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Biomedical subjects

A Besset

Publications and source records attributed to A Besset.

At least 37 records · Page 2Linked to original sources

Use of modafinil in the treatment of narcolepsy: a long term follow-up study.

One hundred and forty patients (104 male and 36 female) aged 42.26 +/- 19.19 (range = 8 to 79.5 years) with narcolepsy-cataplexy were given modafinil (200 to 400 mg) at the Montpellier sleep disorders center from 1984 onwards. The follow-up focused on the reduction of excessive daytime somnolence (EDS), side effects and duration of treatment. In order to determine if any clinical aspect of narcolepsy could be involved in modafinil discontinuation, patients were divided into two groups according to continued or interrupted treatment. When modafinil effect on EDS was evaluated according to a scale varying from 0 (no effect) to 3 (excellent effect), 64.1% of the subjects, scored good or excellent. The mean duration of treatment was 22.05 months +/- 24.9, ranging from 1 to 114 months. Dependency signs were never observed.

Adolescent↗

[Circadian rhythm in normal and pathological sleep].

Different challenges, constraints for quality of sleep and wakefulness, sleep in extreme conditions, search for a better identification of disorders of sleep and wakefulness, spur researches on the circadian rhythm of sleep and on its disorders. Any advance in that field rests on the understanding of different physiologic phenomena: the intrinsic period of our internal clock is not 24-hours but a little less than 25-hours and it must be reset daily by the Zeitgebers. A sudden phase shift provokes an external desynchronisation. In addition not all rhythms resynchronize together resulting in an internal desyncronization. There is a close relationship between quantities of total sleep and REM sleep and the time of sleep onset within the 24-hours. The propensity to sleep follows a circasemidian rhythm with a major peak during the night and a secondary peak in the midafternoon. Disorders of the circadian rhythm of sleep are of two types: related to the misalignment of the sleep-wake schedule and the synchronizer-controlled rest-activity rhythm (shift work sleep disorder and time zone change syndrome) or related to an abnormal escape of the individual rest-activity rhythm from synchronizer control (delayed sleep phase syndrome, advanced sleep phase syndrome and non 24-hour sleep-wake syndrome.

Biological Clocks↗

Dynamics of slow wave activity in narcoleptic patients under bed rest conditions.

Following a baseline night recording, 9 narcoleptic subjects and 9 sex- and age-matched control subjects were maintained on 16 h of diurnal sleep deprivation. Thereafter subjects were submitted to a 32 h bed rest protocol in a sound- and light-attenuated room. The EEG was recorded and processed by a Fast Fourier Transform. Narcoleptics did not differ from controls in total sleep time over the whole 32 h, but spent more time sleeping during the daytime (DT). In both groups slow wave activity (SWA) showed an exponential decaying trend during the first night (N1); a similar exponential trend during the second night (N2) was evident only in controls. In controls SWA showed a circadian-circasemidian distribution that was hardly detectable in nacroleptics. Narcoleptics showed an ultradian distribution of SWA with periodic emergence every 4 h during DT and N2. Our data confirm that a homeostatic mechanism is evident in narcolpetics when stimulated by diurnal sleep deprivation, while circadian and circasemidian mechanisms are less evident during DT and N2. These findings suggest a different coupling between homeostatic sleep regulating and circadian drives to sleep in narcoleptics. Ultradian drives to sleep seem to be predominant in these patients, thus probably acting as a means for the avoidance of stressful attempts to counteract a weaker waking state maintenance mechanism.

Adult↗

Effects of zolpidem on the architecture and cyclical structure of sleep in poor sleepers.

Effects of zolpidem, a short acting non benzodiazepine hypnotic, have been studied in eight female poor sleepers, aged 25 to 54 years, documented during two consecutive adaptation nights. Subjects were recorded according to a 22 day single blind study. Placebo was given orally at bedtime on nights 2-4, zolpidem on nights 5-20 and finally placebo on nights 21-22. Polygraphic recordings (conventional analysis) were performed on nights 1-6; 12, 13; 19-22. Parameters of sleep continuity, sleep architecture and cyclical structure of sleep were studied. Zolpidem 10 mg showed a hypnotic effect on poor sleepers. It reduced sleep latency, increased total sleep time and decreased the number of awakenings during all recorded nights. During the first post-drug night a rebound insomnia was observed in two subjects only. Zolpidem did not increase specifically stage 2 to the detriment of stages 3 and 4 but it restored them during the first nights of administration. Study of the rapid eye movements-non rapid eye movements (REM-NREM) sleep cycles structure showed that the increase of stages 3 and 4 occurred only during the first part of the night. Finally, zolpidem had no effect on REM sleep temporal distribution.

