Christophe Gauld

Régis Lopez

Pierre Geoffroy

Charles Morin

Kelly Guichard

Élodie Giroux

Yves Dauvilliers

Guillaume Dumas

Pierre Philip

Jean-Arthur Micoulaud-Franchi

Gauld Christophe

Lopez Régis

Guichard Kelly

Giroux Élodie

Dauvilliers Yves

Dumas Guillaume

Philip Pierre

Micoulaud-Franchi Jean-Arthur

A systematic analysis of ICSD-3 diagnostic criteria and proposal for further structured iteration

Keywords: Sleep, Harmful dysfunction analysis, Distress, Disability, Classification, Diagnosis, ICSD-3

niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

INTRODUCTION

The third edition of the International Classification of Sleep Disorders (ICSD-3, 3th ed.), promoted by the American Academy of Sleep Medicine, was published in 2014 and represented an important contribution toward a robust classification in sleep medicine for both the clinical ("as a guide in the identification of specific disease states") and the scientific communities ("in guiding future research agendas which will enhance our knowledge and understanding of the clinical features, pathophysiology and treatment response specific to each disorder" p.13) [START_REF]International classification of sleep disorders[END_REF]. Surprisingly, however, it does not provide a consensual and structured definition of a sleep disorder. Such a definition would be useful for knowing what should or should not have gone into the book of sleep disorders, and for organizing the diagnostic criteria of sleep disorders in a comprehensive structured way. It would also follow the aims of the ICSD-3 which is "to define the domain of a given discipline, a factor of particular importance for fields such as sleep medicine which cut across many related specialties" [START_REF]International classification of sleep disorders[END_REF]. Indeed, for sleep disorders, interdisciplinary collaboration is particularly important, because different professional organizations have attempted to develop a classification of sleep disorders [START_REF] Morin | Sleep Disorders Classification and Diagnosis[END_REF][START_REF] Buysse | Clinicians' use of the International Classification of Sleep Disorders: results of a national survey[END_REF] and many medical fields are concerned by them. The ICSD-3 revision workgroup was based on the collaboration of numerous medical and nonmedical specialties (e.g. pulmonary medicine vs. neurology vs. psychiatry vs. psychology vs. neurosciences). Moreover, the classification of sleep disorders has been complicated by the existence of several distinctive nosological classifications that differ markedly. A structured way for organizing the diagnostic criteria of sleep disorders could thus allow better collaboration between the different specialties and approaches involved in sleep medicine.

Ideally, the classification of medical disorders should be based on unambiguous etiology [START_REF] Buysse | Clinicians' use of the International Classification of Sleep Disorders: results of a national survey[END_REF][START_REF] Kleitman | Sleep and Wakefulness[END_REF]. However, there is no identifiable etiology in many chronic disorders, so the diagnostic criteria are based on clinical, physiological or other features according to a combination of empirical data, expert opinion and consensus [START_REF] Morin | Sleep Disorders Classification and Diagnosis[END_REF][START_REF] Zachar | The Philosophy of Nosology[END_REF]. Like many classifications in medicine, the ICSD-3 is based on diagnostic criteria that provide standardized diagnostic criteria for distinctive sleep disorders. The ICSD-3 thus presents diagnostic criteria for the identification of each of the specific sleep disorders included in the manual. While the immediate goal of including such criteria was to improve reliability by minimizing criterion variance, the ultimate one was to help clinicians and researchers make valid diagnoses by identifying underlying sleep dysfunctions and minimizing both false positives and false negatives. However, only a few studies have attempted to empirically establish the reliability and the validity of the diagnostic criteria of the ICSD-3 [START_REF] Morin | Sleep Disorders Classification and Diagnosis[END_REF][START_REF] Edinger | Testing the reliability and validity of DSM-IV-TR and ICSD-2 insomnia diagnoses. Results of a multitraitmultimethod analysis[END_REF], and no comparison has been made between the main sleep disorder categories. To maximize reliability, the variability in the interpretation of the diagnostic criteria between physicians and over time must be minimized.

To maximize validity, the criteria should be related to clear physiological dysfunctions.

Reliability and validity are thus directly dependent on the quality of the diagnostic criteria.

Yet the way in which the diagnostic criteria of disorder are organized in the ICSD-3 lacks clarity. As recently highlighted in the journal of Sleep Medicine Review: "for the classification of some disorders, such as insomnia and restless legs syndrome (RLS), the diagnosis is based solely on subjective complaints whereas for others, such as narcolepsy type 1, it presumes a precise pathophysiology. In others such as obstructive sleep apnea syndrome (OSAS), diagnosis can be solely defined by findings on ancillary investigations (i.e. Apnea Hypopnea Index; AHI)" [START_REF] Lammers | Diagnosis of central disorders of hypersomnolence: A reappraisal by European experts[END_REF]. Therefore, while the ICSD-3 has gone a long way to achieving a high degree of standardization between disorders and includes information for each disorder based on the same structured sections, the category "Diagnostic criteria" for each sleep disorder remains less clear. These definitions of sleep disorders should be standardized and homogenized in order to improve their scientific reliability and validity and to improve the clinical management of patients and the outcome of treatment.

A structured unified approach to defining the diagnostic criteria for each sleep disorder should be encouraged. As recommended by Telles-Correia [START_REF] Telles-Correia | Mental disorder: Are we moving away from distress and disability?[END_REF], this approach seems necessary for several reasons: i) to distinguish what is pathological from what is normal; ii) to know which diagnoses should and should not be included in the classifications; iii) to identify the conditions which, because of their negative consequences, should implicitly make physicians react; iv) to separate the areas of responsibility incumbent on the medical system from those applicable to other societal systems; v) to identify the conditions that justify appropriate societal recognition of those who are sick; vi) to avoid false positives and related problems such as overmedicalization, unnecessary labeling, wasted recourses [START_REF] Cooper | Avoiding false positives: zones of rarity, the threshold problem, and the DSM clinical significance criterion[END_REF]; and vii) to define the role of Sleep Medicine as a medical specialty. Other medical fields have made the effort to propose a definition. In psychiatry, for example, a structured definition of mental disorder has been useful to operationalize the way to determine each category of the Diagnostic and Statistical Manual of Mental Disorder (DSM) by the American Psychiatric Association (APA) [START_REF]Diagnostic and Statistical Manual of Mental Disorders (DSM-5®)[END_REF]. In neurology, the same is true for the field of epilepsy for which the International League Against Epilepsy (ILAE) commissioned a task force to propose such a structured definition in order to better organize the classification of epilepsies [START_REF] Fisher | Epileptic Seizures and Epilepsy: Definitions Proposed by the International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE)[END_REF]. Both the APA and the ILAE have clearly and explicitly discussed the conceptual framework underpinning these definitions, which is essential to the construction of diagnostic criteria.

