Single cell transcriptomics of cerebrospinal fluid cells from patients with recent-onset narcolepsy.

Narcolepsy is a rare cause of hypersomnolence and may be associated or not with cataplexy, i.e. sudden muscle weakness. These forms are designated narcolepsy-type 1 (NT1) and -type 2 (NT2), respectively. Notable characteristics of narcolepsy are that most patients carry the HLA-DQB1*06:02 allele and NT1-patients have strongly decreased levels of hypocretin-1 (synonym orexin-A) in the cerebrospinal fluid (CSF). The pathogenesis of narcolepsy is still not completely understood but the strong HLA-bias and increased frequencies of CD4+ T cells reactive to hypocretin in the peripheral blood suggest autoimmune processes in the hypothalamus. Here we analyzed the transcriptomes of CSF-cells from twelve NT1 and two NT2 patients by single cell RNAseq (scRNAseq). As controls, we used CSF cells from patients with multiple sclerosis, radiologically isolated syndrome, and idiopathic intracranial hypertension. From 27,255 CSF cells, we identified 20 clusters of different cell types and found significant differences in three CD4+ T cell and one monocyte clusters between narcolepsy and multiple sclerosis patients. Over 1000 genes were differentially regulated between patients with NT1 and other diseases. Surprisingly, the most strongly upregulated genes in narcolepsy patients as compared to controls were coding for the genome-encoded MTRNR2L12 and MTRNR2L8 peptides, which are homologous to the mitochondria-encoded HUMANIN peptide that is known playing a role in other neurological diseases including Alzheimer's disease.

Narcolepsy and rapid eye movement sleep.

Since the first description of narcolepsy at the end of the 19th Century, great progress has been made. The disease is nowadays distinguished as narcolepsy type 1 and type 2. In the 1960s, the discovery of rapid eye movement sleep at sleep onset led to improved understanding of core sleep-related disease symptoms of the disease (excessive daytime sleepiness with early occurrence of rapid eye movement sleep, sleep-related hallucinations, sleep paralysis, rapid eye movement parasomnia), as possible dysregulation of rapid eye movement sleep, and cataplexy resembling an intrusion of rapid eye movement atonia during wake. The relevance of non-sleep-related symptoms, such as obesity, precocious puberty, psychiatric and cardiovascular morbidities, has subsequently been recognized. The diagnostic tools have been improved, but sleep-onset rapid eye movement periods on polysomnography and Multiple Sleep Latency Test remain key criteria. The pathogenic mechanisms of narcolepsy type 1 have been partly elucidated after the discovery of strong HLA class II association and orexin/hypocretin deficiency, a neurotransmitter that is involved in altered rapid eye movement sleep regulation. Conversely, the causes of narcolepsy type 2, where cataplexy and orexin deficiency are absent, remain unknown. Symptomatic medications to treat patients with narcolepsy have been developed, and management has been codified with guidelines, until the recent promising orexin-receptor agonists. The present review retraces the steps of the research on narcolepsy that linked the features of the disease with rapid eye movement sleep abnormality, and those that do not appear associated with rapid eye movement sleep.

Identifying time-resolved features of nocturnal sleep characteristics of narcolepsy using machine learning.

The differential diagnosis of narcolepsy type 1, a rare, chronic, central disorder of hypersomnolence, is challenging due to overlapping symptoms with other hypersomnolence disorders. While recent years have seen significant growth in our understanding of nocturnal polysomnography narcolepsy type 1 features, there remains a need for improving methods to differentiate narcolepsy type 1 nighttime sleep features from those of individuals without narcolepsy type 1. We aimed to develop a machine learning framework for identifying sleep features to discriminate narcolepsy type 1 from clinical controls, narcolepsy type 2 and idiopathic hypersomnia. The population included polysomnography data from 350 drug-free individuals (114 narcolepsy type 1, 90 narcolepsy type 2, 105 idiopathic hypersomnia, and 41 clinical controls) collected at the National Reference Centers for Narcolepsy in Montpelier, France. Several sets of nocturnal sleep features were explored, as well as the value of time-resolving sleep architecture by analysing sleep per quarter-night. Several patterns of nighttime sleep evolution emerged that differed between narcolepsy type 1, clinical controls, narcolepsy type 2 and idiopathic hypersomnia, with increased nighttime instability observed in patients with narcolepsy type 1. Using machine learning models, we identified rapid eye movement sleep onset as the best single polysomnography feature to distinguish narcolepsy type 1 from controls, narcolepsy type 2 and idiopathic hypersomnia. By combining multiple feature sets capturing different aspects of sleep across quarter-night periods, we were able to further improve between-group discrimination and could identify the most discriminative sleep features. Our results highlight salient polysomnography features and the relevance of assessing their time-dependent changes during sleep that could aid diagnosis and measure the impact of novel therapeutics in future clinical trials.

