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Narcolepsy is mainly associated with excessive daytime sleepiness, but the characteristic feature is abnormal rapid eye movement (REM) sleep phenomena. REM sleep disturbances can manifest as cataplexy (in narcolepsy type 1), sleep paralysis, sleep-related hallucinations, REM sleep behavior disorder, abnormal dreams, polysomnographic evidence of REM sleep disruption with sleep-onset REM periods, and fragmented REM sleep. Characterization of REM sleep and related symptoms facilitates the differentiation of narcolepsy from other central hypersomnolence disorders and aids in distinguishing between narcolepsy types 1 and 2. A circuit comprising regions within the brainstem, forebrain, and hypothalamus is involved in generating and regulating REM sleep, which is influenced by changes in monoamines, acetylcholine, and neuropeptides. REM sleep is associated with brainstem functions, including autonomic control, and REM sleep disturbances may be associated with increased cardiovascular risk. Medications used to treat narcolepsy (and REM-related symptoms of narcolepsy) include stimulants/wake-promoting agents, pitolisant, oxybates, and antidepressants; hypocretin agonists are a potential new class of therapeutics. The role of REM sleep disturbances in narcolepsy remains an area of active research in pathophysiology, symptom management, and treatment. This review summarizes the current understanding of the role of REM sleep and its dysfunction in narcolepsy., Competing Interests: Declaration of competing interest MJ Thorpy has received research/grant support and consultancy fees from Axsome, Balance Therapeutics, Flamel/Avadel, Harmony Biosciences, LLC, Jazz Pharmaceuticals, Suven Life Sciences Ltd., Takeda Pharmaceutical Co., Ltd, NLS Pharmaceuticals, XW Pharma, Idorsia Pharmaceuticals, and Eisai Pharmaceuticals. JMSiegel receives research support from the National Institutes of HealthDA034748, HLB148574, Jazz Pharmaceuticals, and the US Department of Veterans Affairs. Y Dauvilliers is a consultant for and has participated in advisory boards for Jazz Pharmaceuticals, Centessa, Avadel, Idorsia, Takeda, Harmony Biosciences, and Bioprojet., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

NREM parasomnias are frequent and potentially disabling sleep disorders characterized by recurrent abnormal behaviors emerging from NREM sleep. Recently, several studies provided more detailed clinical and polysomnographic characterization of NREM parasomnia which may enhance the diagnostic process. Several revisions of the diagnostic criteria have been proposed in the classification of sleep disorders, the latest being ICSD-3-TR in 2023 with no changes on NREM parasomnias since ICSD-3 published in 2014. We performed an extensive literature review to assess the evidence on the procedure of its diagnosis. We dissected the inconsistencies and shortcomings in the ICSD-3-TR to propose a revision of the current diagnostic criteria. We highlighted the limits of several clinical criteria which should rather be supportive features than mandatory criteria. Infrared cameras with video-recordings with are promising tools to precisely characterize home episodes. Sensitive and specific polysomnographic markers of NREM parasomnias have been identified and should be considered in future revisions. We also suggest the use of diagnostic specifiers (clinical subtypes, clinical significance, levels of severity, age effect, levels of certainty) to define homogeneous subgroups of patients for therapeutic intervention and research purposes. In conclusion, we advocate for significant changes in the current diagnostic criteria of NREM parasomnias for future classification., Competing Interests: Declaration of competing interest The authors declare no conflict of interest in relation to this work., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Idiopathic hypersomnia is a central hypersomnolence disorder of unknown origin characterized by excessive daytime sleepiness despite normal or long sleep time, and frequent severe sleep inertia. Management strategies have been largely derived from expert consensus, due to a lack of disease-specific assessments and reliance on case series and rare randomized controlled studies. Guidelines recommend treatment with off-label medications. Modafinil, which was approved for idiopathic hypersomnia until 2011 in Europe, is the most commonly used treatment and improved sleepiness in two recent randomized placebo-controlled trials. In 2021, low-sodium oxybate (LXB) was approved in the United States for idiopathic hypersomnia. In a placebo-controlled, double-blind, randomized withdrawal study, LXB reduced daytime sleepiness and sleep inertia, and improved daily functioning. Here, treatment options are reviewed considering the authors' professional experience, current guidelines, and the latest research developments. The choice of pharmacotherapy should be guided by symptom profile, age, comorbidities (eg, depressive symptoms, cardiovascular problems), and concomitant