The ICSD-3 posited a hybrid approach (p.13 of the introduction) [START_REF]International classification of sleep disorders[END_REF], without a clear reference to what was being referred to. Nevertheless, this approach seems to be based on a classical epistemological approach, which has led to several medical classifications where the nature of the disorders remained complex, e.g. mental disorders in the DSM-5 classification and epilepsies in the ILAE classification, but also to much more wide-ranging proposals such as the International Classification of Diseases (ICD-11) developed by the World Health Organization [START_REF]International classification of diseases for mortality and morbidity statistics (11th Revision)[END_REF]. The hybrid approach is related to the conceptual approach of Harmful Dysfunction Analysis (HDA), which has only rarely been applied explicitly in the field of sleep medicine, except once to our knowledge in a discussion aiming to establish an international consensus for defining sleep-related bruxism [START_REF] Raphael | Is bruxism a disorder or a behaviour? Rethinking the international consensus on defining and grading of bruxism[END_REF]. HDA, which was developed in 1992 by Wakefield [START_REF] Wakefield | Disorder as harmful dysfunction: A conceptual critique of DSM-III-R's definition of mental disorder[END_REF] to define which conditions can be considered as disorders or not, can be very useful in constructing more reliable and valid classifications of medical disorders.

It offers a global vision of the nature of disorders despite their heterogeneity by including both the concept of dysfunction (e.g. physiological) and the concept of harm (e.g. value).

HDA posits that a disorder is a hybrid concept whereby a physiological dysfunction, understood as a failure of some feature to perform a naturally selected function, is directly related with the harm caused to the individual, as evaluated by social values.

This theoretical review proposes to analyze systematically the type of "ICSD-3 diagnostic criteria" by labeling each of them for each sleep disorder in order to propose an overview of the way in which the diagnostic criteria are organized through the distinctive disorders of the classification. This analysis will enable to make proposals to improve the organization of the ICSD diagnostic criteria for further iterative developments based on a structured definition of sleep disorders and on the comprehensive framework of the hybrid approach of HDA. We hope that the proposal will serve to guide the evolution of the diagnostic criteria for each sleep disorder based on a structured unified approach to sleep medicine. Recommendations are made for future research and the development of iterations of the ICSD to improve the reliability and validity of sleep disorder diagnoses.

METHOD Sampling strategy

All the sleep disorders listed in the ICSD-3 were selected for the analyses after excluding the following conditions: a) disorders "Unspecified" or "Not otherwise specified"; b) disorders "Due to Other Conditions" and c) "Isolated symptoms and normal variants". These criteria were applied to select only the main sleep disorders.

Units of study

All the diagnostic criteria of the selected ICSD-3 sleep disorders (with the exclusion of notes) were selected. diagnostic category of the ICSD-3, and for all the sleep disorders selected, in order to propose an overview of the way in which the diagnostic criteria are organized in the ICSD-3. Table 1.

RESULTS

Forty-three diagnoses classified into 6 main diagnostic categories were analyzed (2 insomnia disorders, 12 sleep-related breathing disorders, 6 central disorders of hypersomnolence, 6 circadian rhythm sleep-wake disorders, 10 parasomnias and 7 sleep-related movement disorders). Among the 43 diagnoses, 241 single criteria were extracted (from 2 to 18 criteria per diagnosis) and 284 labels were applied (Figure 1). Twenty-nine ICSD diagnostic criteria (12%) were classified into two (N=18) or more types of label (N=11), most frequent clinical manifestation and duration and / or frequency.

Type of diagnostic criteria

Nine labels were consensually determined (Table 1). An example of diagnostic criteria associated with each label is shown in Annex 4. The labels "Clinical manifestation" and "Objective biomarker" found in the introduction of the ICSD-3 were retained.

Supplementary materials show: i) the list of criteria extracted and labeled for each disorder by each of the three raters (Annex 1), and ii) the consensual attribution of a label for each ICSD-3 diagnostic criterion (Annex 2).

Inter-rater reliability

Total interrater reliability for all labels and for all sleep disorders was Cohen's Kappa=0.85, considered as substantial agreement.

Supplementary materials show: i) the kappa calculated (Annex 3); ii) the qualitative details of the inter-rater reliability (Annex 4)

Main findings

Table 1 shows the type of label used for each sleep disorder, the percentage of use and Cohen's Kappa for each label, for each main diagnostic category of the ICSD-3, and for all the sleep disorders selected. "Clinical manifestation" and "Exclusion" criteria were found in most sleep disorders (86%), whereas "Age" was found in very few (18.6%). "Objective marker" was found in around half of sleep disorders, and in all the Sleep-related breathing disorders. "Distress" and "Disability" were found in around one third of sleep disorders.

"Distress" was found in all the Insomnia disorders and Circadian rhythm sleep wake disorders, but not in any Sleep-related breathing disorders or Central disorders of hypersomnolence. Circadian rhythm sleep wake disorders were the main sleep category exhibiting all types of criteria (except age).

DISCUSSION

In this theoretical review article, we provide the first systematic analysis of the ICSD-3 criteria used for the diagnosis of sleep disorders. Using a rigorous iterative process of "aggregation" and "generalization", 241 criteria from 43 main sleep disorders of the ICSD-3 were labeled into nine types, with a high inter-rater reliability (Cohen's Kappa=0.85). The types of criteria were: "Clinical manifestation", "Objective marker", "Distress", "Disability", "Duration", "Frequency", "Age", "Exclusion", and "Associated condition". Interestingly, this overview of the way in which the diagnostic criteria are organized in the ICSD-3 found a structure that is in line with the conceptual framework of the HDA, a classical hybrid approach for defining disorder with the interaction of a dysfunction part (i.e. "Clinical manifestation" and "Objective marker") and a harmful part (i.e. "Distress" and "Disability").

