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Background and ObjectivesRecent studies fueled doubts as to whether all currently defined central disorders of hypersomnolence are stable entities, especially narcolepsy type 2 and idiopathic hypersomnia. New reliable biomarkers are needed, and the question arises of whether current diagnostic criteria of hypersomnolence disorders should be reassessed. The main aim of this data-driven observational study was to see whether data-driven algorithms would segregate narcolepsy type 1 and identify more reliable subgrouping of individuals without cataplexy with new clinical biomarkers.MethodsWe used agglomerative hierarchical clustering, an unsupervised machine learning algorithm, to identify distinct hypersomnolence clusters in the large-scale European Narcolepsy Network database. We included 97 variables, covering all aspects of central hypersomnolence disorders such as symptoms, demographics, objective and subjective sleep measures, and laboratory biomarkers. We specifically focused on subgrouping of patients without cataplexy. The number of clusters was chosen to be the minimal number for which patients without cataplexy were put in distinct groups.ResultsWe included 1,078 unmedicated adolescents and adults. Seven clusters were identified, of which 4 clusters included predominantly individuals with cataplexy. The 2 most distinct clusters consisted of 158 and 157 patients, were dominated by those without cataplexy, and among other variables, significantly differed in presence of sleep drunkenness, subjective difficulty awakening, and weekend-week sleep length difference. Patients formally diagnosed as having narcolepsy type 2 and idiopathic hypersomnia were evenly mixed in these 2 clusters.DiscussionUsing a data-driven approach in the largest study on central disorders of hypersomnolence to date, our study identified distinct patient subgroups within the central disorders of hypersomnolence population. Our results contest inclusion of sleep-onset REM periods in diagnostic criteria for people without cataplexy and provide promising new variables for reliable diagnostic categories that better resemble different patient phenotypes. Cluster-guided classification will result in a more solid hypersomnolence classification system that is less vulnerable to instability of single features.

STUDY OBJECTIVES: To assess the responsiveness of the Idiopathic Hypersomnia Severity Scale (IHSS) to medications and estimate the minimum clinically important difference, to report clinically relevant score ranges, and to confirm its psychometric properties and whether items need to be weighted in drug-free and treated patients with idiopathic hypersomnia (IH). METHODS: Two-hundred twenty-six (166 drug-free and 60 treated) patients with IH (cross-sectional sample) completed the 14-item IHSS to quantify the severity of the 3 major IH symptoms (excessive daytime sleepiness, prolonged nighttime sleep, and sleep inertia) and consequences; 77 untreated patients were evaluated again after treatment (longitudinal sample). Patients filled in the Epworth Sleepiness Scale, Beck Depression Inventory II, and European Quality of Life questionnaires. RESULTS: The IHSS confirmed adequate psychometric properties with a factor analysis indicating a 3-component solution. IHSS total score was lower in treated than untreated patients, with a mean difference of 4–5 points in the cross-sectional and longitudinal samples. Distribution-based methods were used to estimate that 4 points represented the minimum clinically important difference. Four severity levels were defined with between-group differences related to treatment. The probability of having severe sleepiness, depressive symptoms, and low quality of life increased with the severity level. Our results showed that IHSS item-weighting was not necessary. CONCLUSIONS: The IHSS is a valid and reliable tool to quantify IH symptoms, with 4 severity score levels of clinical importance. The IHSS has adequate psychometric properties and can detect symptom changes after treatment. These findings should stimulate its use in clinical settings and in research studies. CITATION: Rassu AL, Evangelista E, Barateau L, et al. Idiopathic Hypersomnia Severity Scale to better quantify symptoms severity and their consequences in idiopathic hypersomnia. J Clin Sleep Med. 2022;18(2):617–629.

Background and ObjectivesNarcolepsy type 1 (NT1) is an orphan brain disorder caused by the irreversible destruction of orexin neurons. Metabolic disturbances are common in patients with NT1 who have a body mass index (BMI) 10% to 20% higher than the general population, with one-third being obese (BMI >30 kg/m2). Besides the destruction of orexin neurons in NT1, the metabolic alterations in obese and nonobese patients with NT1 remain unknown. The aim of this study was to identify possible differences in plasma metabolic profiles between patients with NT1 and controls as a function of their BMI status.MethodsWe used a targeted liquid chromatography–mass spectrometry metabolomics approach to measure 141 circulating, low-molecular-weight metabolites in drug-free fasted plasma samples from 117 patients with NT1 (including 41 obese individuals) compared with 116 BMI-matched controls (including 57 obese individuals).ResultsCommon metabolites driving the difference between patients with NT1 and controls, regardless of BMI, were identified, namely sarcosine, glutamate, nonaylcarnitine (C9), 5 long-chain lysophosphatidylcholine acyls, 1 sphingolipid, 12 phosphatidylcholine diacyls, and 11 phosphatidylcholine acyl-akyls, all showing increased concentrations in NT1. Metabolite concentrations significantly affected by NT1 (n = 42) and BMI category (n = 40) showed little overlap (n = 5). Quantitative enrichment analysis revealed common metabolic pathways that were implicated in the NT1/control differences in both normal BMI and obese comparisons, namely glycine and serine, arachidonic acid, and tryptophan metabolism. The metabolites driving these differences were glutamate, sarcosine, and ornithine (glycine and serine metabolism); glutamate and PC aa C34:4 (arachidonic acid metabolism); and glutamate, serotonin, and tryptophan (tryptophan metabolism). Linear metabolite-endophenotype regression analyses highlight that as part of the NT1 metabolic phenotype, most of the relationships between the sleep parameters (i.e., slow-wave sleep duration, sleep latency, and periodic leg movement) and metabolite concentrations seen in the controls were lost.DiscussionThese results represent the most comprehensive metabolic profiling of patients with NT1 as a function of BMI and propose some metabolic diagnostic biomarkers for NT1, namely glutamate, sarcosine, serotonin, tryptophan, nonaylcarnitine, and some phosphatidylcholines. The metabolic pathways identified offer, if confirmed, possible targets for treatment of obesity in NT1.Classification of EvidenceThis study provides Class II evidence that a distinct metabolic profile can differentiate patients with NT1 from patients without the disorder.

