Search Results (7)

Background/Objectives: There is limited data on well-documented comorbidities with polysomnography (PSG)/multiple sleep latency test (MSLT) findings in idiopathic hypersomnia (IH). We aimed to characterize the clinical, PSG/MSLT characteristics of IH patients in our health network. Methods: We reviewed charts of all IH cases between 2000 and 2023, extracting clinical features, comorbidities, and PSG/MSLT findings. Results: One hundred forty-two patients (83.80% female) with IH were included. Compared to those without mood disorders, both major depressive disorder (MDD) and anxiety patients were older at onset (27.10 ± 8.32 and 26.76 ± 8.40 versus 23.23 ± 6.94 and 24.05 ± 7.31 years; p = 0.003 and p = 0.042) and had lower ESS (15 versus 19; 15.67 versus 17.75; p < 0.0001), more disrupted sleep (28 (36.36%) versus 8 (12.31%); p = 0.001; 24 (35.82%) versus 12 (16%); p = 0.007), and less sleep inertia (30 (38.96%) versus 38 (58.46%); p = 0.021; 26 (38.81%) versus 42 (56%); p = 0.04). Fifteen patients with dysautonomia disorders presented at an earlier age (21.80 ± 6.60 versus 25.75 ± 8, p = 0.0682). On MSLT, MDD, anxiety, and dysautonomia patients had longer sleep latencies than the non-affected counterparts (6.40 (5.40–7.60) minutes versus 3.60 (2.60–5.40) min., <0.0001; 6.20 (5.20–7.40) versus 4 (2.60–6.40) minutes; p < 0.0001; 7.40 (6–7.80) versus 5.40 (3–7); p = 0.008). MDD and anxiety cases had fewer sleep onset REM periods (7 (9.09%) versus 16 (24.62%), p = 0.0124 and 6 (8.96%) versus 17 (22.67%), p = 0.0388) compared to those not affected by these disorders. Conclusions: Our study highlights the importance of recognizing mood disorders and dysautonomia in patients diagnosed with IH. Further research may elucidate management strategies for these patients. Full article

Orexin plays a significant role in the modulation of REM sleep, as well as in the regulation of appetite and feeding. This review explores, first, the current evidence on the role of orexin in the modulation of sleep and wakefulness and highlights that orexin should be considered essentially as a neurotransmitter inhibiting REM sleep and, to a much lesser extent, a wake promoting agent. Subsequently, the relationship between orexin, REM sleep, and appetite regulation is examined in detail, shedding light on their interconnected nature in both physiological conditions and diseases (such as narcolepsy, sleep-related eating disorder, idiopathic hypersomnia, and night eating syndrome). Understanding the intricate relationship between orexin, REM sleep, and appetite regulation is vital for unraveling the complex mechanisms underlying sleep-wake patterns and metabolic control. Further research in this field is encouraged in order to pave the way for novel therapeutic approaches to sleep disorders and metabolic conditions associated with orexin dysregulation. Full article

Background: The clinical evaluation of a patient complaining of excessive daytime sleepiness is of crucial importance for the diagnosis of narcolepsy. The Swiss Narcolepsy Scale (SNS) was developed in 2004 as a screening tool for patients with narcolepsy and shown in three different studies to have a high sensitivity and specificity for narcolepsy type 1 (NT1). The aim of this study was to assess the validity and reliability of the Turkish version of SNS (SNS-TR). Patients and Methods: Twenty-one healthy controls, 26 patients with idiopathic hypersomnia, and 27 patients with narcolepsy were recruited from five accredited sleep centers in Turkey. Pearson’s correlation coefficient and degree of freedom were used to determine the validity of each question. Cronbach’s alpha was calculated to assess the internal consistency or reliability of Likert-type questions. The inter-rater reliability was tested using Cohen’s kappa analysis, and the intra-class correlation coefficient (ICC) was used to evaluate the validity and reliability between two evaluations with a one-month interval. Results: Sensitivity and specificity of SNS-TR were 90.5% and 100%, respectively, for diagnosing NT1. Cronbach’s alpha was 0.976, showing a highly reliable level of internal consistency. The inter-rater reliability of the questions and the validity and reliability between two evaluations were moderate or above. Conclusion: This study provides evidence for the validity and reliability of SNS-TR in diagnosing and discriminating NT1 from other disorders of hypersomnolence with a very high sensitivity and specificity. Full article