Thus, even if the ICSD-3 posited this approach in the introduction without a clear reference to the HDA [START_REF]International classification of sleep disorders[END_REF], the present findings confirm the conceptual foundation of this classification of sleep disorder in the HDA framework, as is the case for the DSM and the ILAE nosological classification [START_REF] Fisher | Epileptic Seizures and Epilepsy: Definitions Proposed by the International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE)[END_REF][START_REF] Wakefield | Disorder as harmful dysfunction: A conceptual critique of DSM-III-R's definition of mental disorder[END_REF]. In line with these results, we can propose a definition of sleep disorder based on the comprehensive framework of the HAD (Annex 5, 6, 7). This structured definition and the comprehensive framework of the hybrid approach of the HDA could serve to organize the diagnostic criteria of sleep disorders in a more comprehensive and structured way, by: i) the definition of a key terminology and its application consistently across all diagnoses, ii) the enlightenment of our understanding and the identification of any inconsistency and omissions in the development of these criteria. Such a proposition could shift sleep medicine from a multidisciplinary approach (i.e. different specialties working side by side, each with their conceptual framework) to a transdisciplinary approach (i.e. different specialties sharing the same conceptual framework). Such a common conceptual framework could be of great interest for studying and validating the diagnoses of sleep disorders [START_REF] Morin | Sleep Disorders Classification and Diagnosis[END_REF].

Nevertheless, this systematic analysis of the "ICSD-3 diagnostic criteria" also found a high level of heterogeneity in the type of criteria used across the different sleep disorders (Table 1). Thus, although the ICSD-3 uses a conceptual framework based on a hybrid approach, the latter does not seem to be homogeneous through its nosological classification. This heterogeneity is particularly manifest for Objective marker and Distress / Disability criteria that are not used equally for each sleep disorder, and in the differences between the Clinical manifestation criteria used for almost all sleep disorders. Such heterogeneity could be due to the fact that sleep medicine investigates different types of sleep disorder, which may call upon different types of ICSD-3 diagnostic criteria. However, the difference is not solely due to differences in specific diagnostic criteria concerning the specificity of disorders but seems to be related to the way disorders, and the boundaries between the normal and the pathological, are conceptualized. Some disorders seem to be based without the use of harmful criteria (i.e. "Distress" and "Disability"), like "Sleep-related breathing disorders", for which the boundaries between the normal and the pathological are defined principally on the supposed pathophysiological mechanism. The consequences of the disorder in terms of distress or disability, or more generally in terms of prognosis, seem to be implicitly included in the diagnostic criteria, as indicated in the section "Onset course and complications" of the ICSD-3 for these disorders. Other sleep disorders seem to be principally based on value criteria, like "Insomnia disorders", for which the boundaries between the normal and the pathological are defined principally on the supposed consequences of distress or disability. In this case, the pathophysiological mechanism is discussed only in the section "Pathology and pathophysiology" of the ICSD-3, without any diagnostic criteria referring to it. For the other main sleep disorder categories, a mixture of dysfunction and harmful diagnostic criteria is generally used. Therefore, there is a clear need to discuss the role of Clinical manifestation, Objective marker, Distress and Disability criteria in a nosological sleep disorder classification, and to propose recommendations for future research and the development of iterations of both ICSD diagnostic criteria and their organization so that they are reliable and valid for identifying sleep disorders.

Proposals for modifying the ICSD diagnostic criteria

Clinical manifestation criteria

This systematic analysis found that a clinical manifestation criterion was included for almost all the main sleep disorders analyzed. Only five diagnoses, i.e. 41.6% of Sleep-related breathing disorders and one Sleep-related movement disorder (Periodic Limb Movement disorder), had no Clinical manifestation criterion. This result confirms that the clinical interview is considered as a very "important assessment component for any sleep disorder" [START_REF] Morin | Sleep Disorders Classification and Diagnosis[END_REF] and that "Clinical manifestation" is the type of criterion that clinicians find the most useful since the ICSD-1 [START_REF] Buysse | Clinicians' use of the International Classification of Sleep Disorders: results of a national survey[END_REF]. However, some Clinical manifestation criteria lacked inter-rater reliability, highlighting the fact that it may be difficult to identify "Clinical manifestation" criteria in the ICSD-3 diagnostic criteria. This could be due to the term used for Clinical manifestation criteria, which may lack precision or sufficient specificity [START_REF] Edinger | Testing the reliability and validity of DSM-IV-TR and ICSD-2 insomnia diagnoses. Results of a multitraitmultimethod analysis[END_REF],

Until now, the terminology and choice of Clinical manifestation criterion for a number of sleep disorders have been based on expert opinions and consensus, which is a classical step in the development of a classification system [START_REF] Morin | Sleep Disorders Classification and Diagnosis[END_REF]. Nevertheless, the following recommendation could be made for the evolution of the Clinical manifestation criteria of the ICSD in order to increase the reliability and validity of the diagnostic criteria and to tend toward the standardization of clinical and research practice:

-Empirical research should be encouraged in order evaluate the reliability (i.e. interrater agreement on identification of a clinical manifestation), validity (i.e. relation of the clinical manifestation with the pathophysiological mechanism) and practicality (i.e. efficiency of the clinical manifestation with regard to the clinical reasoning process) of clinical manifestation criteria. This issue has received little attention until now. Authors have investigated the reliably and validity of the diagnostic criteria of Insomnia disorders [START_REF] Edinger | Testing the reliability and validity of DSM-IV-TR and ICSD-2 insomnia diagnoses. Results of a multitraitmultimethod analysis[END_REF]. Others have investigated the inter-observer reliability of the diagnostic criteria for Parasomnia [START_REF] Vignatelli | Interobserver reliability of ICSD-R minimal diagnostic criteria for the parasomnias[END_REF], specifically for Disorder of arousal [START_REF] Loddo | Interobserver reliability of ICSD-3 diagnostic criteria for disorders of arousal in adults[END_REF] and REM sleep behavior disorder [START_REF] Bologna | Pisa Universities group for the study of REM Sleep Behaviour Disoders in Parksinson's Disease. Interobserver reliability of ICSD-R criteria for REM sleep behaviour disorder[END_REF], and Narcolepsy [START_REF] Vignatelli | ICSD diagnostic criteria for narcolepsy: interobserver reliability. Intemational Classification of Sleep Disorders[END_REF]. In this line, Clinical manifestation criteria that combine very different clinical manifestations in the same criteria, as is the case for Obstructive sleep apnea disorders, criterion A.1 "the patient complains of sleepiness, nonrestorative sleep, fatigue, insomnia symptoms", should be avoided in order to increase the reliability, validity and practicability of diagnostic criteria.