Association between idiopathic hypersomnia and a genetic variant in the PER3 gene.

We aim to identify genetic markers associated with idiopathic hypersomnia, a disabling orphan central nervous system disorder of hypersomnolence that is still poorly understood. In our study, DNA was extracted from 79 unrelated patients diagnosed with idiopathic hypersomnia with long sleep time at the National Reference Center for Narcolepsy-France according to very stringent diagnostic criteria. Whole exome sequencing on the first 30 patients with idiopathic hypersomnia (25 females and 5 males) allowed the single nucleotide variants to be compared with a control population of 574 healthy subjects from the French Exome project database. We focused on the identification of genetic variants among 182 genes related to the regulation of sleep and circadian rhythm. Candidate variants obtained by exome sequencing analysis were then validated in a second sample of 49 patients with idiopathic hypersomnia (37 females and 12 males). Our study characterised seven variants from six genes significantly associated with idiopathic hypersomnia compared with controls. A targeted sequencing analysis of these seven variants on 49 other patients with idiopathic hypersomnia confirmed the relative over-representation of the A➔C variant of rs2859390, located in a potential splicing-site of PER3 gene. Our findings support a genetic predisposition and identify pathways involved in the pathogeny of idiopathic hypersomnia. A variant of the PER3 gene may predispose to idiopathic hypersomnia with long sleep time.

Functional recovery after ischemic stroke: Impact of different sleep health parameters.

Sleep disturbances after ischaemic stroke include alterations of sleep architecture, obstructive sleep apnea, restless legs syndrome, daytime sleepiness and insomnia. Our aim was to explore their impacts on functional outcomes at month 3 after stroke, and to assess the benefit of continuous positive airway pressure in patients with severe obstructive sleep apnea. Ninety patients with supra-tentorial ischaemic stroke underwent clinical screening for sleep disorders and polysomnography at day 15 ± 4 after stroke in a multisite study. Patients with severe obstructive apnea (apnea-hypopnea index ≥ 30 per hr) were randomized into two groups: continuous positive airway pressure-treated and sham (1:1 ratio). Functional independence was assessed with the Barthel Index at month 3 after stroke in function of apnea-hypopnea index severity and treatment group. Secondary objectives were disability (modified Rankin score) and National Institute of Health Stroke Scale according to apnea-hypopnea index. Sixty-one patients (71.8 years, 42.6% men) completed the study: 51 (83.6%) had obstructive apnea (21.3% severe apnea), 10 (16.7%) daytime sleepiness, 13 (24.1%) insomnia, 3 (5.7%) depression, and 20 (34.5%) restless legs syndrome. Barthel Index, modified Rankin score and Stroke Scale were similar at baseline and 3 months post-stroke in the different obstructive sleep apnea groups. Changes at 3 months in those three scores were similar in continuous positive airway pressure versus sham-continuous positive airway pressure patients. In patients with worse clinical outcomes at month 3, mean nocturnal oxygen saturation was lower whereas there was no association with apnea-hypopnea index. Poorer outcomes at 3 months were also associated with insomnia, restless legs syndrome, depressive symptoms, and decreased total sleep time and rapid eye movement sleep.

Home nocturnal infrared video to record non-rapid eye movement sleep parasomnias.