Study Objectives To assess the performances of alternative measures of the multiple sleep latency test (MSLT) to identify hypocretin-deficiency in patients with a complaint of hypersomnolence, including patients with narcolepsy. Methods MSLT parameters from 374 drug-free patients with hypersomnolence, with complete clinical and polysomnographic (PSG) assessment and cerebrospinal hypocretin-1 measurement were collected. Conventional (sleep latency, number of sleep onset REM—SOREM—periods) and alternative (sleep duration, REM sleep latency and duration, sleep stage transitions) MSLT measures were compared as function of hypocretin-1 levels (≤110 vs > 110 pg/mL). We performed receiver-operating characteristics analyses to determine the best thresholds of MSLT parameters to identify hypocretin-deficiency in the global population and in subgroups of patients with narcolepsy (i.e. typical cataplexy and/or positive PSG/MSLT criteria, n = 223). Results Patients with hypocretin-deficiency had shorter mean sleep and REM sleep latencies, longer mean sleep and REM sleep durations and more direct REM sleep transitions during the MSLT. The current standards of MSLT/PSG criteria identified hypocretin-deficient patients with a sensitivity of 0.87 and a specificity of 0.69, and 0.81/0.99 when combined with cataplexy. A mean REM sleep duration ≥ 4.1 min best identified hypocretin-deficiency in patients with hypersomnolence (AUC = 0.932, sensitivity 0.87, specificity 0.86) and ≥ 5.7 min in patients with narcolepsy (AUC = 0.832, sensitivity 0.77, specificity 0.82). Conclusion Compared to the current neurophysiological standard criteria, alternative MSLT parameters would better identify hypocretin-deficiency among patients with hypersomnolence and those with narcolepsy. We highlighted daytime REM sleep duration as a relevant neurophysiological biomarker of hypocretin-deficiency to be used in clinical and research settings.

ObjectiveWe validated the Narcolepsy Severity Scale (NSS) in adults with narcolepsy type 1 (NT1) to quantify the severity, frequency, and consequences of the 5 key narcolepsy symptoms over the last month, and we now developed the Pediatric NSS (NSS-P); thus, the aims of this study were to assess NSS-P psychometric properties, validity, and reliability, and to evaluate its responsiveness to treatment in a well-characterized sample of children and adolescents with NT1.MethodsThe NSS was reformulated for children, and the item about driving was removed. The total score of the 14-item NSS-P ranges from 0 to 54, and higher scores reflect more severe disease. Children and adolescents (n = 209, 6–17 years of age) with NT1 diagnosed in 2 Reference Centers for Narcolepsy in France were consecutively asked to fill in the NSS-P. The scale was fully and correctly completed by 160 (10–18 years of age, 68 untreated). Moreover, 65 participants completed it twice (33 before/during treatment, and 32 under the same treatment). The NSS-P psychometric properties, score changes before/during treatment, and convergent validity with other clinical parameters were assessed.ResultsThe NSS-P showed adequate psychometric properties with significant item–total score correlations. Factor analysis indicated a 4-factor solution with good reliability. The NSS-P score was lower in treated than untreated patients with a mean difference of 3.71 ± 1.45, with a minimum clinically important difference between untreated and treated patients in the longitudinal sample estimated at 4 points. Four severity levels were defined (mild, moderate, severe, very severe) with between-group differences related to treatment. The NSS-P total score was associated with self-reported sleepiness, insomnia, and depressive symptoms. Its temporal stability was satisfactory.DiscussionWe validated a brief instrument to assess NT1 symptom frequency, severity, and consequences in ≥10-year-old children and adolescents with 4 clinically relevant severity score ranges. This scale constitutes a relevant tool to improve and provide guidance for NT1 management in pediatric populations. The ease of administration, its good psychometric properties, and its sensitivity to detect symptom changes after treatment ensure future use of the NSS-P in clinical and research settings.

STUDY OBJECTIVES: To assess the frequency, determinants, and clinical impact of clinical rapid eye movement (REM) and non-REM (NREM) parasomnias in adult patients with narcolepsy type 1 (NT1), narcolepsy type 2 (NT2), and idiopathic hypersomnia compared with healthy controls. METHODS: Familial and past and current personal parasomnias were assessed by questionnaire and medical interviews in 710 patients (220 NT1, 199 NT2, and 221 idiopathic hypersomnia) and 595 healthy controls. RESULTS: Except for sleep-related eating disorder, current NREM parasomnias were rare in all patient groups and controls. Sleep-related eating disorder was more frequent in NT1 patients (7.9% vs 1.8% in NT2 patients, 2.1% in patients with idiopathic hypersomnia, and 1% in controls) and associated with disrupted nighttime sleep (odds ratio = 3.9) and nocturnal eating in full awareness (odds ratio = 6.9) but not with sex. Clinical REM sleep behavior disorder was more frequent in NT1 patients (41.4%, half being violent) than in NT2 patients (13.2%) and affected men more often than women (odds ratio = 2.4). It was associated with disrupted nighttime sleep, depressive symptoms, and antidepressant use. Frequent (> 1/week) nightmares were reported by 39% of patients with NT1, 29% with NT2, and 27.8% with idiopathic hypersomnia (vs 8.3% in controls) and were associated with depressive symptoms in narcolepsy. No parasomnia (except sleep-related hallucinations) worsened daytime sleepiness. CONCLUSIONS: In patients with central disorders of hypersomnolence, comorbid NREM parasomnias (except for sleep-related eating disorder) are rare and do not worsen sleepiness. In contrast, REM parasomnias are prevalent (especially in NT1) and are associated with male sex, disrupted nighttime sleep, depressive symptoms, and antidepressant use. CITATION: Leu-Semenescu S, Maranci J-B, Lopez R, et al. Comorbid parasomnias in narcolepsy and idiopathic hypersomnia: more REM than NREM parasomnias. J Clin Sleep Med. 2022;18(5):1355–1364.