-A consensual terminology of sleep manifestations in sleep medicine should be developed. For example, for Parasomnias, subjective experiences and behavior during sleep, or for Central disorders of hypersomnolence (excessive daytime sleepiness, excessive need for sleep, sleep attack) should be described with a more precise, well defined and specific clinical terminology [START_REF] Lammers | Diagnosis of central disorders of hypersomnolence: A reappraisal by European experts[END_REF][START_REF] Lopez | Diagnostic criteria for disorders of arousal: A video-polysomnographic assessment[END_REF]. Interestingly, the ILAE developed a specific task force for the classification and definition of "ictal semiology" [START_REF] Blume | Glossary of Descriptive Terminology for Ictal Semiology: Report of the ILAE Task Force on Classification and Terminology[END_REF]. A similar initiative could be launched to develop a "Sleep semiology task force", in order to avoid the pitfalls of the undefined terms in the Clinical manifestation criteria, and to reduce the variability in how clinical manifestations are defined in the sleep literature.

-A standardized clinical interview based on the ICSD diagnostic criteria and on a consensual terminology of sleep manifestations should be developed in order to assess clinical manifestations more systematically. Moreover, as many clinical manifestations occur during sleep, these standardized clinical interviews should include the bed partner.

Objective marker criteria

This systematic analysis found that "Objective marker" criteria were included for half of the sleep disorders analyzed, with large discrepancies between the main diagnostic categories (from 0% for Insomnia disorders or 10% for Parasomnias, to 83.3% for Circadian rhythm sleep wake disorders and 100% for Sleep-related breathing disorders). PSG diagnostic criteria were found in only (12/43) 27.9% of the main sleep disorders analyzed. Cardio-respiratory objective measures were systematically found for each "Sleep-related breathing disorder", in contrast to "Insomnia disorders", which did not have any Objective marker criterion. For the "Circadian rhythm sleep wake disorders" main category, "sleep log" and "whenever possible, actigraphy monitoring" are indicated. There was also discrepancy in the use of Objective marker criteria for disorders listed in the same main sleep disorder category. In "Central disorders of hypersomnolence", the criterion "mean sleep latency" or "24-hour polysomnographic monitoring" were explicitly indicated for "Narcolepsy type 1 and type 2" and "Idiopathic hypersomnia" but not for the other Central disorders of hypersomnolence [START_REF] Lammers | Diagnosis of central disorders of hypersomnolence: A reappraisal by European experts[END_REF][START_REF] Gauld | Diagnosis of central disorders of hypersomnolence: A reappraisal by European experts": From clinic to clinic via ontology and semantic analysis on a bullet point path[END_REF]. For "Parasomnias", such Objective markers exist for REM sleep behavior disorder (i.e. REM sleep without atonia) [START_REF] Montplaisir | Polysomnographic diagnosis of idiopathic REM sleep behavior disorder[END_REF], but are lacking for other parasomnias, often characterized only by subjective experiences such as nightmares or sleep-related hallucinations. Lastly, only one diagnosis listed in the main category "Sleep-related movement disorders" (i.e. PLM disorder) has an Objective marker, while other disorders such as Sleep-related bruxism or Sleep-related rhythmic movement disorders do not. Nevertheless, they can also be objectively quantified with well-defined criteria from the AASM scoring manual [START_REF] Academic | AASM Manual for the Scoring of Sleep and Associated Events[END_REF]. For example, masseter muscle activity, as an Objective marker of sleep-related bruxism, is "ideally recorded" in the ICSD-3.

Thus, in the present systematic analysis, many disorders did not require an objective marker (obtained by a PSG or other electrophysiological techniques). Yet an objective marker is crucial to increase the reliability and validity of sleep disorder diagnoses and to obtain a more robust classification. Thus, the following recommendation could be made for the evolution of the Objective marker criteria in the ICSD:

-Empirical research should be encouraged to evaluate the relationship of the Objective marker with a sleep dysfunction or a physiological dysfunction occurring during sleep (like decrease in CSF hypocretine-1 concentration in narcolepsy type 1, PHOX2B mutation in Congenital Central Alveolar Hypoventilation Syndrome, or loss of physiological atonia during REM sleep in REM sleep behavior disorder). To be included in the future revisions of the ICSD, Objective markers developed for the diagnosis of sleep disorders should not only have good performance but should also be clearly related to a physiological dysfunction that reflects the pathophysiology of the disease. If such a requirement appears to be met for the new polysomnographic diagnostic criteria for Disorders of arousal [START_REF] Lopez | Diagnostic criteria for disorders of arousal: A video-polysomnographic assessment[END_REF], further studies are needed to validate such criteria for Sleep-related bruxism [START_REF] Lobbezoo | International consensus on the assessment of bruxism: Report of a work in progress[END_REF] or for the newly proposed diagnostic category Trauma-associated sleep disorder [START_REF] Mysliwiec | Trauma associated sleep disorder: A parasomnia induced by trauma[END_REF]. The current state of knowledge indicates that objective markers are not possible for all sleep disorders, although research should be encouraged for all of them.