medications (eg, oral contraceptives). Nonpharmacologic approaches have a role in management. An instrument (idiopathic hypersomnia severity scale) has been validated in idiopathic hypersomnia specifically, opening a path to better assessment of symptoms, impact, and response to treatment. Continued research on idiopathic hypersomnia is needed to support treatment algorithms., Competing Interests: Declaration of competing interest Isabelle Arnulf has participated in advisory boards for UCB Pharma, Idorsia (2020), Ono Pharma (2019), and Roche Pharma (2019). Robert Thomas has patents and licenses for ECG-spectrogram, licensed to MyCardio, LLC through the Beth Israel Deaconess Medical Center, and for auto-CPAP algorithm, licensed by BIDMC to DeVilbiss-Drive; holds an unlicensed patent for a CO(2) device for central/complex sleep apnea; is a general sleep medicine consultant for GLG Councils and Guidepoint Global; and is a consultant for and has participated in advisory boards for Jazz Pharmaceuticals. Asim Roy has received consultancy fees from Jazz Pharmaceuticals and Harmony Biosciences. Yves Dauvilliers is a consultant for and has participated in advisory boards for Jazz Pharmaceuticals, UCB Pharma, Avadel, Idorsia, Takeda, Harmony Biosciences, and Bioprojet., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Sleepiness involves many dimensions that require investigation. Since sleepiness is often defined operationally, we exhaustively inventoried all the assessment tools designed to measure it in an umbrella review, without any preconceptions, i.e. a review of reviews. We included all reviews and systematic reviews related to sleepiness assessment tools published up to March 2021. Three investigators independently assessed the eligibility of studies for inclusion and identified 36 relevant reviews. In total, 99 tools were identified and classified into 8 categories. We classified them depending on their category, their publication year and the number of mentions in the 36 included reviews. The 6 most frequently cited were the Epworth sleepiness scale, the multiple sleep latency test, the maintenance of wakefulness test, the Stanford sleepiness scale, the Karolinska sleepiness scale, and the psychomotor vigilance task. Despite the limitation that we may have missed some recently developed tools, this historical perspective on sleepiness measurement is a first step toward a better delineation of the different dimensions underlying the constructs of sleepiness, and will serve as a basis for further discussion in the clinical and research sleep community., Competing Interests: Declaration of competing interest The author reports no conflict of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Idiopathic hypersomnia is a sleep disorder of neurologic origin characterized by excessive daytime sleepiness, with sleep inertia, long, unrefreshing naps, and prolonged nighttime sleep being key symptoms in many patients. Idiopathic hypersomnia is described in the International Classification of Sleep Disorders, 3rd Edition as a central disorder of hypersomnolence with distinct clinical features and diagnostic criteria; however, confirming the diagnosis of idiopathic hypersomnia is often challenging. Diagnosis of idiopathic hypersomnia is based on objective sleep testing and the presence of associated clinical features but may be difficult for clinicians to recognize and correctly diagnose because of its low prevalence, clinical heterogeneity, and symptoms, which are similar to those of other sleep disorders. The testing required for diagnosis of idiopathic hypersomnia also presents logistical barriers, and reliability of objective sleep measures is suboptimal. The pathophysiology of idiopathic hypersomnia remains unknown. In this review, clinical considerations related to the pathogenesis, diagnosis, and management of idiopathic hypersomnia will be discussed, including perspectives from the European Union and United States., Competing Interests: Declaration of competing interest Y Dauvilliers is a consultant for and has participated in advisory boards for Jazz Pharmaceuticals, UCB Pharma, Avadel, Harmony Biosciences, Idorsia, Orexia, Takeda, Paladin, and Bioprojet. RK Bogan is a shareholder of Watermark Medical and Healthy Humming, LLC; serves on the board of directors for Watermark; is a medical consultant to Jazz Pharmaceuticals, Harmony Biosciences, Avadel Pharmaceuticals, Takeda, and Oventus; has conducted industry-funded research for Avadel, Axsome, Bresotec, Bayer, Idorsia, Suven, Jazz, Balance, NLS, Vanda, Merck, Eisai, Philips, Fresca, Takeda, LivaNova, Roche, Sanofi, Sommetrics, and Noctrix; and is on the speakers bureau for Jazz, Eisai, and Harmony. I Arnulf has participated in advisory boards for UCB Pharm, Idorsia, Ono Pharma, and Roche Pharma. TE Scammell has consulted for Avadel, Axsome, Consynance, Eisai, Harmony Biosciences, Idorsia, Jazz Pharmaceuticals, Merck, Orion Pharma, Takeda, and Tris Pharmaceuticals and has received research grants from the National Institutes of Health, Merck, Jazz, and Takeda. EK