Adult↗

Hypersomnia associated with mood disorders: a new perspective.

Thirty-six subjects affected with hypersomnia associated with mood disorders, 31 with a diagnosis of dysthymia, 4 with a diagnosis of bipolar disorder and one with a diagnosis of major recurrent depression underwent standardized polysomnographic procedures including night 1, MSLT and night 2 (uninterrupted). 36.1% of these subjects had a reduced or intermediate mean sleep latency on the MSLT and 13.8% slept over 9 hr at night. In addition 17 of these subjects underwent prolonged polysomnography during day 2. In comparison with eight subjects affected with idiopathic hypersomnia, mean sleep latency on the MSLT was significantly longer and total sleep time during night 2 and during night 2 plus day 2 was significantly lower in subjects affected with hypersomnia associated with mood disorders. It is concluded that a positive diagnosis of hypersomnia associated with a mood disorder requires both behavioral observation and polysomnography. Among these subjects there may be subjects with well-documented hypersomnia and subjects with anergia facilitating or mimicking sleep.

Adult↗

Modafinil: a double-blind multicentric study.

Modafinil is a central putative alpha-1 postsynaptic agonist with vigilance-promoting properties. Fifty narcoleptics (33 male and 17 female) participated in a multicentric study aimed at assessing the effects of the compound on night sleep, feeling on awakening, excessive daytime sleepiness and cataplexy. Modafinil was administered in a double-blind cross-over design at a daily dosage of 300 mg versus placebo. The duration of the study was 12 weeks, including a 2-week "run in" period with placebo, a first 4-week treatment period with either modafinil or placebo, a 2-week wash-out period with placebo and a second 4-week treatment period with either placebo or modafinil. Daily evaluation was based on a sleep log, visual analog scales, a sleep questionnaire and a clinical global index. Sleep laboratory evaluation took place on nights 1, 28, 42 and 70. It included 1 night of polysomnography preceded by a questionnaire on therapeutic and side effects, and a maintenance of wakefulness test (MWT). Sleep logs did not show any modification of night sleep, but a reduction of daytime sleepiness and sleep. Feeling on awakening was not modified. An overall benefit was noted by physicians as well as by patients. MWT disclosed a positive effect of modafinil on excessive daytime sleepiness. Cataplexy was not modified.

Adult↗

Life events in the year preceding the onset of narcolepsy.

A multifactorial etiology for narcolepsy has been postulated, stressing the importance of environmental factors in the clinical onset of the condition. Our study evaluated the occurrence of stressful life events in the year preceding the onset of narcolepsy. Fifty narcoleptic and 50 control subjects completed a life event questionnaire (the Schedule of Recent Experiences). The proportion of narcoleptic subjects reporting the presence of life events in the year preceding the onset of narcolepsy was significantly greater than the proportion of control subjects reporting life events in the corresponding year. Moreover the weight of life events was increased in narcoleptic subjects in comparison with controls. In conclusion life events seem to be increased in narcoleptic subjects in the year preceding the onset of their condition. However a number of other factors could not be taken into consideration, which limits the full significance of these data.

Adolescent↗

Family studies in narcolepsy.

Out of a population of 188 unrelated narcoleptic probands, we identified 14 probands (7.44%) with a family history of narcolepsy, 23 (12.23%) with a family history of isolated repeated episodes of naps and/or lapses into sleep and 151 (80.31%) without a family history of either condition. Clinical, polysomnographic or zygotic differences could not be evidenced in the three groups. Empirical risk for narcolepsy was 40.7 times greater among first-degree relatives of narcoleptics than in the general population. Narcolepsy and the condition characterized by isolated repeated episodes of naps and/or lapses into sleep have a common genetic component. This finding has important implications. Indeed, when the latter condition is included in the spectrum of narcolepsy, the empirical risk figure is relatively close to that expected in cases of simple mode of inheritance. A trend in favor of a more frequent transmission through mothers than fathers is emphasized.

Age of Onset↗

Homeostasis and narcolepsy.