-Sleep function should continue to be investigated to better define what normal sleep is compared to pathological sleep. Two approaches should be encourages [START_REF] Giroux | Après Canguilhem : définir la santé et la maladie[END_REF]: an evolutionary approach to sleep functioning, and a homeostatic and integrative approach to it [START_REF] Eckert | Phenotypic approaches to obstructive sleep apnoea -New pathways for targeted therapy[END_REF][START_REF] Zinchuk | Phenotypes in obstructive sleep apnea: A definition, examples and evolution of approaches[END_REF][START_REF] Jullian-Desayes | Impact of obstructive sleep apnea treatment by continuous positive airway pressure on cardiometabolic biomarkers: a systematic review from sham CPAP randomized controlled trials[END_REF][START_REF] Lim | Reinventing polysomnography in the age of precision medicine[END_REF]. In this line, a large population normative sleep data base should be developed, taking into account the evolution of sleep parameters with age [START_REF] Lim | Reinventing polysomnography in the age of precision medicine[END_REF][START_REF] Franco | Sleep during development: Sex and gender differences[END_REF].

-A sleep task force for sleep disorder classification (for the ICSD-3 manual) should collaborate with a task force involved in PSG techniques and scoring (for the AASM scoring manual), in order to investigate ways to rigorously operationalize Objective markers so as to obtain reliable, valid, practical and specific markers of sleep pathophysiology.

Distress / Disability criteria

This systematic analysis found that distress / disability criteria were included in around half of the sleep disorders analyzed. These Distress and Disability criteria can be related to the "clinical significance" proposed in the ICSD-3 introduction. However, the use of "distress" or "disability" criteria is formulated in several ways across the sleep disorders analyzed (as shown in Table 1) and the exact term "clinically significant" was found in only (8/43) 18.6% of the Distress and / or Disability criteria (for Circadian rhythm sleep wake disorders, Recurrent isolated sleep paralysis, and Nightmare disorder). Moreover, the use of such criteria can vary considerably across a main sleep disorder category of the ICSD-3. For example, in the "Sleep-related breathing disorders" main category, "Disability" was found only for Obstructive sleep apnea disorder in children and for Late-Onset Central Hypoventilation with Hypothalamic Dysfunction; and for the "Central hypersomnolence disorder" main category only for Kleine-Levin Syndrome and for Insufficient Sleep Syndrome. For the "Parasomnias" main category, "Distress" and / or "Disability" were found for half of the parasomnia disorders. In contrast, the "Circadian rhythm sleep wake disorders" main category is homogenous, as distress or disability were found for all disorders.

Clinically significant meant that the clinical manifestations are related to significant distress or disability, which should help to establish the threshold for the diagnosis of a sleep disorder in situations in which the sleep manifestation (Clinical manifestation or Objective marker) per se is not sufficient to establish the boundaries between the normal and the pathological. This point is clearly indicated in the notes for Sleep-related rhythmic movement disorder: "when there are no clinical consequences of the rhythmic movements, the rhythmic movements are simply noted but the term rhythmic movement disorder is not employed" [START_REF]International classification of sleep disorders[END_REF]. However, "clinical significance" has been largely discussed in the literature on diagnostic criteria and raises some important issues [START_REF] Bolton | Overdiagnosis Problems in the DSM-IV and the New DSM-5: Can They Be Resolved by the Distress-Impairment Criterion?[END_REF][START_REF] Spitzer | DSM-IV diagnostic criterion for clinical significance: does it help solve the false positives problem?[END_REF]: i) it could be unclear whether "distress" and [START_REF]Diagnostic classification of sleep and arousal disorders. 1979 first edition. Association of Sleep Disorders Centers and the Association for the Psychophysiological Study of Sleep[END_REF], Sleep-related distress and disability were grouped together under the terms : DIMS for "Disorders of initiating and maintaining wakefulness" and DOES for "disorders of excessive somnolence". Such terms could be viewed as a simplistic categorization and should be more detailed. Nevertheless, it could be the first step in developing such a terminology to better identify and classify distress and disability related to sleep disorders. Indeed, such an approach is encouraged by a sleep clinician [START_REF] Buysse | Clinicians' use of the International Classification of Sleep Disorders: results of a national survey[END_REF] because it matched with the clinician's experience of how their patients presented (e.g. with complaints of insomnia, hypersomnolence or unusual behavior during sleep), and with the ability of the clinician to differentiate the normal and the pathological based on the significance of these manifestations.

-Empirical research should be encouraged to evaluate the relationship between the Distress / Disability and their underlying pathophysiological mechanisms. Indeed, the HDA framework supposes that both distress and disability, which are inherent in sleep disturbances and the consequences of the dysfunction, are relevant to its status as a disorder -otherwise, marked distress or disability about having a non-disordered condition may lead to a false positive diagnosis [START_REF] Cooper | Avoiding false positives: zones of rarity, the threshold problem, and the DSM clinical significance criterion[END_REF]. Indeed, 'harmful' is to be considered as an adjective that conveys a value judgment about the dysfunctional component of a disorder. This relationship between dysfunction and harmful was underlined by Spitzer when citing Wakefield's words from a personal communication in 1988 concerning Insomnia disorder [START_REF] Spitzer | DSM-IV diagnostic criterion for clinical significance: does it help solve the false positives problem?[END_REF]. In particular, to establish the relationship between the harmful and the dysfunction within a disorder, it is important to specify that the harmful is not the only consequence of inadequate environmental circumstances for sleep. Interestingly, the concept of DIMS and DOES in the DCSAD was a first attempt to emphasize the required relationship between Distress / Disability and a pathophysiological mechanism.

-A sleep task force for sleep disorder classification should attempt to rigorously operationalize Sleep-related distress and disability, in order to avoid false positives. Such criteria of harmful could be clinically related but could also involve an Objective marker. For example, concerning somnolence, many studies have been conducted with the Maintenance Wakefulness Test (MWT) [START_REF] Littner | Practice Parameters for Clinical Use of the Multiple Sleep Latency Test and the Maintenance of Wakefulness Test[END_REF]. Indeed, unlike the Multiple Sleep Latency Test (MSLT), which is an objective test of sleep dysfunction measuring the tendency to fall asleep, the MWT can be considered strictly speaking as an objective test of wakefulness-related harm. Even if further research is needed, the aim is indeed to correlate the degree of sleepiness and the ability to maintain wakefulness (related to the function sleep) with safety and the putative occupational risks for the individual and for society in "real life" circumstances, and according to social norms. Such an approach could be encouraged for other objective tests of sleepspecific distress or disability.