Study Objectives Despite its high frequency in narcolepsy type 1(NT1), disrupted nocturnal sleep (DNS) remains understudied, and its determinants have been poorly assessed. We aimed to determine the clinical, polysomnographic (PSG), and biological variables associated with DNS in a large sample of patients with NT1, and to evaluate the effect of medication on DNS and its severity. Methods Two hundred and forty-eight consecutive adult patients with NT1 (145 untreated, 103 treated) were included at the National Reference Center for Narcolepsy-France; 51 drug-free patients were reevaluated during treatment. DNS, assessed with the Narcolepsy Severity Scale (NSS), was categorized in four levels (absent, mild, moderate, severe). Clinical characteristics, validated questionnaires, PSG parameters (sleep fragmentation markers: sleep (SB) and wake bouts (WB), transitions), objective sleepiness, and orexin-A levels were assessed. Results In drug-free patients, DNS severity was associated with higher scores on NSS, higher sleepiness, anxiety/depressive symptoms, autonomic dysfunction, worse quality of life (QoL). Patients with moderate/severe DNS (59%) had increased sleep onset REM periods, lower sleep efficiency, longer wake after sleep onset, more N1, SB, WB, sleep instability, transitions. In treated patients, DNS was associated with the same clinical data, and antidepressant use; but only with longer REM sleep latency on PSG. During treatment, sleepiness, NSS scores, depressive symptoms decreased, as well as total sleep time, WB, SB, transitions. DNS improved in 55% of patients, without predictors except more baseline anxiety. Conclusion DNS complaint is frequent in NT1, associated with disease severity based on NSS, several PSG parameters, and objective sleepiness in untreated and treated conditions. DNS improves with treatment. We advocate the systematic assessment of this symptom and its inclusion in NT1 management strategy.

ObjectivesTo highlight the slow-wave sleep (SWS) fragmentation and validate the video-polysomnographic (vPSG) criteria and cutoffs for the diagnosis of disorders of arousal (DOA) in children, as already reported in adults.MethodsOne hundred children (66 boys, 11.0 ± 3.3 years) with frequent episodes of DOA and 50 nonparasomniac children (32 boys, 10.9 ± 3.9 years) underwent vPSG recording to quantify SWS characteristics (number of N3 sleep interruptions, fragmentation index, slow/mixed and fast arousal ratios, and indexes per hour) and associated behaviors. We compared SWS characteristics in the 2 groups and defined the optimal cutoff values for the diagnosis of DOA using receiver operating characteristic curves.ResultsPatients with DOA had higher amounts of N3 and REM sleep, number of N3 interruptions, SWS fragmentation, and slow/mixed arousal indexes than controls. The highest area under the curve (AUC) values were obtained for SWS fragmentation and slow/mixed arousal indexes with satisfactory classification performances (AUC 0.80, 95% confidence interval [CI] 0.73–0.87; AUC 0.82, 95% CI 0.75–0.89). SWS fragmentation index cutoff value of 4.1/h reached a sensitivity of 65.0% and a specificity of 84.0%. Slow/mixed arousal index cutoff of 3.8/h reached a sensitivity of 69.0% and a specificity of 82.0%. At least one parasomniac episode was recorded in 63.0% of patients and none of the controls. Combining behavioral component by vPSG increased sensitivity of both biomarkers to 83% and 89%, respectively.ConclusionsWe confirmed that SWS fragmentation and slow/mixed arousal indexes are 2 relevant biomarkers for the diagnosis of DOA in children, with different cutoffs obtained than those validated in adults.Classification of EvidenceThis study provides Class III evidence that SWS fragmentation and slow/mixed arousal indexes on vPSG accurately identify children with DOA.

ObjectivesTo assess the frequency and determinants of depressive symptoms and suicidal thoughts in adults with narcolepsy type 1 (NT1) and controls, as well as the changes after NT1 management and the risk factors of major depressive episode (MDE) and suicide risk (SR) in NT1.MethodsTwo hundred ninety-seven patients with NT1 (age 39 ± 17 years, 172 drug-free) and 346 controls (age 38 ± 16 years) underwent a comprehensive clinical evaluation including the Beck Depression Inventory-II (BDI-II) self-questionnaire, with 1 item on suicidal thoughts. One hundred one drug-free patients with NT1 completed the BDI-II a second time during treatment. In 162 patients with NT1, the face-to-face Mini International Neuropsychiatric Interview was performed to formally diagnose current MDE and SR.ResultsBDI-II total scores were higher in patients with NT1 than controls and in untreated than treated patients. Patients with moderate to severe BDI-II scores (24.9%) were less educated, were more frequently obese, and had more severe narcolepsy symptoms, more autonomic dysfunctions, and poorer quality of life. Results were unchanged in models adjusted for NT1 medication intake. Suicidal thoughts were more frequent in untreated patients than controls (22.7% vs 12.4%). Patients with suicidal thoughts were more likely to be men and to have more severe narcolepsy symptoms. After narcolepsy management, BDI-II total score and suicidal thoughts decreased. MDE was diagnosed in 29 (18.1%) and SR in 27 (16.9%) patients.ConclusionsDepression, depressive symptoms, suicidal thoughts, and SR were frequent in patients with NT1, especially those without treatment, and were associated with NT1 severity. Depressive symptoms and suicidal thoughts improved after NT1 management.

