Investigation and Treatment of Ovulatory Failure

After gonadal dysgenesis or developmental failure have been ruled out and therapy initiated for secondary amenorrhea in appropriate cases, there remains a group of women in whom measures to overcome infertility can be undertaken with reasonable expectation of success. The first need is to determine if ovulation is occurring; if it is not, a variety of means is now available to induce it.     

Levodopa-induced sleepiness in the Parkinson variant of multiple system atrophy.

Recent observations suggest that levodopa can induce irresistible sleep onset in multiple system atrophy (MSA). Therefore, we assessed sleepiness during a levodopa challenge in 17 MSA compared with 23 Parkinson's disease (PD) patients using the Stanford Sleepiness Scale (SSS). SSS scores during the levodopa challenge compared with baseline were significantly increased in the MSA compared with the PD group. These findings suggest greater potential of levodopa to induce sleepiness in MSA compared with PD, which may be related to differences in basal ganglia and brainstem pathology between the two disorders.     

Fatigue and sleep disturbance in multiple sclerosis

Considering the association of sleep disturbance and fatigue in multiple sclerosis (MS), we investigated the presence of sleep disturbances that may be related to fatigue by using objective and subjective measures. We included 27 MS patients with fatigue, 10 MS patients without fatigue and 13 controls. The Pittsburgh sleep quality index score showed significant differences between patient groups and controls. Beck depression inventory scores were significantly higher in fatigued than non-fatigued patients. Comparison of patient groups and controls revealed significant differences for time in bed, sleep efficiency index, sleep continuity index, wake time after sleep onset, total arousal index and periodic limb movement arousal index. Our study confirms that MS causes sleep fragmentation in terms of both macro and microstructure. Fatigue in MS could be partially explained by disruption of sleep microstructure, poor subjective sleep quality and depression.     

EFNS guidelines on management of narcolepsy

Management of narcolepsy with or without cataplexy relies on several classes of drugs, namely stimulants for excessive daytime sleepiness and irresistible episodes of sleep, antidepressants for cataplexy and hypnosedative drugs for disturbed nocturnal sleep. In addition, behavioral measures can be of notable value. Guidelines on the management of narcolepsy have already been published. However contemporary guidelines are necessary given the growing use of modafinil to treat excessive daytime sleepiness in Europe within the last 5–10 years, and the decreasing need for amphetamines and amphetamine‐like stimulants; the extensive use of new antidepressants in the treatment of cataplexy, apart from consistent randomized placebo‐controlled clinical trials; and the present re‐emergence of gamma‐hydroxybutyrate under the name sodium oxybate, as a treatment of all major symptoms of narcolepsy. A task force composed of the leading specialists of narcolepsy in Europe has been appointed. This task force conducted an extensive review of pharmacological and behavioral trials available in the literature. All trials were analyzed according to their class evidence. Recommendations concerning the treatment of each single symptom of narcolepsy as well as general recommendations were made. Modafinil is the first‐line pharmacological treatment of excessive daytime sleepiness and irresistible episodes of sleep in association with behavioral measures. However, based on several large randomized controlled trials showing the activity of sodium oxybate, not only on cataplexy but also on excessive daytime sleepiness and irresistible episodes of sleep, there is a growing practice in the USA to use it for the later indications. Given the availability of modafinil and methylphenidate, and the forseen registration of sodium oxybate for narcolepsy (including excessive daytime sleepiness, cataplexy, disturbed nocturnal sleep) in Europe, the place of other compounds will become fairly limited. Since its recent registration cataplexy sodium oxybate has now become the first‐line treatment of cataplexy. Second‐line treatments are antidepressants, either tricyclics or newer antidepressants, the later being increasingly used these past years despite few or no randomized placebo‐controlled clinical trials. As for disturbed nocturnal sleep the best option is still hypnotics until sodium oxybate is registered for narcolepsy. The treatments used for narcolepsy, either pharmacological or behavioral, are diverse. However the quality of the published clinical evidences supporting them varies widely and studies comparing the efficacy of different substances are lacking. Several treatments are used on an empirical basis, specially antidepressants for cataplexy, due to the fact that these medications are already used widely in depressed patients, leaving little motivation from the manufacturers to investigate efficacy in relatively rare indications. Others, in particular the more recently developed substances, such as modafinil or sodium oxybate, are evaluated in large randomized placebo‐controlled trials. Our objective was to reinforce the use of those drugs evaluated in randomized placebo‐controlled trials and to reach a consensus, as much as possible, on the use of other available medications.     

Nocturnal sleep, daytime sleepiness, and napping among women with significant emotional/behavioral premenstrual symptoms

The objective of this study is to examine daytime sleepiness and alertness and nap characteristics among women with significant emotional/behavioral premenstrual symptoms, and to determine their relationship with nocturnal sleep. Participants spent one night during the follicular phase and two nights during the late-luteal phase, one of which occurred after a 40 min opportunity to nap, sleeping in the laboratory. Subjective measures of sleepiness and alertness were completed during the afternoon of each recording. Setting took place at the sleep laboratory at the University of Ottawa. A total number of participants were 10 women with significant and nine women with minimal emotional/behavioral premenstrual symptoms (mean age 26 years). The results were compared with the follicular phase, both groups of women had less slow wave sleep and more stage 2 sleep at night, as well as a higher daytime and nocturnal mean and maximum temperature during the late-luteal phase. Women with significant symptoms were sleepier and less alert during the late-luteal phase and had a higher overall mean nocturnal temperature compared with women with minimal symptoms. No significant differences were found between the two groups on nap characteristics and nocturnal sleep characteristics. Results show that women with more severe premenstrual symptoms are sleepier during the late-luteal phase than women with minimal symptoms. The increased daytime sleepiness seems to be unrelated to nocturnal sleep or nap characteristics.     