Proposals for organizing the ICSD diagnostic criteria

To reduce the heterogeneity in the type of criteria used across the different sleep disorders and to better implement the conceptual framework based on a "hybrid approach" as introduced in the ICSD-3, a framework for organizing the ICSD diagnostic criteria could be proposed in order i) to highlight the way sleep disorders are conceptualized in the nosological classification, ii) to integrate the different sleep disorders and types of diagnostic criteria specific to the characteristics of each sleep disorder.

Importantly, we analyzed only the main sleep disorders of the ICSD-3, i.e. 43 sleep disorders out of the 67 (65 %) that are included in the ICSD-3. These sleep disorders should be reintegrated in the proposed framework for ICSD diagnostic criteria. Our systematic conceptual analysis of the main ICSD-3 sleep disorders and the comprehensive framework of the hybrid approach of HAD (Annex 7) suggests considering "Clinical manifestation", "Objective marker", and "Distress / Disability" as the central core of the diagnostic criteria for sleep disorders. Other type of ICSD diagnostic criteria should be incorporated with regard to these central core criteria (Table 2). Thus, the following recommendations could be made for re-organizing the ICSD diagnostic criteria:

-"Clinical manifestation", "Objective marker", and "Distress / Disability" diagnostic criteria should be systematically discussed for each sleep disorder. This does not mean that these types of diagnostic criteria should be present systematically for each sleep disorder. Some of these criteria could be sufficiently related to pathophysiological mechanisms and to harmful consequence to not require other criteria. For example, for Narcolepsy type 1, the Objective marker "CSF hypocretin-1" of the ICSD-3 criteria may not be present, because the clinical manifestation "cataplexy" is strongly associated with the pathophysiological mechanisms of Hypocretin-1 deficiency. For REM sleep behavior disorder, the Distress / Disability criteria might not be necessary, because the objective marker "REM sleep without atonia" is epidemiologically strongly associated with future Distress or Disability related to Parkinson disease. Nevertheless, these three types of diagnostic criteria offer the opportunity systematically to discuss and structure the central core of a sleep disorder in light of the conceptual framework of the HDA and the structured definition of sleep disorder proposed (Annex 7).

-The other types of criteria of the ICSD-3 ("Duration", "Frequency", "Age", "Exclusion", "Associated condition") could be considered as specific criteria of sleep disorders. In line with the recent proposition for Hypersomnolence disorders [START_REF] Lammers | Diagnosis of central disorders of hypersomnolence: A reappraisal by European experts[END_REF], three other criteria could be added: "Level of certainty criteria", "Level of severity criteria", "Subtype criteria". These three criteria are not present in the current ICSD-3. Despite the fact that they require further research to be added in the evolution of the ICSD diagnosis criteria, an expert consensus has highlighted their interest for classifying disorders [START_REF] Lammers | Diagnosis of central disorders of hypersomnolence: A reappraisal by European experts[END_REF].

-Level of certainty would make it possible to indicate the degree of association of the sleep condition identified with a sleep dysfunction [START_REF] Lammers | Diagnosis of central disorders of hypersomnolence: A reappraisal by European experts[END_REF]. For example, hypocretin deficiency is a useful criterion for separating Narcolepsy type 1 from Narcolepsy type 2 in ICSD-3 [START_REF] Lammers | Diagnosis of central disorders of hypersomnolence: A reappraisal by European experts[END_REF].

-Level of severity would indicate the quantification of the clinical manifestation, the dysfunction or the Distress / Disability, as proposed in the first version of the ICSD in addition to the diagnostic criteria [START_REF]International Classification of Sleep Disorders[END_REF]. However, our systematic analysis found a lack of precision concerning the degree of severity in the ICSD-3 diagnostic criteria. The term "difficulty" found in three Clinical manifestation criteria, as well as the summary term "sleep disturbance" for Insomnia disorders, or the term "irrepressible need to sleep" for Central disorders of hypersomnolence are just some examples of the lack of detail in the way the general population formulates complaints [START_REF] Ohayon | Epidemiology of insomnia: what we know and what we still need to learn[END_REF][START_REF] Ohayon | Epidemiology of Excessive Daytime Sleepiness[END_REF]. This imprecision can leave to a wide variability of interpretation of the Clinical manifestation diagnostic criteria. Interestingly, the analysis of Buysse et al. on clinicians' use of the ICSD-1 found a very low useful rating for severity criteria of the ICSD-1. This may reflect "disagreements with the specific method for rating severity, difficulty with applying the severity criteria, or a lack of relevance to clinical decision making" [START_REF] Buysse | Clinicians' use of the International Classification of Sleep Disorders: results of a national survey[END_REF]. Thus, they suggest that "future revisions of the ICSD [first version] will need to re-examine severity ratings to ensure that they are anchored to treatment or outcome data and that they are sufficiently "user-friendly" for clinical practice". This criterion was removed from the ICSD-2 [START_REF]International Classification of Sleep Disorders[END_REF] and the ICSD-3 [START_REF]International classification of sleep disorders[END_REF]. We suggest re-examining this omission in the future revision of the ICSD.

-Lastly, subtype criteria would make it possible to include all specific and relevant criteria for a sleep disorder that need to be clearly indicated with regard to the clinical or pathophysiological purpose. Such an approach offers the opportunity to include ICSD iteration in the precision medicine paradigm [START_REF] Gauld | Personalized Medicine for OSAS in a Nutshell: Conceptual Clarification for Integration[END_REF], in order to clarify the relationships between specific sleep disorders and pathophysiological mechanisms, as proposed by Eckert for OSAS [START_REF] Eckert | Phenotypic approaches to obstructive sleep apnoea -New pathways for targeted therapy[END_REF], and between prognosis and therapeutic outcome, as proposed by Zinchuk for OSAS [START_REF] Zinchuk | Phenotypes in obstructive sleep apnea: A definition, examples and evolution of approaches[END_REF]. This would make it possible to create a dynamic modifiable framework over time that ensures validity through the implementation of data from Evidence-Based Medicine without reducing the importance of having a solid stable clinical framework over time that possesses central core criteria that ensure that practitioners from different disciplines share the same understanding of disorders.

-The sleep disorders not included in our systematic analysis (1. "Unspecified" or "Not otherwise specified" disorders; 2. disorders "Due to Other Conditions" and 3.