Narcolepsy is characterized by irresistible daytime sleep episodes and cataplectic attacks. Because of the finding of an ultradian rhythmicity of slow-wave sleep in narcolepsy, an alteration of nonrapid eye movement sleep homeostatic regulation has been hypothesized to explain the impairment of the sleep-wakefulness cycle. This hypothesis was tested by two different methods: 1) a sleep-deprivation method (16 or 24 hours) increasing the prior sleep wakefulness and 2) a bed-rest method shortening the prior sleep wakefulness. In both studies normal subjects, sex- and age-matched to narcoleptic subjects, served as controls. Although some differences could be evidenced between the two groups, it was clearly shown that the homeostatic process was functional in narcolepsy and that narcoleptics seemed to be more sensitive to homeostatic regulation of sleep than normal subjects.

Adolescent↗

[The effects of modafinil (300mg) on sleep, sleepiness and arousal in narcoleptic patients].

CNS stimulants are the most widely used drugs to treat narcolepsy which is characterized by the excessive daytime sleepiness and typically associated with cataplexy. However, a number of side effects may often arise with this therapeutic approach. Thus, investigating new drugs which are efficient but well tolerated is of utmost importance in the treatment of narcolepsy. Although modafinil, an alpha-1 adreno-receptor agonist, has been reported to bring substantial awakening properties in animals, the studies performed in man, particularly in narcoleptic subjects, are few. In the present study, we evaluated the effects of a 300 mg daily dose of modafinil on sleepiness and psychomotor performance of 16 narcoleptic subjects. The major effect of modafinil in narcoleptic subjects was a decrease of daytime sleepiness and corresponding improvement of performances involving attentive functions. However, the learning effect in psychomotor tests may mask the drug effect.

Adolescent↗

Sleep polygraphic studies using cystomanometry in twenty patients with enuresis.

Polygraphic exploration during sleep using cystomanometry was performed in 20 patients aged 7-17 years with primary (17) or secondary (3) enuresis. In this group of patients, 9 presented with isolated nocturnal enuresis while 11 patients had associated diurnal micturition troubles. During this study we documented 24 episodes of enuresis. There was no disturbance in sleep architecture or correlation between the uncontrolled micturition and any particular state or stage of sleep. Most episodes of enuresis occurred in a unique pattern in which a sudden or progressive intravesical increased pressure was associated with an awakening reaction. From a physiopathologic point of view, our findings are in favor of immaturity of the central system of inhibition of micturition reflex during sleep.

Adolescent↗

Sleep deprivation in narcoleptic subjects: effect on sleep stages and EEG power density.

Sleep of 8 narcoleptic and 8 control subjects was recorded under baseline (i.e., prior wakefulness 16 h) and after 24 h without sleep. During both baseline and recovery total sleep time and stage 2 non-REM sleep were significantly decreased in narcoleptic subjects. Slow wave activity (i.e., EEG power density in the range of 0.75-4.5 Hz) decayed exponentially during baseline and after sleep deprivation in both narcoleptic and control subjects. During both baseline and recovery EEG power density in delta and sigma frequencies in non-REM sleep was enhanced in narcoleptic subjects relative to controls. In REM sleep differences in the same direction were present in delta and beta frequencies. After sleep deprivation EEG power density in non-REM sleep was elevated in delta and some higher frequencies in both patients and controls, but the response to sleep deprivation was stronger in narcoleptic subjects. These data show that in narcoleptic subjects regulatory processes underlying non-REM sleep homeostasis are operative and indicate that the response to sleep deprivation is stronger than in control subjects.

Adolescent↗

Effects of zopiclone on subjective evaluation of sleep and daytime alertness and on psychomotor and physical performance tests in athletes.

1. In a double-blind cross-over study 8 athletes received during 2 sessions of 2 nights zopiclone (7.5 mg) or placebo. 2. Residual effects on subsequent daytime functions were evaluated both subjectively by visual analogue scales as well as objectively by a test battery measuring psychomotor and physical skills. 3. Zopiclone had some favourable effects on self-estimated sleep quality and daytime sleepiness. 4. Psychomotor and physical performance tests did not show any significant difference between zopiclone and placebo. 5. We conclude that zopiclone has useful hypnotic activity without significant adverse effects on athletic performance.

Adult↗

Sleep in human narcolepsy revisited with special reference to prior wakefulness duration.