St Louis receives research support from the National Institutes of Health, the National Institute of Neurological Disease and Stroke, the National Institute on Aging, and the National Heart, Lung, and Blood Institute. MJ Thorpy has received research/grant support and consultancy fees from Jazz Pharmaceuticals, Harmony Biosciences, Balance Therapeutics, Axsome Therapeutics, and Avadel Pharmaceuticals., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The main objective of this theoretical review is to systematically analyze the type of International Classification of Sleep Disorders-3 (ICSD-3) diagnostic criteria by labeling each of them in order to propose an overview of the way in which the diagnostic criteria are organized. Labeling of diagnostic criteria using a rigorous iterative process of "aggregation" and "generalization" was conducted and inter-rater reliability calculation (Cohen's Kappa with three raters) was calculated. 241 criteria from 43 main sleep disorders of the ICSD-3 were labeled into nine types (Clinical manifestation 86.0% of sleep disorders, Objective markers 53.5%, Distress 30.2%, Disability 30.2%, Duration 30.2%, Frequency 58.1%, Age in 18.6%, Exclusion condition 81.4% and Associated condition 34.8%), with a high inter-rater reliability (Cohen's Kappa = 0.85). This analysis assumes that the structuring of the ICSD-3 diagnostic criteria is based on the Harmful Dysfunction Analysis (HDA). Some criteria correspond to the dysfunction part of the HDA while others refer to the harmful part. However, the approach does not seem to be homogeneous across the nosological classification. The use of a structured definition of sleep disorder and a framework to organize the ICSD diagnostic criteria is discussed with regard to the reliability and validity of criteria for diagnosing sleep disorders., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Narcolepsy type 1 (NT1) is a lifelong disorder of sleep-wake dysregulation defined by clinical symptoms, neurophysiological findings, and low hypocretin levels. Besides a role in sleep, hypocretins are also involved in regulation of heart rate and blood pressure. This literature review examines data on the autonomic effects of hypocretin deficiency and evidence about how narcolepsy is associated with multiple cardiovascular risk factors and comorbidities, including cardiovascular disease. An important impact in NT1 is lack of nocturnal blood pressure dipping, which has been associated with mortality in the general population. Hypertension is also prevalent in NT1. Furthermore, disrupted nighttime sleep and excessive daytime sleepiness, which are characteristic of narcolepsy, may increase cardiovascular risk. Patients with narcolepsy also often present with other comorbidities (eg, obesity, diabetes, depression, other sleep disorders) that may contribute to increased cardiovascular risk. Management of multimorbidity in patients with narcolepsy should include regular assessment of cardiovascular health (including ambulatory blood pressure monitoring), mitigation of cardiovascular risk factors (eg, cessation of smoking and other lifestyle changes, sleep hygiene, and pharmacotherapy), and prescription of a regimen of narcolepsy medications that balances symptomatic benefits with cardiovascular safety., Competing Interests: Conflicts of interest PJ Jennum has participated in advisory boards for UCB Europe, Bioprojet, and Jazz Pharmaceuticals. G Plazzi is a consultant and has participated in advisory boards for UCB Pharma, Bioprojet, Idorsia, Jazz Pharmaceuticals, and Takeda. A Silvani reports no conflicts of interest. LA Surkin has participated in advisory boards for Jazz Pharmaceuticals. Y Dauvilliers is a consultant for and has participated in advisory boards for Jazz Pharmaceuticals, UCB Pharma, Flamel Technologies, Idorsia, Theranexus, and Bioprojet., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The aim of this European initiative is to facilitate a structured discussion to improve the next edition of the International Classification of Sleep Disorders (ICSD), particularly the chapter on central disorders of hypersomnolence. The ultimate goal for a sleep disorders classification is to be based on the underlying neurobiological causes of the disorders with clear implication for treatment or, ideally, prevention and or healing. The current ICSD classification, published in 2014, inevitably has important shortcomings, largely reflecting the lack of knowledge about the precise neurobiological mechanisms underlying the majority of sleep disorders we currently delineate. Despite a clear rationale for the present structure, there remain important limitations that make it difficult to apply in routine clinical practice. Moreover, there are indications that the current structure may even prevent us from gaining relevant new knowledge to better understand certain sleep disorders and their neurobiological causes. We suggest the creation of a new consistent, complaint driven, hierarchical classification for central disorders of hypersomnolence; containing