Post‐CPAP sleepiness – a specific syndrome?

Following treatment with continuous positive airway pressure (CPAP), some patients with obstructive sleep apnoea (OSA) remain sleepy despite effective CPAP and attention to other diagnoses that can provoke sleepiness. It is unclear if this residual sleepiness is an irreversible result of their previous OSA and merits consideration for pharmacological treatment or simply because of the many and varied causes of sleepiness normally found in the community. We have measured levels of sleepiness, using the Epworth Sleepiness Score (ESS), in 572 patients on CPAP and compared them with a control group of 525 subjects from a community survey, which would have included the usual lifestyle reasons for sleepiness as well as any undiagnosed sleep disorders. There was no difference in the percentage of patients with an ESS >10 in the CPAP group compared with the controls (16.1 versus 14.3, P = 0.54). Thus, although there clearly are sleepy patients within the CPAP group, the prevalence is no higher than in the community. We question whether so-called 'post-CPAP sleepiness' should be regarded as any more abnormal and worthy of treatment than a 'normal' population. Post-CPAP sleepiness as a specific disorder may not exist.     

Prospective comparison of subjective arousal during the pre-sleep period in primary sleep-onset insomnia and normal sleepers

Psychophysiological insomnia (PI) is the most common insomnia subtype, representing 12-15% of all sleep centre referrals. Diagnostic guidelines describe PI as an intrinsic sleep disorder involving both hyperarousal and learned sleep-preventing associations. Whilst evidence for the first component is reasonably compelling, evidence for learned (conditioned) sleep effects is markedly lacking. Indeed, to date no study has attempted to capture directly the conditioned arousal effect assumed to characterize the disorder. Accordingly, the present study explored variations in subjective arousal over time in 15 PI participants (sleep onset type) and 15 normal sleepers (NS). Self-report measures of cognitive arousal, somatic arousal and sleepiness were taken at three time points: 3 h before bedtime (early to mid-evening); 1 h before bedtime (late evening); and in the bedroom at lights out (bedtime) across four, 24-h cycles. Fluctuations in mean arousal and sleepiness values, and in day-to-day variation were examined using analyses of variance. Participants with PI were significantly more cognitive aroused and significantly less sleepy relative to NS, within the bedroom environment. These results support the tenet of conditioned mental arousal to the bedroom, although competing explanations cannot be ruled out. Results are discussed with reference to extant insomnia models.     

Determinants of excessive daytime sleepiness in a French community-dwelling elderly population

Epidemiological studies have suggested that excessive daytime sleepiness (EDS) is associated with depression, but the association between EDS and other psychiatric disorders has not been investigated. The aim of this study was to investigate the association of EDS with a wide range of psychiatric disorders and health-related conditions in the elderly population. Two thousand two hundred and fifty-nine non-institutionalised persons aged 65-years and over randomly recruited from the Montpellier district, France, completed the Epworth Sleepiness Scale (ESS). Psychiatric status was assessed by the Mini International Neuropsychiatric Interview and demographic and other health information was obtained. This cross-sectional study was conducted from March 1999 to February 2001. Men were significantly more likely to report EDS (ESS score>10) compared with women (12.0% versus 6.0% respectively). EDS was significantly associated in univariate analyses with chronic diseases, early awakening, snoring, severity of depression and lifetime prevalence of manic and hypomanic episodes. A multivariate analysis revealed that the lifetime prevalence of manic and hypomanic episodes, snoring and gender (male) were independently associated with EDS. No independent association with other psychiatric disorders was found.     

The dynamics of neurobehavioural recovery following sleep loss

Rate of recovery of daytime performance and sleepiness following moderate and severe sleep deprivation (SD) was examined when recovery opportunity was either augmented or restricted. Thirty healthy non-smokers, aged 18-33 years, participated in one of three conditions: moderate SD with augmented (9-h) recovery opportunities, moderate SD with restricted (6-h) recovery opportunities, or severe SD with augmented recovery opportunities. Each participant attended the laboratory for 8-9 consecutive nights: an adaptation and baseline night (23:00-08:00 hours), one or two night(s) of wakefulness, and five consecutive recovery sleep opportunities (23:00-08:00 hours or 02:00-08:00 hours). On each experimental day, psychomotor vigilance performance (PVT) and subjective sleepiness (SSS) were assessed at two-hourly intervals, and MSLTs were performed at 1000 h. PSG data was collected for each sleep period. For all groups, PVT performance significantly deteriorated during the period of wakefulness, and sleepiness significantly increased. Significant differences were observed between the groups during the recovery phase. Following moderate SD, response speed, lapses and SSS returned to baseline after one 9-h sleep opportunity, while sleep latencies required two 9-h opportunities. When the recovery opportunity was restricted to six hours, neither PVT performance nor sleepiness recovered, but stabilised at below-baseline levels. Following severe SD, sleepiness recovered after one (SSS) or two (physiological) 9-h sleep opportunities, however PVT performance remained significantly below baseline for the entire recovery period. These results suggest that the mechanisms underlying the recovery process may be more complicated than previously thought, and that we may have underestimated the impact of sleep loss and/or the restorative value of subsequent sleep.