Abstract
Idiopathic hypersomnia (IH) is an orphan disease with unknown physiopathology. The diagnosis of IH is based on a body of clinical arguments and polysomnographic criteria which have limitations, and no reliable biomarkers were discovered so far. The HI represents an experimental model to study the different inter-individual natural sleep durations (short and long sleepers vs. extreme conditions as IH) and awakening mechanisms, likely with a genetic predisposition and a slow wave sleep dysregulation.In this PhD work we proposed reliable and valid measures of the three main dimensions of hypersomnolence, namely excessive quantity of sleep, excessive daytime sleepiness (EDS) and sleep inertia. We also investigated the clinical and neurophysiological phenotype of IH in comparison with other disorders associated with hypersomnolence.In our first study, we validated the 32-hour standardized and bed-rest controlled recording protocol, which allows a better phenotypical characterization of IH and more specific diagnostic criteria.Our second study aimed to determine the clinical and polysomnographic characteristics associated with an EQS and EDS, assessed by both subjective and objective measures, in a sample of 266 patents with hypersomnolence including only 71 patients who fulfilled the more stringent criteria for IH proposed in this study. A better phenotypical characterization will help to differentiate patients with idiopathic hypersomnia, patients with hypersomnia due to other conditions or disorders and long sleepers, to understand their biology and to identify specific biomarkers. The third study aimed to validate a clinical tool for the evaluation of the whole spectrum of symptoms of IH and their consequences, the idiopathic hypersomnia severity scale (IHSS). The fourth study focused on the sleep inertia, a poorly defined symptom of IH and without valid objective measures. We proposed a standardized assessment of the sleep inertia based on the IHSS that allows quantifying its severity by its frequency, duration, and association with sleep drunkenness. We also validated the psychomotor vigilance task, a sustained attention test, as a reliable objective measure of the sleep inertia in IH. An additional study is currently ongoing to determine the pathological cut-offs of the PVT metrics at awakening that allow identifying the patients with IH with more severe performance impairment related to the sleep inertia and, thus, more at risk of severe consequences.This PhD work provides novel measures of hypersomnolence in IH and contributes to clarify the phenotype of IH. It represents the beginning of a larger project aimed to better understand the physiopathology of IHKeywords: idiopathic hypersomnia, long sleep, excessive quantity of sleep, excessive diurnal sleepiness, sleep inertia, sleep drunkenness, hypersomnolence, psychomotor vigilance task