To assess the feasibility, the acceptability and the usefulness of home nocturnal infrared video in recording the frequency and the complexity of non-rapid eye movement sleep parasomnias in adults, and in monitoring the treatment response. Twenty adult patients (10 males, median age 27.5 years) with a diagnosis of non-rapid eye movement parasomnia were consecutively enrolled. They had a face-to-face interview, completed self-reported questionnaires to assess clinical characteristics and performed a video-polysomnography in the Sleep Unit. Patients were then monitored at home during at least five consecutive nights using infrared-triggered cameras. They completed a sleep diary and questionnaires to evaluate the number of parasomniac episodes at home and the acceptability of the home nocturnal infrared video recording. Behavioural analyses were performed on home nocturnal infrared video and video-polysomnography recordings. Eight patients treated by clonazepam underwent a second home nocturnal infrared video recording during five consecutive days. All patients had at least one parasomniac episode during the home nocturnal infrared video monitoring, compared with 75% during the video-polysomnography. A minimum of three consecutive nights with home nocturnal infrared video was required to record at least one parasomniac episode. Most patients underestimated the frequency of episodes on the sleep diary compared with home nocturnal infrared video. Episodes recorded at home were often more complex than those recorded during the video-polysomnography. The user-perceived acceptability of the home nocturnal infrared video assessment was excellent. The frequency and the complexity of the parasomniac episodes decreased with clonazepam. Home nocturnal infrared video has good feasibility and acceptability, and may improve the evaluation of the phenotype and severity of the non-rapid eye movement parasomnias and of the treatment response in an ecological setting.

Cognitive strategies to improve symptoms of restless legs syndrome.

Symptoms of restless legs syndrome are relieved by movement. Whether a cognitive task decreases sensory discomfort remains understudied. We aimed to assess the frequency of patients with restless legs syndrome who report decreased sensory discomfort during cognitive activities, and quantify this decrease during a cognitive task. Three-hundred and fifty-eight consecutive adults with restless legs syndrome (age 55.17 ± 14.62 years; 55.87% women; 27.65% treated) answered the question: "Does the intensity of your restless legs syndrome symptoms decrease when you perform activities other than moving your legs?" rated on a nine-point Likert scale (from fully-agree to totally-disagree). A subgroup of 65 consecutive drug-free patients underwent an 80-min suggested immobilisation test at 20:00 hours to quantify legs discomfort on a visual analogue scale before polysomnography, including 40 patients performing a cognitive task (balloon analogue risk task) from the 60 to 80 min. A total of 130 (36.3%) patients reported a decrease, 158 (44.1%) no decrease, and 70 (19.5%) uncertain changes in severity of restless legs syndrome symptoms during cognitive activities, with a similar proportion whether treated or not. Patients experiencing a decrease had less severe restless legs syndrome symptoms. In the suggested immobilisation test, mixed-effect regression models showed that legs discomfort decreased in patients performing the cognitive task while it continued to increase in those without task, with a larger difference in patients reporting a self-reported decrease in restless legs syndrome during cognitive activities. In conclusion, one-third of patients reported a self-reported decrease of restless legs syndrome symptoms during cognitive activities, this improvement in restless legs syndrome was confirmed during a sustained cognitive task. Cognitive strategies could be implemented for the management of restless legs syndrome.

Depressive Symptoms and Suicidal Thoughts in Restless Legs Syndrome.