STUDY OBJECTIVES: To identify the most relevant clinical and video-polysomnographic characteristics of patients with sleep-related dissociative disorders (SRDDs) and to propose a framework for new diagnostic criteria. METHODS: We searched potential SRDD cases from the scientific literature and from a database of patients referred for clinical and video-polysomnographic assessment in a single sleep disorders center for disruptive nocturnal behaviors (n = 731). The most relevant clinical and neurophysiological characteristics of the cases were extracted and a descriptive analysis was performed. RESULTS: Twenty-six SRDD cases (8 new and 18 previously published cases) were reviewed. Almost all cases of SRDDs occurred in a context of past traumatic events or abuse and were associated with at least 1 comorbid psychiatric disorder. We highlighted 4 relevant clinical characteristics of SRDD useful for the differential diagnosis with parasomnias: episodes of long duration of more than 1 hour (90.9%), self-inflicted injuries (83.3%), occurrence while awake close to bedtime (35.7%), and the presence of daytime dissociative symptoms (72.7%). The video-polysomnography documented typical episodes of SRDD with prolonged wakefulness before, during, and after the event in 11/26 cases. New diagnostic criteria for SRDD were proposed, with 3 levels of certainty for the diagnosis based on clinical, video-polysomnographic, and homemade video findings. CONCLUSIONS: More than 30 years after its formal identification, SRDD is not currently recognized as an official diagnostic entity. We better delineate the clinical and neurophysiological features of SRDD and propose a framework for its reinstatement in the next revisions of the sleep and psychiatric disorders classifications. CITATION: Lopez R, Lefevre L, Barateau L, Micoulaud-Franchi J-A, Dauvilliers Y, Schenck CH. A series of 8 cases of sleep-related psychogenic dissociative disorders and proposed updated diagnostic criteria. J Clin Sleep Med. 2022;18(2):563–573.

Background and ObjectivesTo explore the first coronavirus disease 2019 (COVID-19) lockdown effect on sleep symptoms in patients with narcolepsy, idiopathic hypersomnia (IH), and restless legs syndrome (RLS).MethodsBetween March and May 2020, a sample of adult patients regularly followed up in a Reference Hospital Sleep Unit (299 with narcolepsy, 260 with IH, and 254 with RLS) was offered an online survey assessing their sleep-wake habits, daily activities, medication intake, and validated scales: International RLS Study Group questionnaire, Narcolepsy Severity Scale (NSS), IH Severity Scale (IHSS), Epworth Sleepiness Scale (ESS), Insomnia Severity Index, Beck Depression Inventory–II, and European Quality of Life (QoL) scale. The survey was proposed once, and the questions were answered for the prelockdown (recall of the month before the confinement) and the lockdown (time of study) periods.ResultsOverall, 331 patients completed the survey (response rate 40.7%): 102 with narcolepsy, 81 with IH, and 148 with RLS. All patients reported later bedtimes, with reduced differences for time in bed (TIB) and total sleep time (TST) over 24 hours between weekdays and weekends. Patients with narcolepsy spent more TIB and increased TST overnight, with more daytime napping. They had more awakenings, higher ESS scores, lower QoL, and no NSS changes. Patients with IH also increased their TIB, TST overnight and 24 hours on weekdays. Nocturnal sleep latency and the number of awakenings increased but with no change in ESS, QoL, and IHSS scores. Patients with RLS reported longer nocturnal sleep latency, more awakenings, more naps, decreased TIB, and TST overnight. RLS severity increased while QoL decreased. A significant portion of patients reported disease worsening during the lockdown (narcolepsy: 39.4%, IH: 43.6%, and RLS: 32.8%), and some patients stopped or lowered their medication (narcolepsy: 22.5%, IH: 28%, and RLS: 9.5%).DiscussionDuring the lockdown, all patients reported later bedtimes; those with narcolepsy and IH extended their sleep duration unlike patients with RLS. These changes were often associated with negative consequences on QoL. In the current context of recurrent COVID-19 waves, the recent development of teleconsultations should enable physicians to monitor patients with chronic sleep disorders more closely and to recommend optimized sleep schedules and duration, in order to prevent psychological problems and improve their QoL.

Whether depression and suicide thoughts relate to restless legs syndrome (RLS) or comorbidities associated with RLS remain unclear.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.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.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.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.

Study Objectives Sleep inertia is a frequent and disabling symptom in idiopathic hypersomnia (IH), but poorly defined and without objective measures. The study objective was to determine whether the psychomotor vigilance task (PVT) can reliably measure sleep inertia in patients with IH or other sleep disorders (non-IH). Methods A total of 62 (51 women, mean age: 27.7 ± 9.2) patients with IH and 140 (71 women, age: 33.3 ± 12.1) with non-IH (narcolepsy = 29, non-specified hypersomnolence [NSH] = 47, obstructive sleep apnea = 39, insomnia = 25) were included. Sleep inertia and sleep drunkenness in the last month (M-sleep inertia) and on PVT day (D-sleep inertia) were assessed with three items of the Idiopathic Hypersomnia Severity Scale (IHSS), in drug-free conditions. The PVT was performed four times (07:00 pm, 07:00 am, 07:30 am, and 11:00 am) and three metrics were used: lapses, mean 1/reaction time (RT), and slowest 10% 1/RT. Results Sleep inertia was more frequent in patients with IH than non-IH (56.5% and 43.6% with severe sleep inertia in the past month, including 24% and 12% with sleep drunkenness). Lapse number increase and slowest 10% 1/RT decrease, particularly at 07:00 am and 07:30 am, were proportional with M-sleep inertia severity, but regardless of sleep drunkenness and sleep disorders. Similar results were obtained when PVT results were compared in patients with/without D-sleep inertia, with the largest increase of the lapse number at 07:00 am and 07:30 am associated with severe sleep inertia and sleep drunkenness. Conclusions PVT is a reliable and objective measure of sleep inertia that might be useful for its characterization, management, and follow-up in patients with IH.