Sleep of 11 narcoleptic subjects was recorded on baseline and after 16 and 24 hours of prior wakefulness (16 and 24 hours sleep deprivation). Eleven sex- and age-matched control subjects were recorded for comparisons. All recordings in narcoleptic subjects were characterized by frequent sleep onset rapid eye movement (REM) episodes, increased amounts of wake time after sleep onset and low sleep efficiencies. Mean total sleep time (TST) was significantly decreased in narcoleptic subjects after sleep deprivation (SD). Recovery sleep after 24 hours SD showed reduced nonREM (NREM) sleep stage 2 percentage, whereas percentages of stage 4 and slow-wave sleep (SWS = stages 3 + 4) were significantly increased. The values of REM sleep percentage of TST were remarkably constant throughout and did not differ significantly as a function of experimental conditions, indicating a normal REM sleep pressure in narcolepsy. Sleep stage analysis per sleep cycles revealed significant differences between the two groups. Percentages of stage 4 and SWS were increased during the first cycle of recovery sleep in narcoleptic subjects. Stage 2 was decreased during the third cycle, and SWS decreased rapidly from cycle 1 to cycle 2 and slightly increased thereafter. These results indicate that sleep need is increased in narcolepsy, whereas its decrease over the first NREM-REM cycle is accelerated. We hypothesize that this could reflect an alteration of the homeostatic process of sleep regulation in narcolepsy.

Adolescent↗

Sleep onset rapid-eye-movement episodes in narcolepsy: REM sleep pressure or nonREM-REM sleep dysregulation?

Thirty-two narcoleptic subjects with excessive daytime sleepiness and cataplexy were recorded for 33 continuous hours. The continuous polysomnographic recording (CPSG) was followed by a standard MSLT at 2-h intervals. There were 64 sleep onset REM episodes (SOREMs) vs 64 sleep onset nonREM episodes (SONREMs) during the CPSG, and 102 SOREMs vs 50 SONREMS during the MSLT. Both sleep onset types peaked at 13-15 h during the CPSG while sleep onsets were evenly distributed during the MSLT. In the latter procedure, the mean sleep latency was significantly shorter with SOREMs occurrence than with SONREMs occurrence. Two factors were extracted in each procedure by means of a Varimax Rotated Factor Analysis. During the CPSG, SOREMs were related to the preceding nocturnal sleep parameters in the first factor, and to the daytime total sleep time and the total number of sleep onsets in the second factor. During the MSLT, SOREMs were related only to the mean sleep latency and the total number of sleep onsets. It was concluded that the occurrence of SOREMs is primarily due to the residual somnolence in narcoleptic subjects. However, their occurrence during the MSLT is largely independent of the prior history of sleep and waking. Thus, we propose a nonREM-REM sleep dysregulation hypothesis to account for the appearance of SOREMs in narcolepsy.

Journal Article↗

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↗

[Effects of zopiclone on sleep, daytime somnolence and nocturnal and daytime performance in healthy volunteers].

Ten healthy volunteers, aged 20 to 39, underwent 2 adaptation nights and 3 sessions of 2 consecutive experimental nights and days at 1 week intervals. In the 3 sessions, subjects received under double blind conditions either Zopiclone 3.75 mg or 7.5 mg or placebo, according to a latin-square design. On nights 1 and 2 of each session, subjects were continuously polygraphically monitored, except for a 45 min provoked wake episode 135 min after sleep onset on night 2. Sleep continuity and architecture were evaluated during night 1, degree of daytime somnolence during day 1 and residual effects during night 2 (0 h 00) and day 2 (8 h 00 and 12 h 00). Sleep continuity was not modified, except for a reduction of the number of night awakenings. NREM sleep stage 1 was reduced and stage 2 was increased (in duration but not in percentage) with Zopiclone 3.75 and 7.5 mg. NREM sleep stages 3 and 4 were increased with Zopiclone 3.75 mg only. REM sleep was reduced (in percentage only) with Zopiclone 3.75 and 7.5 mg. Daytime somnolence varied according to the time but not with the 3 different conditions. One performance test only (choice reaction time test) showed a significant impairment at 0 h 00 with Zopiclone 7.5 mg. From a subjective point of view, sleep quality was improved and night time awakening was reduced with Zopiclone 7.5 mg.

Adult↗