BACKGROUND: Whether depression and suicide thoughts relate to restless legs syndrome (RLS) or comorbidities associated with RLS remain unclear. OBJECTIVES: To determine frequency of depressive symptoms and suicidal thoughts in patients with RLS and their change after RLS treatment, associated clinical and polysomnographic factors, and current major depressive episode (MDE) frequency and suicide risk in RLS. METHODS: Overall, 549 untreated patients with RLS and 549 age-, sex-, and education level-matched controls completed a standardized evaluation, including the Beck Depression Inventory-II that has one item on suicide thoughts. Patients underwent a polysomnographic recording and completed the Urgency, Premeditation, Perseverance, Sensation Seeking Impulsive Behavior scale. In a subgroup of 153 patients, current MDE and suicide risk were assessed with the face-to-face Mini-International Neuropsychiatric Interview (MINI). A subgroup of 152 patients were evaluated in untreated and treated conditions. RESULTS: The frequency of depressive symptoms (32.5%) and suicidal thoughts (28%) was 10-fold and 3-fold higher, respectively, in patients with RLS than controls. Current MDE (10.5%) and suicidal risk (19.9%) (MINI) were also high. Moderate-to-severe depressive symptoms were associated with young age, female sex, insomnia symptoms, and urgency dimension. The suicide risk was associated with depression, impulsiveness, and RLS severity. RLS treatment improved depressive symptoms but not suicidal thoughts. CONCLUSION: The rate of depressive symptoms, depression, and suicidal thoughts/risk was higher in patients with RLS, with key associations with insomnia symptoms, urgency dimension, and RLS severity. These results emphasize the importance of detecting these symptoms in current practice and of evaluating their change after treatment, especially in young women, to improve RLS management. © 2022 International Parkinson and Movement Disorder Society.

Narcolepsy.

This article addresses the clinical presentation, diagnosis, pathophysiology and management of narcolepsy type 1 and 2, with a focus on recent findings. A low level of hypocretin-1/orexin-A in the cerebrospinal fluid is sufficient to diagnose narcolepsy type 1, being a highly specific and sensitive biomarker, and the irreversible loss of hypocretin neurons is responsible for the main symptoms of the disease: sleepiness, cataplexy, sleep-related hallucinations and paralysis, and disrupted nocturnal sleep. The process responsible for the destruction of hypocretin neurons is highly suspected to be autoimmune, or dysimmune. Over the last two decades, remarkable progress has been made for the understanding of these mechanisms that were made possible with the development of new techniques. Conversely, narcolepsy type 2 is a less well-defined disorder, with a variable phenotype and evolution, and few reliable biomarkers discovered so far. There is a dearth of knowledge about this disorder, and its aetiology remains unclear and needs to be further explored. Treatment of narcolepsy is still nowadays only symptomatic, targeting sleepiness, cataplexy and disrupted nocturnal sleep. However, new psychostimulants have been recently developed, and the upcoming arrival of non-peptide hypocretin receptor-2 agonists should be a revolution in the management of this rare sleep disease, and maybe also for disorders beyond narcolepsy.

The orexin story, sleep and sleep disturbances.

The orexins, also known as hypocretins, are two neuropeptides (orexin A and B or hypocretin 1 and 2) produced by a few thousand neurons located in the lateral hypothalamus that were independently discovered by two research groups in 1998. Those two peptides bind two receptors (orexin/hypocretin receptor 1 and receptor 2) that are widely distributed in the brain and involved in the central physiological regulation of sleep and wakefulness, orexin receptor 2 having the major role in the maintenance of arousal. They are also implicated in a multiplicity of other functions, such as reward seeking, energy balance, autonomic regulation and emotional behaviours. The destruction of orexin neurons is responsible for the sleep disorder narcolepsy with cataplexy (type 1) in humans, and a defect of orexin signalling also causes a narcoleptic phenotype in several animal species. Orexin discovery is unprecedented in the history of sleep research, and pharmacological manipulations of orexin may have multiple therapeutic applications. Several orexin receptor antagonists were recently developed as new drugs for insomnia, and orexin agonists may be the next-generation drugs for narcolepsy. Given the broad range of functions of the orexin system, these drugs might also be beneficial for treating various conditions other than sleep disorders in the near future.

Reduced brain amyloid burden in elderly patients with narcolepsy type 1.

