Sleep Disorders in Adults with Prader-Willi Syndrome: Review of the Literature and Clinical Recommendations Based on the Experience of the French Reference Centre

Prader–Willi syndrome (PWS) is a rare, genetic, multisymptomatic, neurodevelopmental disease commonly associated with sleep alterations, including sleep-disordered breathing and central disorders of hypersomnolence. Excessive daytime sleepiness represents the main manifestation that should be addressed by eliciting the detrimental effects on quality of life and neurocognitive function from the patients’ caregivers. Patients with PWS have impaired ventilatory control and altered pulmonary mechanics caused by hypotonia, respiratory muscle weakness, scoliosis and obesity. Consequently, respiratory abnormalities are frequent and, in most cases, severe, particularly during sleep. Adults with PWS frequently suffer from sleep apnoea syndrome, sleep hypoxemia and sleep hypoventilation. When excessive daytime sleepiness persists after adequate control of sleep-disordered breathing, a sleep study on ventilatory treatment, followed by an objective measurement of excessive daytime sleepiness, is recommended. These tests frequently identify central disorders of hypersomnolence, including narcolepsy, central hypersomnia or a borderline hypersomnolent phenotype. The use of wake-enhancing drugs (modafinil, pitolisant) is discussed in multidisciplinary expert centres for these kinds of cases to ensure the right balance between the benefits on quality of life and the risk of psychological and cardiovascular side effects

Sleepiness in Parkinson's disease.

International audienceExcessive daytime sleepiness is a disabling and vital problem in patients with PD. It affects around 33% patients and culminates in sleep attacks (without prodroma) in 1 to 4% of the patients. When monitored, short, narcolepsy-like naps with abnormal intrusion of REM sleep during daytime (and hypnagogic hallucinations as wakeful dreams) are observed in 33-41% patients, while other patients display naps with non REM sleep. Although insomnia, sleep apnea and periodic leg movements are common in these patients, there is no clear link between the night events and the level of sleepiness. Patients treated with dopamine agonists are two to three fold more exposed to sleep attacks than those on levodopa, with large variability between patients. Sleepiness may exist, to a lesser degree, before the onset of parkinsonism and before the use of dopamine agents, suggesting that other, disease-dependant factors contribute to the sleepiness. Most arousal systems are indeed damaged in PD brains, including the locus coeruleus (noradrenalin), the pedunculo-pontine nucleus and the basal forebrain (acetylcholine), the median raphe (serotonin), and the lateral hypothalamus (orexin), while histamine dopamine arousal system are normal. Treating patients with stimulants such as modafinil is only partially efficacious, while trials of anti-H3 drugs and sodium oxybate seem more active. Eventually, the recent stimulation of the pedunculopontine nucleus has stimulant or sedative effects in patients, depending on the frequency of stimulation. These results provide new insights into the mechanisms of arousal in PD

Sleep disorders in neurology French consensus. Idiopathic hypersomnia: Investigations and follow-up

International audienceIdiopathic hypersomnia is a rare, central hypersomnia, recently identified and to date of unknown physiopathology. It is characterised by a more or less permanent, excessive daytime sleepiness, associated with long and unrefreshing naps. Night-time sleep is of good quality, excessive in quantity, associated with sleep inertia in the subtype previously described as "with long sleep time". Diagnosis of idiopathic hypersomnia is complex due to the absence of a quantifiable biomarker, the heterogeneous symptoms, which overlap with the clinical picture of type 2 narcolepsy, and its variable evolution over time. Detailed evaluation enables other frequent causes of somnolence, such as depression or sleep deprivation, to be eliminated. Polysomnography and multiple sleep latency tests (MSLT) are essential to rule out other sleep pathologies and to objectify excessive daytime sleepiness. Sometimes the MSLT do not show excessive sleepiness, hence a continued sleep recording of at least 24hours is necessary to show prolonged sleep (>11h/24h). In this article, we propose recommendations for the work-up to be carried out during diagnosis and follow-up for patients suffering from idiopathic hypersomnia

Loss of REM sleep features across nighttime in REM sleep behavior disorder

International audienceObjectivesMelatonin is a chronobiotic treatment which also alleviates rapid eye movement (REM) sleep behavior disorder (RBD). Because the mechanisms of this benefit are unclear, we evaluated the clock-dependent REM sleep characteristics in patients with RBD, whether idiopathic (iRBD) or associated with Parkinson's Disease (PD), and we compared findings with PD patients without RBD and with healthy subjects.MethodsAn overnight videopolysomnography was performed in ten iRBD patients, ten PD patients with RBD (PD + RBD+), ten PD patients without RBD (PD + RBD−), and ten controls. The rapid eye movement frequency per minute (REMs index), the tonic and phasic electromyographic (EMG) activity of the levator menti muscle, and the duration of each REM sleep episode were evaluated. A generalized linear model was applied in each group, with the REM sleep cycle (four ordinal levels) as the dependent variable, as a function of REMs index, REM sleep duration, and tonic and phasic EMG activity.ResultsFrom the first to the fourth sleep cycle, REM sleep duration progressively increased in controls only, REMs index increased in subjects without RBD but not in patients with RBD, whether idiopathic or associated with PD, whereas tonic and phasic EMG activity did not change.ConclusionsPatients with PD or iRBD lost the physiologic nocturnal increase in REM sleep duration, and patients with RBD (either with or without PD) lost the increase of REMs frequency across the night, suggesting an alteration in the circadian system in RBD. This supports the hypothesis of a direct effect of melatonin on RBD symptoms by its chronobiotic activity