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

Study Objectives Sleep-related head jerks (SRHJ) are often considered as a physiological motor phenomenon, occurring mainly during rapid eye movement (REM) sleep. Their clinical relevance and links with other sleep parameters are unclear. We characterized the clinical and polysomnographic features of patients with excessive SRHJ and compare them with healthy controls and patients with isolated REM sleep behavior disorder (iRBD). Methods A total of 30 patients (19 males, 27.5 y.o., 16.0–51.0) with a REM-HJ index >30/h were identified over a period of 5 years. All had a video-polysomnographic (PSG) recording to characterize the SRHJ, to assess associations with other sleep parameters and to quantify phasic and tonic electromyographic activity during REM sleep, compared with 30 healthy controls and 30 patients with iRBD. Results Five among the 30 patients had a primary complaint of involuntary nighttime head movements associated with sleepiness or non-restorative sleep. The mean REM-HJ index was 57.22/h ± 24.42, a nonperiodic pattern, stable across the sleep cycles, and with a low between-test variability (for the nine patients with two PSG assessments in untreated condition). REM-HJs were often associated with arousals (65.2%) and leg movements (38.1%) and less with respiratory events (9.6%), without association with increased phasic and tonic electromyographic activities. SRHJ were also found in 36.7% of controls and 56.7% of iRBD patients, but with a lower index in REM sleep (0.79/h ± 1.59 and 2.76/h ± 4.57). Conclusions Although SRHJ are frequent in the general population and with uncertain clinical significance, rare severe symptomatic forms should be individualized and eventually be categorized as a new sleep-related movement disorder, distinct from RBD and periodic leg movements.

International audience; 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.

Study Objectives Hypersomnolence, defined by excessive daytime sleepiness (EDS) or excessive quantity of sleep (EQS), has been associated with increased morbidity. The aim of this study was to determine the clinical and polysomnographic characteristics associated with EQS and EDS assessed objectively during extended polysomnography recording. Methods A total of 266 drug-free subjects (201 women; mean age: 26.5 years [16.08; 60.87]) underwent 32-h bed-rest polysomnography recording preceded by polysomnography and modified multiple sleep latency test (mMSLT). Participants were categorized according to their total sleep time (bed-rest TST ≥19 h, hypersomnia), objective EDS (mean sleep latency on MSLT ≤8 min), and self-reported EDS (Epworth sleepiness scale score >10) and EQS (≥9 h/24 h per week). Results Subjects with hypersomnia were often younger, with normal sleep architecture, high nighttime sleep efficiency, and severe objective EDS. No association with sex, body mass index, Epworth sleepiness scale, EQS, and depressive symptoms was detected. Subjects with objective EDS had less EQS, higher sleep efficiency, and increased hypersomnia. Discrepancies were observed between objective and self-reported measures of sleep duration and EDS. Finally, 71 subjects were identified who had objective hypersomnia and/or EDS, no medical and psychiatric conditions and normal polysomnography parameters, and therefore met the stringent criteria of idiopathic hypersomnia, an orphan disorder. Conclusions Sleep duration and EDS should be quantified using self-reported and objective measures in a controlled procedure to differentiate long sleepers, patients with hypersomnia, and patients with idiopathic hypersomnia. This will help to better understand their biology, to identify specific biomarkers, and to assess related health outcomes.

Study Objectives Whether the cause of daytime sleepiness in narcolepsy type 1 (NT1) is a direct consequence of the loss of orexin (ORX) neurons or whether low orexin reduces the efficacy of the monoaminergic systems to promote wakefulness is unclear. The neurobiology underlying sleepiness in other central hypersomnolence disorders, narcolepsy type 2 (NT2), and idiopathic hypersomnia (IH), is currently unknown. Methods Eleven biogenic amines including the monoaminergic neurotransmitters and their metabolites and five trace amines were measured in the cerebrospinal fluid (CSF) of 94 drug-free subjects evaluated at the French National Reference Center for Narcolepsy: 39 NT1(orexin-deficient) patients, 31 patients with objective sleepiness non orexin-deficient (NT2 and IH), and 24 patients without objective sleepiness. Results Three trace amines were undetectable in the sample: tryptamine, octopamine, and 3-iodothyronamine. No significant differences were found among the three groups for quantified monoamines and their metabolites in crude and adjusted models; however, CSF 5-hydroxyindoleacetic acid (5-HIAA) levels tended to increase in NT1 compared to other patients after adjustment. Most of the biomarkers were not associated with ORX-A levels, clinical or neurophysiological parameters, but a few biomarkers (e.g. 3-methoxy-4-hydroxyphenylglycol and norepinephrine) correlated with daytime sleepiness and high rapid eye movement (REM) sleep propensity. Conclusions We found no striking differences among CSF monoamines, their metabolites and trace amine levels, and few associations between them and key clinical or neurophysiological parameters in NT1, NT2/IH, and patients without objective sleepiness. Although mostly negative, these findings are a significant contribution to our understanding of the neurobiology of hypersomnolence in these disorders that remain mysterious and deserve further exploration.