OBJECTIVE: To determine whether brain amyloid burden in elderly patients with narcolepsy type 1 (NT1) is lower than in controls, and to assess in patients with NT1 the relationships between amyloid burden, cerebral spinal fluid (CSF) markers of Alzheimer disease (AD), CSF orexin-A, and cognitive profile. METHODS: Cognitive and 18 F-florbetapir positron emission tomography (PET) data were compared in patients with NT1 aged ≥ 65 years (n = 23) and in age- and sex-matched controls free of clinical dementia selected from the Alzheimer's Disease Neuroimaging Initiative (ADNI; n = 69) and the Multi-Domain Intervention Alzheimer's Prevention Trial (MAPT-18F AV45-PET; n = 23) cohorts. The standardized uptake values (SUVs) of the cortical retention index for 6 regions of interest were computed and averaged to create a mean SUV ratio normalized to 3 subcortical reference regions (cerebellum, pons, and a composite region). A cortical/cerebellum SUV ratio ≥ 1.17 defined positive PET amyloid. RESULTS: Lower cortical amyloid burden was observed in the NT1 than in the ADNI and MAPT-AV45 groups (mean cortical/cerebellum SUV ratios = 0.95 ± 0.15, 1.11 ± 0.18 [p < 0.0001], and 1.14 ± 0.17 [p = 0.0005], respectively). Similar results were obtained with all subcortical reference regions and for all cortical regions of interest, except cingulum. Only 1 patient with NT1 (4.4%) had positive PET amyloid compared with 27.5% in the ADNI and 30.4% in the MAPT-AV45 group. In the NT1 group, cortical or regional amyloid load was not associated with CSF orexin-A, CSF AD biomarkers, or neuropsychological profile. INTERPRETATION: Lower brain amyloid burden, assessed by 18 F-florbetapir PET, in patients with NT1 suggests delayed appearance of amyloid plaques. ANN NEUROL 2019;85:74-83.

Increased Blood Pressure Dipping in Restless Legs Syndrome With Rotigotine: A Randomized Trial.

OBJECTIVE: The objective of this study was to assess the rotigotine effect on the nocturnal blood pressure (BP) dip by 24-hour ambulatory BP monitoring and on endothelial function in patients with restless legs syndrome (RLS) compared with placebo. METHODS: In this double-blind, placebo-controlled trial, 76 adult patients with moderate to severe RLS and periodic legs movements in sleep index ≥10/hour were randomized to rotigotine at optimal dose of 3 mg per day or placebo for 6 weeks. A total of 6 patients had a major protocol deviation. Polysomnography, ambulatory BP monitoring, and endothelial function were assessed at baseline and end point. The primary outcome was the between-group difference in the percentage of BP nondipper profiles at end point. The main secondary outcomes were the mean BP dip, periodic legs movements in sleep index, and endothelial function. RESULTS: Of the 70 patients (age, 59.4 ± 11.40; 43 women) randomized to rotigotine (n = 34) and placebo (n = 36), 66 (33 rotigotine, 33 placebo) completed the study. The percentage of BP nondippers at end point was higher in the placebo than in the rotigotine group (systolic BP, 72.22% vs 47.06%; diastolic BP, 47.22% vs 20.59%; P < 0.05). Mean BP dip at end point was higher in the rotigotine than in the placebo group (systolic BP, 11.24 ± 6.15 vs 6.12 ± 7.98; diastolic BP, 15.12 ± 7.09 vs 9.36 ± 10.23; P < 0.05). Endothelial function was comparable between the groups. No significant safety concerns were reported with similar incidences of adverse events between groups. CONCLUSION: Rotigotine increased the percentage of BP dipper profiles and the BP dip in patients with RLS. Future studies should assess whether this change is associated with a reduction in the long-term cardiovascular risk in RLS. © 2020 International Parkinson and Movement Disorder Society.

Shared T cell receptor chains in blood memory CD4+ T cells of narcolepsy type 1 patients.

Convergent evidence points to the involvement of T cells in the pathogenesis of narcolepsy type 1 (NT1). Here, we hypothesized that expanded disease-specific T cell clones could be detected in the blood of NT1 patients. We compared the TCR repertoire of circulating antigen-experienced CD4+ and CD8+ T cells from 13 recently diagnosed NT1 patients and 11 age-, sex-, and HLA-DQB1*06:02-matched healthy controls. We detected a bias in the usage of TRAV3 and TRAV8 families, with public CDR3α motifs only present in CD4+ T cells from patients with NT1. These findings may offer a unique tool to identify disease-relevant antigens.

Alternative diagnostic criteria for idiopathic hypersomnia: A 32-hour protocol.