Lucid Dreaming in Narcolepsy

International audienceObjective:To evaluate the frequency, determinants and sleep characteristics of lucid dreaming in narcolepsyMethods:Participants were interviewed regarding the frequency and determinants of lucid dreaming. Twelve narcolepsy patients and 5 controls who self-identified as frequent lucid dreamers underwent nighttime and daytime sleep monitoring after being given instructions regarding how to give an eye signal when lucid.Results:Compared to 53 healthy controls, the 53 narcolepsy patients reported more frequent dream recall, nightmares and recurrent dreams. Lucid dreaming was achieved by 77.4% of narcoleptic patients and 49.1% of controls (P < 0.05), with an average of 7.6 ± 11 vs. 0.3 ± 0.8 lucid dreams/month (P < 0.0001). The frequency of cataplexy, hallucinations, sleep paralysis, dyssomnia, HLA positivity, and the severity of sleepiness were similar in narcolepsy with and without lucid dreaming. Seven of 12 narcoleptic (and 0 non-narcoleptic) lucid dreamers achieved lucid REM sleep across a total of 33 naps, including 14 episodes with eye signal. The delta power in the electrode average, in delta, theta, and alpha powers in C4, and coherences between frontal electrodes were lower in lucid than non-lucid REM sleep in spectral EEG analysis. The duration of REM sleep was longer, the REM sleep onset latency tended to be shorter, and the percentage of atonia tended to be higher in lucid vs. non-lucid REM sleep; the arousal index and REM density and amplitude were unchanged.Conclusion:Narcoleptics have a high propensity for lucid dreaming without differing in REM sleep characteristics from people without narcolepsy. This suggests narcolepsy patients may provide useful information in future studies on the nature of lucid dreaming

Hallucinatory choking from slow wave sleep Choking during sleep: can it be expression of arousal disorder?

International audienceBackgroundChoking during sleep may be caused by various respiratory and non-respiratory problems.ObjectiveWe aimed at documenting a new, rare cause of hallucinatory choking.MethodsWe documented the clinical and video-polysomnographic features of 11 adult patients referred for swallowing and choking during sleep. We conducted a systematic search for similar sensations in 68 consecutive adult patients with sleepwalking/sleep terrors and in 37 patients with obstructive sleep apnea.Results.The 11 patients with sleep-related swallowing and choking were all current or former sleepwalkers. The symptoms occurred during the first third of the night. Patients consistently reported the frequent hallucinatory feeling of swallowing an unusual object (ring, nails, pebble, chewing gum, spoon, fork, electrical cables, lizard tail, needles, brush, computer, gas container) that blocked the upper airways during sleep, followed by attempts to unblock them by spitting or swallowing water. When monitored, the choking sensations were not stereotypic, and occurred exclusively during arousals from N3 sleep, despite normal airway patency and absence of epileptic activity. The patients demonstrated simultaneous intense adrenergic stimulation and emotional distress. Of the 68 sleepwalkers, 13% had occasional choking sensations and 4% once inhaled a fictitious object. In the sleep apnea group, choking was never the motive of referral, but 38% of patients had occasional choking sensations, and 5% once inhaled something fictitious.ConclusionWhile insular seizure could also be discussed, these results suggest that sleep-related swallowing and choking syndrome may be in some cases a rare, specialized variant of the arousal disorders

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

International audienceObjectiveTo 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

Is there a common motor dysregulation in sleepwalking and REM sleep behaviour disorder?

International audienceThis study sought to determine if there is any overlap between the two major non-rapid eye movement and rapid eye movement parasomnias, i.e. sleepwalking/sleep terrors and rapid eye movement sleep behaviour disorder. We assessed adult patients with sleepwalking/sleep terrors using rapid eye movement sleep behaviour disorder screening questionnaires and determined if they had enhanced muscle tone during rapid eye movement sleep. Conversely, we assessed rapid eye movement sleep behaviour disorder patients using the Paris Arousal Disorders Severity Scale and determined if they had more N3 awakenings. The 251 participants included 64 patients with rapid eye movement sleep behaviour disorder (29 with idiopathic rapid eye movement sleep behaviour disorder and 35 with rapid eye movement sleep behaviour disorder associated with Parkinson's disease), 62 patients with sleepwalking/sleep terrors, 66 old healthy controls (age-matched with the rapid eye movement sleep behaviour disorder group) and 59 young healthy controls (age-matched with the sleepwalking/sleep terrors group). They completed the rapid eye movement sleep behaviour disorder screening questionnaire, rapid eye movement sleep behaviour disorder single question and Paris Arousal Disorders Severity Scale