Study Objectives Rhythmic movements (RMs) during sleep are frequent and often considered as benign in children. Disabling forms are diagnosed as RM disorder and may persist in adulthood. Whether RMs severely impact sleep architecture in patients with RM disorder remain unclear. We performed a case–control study to characterize the clinical and polysomnographic patterns of children and adults with a diagnosis of RM disorder in comparison to controls, and to assess the associations between the RMs and the sleep architecture. Methods All consecutive patients (n = 50; 27 children, 35 males) with RM disorder from a single sleep clinic (from 2006 to 2019) underwent a comprehensive clinical evaluation and a polysomnographic recording in comparison to 75 controls (42 children and 53 males). Results About 82% of children and adult patients had a complaint of disturbed nighttime sleep. Comorbid neurodevelopmental, affective or sleep disorders were found in 92% of patients. While RM sequences defined by video polysomnographic criteria were observed in 82% of patients (in wakefulness and in all sleep stages), no similar sequences were observed in controls. Patients had altered sleep continuity, with low sleep efficiency, increased wake time after sleep onset, and frequent periodic leg movements and apnea events. The severity of RMs was associated with disrupted nighttime sleep, even after controlling for comorbid motor and respiratory events. Conclusions RM disorder is a rare, highly comorbid and disabling condition both in children and adults with frequent disturbed nighttime sleep that may contribute to the burden of the disease.

Study Objectives To define clinically relevant Narcolepsy Severity Scale (NSS) score ranges, confirm its main performances and sensitivity to medications, and determine whether items need to be weighted. Methods One hundred and forty-three consecutive untreated and 238 treated adults with narcolepsy type 1 (NT1) completed the NSS, a 15-item self-administered questionnaire (score: 0–57) that assesses the severity and consequences of the five major narcolepsy symptoms such as daytime sleepiness, cataplexy, hallucinations, sleep paralysis, and disturbed nighttime sleep (DNS). They also completed the Epworth Sleepiness scale (ESS; daytime sleepiness), Beck Depression Inventory (BDI; depressive symptoms), and EQ5D (quality of life). Results The mean symptom number (4.3 vs 3.5), NSS total score (33.3 ± 9.4 vs 24.3 ± 10.2), and number of narcolepsy symptoms (five symptoms: 53.1% vs 24.8%; four symptoms: 26.6% vs 22.7%; three symptoms: 15.4% vs 32.4%; two symptoms: 4.9% vs 20.2%) were significantly different between untreated and treated patients (p < 0.0001). DNS was often the third symptom (95.5 per cent). The symptom number was associated with diagnosis delay, age at onset, and ESS and BDI scores. Comparisons with ESS, BDI and EQ5D showed that NSS item weighting was not necessary to highlight between-group differences. Four NSS severity levels were defined (mild, moderate, severe, and very severe) with between-group differences related to treatment. The probability of having ESS ≥ 16, BDI ≥ 20, and EQ-5D < 60 increased with the severity level. Conclusion NSS is valid, reliable, and responsive to treatment in patients with NT1, with four clinically relevant severity score ranges provided. NSS has adequate clinimetric properties for broadening its use for both clinic and research.

ObjectiveTo evaluate the associations between CSF orexin-A (ORX) levels and markers of nocturnal sleep stability, assessed by polysomnography.MethodsNocturnal polysomnography data and ORX levels of 300 drug-free participants (55% men, 29.9±15.5 years, ORX level 155.1±153.7 pg/mL) with hypersomnolence were collected. Several markers of nocturnal sleep stability were analyzed: sleep and wake bouts and sleep/wake transitions. Groups were categorized according to ORX levels, in 2 categories (deficient ≤110; >110), in tertiles (≤26, 26–254, >254), and compared using logistic regression models. Results were adjusted for age, sex, and body mass index.ResultsWe found higher number of wake bouts (43 vs 25, p < 0.0001), sleep bouts (43 vs 25.5, p < 0.0001), and index of sleep bouts/hour of sleep time, but lower index of wake bouts/hour of wake time (41.4 vs 50.6, p < 0.0001), in patients with ORX deficiency. The percentage of wake bouts p < 0.001) and of wake bouts ≥1 minutes 30 seconds higher (7.7% vs 6.7%, p = 0.02) when ORX deficient. The percentage of sleep bouts ≤14 minutes was higher (2–5 minutes: 23.7% vs 16.1%, p < 0.0001), and of long sleep bouts lower (>32 minutes 30 seconds: 7.3% vs 18.3%, p < 0.0001), when ORX deficient. These findings were confirmed when groups were categorized according to ORX tertiles, with a dose–response effect of ORX levels in post hoc comparisons, and in adjusted models.InterpretationThis study shows an association between ORX levels and nocturnal sleep stabilization in patients with hypersomnolence. Sleep and wake bouts are reliable markers of nighttime sleep stability that correlate with CSF ORX levels in a dose-dependent manner.