"Isolated symptoms and normal variants") could be included in the proposed framework. With such a framework, the organization of the criteria for "Sleep Wake Phase Disorder" and for "Disorders of arousal", with general criteria for these main sleep disorder categories, and specific diagnostic criteria for sleep disorders of the main category, could be generalized to the entire classification. This offers the opportunity to include "unspecified and not otherwise specified" sleep disorder within the criteria concerning the level of certainty, "due to other condition" sleep disorder within the association criteria, and "isolated symptoms" and "normal variant" within the severity criteria. Moreover, age (i.e. Child, Adult, Elderly) would be taken into account for each sleep disorder as a specifier, whereas in fact it sometimes serves as a diagnostic criterion and at others as a sleep disorder category (e.g. "Obstructive sleep apnea, pediatric"). It should be considered as an important improvement for the future evolution of the ICSD diagnostic criteria.

Limitations

There are several limitations to the methodology proposed herein.

First, the systematic analysis focuses on main sleep disorders but excludes others. The latter were excluded since they provide no useful diagnostic criteria for addressing the aims of this study. Nevertheless, in view of consensual development and evidence from empirical studies, diagnostic criteria are needed for these sleep disorder categories and could subsequently be included.

Second, it should be noted that the proposed diagnostic criteria analysis (Table 1) and the framework for organizing the ICSD diagnostic criteria (Table 2), based on the structured definition of sleep disorders (Annex 7), reflect only the consensus of the authors. However, the methodology is rigorous and was adapted from the standards for reporting qualitative research for the labeling for ICSD-3 diagnostic criteria [START_REF] Tong | Consolidated criteria for reporting qualitative research (COREQ): a 32-item checklist for interviews and focus groups[END_REF][START_REF] O'brien | Standards for Reporting Qualitative Research: A Synthesis of Recommendations[END_REF] (Annex 8) and from the steps defined by Edinger and Morin for the definition of sleep disorders [START_REF] Morin | Sleep Disorders Classification and Diagnosis[END_REF]. Moreover, the analysis and proposals were supervised by a philosopher (EG) specialized in medical classification and a neuroscientist (GD) specialized in the link between physiological and sociological data in order to ensure the theoretical coherence of the process. Nevertheless, future refinements will be needed. Data-driven analysis based on bioinformatics methodologies, and in particular text-mining techniques [START_REF] Gauld | Diagnosis of central disorders of hypersomnolence: A reappraisal by European experts": From clinic to clinic via ontology and semantic analysis on a bullet point path[END_REF] which enable the extraction of unknown knowledge from the number of criteria of a classification, or ontological analysis which makes it possible to create a structured representation of a set of objects (e.g. diagnostic criteria), their characteristics (e.g. label) and their relationship, could be used in further research to better understand the structure of the classification. Comments and criticism from all stakeholders are now needed, as was the case for the DSM criteria [START_REF]Diagnostic and Statistical Manual of Mental Disorders (DSM-5®)[END_REF]. A separate expert panel could be appointed to review and incorporate the public comments to reinforce the iterative process outlined in this paper (Figure 1 & Annex 6). Discrepancies across different sleep disorders diagnostic systems (ICSD, DSM, and ICD) should also be analyzed and the current efforts concerning the DSM revision and the development of a separate sleep disorders chapter in the ICD-11 (which very closely parallels the ICSD) have to be reinforced. Moreover, studies should be conducted to attempt to establish empirically how often the correct application of the mooted diagnostic criteria are truly applicable in sleep medicine and result in a more reliable and valid diagnosis of an individual as having a sleep disorder [START_REF] Morin | Sleep Disorders Classification and Diagnosis[END_REF].

Lastly, the structured organization of sleep disorder criteria proposed herein is not intended to limit the clinical assessment of patients with sleep disorder or the scope of research into better defining and delineating sleep disorders. Alternative approaches might prove to be preferable. Moreover, the organization of classification is in continuous development, like the organization of the successive ICSD versions [START_REF]International classification of sleep disorders[END_REF][START_REF]International Classification of Sleep Disorders[END_REF][START_REF]International Classification of Sleep Disorders[END_REF][START_REF]International classification of sleep disorders[END_REF]. For example, the first revised version of the ICSD [START_REF]International classification of sleep disorders[END_REF] included the notion of "Minimal criteria" necessary for a diagnosis. Such a set of criteria was removed from the second version, which indicated "only one set of criteria" that have to be entirely present [START_REF]International Classification of Sleep Disorders[END_REF]. Here, we propose the term "central core criteria" which is in line with the HDA framework, keeping in mind that a conceptual framework is preferable than no framework at all. In addition, the proposal does not solve some issues like the following: i) the problem related to the lumping versus splitting controversy for sleep disorders [START_REF] Gauld | Diagnosis of central disorders of hypersomnolence: A reappraisal by European experts": From clinic to clinic via ontology and semantic analysis on a bullet point path[END_REF][START_REF] Hauri | A Cluster Analysis of Insomnia[END_REF]; ii) the problem of matching between phenotypes and treatments to use a classification to optimize a therapeutic response in line with the future of precision medicine in sleep [START_REF] Strollo | The Future of Sleep Medicine[END_REF]. Work should now focus on establishing a model of precision medicine that optimizes the categorization of patient groups in relation to clearly defined phenotypes for the purpose of medical classification [START_REF] Eckert | Phenotypic approaches to obstructive sleep apnoea -New pathways for targeted therapy[END_REF][START_REF] Zinchuk | Phenotypes in obstructive sleep apnea: A definition, examples and evolution of approaches[END_REF][START_REF] Lim | Reinventing polysomnography in the age of precision medicine[END_REF].

Conclusion

As stated by Edinger and Morin: "Clinicians as well as researchers would benefit from the ongoing evolution of sleep disorder classification schemes toward a unitary system" [START_REF] Morin | Sleep Disorders Classification and Diagnosis[END_REF]. To promote collaborative multicenter studies, to add more Objective marker criteria to the current official diagnostic definitions and to develop clinical practice guidelines, multidisciplinary research approaches and evidence-based medical care, we need to be more explicit in the way sleep disorders are defined. As Demazeux [START_REF] Demazeux | The Function Debate and the Concept of Mental Disorder[END_REF] claims, "The common belief [of Boorse, like Wakefield] is that science and conceptual clarity can clear up a number of contentious issues". Thus, we hope that such a definition of sleep disorders and the ensuing comprehensive framework will be useful to better justify the evolution of the diagnostic criteria for each sleep disorder based on a structured and unified approach to sleep medicine.