levels of certainty, and giving diagnostic tests, particularly the MSLT, a weighting based on its specificity and sensitivity in the diagnostic context. We propose and define three diagnostic categories (with levels of certainty): 1/"Narcolepsy" 2/"Idiopathic hypersomnia", 3/"Idiopathic excessive sleepiness" (with subtypes)., Competing Interests: Conflict of Interest The authors do not have any conflicts of interest to disclose., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Narcolepsy type 1 is a life-long, severe, multifaceted disease often arising in childhood or adolescence. Beyond the classical symptoms (excessive daytime sleepiness, cataplexy, hallucinations, sleep paralysis and nocturnal fragmented sleep), metabolic, endocrinological, psychiatric and psychosocial aspects must be considered. Despite the increased awareness after H1N1 pandemic influenza and vaccination, narcolepsy is still misdiagnosed and unrecognized. The peculiar presentation of symptoms in narcoleptic children could in part explain the misdiagnoses. Excessive daytime sleepiness presenting as chronic drowsiness or irritability could be stigmatized as laziness or misinterpreted as behavior or inattention disorder. The persistent hypotonia and the complex hyperkinetic movements that characterize cataplexy close to the onset, could be misdiagnosed as a movement disorder or as other neurologic conditions. The consequent therapeutic delay could turn into dramatic consequences. The narcolepsy onset, indeed, is associated with abrupt weight gain and sometimes with precocious puberty that require a prompt recognition and treatment to avoid auxological and metabolic complications. Moreover, narcoleptic children could have behavioral and psychiatric disorders ranging from mood to psychotic ones that need ad hoc management. Accordingly, spreading the awareness outside the sleep specialist community is necessary in order to reduce the diagnostic delay and to obtain prompt and multidisciplinary management., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The states of being are conventionally defined by the simultaneous occurrence of behavioral, neurophysiological and autonomic descriptors. State dissociation disorders are due to the intrusion of features typical of a different state into an ongoing state. Disorders related to these conditions are classified according to the ongoing main state and comprise: 1) Dissociation from prevailing wakefulness as seen in hypnagogic or hypnopompic hallucinations, automatic behaviors, sleep drunkenness, cataplexy and sleep paralysis 2) Dissociation from rapid eye movement (REM) sleep as seen in REM sleep behavior disorder and lucid dreaming and 3) Dissociation from NREM sleep as seen in the disorders of arousal. The extreme expression of states dissociation is characterized by the asynchronous occurrence of the various components of the different states that prevents the recognition of any state of being. This condition has been named status dissociatus. According to the underlying disorders/diseases and to their severity, among status dissociatus we may recognize disorders in which such an extreme dissociation occurs only at night time or intermittently (i.e., autoimmune encephalopathies, narcolepsy type 1 and IgLON5 parasomnia), and others in which it occurs nearly continuously with complete loss of any conventionally defined state of being, and of the circadian pattern (agrypnia excitata). Here, we render a comprehensive review of all diseases/disorders associated with state dissociation and status dissociatus and propose a critical classification of this complex scenario., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Sleep and sleep disorders are complex and highly variable phenotypes regulated by many genes and environment. The catechol-O-methyltransferase (COMT) gene is an interesting candidate, being one of the major mammalian enzymes involved in the catabolism of catecholamines. The activity of COMT enzyme is genetically polymorphic due to a guanine-to-adenine transition at codon 158, resulting in a valine (Val) to methionine (Met) substitution. Individuals homozygous for the Val allele show higher COMT activity, and lower dopaminergic signaling in prefrontal cortex (PFC) than subjects homozygous for the Met allele. Since COMT has a crucial role in metabolising dopamine, it was suggested that the common functional polymorphism in the COMT gene impacts on cognitive function related to PFC, sleep-wake regulation, and potentially on sleep pathologies. The COMT Val158Met polymorphism may predict inter-individual differences in brain electroencephalography (EEG) alpha oscillations and recovery processes resulting from partial sleep loss in healthy individuals. The Val158Met polymorphism also exerts a sexual dimorphism and has a strong effect on objective daytime sleepiness in patients with narcolepsy-cataplexy. Since the COMT enzyme inactivates catecholamines, it was hypothesized that the response to stimulant drugs differs between COMT genotypes. Modafinil maintained executive functioning