International audience; Background: Despite cognitive-behavioral therapy for insomnia (CBT-I) being the recommended treatment for insomnia disorder, its access remains very limited. Automated Internet-delivered CBT-I (eCBT-I) is an emerging cost-effective strategy for adults with insomnia, however no such program is currently available in French Language. We evaluated a French-speaking, eCBT-I intervention to improve insomnia disorder in comparison to minimal psychoeducation therapy (mPT). Methods: Forty-six adults with insomnia disorder were randomly allocated to eCBT-I or mPT. The eCBT-I program consisted of seven sessions that delivered the typical components of CBT-I during 12 weeks. The mPT provided structured and non-tailored information about sleep and insomnia during a 1 h session. Insomnia severity Index (ISI, primary outcome), measures of fatigue, sleepiness, anxiety, depressive symptoms and quality of life were collected at baseline and endpoint. Electronic sleep diaries were completed over 2 week periods pre- and post-intervention. Results: Compared to mPT, eCBT-I resulted in greater decrease in ISI scores between baseline and endpoint. Sleep diaries parameters improved in both groups, with a greater improvement in the eCBT-I group. Patients allocated to eCBT-I group also improved depressive, fatigue, anxiety symptoms, and quality of life. Among patients with CNS-active drug at baseline, 91.7% reduced or stopped their hypnotic medication, and 16.7% in the mPT group. Conclusions: The present eCBT-I program seems feasible, acceptable and effective in reducing insomnia severity and insomnia-related functional outcomes in this small clinically-derived population. Given the high prevalence of insomnia, our data are supportive of the use of such program as an effective alternative to treat insomnia in daily clinical practice in French speaking countries.

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.

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.

Objectif Etudier et comparer les profils tensionnels de patients atteints de narcolepsie de type 1 (NT1), de type 2 (NT2), et d’hypersomnie idiopathique (HI). Methodes Un total de 287 patients adultes consecutifs non traites (153NT1, 40NT2, 94HI) ont beneficie d’une evaluation clinique, biologique, polysomnographique et d’une mesure ambulatoire de la pression arterielle (PA) sur 24 h. Le dipping est defini par une baisse > 10 % de la PA entre la nuit et le jour. Resultats Les NT1 etaient plus âges, avec un IMC plus eleve, et prenaient plus d’antihypertenseurs. Les HI etaient plus souvent des femmes. Les PA systoliques (PAS) la journee, la nuit, et sur les 24 h etaient plus elevees chez les NT1 que les HI, sans difference NT1/NT2. La PA diastolique (PAD) la nuit etait plus elevee chez les NT1 que chez les HI, sans difference NT1/NT2. Les frequences cardiaques etaient plus basses la journee, la nuit, et sur les 24 h chez les NT1 que chez les HI, sans difference NT1/NT2. La frequence de non-dippers n’etait pas differente entre les groupes. Le profil de non-dipper sur la PAS et la PAD etait associe au sexe masculin, a la presence de SOREMP nocturne, et a plus d’apnees et de mouvements periodiques. Il n’y avait pas d’association avec le diagnostic, l’âge, l’IMC, la severite de la somnolence, l’efficacite de sommeil, les reactions d’eveil, l’index de severite de l’insomnie, ni les taux d’orexine. Conclusion Les patients atteints d’hypersomnolence d’origine centrale ont une dysregulation du profil tensionnel sur 24 h, en particulier nocturne ; qu’il faudra d’autant plus surveiller qu’ils seront traites au long court par psychostimulants.

Hypersomnolence is a clinically defined syndrome characterized by the association of prolonged nocturnal sleep, impaired arousal quality, and sleep inertia. Hypersomnolence is the major feature of central hypersomnias and is frequently reported in various mood disorders, such as major depressive disorder, bipolar disorder, or seasonal affective disorder. Assessment of hypersomnolence is challenging in depressed patients, with objective tests often in the normal range despite a high level of sleepiness complaint. On the other hand, many patients with central hypersomnias reported depressive symptoms. The self-assessment of mood symptoms in patients with central hypersomnias may overdiagnose depression with an overlap between both conditions.

Objectif Decrire les caracteristiques cliniques et polysomnographiques (PSG) d’enfants et d’adultes presentant un trouble des mouvements rythmiques du sommeil (TMR) en comparaison a des sujets sains. Methodes Cinquante patients avec TMR (23 enfants) ont beneficie d’une evaluation clinique detaillee et d’une PSG. Les caracteristiques PSG etaient comparees a celles de 75 sujets temoins apparies en âge et sexe (41 enfants). Resultats Les patients avec TMR rapportaient des plaintes de mauvais sommeil de nuit (82 %) et de fatigue/somnolence (80 %). Un total de 43,2 % avaient une histoire familiale de rythmies, 46 % des troubles neurodeveloppementaux, et 32 % un syndrome des jambes sans repos (SJSR). 82 % des patients ont presente au moins un episode de rythmies en vPSG (mediane 28, de 1 a 381 episodes), sans differences sur les caracteristiques des rythmies chez les enfants et les adultes. Comparativement aux temoins, les patients presentaient un index apnees-hypopnees (IAH), de mouvements periodiques (IMP) plus eleve, une augmentation de la latence d’endormissement, de la veille intrasommeil, des micro-eveils, et une plus faible efficacite de sommeil. Ces parametres etaient correles a diverses caracteristiques cliniques des rythmies apres ajustement pour l’âge, l’IAH, l’IMP et le SJSR. Conclusion Les TMR s’associent a des alterations du sommeil de nuit, en lien avec des troubles du sommeil associes d’une part, et avec la severite des rythmies, d’autre part. Une evaluation PSG de ce trouble potentiellement severe est requise pour une guider une prise en charge souvent multimodale.