Practice points:

1. 241 criteria from 43 main sleep disorders of the ICSD-3 were labeled into nine types, with a high inter-rater reliability (Cohen's Kappa=0.85).

2. The label "Clinical manifestation" was present in 86.0% (N = 37/43) of the sleep disorders analyzed, "Objective markers" in 53.5% (N = 23), "Distress" in 30.2% (N = 16), "Disability" in 30.2 % (N = 16), "Duration" in 30.2% (N = 16), "Frequency" in 58.1% (N = 25), "Age" in 18.6% (N = 8), "Exclusion condition" in 81.4% (N = [START_REF]Diagnostic classification of sleep and arousal disorders. 1979 first edition. Association of Sleep Disorders Centers and the Association for the Psychophysiological Study of Sleep[END_REF] and "Associated condition" in 34.8% (N = 15).

3. The diagnostic criteria are organized in the ICSD-3 in line with a hybrid approach (called Harmful Dysfunction Analysis) for defining disorder as the interaction between factual (i.e. "Clinical manifestation" and "Objective marker") and value (i.e. "Distress" and "Disability") criteria.

4. The hybrid approach of the ICSD-3 is not homogenous across sleep disorders of the ICSD-3. 5. "Clinical manifestation" criteria are used for almost all sleep disorders but may lack precision or sufficient specificity, leading to a reduction of inter-rater reliability. 5. Investigate the way to rigorously operationalize "Sleep-related harmful", in order to better take into account the specific consequences of sleep disturbances on "Distress" and "Disability".

6. Propose an international working group in order to discuss the proposal as a conceptual framework for the evolution of ICSD diagnostic criteria. 7. Propose an international working group in order to carefully homogenize the structure and the terminology of ICSD diagnostic criteria across sleep disorders.

8. Use data-driven analysis based on bioinformatics methodologies or ontological analysis to better build the structure of the ICSD diagnostic criteria. 9. Promote links between sleep disorder classification, ICSD diagnostic criteria and new methods of stratification made possible by the advent of precision medicine models. • Is the sleep condition a "normal variant" or an "isolated symptom"?

"

  disability" refer only to the intrinsic consequence of sleep disturbances (e.g., the intrinsic discomfort of snoring, or the presence of cardiovascular consequences of sleep disturbances) or also to distress or disability about having sleep disturbances (e.g., being upset about the consequence of snoring on the sleep partner, or about the risk of the cardiovascular consequences of sleep disturbances); ii) it could be unclear what the relation is between clinical significance and the underlying physiological dysfunction in the organism, i.e. the very way in which a condition may be considered pathological. Such a nuance could be very theoretical and difficult to disentangle in routine clinical practice. Thus, the following recommendation could be made for the evolution of the Distress / Disability criteria of the ICSD: -A consensual clinical terminology of sleep Distress and Disability should be developed. In the first Diagnostic Classification of Sleep and Arousal Disorders (DCSAD) proposed by the "Association of Sleep Disorders Centers" and the "Association for the Psychophysiological Study of Sleep" published in Sleep in 1979

6 .

 6 "Objective marker" criteria are used for half of the sleep disorders analyzed, and PSG diagnostic criteria were found in only (12/43) 27.9 %. 7. Use of "Distress" or "Disability" criteria is formulated in a very heterogeneous way across the sleep disorders analyzed. 8. A structured definition of sleep disorders could provide a useful framework to homogenize the way in which diagnostic criteria across sleep disorders are organized.Research agendaFuture research should:1. Evaluate the reliability, validity and practicality of the different "Clinical manifestation" criteria. 2. Develop a consensual terminology of sleep manifestation in sleep medicine and a standardized clinical interview to capture it. 3. Evaluate the relationship of an "Objective marker" with a sleep dysfunction or a physiological dysfunction occurring during sleep. 4. Seek to develop a large population normative sleep data base, taking into account the evolution of sleep parameters with age.

Figure 1 . 1 Table 2 .•••••• 2 ••

 1122 Figure 1. Flowchart of ICSD-3 diagnostic criteria extraction and labeling.

Part of the general diagnostic criteria for Circadian Rhythm Sleep Wake Disorders(3 criteria)

Part of the general diagnostic criteria for Disorders of Arousal(5 criteria)

Funding

None

Data extraction and collection

All the diagnostic criteria of the selected ICSD-3 were extracted and processed in a Microsoft Excel spreadsheet (macOS, Version 15.37)

Data analysis

The type of "ICSD-3 diagnostic criteria" was labeled according to a rigorous qualitative method. Labels were established in order to group each diagnostic criterion into a type of higher order of abstraction through a process of "aggregation" and "generalization" [START_REF] Smith | Database abstractions: aggregation and generalization[END_REF]. For methodological details, see Figure 1 andAnnex 4.

Data processing

The diagnostic criteria of the selected ICSD-3 sleep disorders were extracted independently and labeled into one or more labels in a standard electronic form by three authors (JAM, CG, RL). The labeling was compared between the three raters to assure the trustworthiness and credibility of the full diagnostic criteria list. Inter-rater reliability was calculated by means of Kappa statistics. For methodological details, see Annex 3.

Data synthesis

The presence of each type of diagnostic criterion was listed according to the selected diagnoses. The percentage of each type of diagnostic criterion was calculated for each main

Abbreviations

AHI apnea hypopnea index

Conflict of interest

The authors declare that there is no conflict of interest.

Table 1.

Type of ICSD-3 diagnostic criteria for 43 sleep disorders. For detailed tables, see Annex 1 and 2. The " " sign indicates that the type of label is included in the diagnostic criteria and the " " sign indicates that it is not included. Cohen's Kappa 0.78 0.96 0.48 0.78 0.95 1.00 0.95 0.97 0.75 1 Age criterion is mentioned in the title (Adult, Pediatric) 1