OBJECTIVE: To assess the diagnostic value of extended sleep duration on a controlled 32-hour bed rest protocol in idiopathic hypersomnia (IH). METHODS: One hundred sixteen patients with high suspicion of IH (37 clear-cut IH according to multiple sleep latency test criteria and 79 probable IH), 32 with hypersomnolence associated with a comorbid disorder (non-IH), and 21 controls underwent polysomnography, modified sleep latency tests, and a 32-hour bed rest protocol. Receiver operating characteristic curves were used to find optimal total sleep time (TST) cutoff values on various periods that discriminate patients from controls. RESULTS: TST was longer in patients with clear-cut IH than other groups (probable IH, non-IH, and controls) and in patients with probable IH than non-IH and controls. The TST cutoff best discriminating clear-cut IH and controls was 19 hours for the 32-hour recording (sensitivity = 91.9%, specificity = 85.7%) and 12 hours (100%, 85.7%) for the first 24 hours. The 19-hour cutoff displayed a specificity and sensitivity of 91.9% and 81.2% between IH and non-IH patients. Patients with IH above the 19-hour cutoff were overweight, had more sleep inertia, and had higher TST on all periods compared to patients below 19 hours, whereas no differences were found for the 12-hour cutoff. An inverse correlation was found between the mean sleep latency and TST during 32-hour recording in IH patients. INTERPRETATION: In standardized and controlled stringent conditions, the optimal cutoff best discriminating patients from controls was 19 hours over 32 hours, allowing a clear-cut phenotypical characterization of major interest for research purposes. Sleepier patients on the multiple sleep latency test were also the more severe in terms of extended sleep. Ann Neurol 2018;83:235-247.

Diagnostic criteria for disorders of arousal: A video-polysomnographic assessment.

OBJECTIVE: To assess video-polysomnographic (vPSG) criteria and their cutoff values for the diagnosis of disorders of arousal (DOAs; sleepwalking, sleep terror). METHODS: One hundred sixty adult patients with DOAs and 50 sex- and age-matched healthy participants underwent a clinical evaluation and vPSG assessment to quantify slow wave sleep (SWS) interruptions (SWS fragmentation index, slow/mixed and fast arousal ratios, and indexes per hour) and the associated behaviors. First, a case-control analysis was performed in 100 patients and the 50 controls to define the optimal cutoff values using receiver operating characteristic curves. Their sensitivity was then assessed in the other 60 patients with DOAs. RESULTS: The SWS fragmentation index and the mixed, slow, and slow/mixed arousal indexes and ratios were higher in patients with DOAs than controls. The highest area under the curve (AUC) values were obtained for the SWS fragmentation and slow/mixed arousal indexes (AUC = 0.88 and 0.90, respectively). The SWS fragmentation index cutoff value of 6.8/h reached a sensitivity of 79% and a specificity of 82%. The slow/mixed arousal index had a sensitivity of 94% for the 2.5/h cutoff, and 100% specificity for 6/h. Both parameters showed good interrater agreement, and their sensitivities were confirmed in the second group of patients. Combining electroencephalographic parameters and video-based behavioral analyses increased the correct classification rate up to 91.3%. INTERPRETATION: Frequent slow/mixed arousals in SWS and complex behaviors during vPSG are strongly associated with DOAs, and could be promising biomarkers for the diagnosis of non-rapid eye movement parasomnias. Ann Neurol 2018;83:341-351.

Absence of γ-aminobutyric acid-a receptor potentiation in central hypersomnolence disorders.