Objectif Explorer les liens entre les taux d’orexine(ORX) dans le liquide cephalo-rachidien et des marqueurs de fragmentation du sommeil nocturne a la polysomnographie(PSG). Methodes Les PSG de 300 sujets non traites (45 % F, 30 ± 16 ans, ORX 155 ± 154 pg/mL) ont ete analysees. Les marqueurs etudies etaient : les Wake Bouts (WB) (sequence continue d’epoques de veille apres endormissement), Sleep Bouts (SB) (sequence continue d’epoques de sommeil), et transitions veille/sommeil. Les sujets ont ete categorises en fonction de l’ORX : en tertiles (≤ 26, [26 ;254], > 254 pg/mL) et en 2 categories (110 pg/mL) ; et compares par des modeles de regression logistiques ; les resultats ajustes sur âge, sexe et IMC. Resultats Les sujets dans le tertile d’ORX bas avaient plus de transitions, et un nombre de WB plus eleve que ceux dans les tertiles moyen et haut, avec un effet dose (45,33,25, p 2 min) qui augmentaient (9.6,10.4,13.4 %, p = 0.0001). Le nombre de SB augmentait quand l’ORX diminuait (26,34,45, p Conclusion Cette etude objective l’effet direct de l’ORX sur la stabilisation du sommeil. Les SB et WB sont des biomarqueurs de la fragmentation du sommeil, fortement correles aux taux d’ORX, avec un effet dose-dependant.

Objective To investigate the relationship between sensory discomfort/motor component and cardiovascular autonomic response by continuous beat-to-beat blood pressure monitoring (CBPM) during the suggested immobilization test (SIT) in patients with restless legs syndrome (RLS). Methods Thirty-two drug-free patients with primary RLS (10 men; mean age 60.29 ± 10.81 years) and 17 healthy controls (2 men; mean age 58.82 ± 11.86 years) underwent a 1-hour SIT starting at 8 pm with concomitant CBPM to measure the heart rate (HR) and systolic/diastolic blood pressure (SBP, DBP). In all subjects, the presence of sensory discomfort and motor component during the SIT (S-SIT+ and M-SIT+, respectively) was quantified. Mixed regression models were used to compare the SBP, DBP, and HR profiles during the SIT by taking into account the repeated measures (6 time periods of 10 minutes). Results In patients with S-SIT+ (n = 17), SBP (p < 0.0001), DBP (p = 0.0007), and HR (p = 0.03) increased during the SIT compared with other patients and controls. Seventeen patients had M-SIT+ (none among healthy controls). Classifying patients in 4 groups in function of the presence/absence of the SIT sensory and motor components revealed that SDB and DBP increased throughout the SIT in patients with S-SIT+, independently of the motor component (p < 0.0001 and p = 0.0008 for SBD; p < 0.0001 and p = 0.01 for DBP in the S-SIT+/M-SIT− and S-SIT+/M-SIT+ groups, respectively). Conclusion During the SIT, BP concomitantly increased only in patients with RLS and sensory discomfort, with or without motor component. This highlights the link between evening sensory RLS symptoms, autonomic activation, and potential long-term cardiovascular consequences.

Study Objectives(1) To compare the presence of autonomic symptoms using the validated SCOPA-AUT questionnaire in untreated patients with narcolepsy type 1 (NT1) to healthy controls, (2) to study the determinants of a high total SCOPA-AUT score in NT1, and (3) to evaluate the effect of drug intake on SCOPA-AUT results in NT1.MethodsThe SCOPA-AUT questionnaire that evaluates gastrointestinal, urinary, cardiovascular, thermoregulatory, pupillomotor, and sexual dysfunction was completed by 92 consecutive drug-free adult NT1 patients (59 men, 39.1 ± 15.6 years old) and 109 healthy controls (63 men, 42.6 ± 18.2 years old). A subgroup of 59 NT1 patients completed the questionnaire a second time, under medication (delay between two evaluations: 1.28 ± 1.14 years).ResultsCompared to controls, NT1 patients were more frequently obese, had more dyslipidemia, with no difference for age and gender. The SCOPA-AUT score of NT1 was higher than in controls in crude and adjusted models. Patients experienced more problems than controls in all subdomains. A higher score in NT1 was associated with older age, longer disease duration, altered quality of life and more depressive symptoms, but not with orexin levels and disease severity. Among patients evaluated twice, the SCOPA-AUT score total did not differ according to treatment status, neither did each subdomain.ConclusionWe captured a frequent and large spectrum of clinical autonomic dysfunction in NT1, with impairment in all SCOPA-AUT domains, without key impact of medication intake. This assessment may allow physicians to screen and treat various symptoms, often not spontaneously reported but associated with poor quality of life.

ObjectiveTo validate the Idiopathic Hypersomnia Severity Scale (IIHSS), a self-report measure of hypersomnolence symptoms, consequences, and responsiveness to treatment.MethodsThe 14-item IHSS (developed and validated by sleep experts with patients' feedback) was filled in by 218 participants (2.3% missing data). Among the 210 participants who fully completed the IHSS, there were 57 untreated and 43 treated patients with idiopathic hypersomnia (IH) aged 16 years or older, 37 untreated patients with narcolepsy type 1 (NT1), and 73 controls without sleepiness. IHSS psychometric properties, discriminant diagnostic validity, and score changes with treatment were assessed.ResultsThe IHSS showed good internal consistency and content validity. Factor analysis indicated a 2-component solution with good reliability expressed by satisfactory Cronbach α values. IHSS scores were reproducible without changes in the test–retest evaluation (13 treated and 14 untreated patients). Convergent validity analysis showed that IHSS score was correlated with daytime sleepiness, depressive symptoms, and quality of life in patients with IH. The IHSS score was lower in treated than untreated patients (5–8 unit difference, without ceiling effect). The cutoff value for discriminating between untreated and treated patients was 26/50 (sensitivity 55.8%, specificity 78.9%). IHSS scores were higher in drug-free IH patients than NT1 and controls. The best cutoff value to differentiate between untreated IH patients and controls was 22 (sensitivity 91.1%, specificity 94.5%), and 29 with NT1.ConclusionsThe IHSS is a reliable and valid clinical tool for the quantification of IH symptoms and consequences that might be useful for patient identification, follow-up, and management.