMed2000

Effects of lamotrigine on nocturnal sleep, daytime somnolence and cognitive functions in focal epilepsy.

OBJECTIVES: The aim of our study was to evaluate possible changes in nocturnal sleep, daytime somnolence and cognitive functions induced by add-on therapy with lamotrigine (LTG). MATERIAL AND METHODS: Thirteen patients affected by seizures resistant to common antiepileptic drugs (AEDs) underwent nocturnal polysomnographic monitorings, daytime somnolence evaluations and a neuropsychological battery before and after 3 months of treatment with LTG. RESULTS: With LTG therapy we observed a significant increase in REM sleep and a significant reduction in the number of entries into REM and stage shifts. No significant correlation was observed between the decrease in nocturnal epileptiform activity and the increase in REM sleep. Other sleep parameters were unmodified. No significant changes were observed in daytime somnolence and in cognitive performances. CONCLUSION: LTG may produce positive effects on epileptic seizures and interictal abnormalities without interfering negatively on REM sleep, with improvement of sleep stability and without changes in daytime somnolence and neuropsychological performances. For these reasons it could be an important drug for improving epileptic patients' quality of life.

Adolescent↗

PubMed1989

Automatic versus visual EEG sleep staging in preadolescent children.

Ambulant sleep polygrams were obtained from 14 normal subjects (9 boys and 5 girls) and from 3 boys with attention deficit disorder. The children were aged 8-12 years. Two consecutive nights were recorded with an eight-channel electroencephalographic (EEG) tape cassette recorder. The results were analyzed automatically by the Oxford Medilog 9000 Sleep Stager and by visual scoring from the Medilog Display Unit. Twenty-seven nights were analyzed; 7 nights were excluded because of electrode problems or other technical failures. The main sleep stage shifts and the length of sleep cycles as measured from the hypnogram of the automatic printout agreed well with corresponding values from our visual scoring. In the automatic scoring, rapid eye movement (REM) sleep time was shorter and slow wave sleep was longer than in the visual rating. This can be explained partly by specific properties of the EEG in this age group. The Oxford Medilog 9000 sleep stager can be used to survey sleep quality, but the results must be carefully checked visually. In cases of EEG pathology or sleep abnormalities in childhood it is doubtful if any time or labor is saved by using automatic scoring.

Child↗

PubMed2002

Acute placebo-controlled sleep laboratory studies and clinical follow-up with pramipexole in restless legs syndrome.

In a single-blind, placebo-controlled crossover trial, the acute efficacy of the dopamine agonist pramipexole was investigated in 11 restless legs syndrome (RLS) patients by sleep laboratory methods, with a clinical follow-up for 4 weeks. In 3 nights (pre-treatment, placebo and drug night), objective sleep quality was determined by polysomnography (PSG), subjective sleep and awakening quality by rating scales, objective awakening quality by psychometry. Clinical follow-up consisted of completion of the International RLS Study Group (IRLSSG) Scale, Zung Depression (SDS) and Anxiety (SAS) Scale, Quality of Life Index, Pittsburgh Sleep Quality Index and Epworth Sleepiness Scale. Concerning acute effects, an omnibus significance test for PSG variables demonstrated a global difference between placebo and pramipexole, but none between pre-treatment and placebo. Pramipexole 0.27 mg significantly decreased the target variable periodic leg movements (PLM)/h of sleep as well as all other RLS/PLM variables and improved objective sleep efficiency and subjective sleep quality as compared with placebo. In sleep architecture, sleep stages S1 and S2 and stage shifts increased, while slow-wave sleep and SREM decreased. After 4 weeks of therapy, the total scores of the IRLSSG questionnaire, sleep quality and daytime sleepiness, depression and quality of life also improved. Thus, acute pramipexole markedly reduced PLM measures and slightly improved objective and subjective sleep quality. Follow-up ratings showed a moderate improvement of RLS and sleep quality, and to a lesser extent of daytime sleepiness, depression and quality of life. The psychopathological findings as well as acute sleep architecture changes are reminiscent of those seen after activating antidepressants.

Adult↗

PubMed1996

Sleep apnea after 1 year domiciliary nasal-continuous positive airway pressure and attempted weight reduction. Potential for weaning from continuous positive airway pressure.

STUDY OBJECTIVE: To assess the effect of 1 year of therapy for sleep apnea syndrome (SAS) combining domiciliary nasal-continuous positive airway pressure (N-CPAP) and attempted weight loss on the severity of disease and to evaluate the potential for weaning from continuous positive airway pressure (CPAP). METHODS AND PROCEDURES: Ninety-five patients having a baseline apnea hypopnea index (AHI) greater than 10/h were prescribed N-CPAP at home. Weight loss was attempted by dietary counseling and by single ring vertical gastroplasty in those patients with a body mass index (BMI) greater than 40 kg/m2. Subjects were asked to return after 1 year for a full-night polysomnography (PSG) without CPAP and the results were compared with baseline PSG. RESULTS: Thirty-nine patients compliant to CPAP were evaluated. Weight had decreased from 108.3 +/- 29.0 to 99.7 +/- 17.7 kg as a result of dietary counseling (n = 36) or gastroplasty (n = 3). A significant improvement was found in AHI (66.5 +/- 28.7-->50.3 +/- 38.4/h; p < 0.05), maximal duration of apnea or hypopnea (66 +/- 22-->47 +/- 18 s; p < 0.001), minimal oxyhemoglobin saturation (62 +/- 16-->78 +/- 7%; p < 0.001), and stage shift index (SSI) (76 +/- 29-->62 +/- 28/h; p < 0.05). The drop in AHI correlated with the reduction in BMI (r = 0.47; p < 0.01) and with the decrease in SSI (r = 0.50; p < 0.001). Weaning from CPAP was proposed to six patients and succeeded in four (three with 29, 93, and 94 kg weight loss, respectively, and one subject with a normal unchanged weight). CONCLUSION: In 39 patients with SAS, 1-year domiciliary N-CPAP combined with weight loss resulted in a significant improvement in breathing during sleep and in sleep fragmentation, as judged from PSG without CPAP. Four subjects were successfully weaned, three of whom had in parallel a substantial decrease in weight.

Body Mass Index↗

PubMed1999

Melatonin as a therapy in REM sleep behavior disorder patients: an open-labeled pilot study on the possible influence of melatonin on REM-sleep regulation.

REM sleep behavior disorder (RBD) is clinically impressive by virtue of its vigorous sleep behaviors usually accompanying vivid, striking dreams. The main feature of the disorder, REM sleep without muscle atonia, has been shown in a variety of diseases; therefore, the disorder might possibly be underestimated. In an open-labeled trial, we treated six consecutive RBD patients over a 6-week period with 3 mg melatonin given within 30 minutes before bedtime. There was a dramatic clinical improvement in five of the six patients within a week which extended beyond the end of treatment for weeks or months. A second polysomnogram performed 6 weeks after the beginning of treatment showed a significant tendency toward normalization of the percentage of REM sleep, a significant reduction of 30-second epochs, scored as REM sleep without muscle atonia, a significant reduction of stage-shifts in REM, and a significant reduction in epochs considered as movement time in REM. All other sleep parameters were not changed consistently. We hypothesize that internal desynchrony might be a part of the underlying pathophysiology in RBD. Our data might give first evidence to the hypothesis that exogenous melatonin, administered to patients with internal desynchrony at the time of the maximal rise of melatonin secretion, might increase the overall amplitude of the circadian pacemaker by reentraining the suprachiasmatic nucleus and thereby restore circadian driven rhythms, one of them being the circadian modulation of REM sleep.

Adult↗