OBJECTIVE: The pathophysiology of idiopathic hypersomnia (IH) remains unclear. Recently, cerebrospinal fluid (CSF)-induced enhancement of γ-aminobutyric acid (GABA)-A receptor activity was found in patients with IH compared to controls. METHODS: Fifteen unrelated patients (2 males and 13 females) affected with typical IH, 12 patients (9 males and 3 females) with narcolepsy type 1, and 15 controls (9 males and 6 females) with unspecified hypersomnolence (n = 7) and miscellaneous neurological conditions (n = 8) were included. A lumbar puncture was performed in all participants to measure CSF hypocretin-1 and GABA-A response. We used a voltage-clamp assay on Xenopus oocytes injected with the RNAs that encode the α1 ß2 γ2 or the α2 ß2 γ2 subunits of the human GABA-A receptor. A sequence of 6 different applications (GABA, GABA/CSF, and CSF alone) with 2 to 4 oocytes per CSF sample was performed in a whole-cell voltage-clamp assay. RESULTS: Representative current traces from oocytes expressing human α1 ß2 γ2 or α2 ß2 γ2 GABA-A receptors were recorded in response to 6 successive puffs of GABA diluted in the survival medium (SM), showing stable and reliable response. GABA puffs diluted in SM/CSF solution or SM/CSF solution alone showed no significant differences in the CSF of IH, narcolepsy, or control groups. No associations were found between GABA responses, demographic features, disease duration, or disease severity in the whole population or within groups. INTERPRETATION: Using the Xenopus oocyte assay, we found an absence of GABA-A receptor potentiation with CSF from patients with central hypersomnolence disorders, with no significant differences between hypocretin-deficient and non-hypocretin-deficient patients compared to controls. Ann Neurol 2016;80:259-268.

Hypersomnolence, Hypersomnia, and Mood Disorders.

Relationships between symptoms of hypersomnolence, psychiatric disorders, and hypersomnia disorders (i.e., narcolepsy and idiopathic hypersomnia) are complex and multidirectional. Hypersomnolence is a common complaint across mood disorders; however, patients suffering from mood disorders and hypersomnolence rarely have objective daytime sleepiness, as assessed by the current gold standard test, the Multiple Sleep Latency Test. An iatrogenic origin of symptoms of hypersomnolence, and sleep apnea syndrome must be considered in a population of psychiatric patients, often overweight and treated with sedative drugs. On the other hand, psychiatric comorbidities, especially depression symptoms, are often reported in patients with hypersomnia disorders, and an endogenous origin cannot be ruled out. A great challenge for sleep specialists and psychiatrists is to differentiate psychiatric hypersomnolence and a central hypersomnia disorder with comorbid psychiatric symptoms. The current diagnostic tools seem to be limited in that condition, and further research in that field is warranted.

[CLINICAL INVESTIGATION OF AN EXCESSIVE SLEEPINESS COMPLAINT]. / Consultation initiale, analyse de la plainte et enquête étiologique devant une hypersomnolence. Peu diagnostiquée malgré l'important handicap fonctionnel provoqué.

Excessive sleepiness is a common problem, defined by a complaint of excessive daytime sleepiness almost daily with an inability to stay awake and alert dosing periods at sleep, with episodes of irresistible sleep need or drowsiness or non-intentional sleep, or by a night's sleep time overly extended often associated with sleep inertia. This sleepiness is variable in terms of phenotype and severity to be specified by the out-patient clinic. It is considered to be chronic beyond three months and often responsible for significant functional impairment of school and professional performance, of the accidents and cardiovascular risk. We need to decipher the causes of excessive sleepiness: sleep deprivation, toxic and iatrogenic, psychiatric disorders (including depression), non-psychiatric medical problems (obesity, neurological pathologies...), sleep disorders (as for example the sleep apnea syndrome), and finally the central hypersomnias namely narcolepsy type 1 and 2, idiopathic hypersomnia, and Kleine-Levin syndrome. If careful questioning often towards one of these etiologies, need most of the time a paraclinical balance with a sleep recording to confirm the diagnosis. Patients affected with potential central hypersomnia must be referred to the Sleep Study Centers that have the skills and the appropriate means to achieve this balance sheet.

Somnambulism.

Somnambulism, also called sleepwalking, classified as a non-rapid eye movement sleep parasomnia, encompasses a range of abnormal paroxysmal behaviors, leading to sleepwalking in dissociated sleep in an altered state of consciousness with impaired judgment and configuring a kind of hierarchical continuum with confusional arousal and night terror. Despite being generally regarded as a benign condition, its potential severity entails social, personal, and even forensic consequences. This comprehensive review provides an overview on the current state of knowledge, elucidating the phenomenon of somnambulism and encompassing its clinical manifestations and diagnostic approaches.