performance and vigilant attention throughout sleep deprivation in subjects with Val/Val genotype, but less in those with Met/Met genotype. Also, homozygous Met/Met patients with narcolepsy responded to lower doses of modafinil compared to Val/Val carriers. We review here the critical role of the common functional COMT gene polymorphism, COMT enzyme activity, and the prefrontal dopamine levels in the regulation of sleep and wakefulness in normal subjects, in narcolepsy and other sleep-related disorders, and its impact on the response to psychostimulants., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Autonomic cardiovascular control changes across sleep stages. Thus, blood pressure (BP), heart rate and peripheral vascular resistance progressively decrease in non-rapid eye movement sleep. Any deterioration in sleep quality or quantity may be associated with an increase in nocturnal BP which could participate in the development or poor control of hypertension. In the present report, sleep problems/disorders, which impact either the quality or quantity of sleep, are reviewed for their interaction with BP regulation and their potential association with prevalent or incident hypertension. Obstructive sleep apnea syndrome, sleep duration/deprivation, insomnia, restless legs syndrome and narcolepsy are successively reviewed. Obstructive sleep apnea is clearly associated with the development of hypertension that is only slightly reduced by continuous positive airway pressure treatment. Shorter and longer sleep durations are associated with prevalent or incident hypertension but age, gender, environmental exposures and ethnic differences are clear confounders. Insomnia with objective short sleep duration, restless legs syndrome and narcolepsy may impact BP control, needing additional studies to establish their impact in the development of permanent hypertension. Addressing sleep disorders or sleep habits seems a relevant issue when considering the risk of developing hypertension or the control of pre-existent hypertension. Combined sleep problems may have potential synergistic deleterious effects., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Objectives: Gamma-hydroxybutyrate (GHB) is currently authorized by the European Medicines Agency (EMA) to treat narcolepsy with cataplexy in adults, and by the Food and Drug Administration (FDA) to treat cataplexy in patients with narcolepsy, with an expanded indication for the treatment of excessive daytime sleepiness. This study meta-analyses and reviews the effectiveness of GHB on the clinical features of narcolepsy and its neurophysiological correlates., Methods: A systematic review of the literature using Medline, Embase, Web of Science, Cochrane reviews, clinical-trials.gov, Scopus, Scirus, and a subsequent meta-analysis were performed. Considered outcomes were: cataplexy attacks, subjective daytime sleepiness, sleep attacks, clinical global impression change (CGI-c), quality of life (QoL), hypnagogic hallucinations, sleep paralysis, mean sleep latencies on the multiple sleep latency test (MSLT) and maintenance of wakefulness test (MWT), nocturnal polysomnographic data., Results: Nine randomized controlled trials reporting data on the effectiveness of GHB on narcolepsy were identified, for a total of 1,154 patients (771 patients in the GHB-treated group and 383 in the placebo group). The meta-analysis showed that GHB reduced cataplexy attacks both on a daily (weighted mean difference (WMD) -1.10; 95% confidence interval (CI) -1.29/-0.90, p < 0.00001) and a weekly basis (WMD -7.04; 95% CI -12.45/-1.63, p = 0.01), subjective nocturnal awakenings (WMD -1.33; 95% CI -1.78/-0.88, p < 0.00001), daytime sleep attacks on a weekly basis (WMD -9.30; 95% CI -15.92/-2.68, p = 0.006), subjective daytime sleepiness (WMD -2.81; 95% CI -4.13/-1.49, p < 0.0001) and sleep stage shifts (WMD -9.69; 95% CI -17.14/-2.24, p = 0.01). GHB increased sleep stages 3 + 4 (WMD 4.11; 95% CI 0.07/8.16, p = 0.05) and improved the CGI-c score (odds ratio (OR) 3.45; 95% CI 2.47/4.80, p < 0.00001). No significant changes were observed in night sleep latency, total sleep time, rapid-eye movement (REM) sleep and sleep stages 1 and 2., Conclusions: This meta-analysis demonstrates the effectiveness of GHB in treating major, clinically relevant narcolepsy symptoms and sleep architecture abnormalities., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

The objective of this review is to highlight the impact of insomnia in central neurological disorders by providing information on its prevalence and give recommendations for diagnosis and treatment. Insomnia in neurological disorders is a frequent, but underestimated symptom. Its occurrence may be a direct consequence of the disease itself or may be secondary to pain, depression, other sleep disorders or the effects of medications. Insomnia can have a significant impact on the patient's cognitive and physical function and may be associated with psychological distress and depression. Diagnosis of insomnia is primarily based on medical history and validated questionnaires. Actigraphy is a helpful diagnostic tool for assessing the circadian sleep-wake rhythm. For differential diagnosis and to measure the duration of sleep full polysomnography may be recommended. Prior to initiating treatment the cause of insomnia must be clearly identified. First line treatment aims at the underlying neurologic disease. The few high quality treatment studies show that short term treatment with hypnotics may be recommended in most disorders after having ruled out high risk for adverse effects. Sedating antidepressants may be an effective treatment for insomnia in stroke and Parkinson's disease (PD) patients. Melatonin and light treatment can stabilize the sleep-wake circadian rhythm and shorten sleep latency in dementias and PD. Cognitive behavioral therapy (CBT) can be effective in treating insomnia symptoms associated with most of the central neurological diseases. The prevalence and treatment of insomnia in neurological diseases still need to be studied in larger patient groups with randomized clinical trials to a) better understand their impact and causal relationship and b) to develop and improve specific evidence-based treatment strategies., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Based on 339 cases this review identifies, quantifies and compares 4 clinical forms of recurrent hypersomnia (1) Kleine-Levin syndrome (KLS) (239 cases), (2) Kleine-Levin syndrome without compulsive eating (KLS WOCE) (54 cases), (3) Menstrual related hypersomnia (MRH) (18 cases) and Recurrent hypersomnia with comorbidity (RHC) (28 cases). A second part of the review considers the main current issues on recurrent hypersomnia: the predisposing factors, including a window on family cases; the pathophysiology based on clinical patterns, neuroimaging data, neuropathological examinations and cerebrospinal fluid (CSF) hypocretin-1 measurements; the issues of recurrence and of a possible disruption of the circadian timing system; the relationships between recurrent hypersomnia and mood disorders; and a note on the atypical Kleine-Levin syndrome. The main outcomes of this study are a clear nosologic distinction of the different forms of recurrent hypersomnia, the finding that the prevalence of familial cases of KLS is in the same range as in narcolepsy, the suggestion of the possible involvement of a large set of cortical and subcortical structures in recurrent hypersomnia and some clues in favour of a relationship between recurrent hypersomnia and mood disorders., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

The complexity of sleep-wake regulation, in addition to the many environmental influences, includes genetic predisposing factors, which begin to be discovered. Most of the current progress in the study of sleep genetics comes from animal models (dogs, mice, and drosophila). Multiple approaches using both animal models and different genetic techniques are needed to follow the segregation and ultimately to identify 'sleep genes' and molecular bases of sleep disorders. Recent progress in molecular genetics and the development of detailed human genome map have already led to the identification of genetic factors in several complex disorders. Only a few genes are known for which a mutation causes a sleep disorder. However, single gene disorders are rare and most common disorders are complex in terms of their genetic susceptibility, environmental factors, gene-gene, and gene-environment interactions. We review here the current progress in the genetics of normal and pathological sleep and suggest a few future perspectives.

In contrast to narcolepsy and the Kleine-Levin syndrome, idiopathic hypersomnia is a recently described sleep disorder. Absence of associated clinical features such as cataplexy or megaphagia and characteristic polysomnographic features such as sleep-onset REM episodes render positive diagnosis more uncertain in idiopathic hypersomnia than in the fwo former conditions. Consequently there has been an unfortunate tendency to label all difficult to classify cases of excessive daytime sleepiness as idiopathic hypersomnia. At present due to the description of new disorders such as upper airway resistance syndrome, narcolepsy without cataplexy, delayed sleep phase syndrome, all of which were formerly confused with idiopathic hypersomnia and the clear identification of a "polysymptomatic" or "classic" form of idiopathic hypersomnia, the limits of the disorder become more precise. Still there are a number of cases of isolated excessive daytime sleepiness with no prolonged night sleep, no difficulty waking up, which lay between narcolepsy and genuine idiopathic hypersomnia. Thus there is a definite need to further develop laboratory investigations to help identify and classify these cases. Moreover pathophysiology and pathogenesis are still in their infancy and efforts have to be pursued in this direction. Treatment has not made consistent progress except for the use of a new wake promoting compound, modafinil, which has not yet been evaluated in controlled studies.