GABA_A receptor-positive modulators are well-known to induce sedation, sleep, and general anesthesia. Conversely, GABA_A receptor negative allosteric modulators (GABA_ARNAMs) can increase arousal and induce seizures. Motivated by our studies with patients with hypersomnia, and our discovery that two GABA_ARNAMs can restore the Excitation/Inhibition (E/I) balance in vitro and arousal in vivo, we chose to screen 11 compounds that have been reported to modulate arousal, to see if they shared a GABA-related mechanism. We determined modulation with both conventional and microfluidic patch clamp methods. We found that receptor activation was variably modulated by all 11 compounds: Rifampicin (RIF), Metronidazole (MET), Minocycline (MIN), Erythromycin (ERY), Ofloxacin (OFX), Chloroquine (CQ), Hydroxychloroquine sulfate (HCQ), Flumazenil (FLZ), Pentylenetetrazol (PTZ), (-)-Epigallocatechin Gallate (EGCG), and clarithromycin (CLR). The computational modeling of modulator–receptor interactions predicted drug action at canonical binding sites and novel orphan sites on the receptor. Our findings suggest that multiple avenues of investigation are now open to investigate large and brain-penetrant molecules for the treatment of patients with diminished CNS E/I balance. Full article

Fatigue, depression, and sleep inertia are frequently underdiagnosed manifestations in narcolepsy and idiopathic hypersomnia. Our cross-sectional study design included diagnostic interview accompanied by assessment instruments and aimed to explore how these factors influence disease severity as well as to elucidate any sex predisposition. One hundred and forty-eight subjects (female 63%) were divided into narcolepsy type 1 (NT1; n = 87, female = 61%), narcolepsy type 2 (NT2; n = 22, female = 59%), and idiopathic hypersomnia (IH; n = 39, female = 69%). All subjects completed a set of questionnaires: Epworth Sleepiness Scale (ESS), Hospital Anxiety and Depression Scales (HADS), Fatigue Severity Scale (FSS), and Sleep Inertia Questionnaire (SIQ). In narcoleptic subjects, questionnaire data were correlated with the Narcolepsy Severity Scale (NSS), and in subjects with idiopathic hypersomnia, with the Idiopathic Hypersomnia Severity Scale (IHSS). The highest correlation in narcoleptic subjects was found between NSS and ESS (r = 0.658; p < 0.0001), as well as FSS (r = 0.506; p < 0.0001), while in subjects with idiopathic hypersomnia, the most prominent positive correlations were found between IHSS and SIQ (r = 0.894; p < 0.0001), FSS (r = 0.812; p < 0.0001), HADS depression scale (r = 0.649; p = 0.0005), and HADS anxiety scale (r = 0.528; p < 0.0001). ESS showed an analogic correlation with disease severity (r = 0.606; p < 0.0001). HADS anxiety and depression scores were higher in females (p < 0.05 and p < 0.01), with similar results for FSS and SIQ scales (p < 0.05 for both), and a trend toward higher ESS values in females (p = 0.057). Our study illustrates that more attention should be focused on pathophysiological mechanisms and associations of fatigue, depression, as well as sleep inertia in these diseases; they influence the course of both illnesses, particularly in women. Full article

Narcolepsy types 1 (NT1) and 2 (NT2) and idiopathic hypersomnia (IH) are thought to be a disease continuum known as narcolepsy spectrum disorders (NSDs). This study aimed to assess the prevalence of and factors associated with metabolic-syndrome-related disorders (MRDs) among patients with NSD. Japanese patients with NSD (NT1, n = 94; NT2, n = 83; and IH, n = 57) aged ≥35 years were enrolled in this cross-sectional study. MRD was defined as having at least one of the following conditions: hypertension, diabetes, or dyslipidemia. Demographic variables and MRD incidence were compared among patients in the respective NSD categories. Multivariate logistic regression analysis was used to investigate the factors associated with MRDs. Patients with NT1 had a higher body mass index (BMI) and incidence of MRD than that had by those with NT2 or IH. Age, BMI, and the presence of OSA were significantly associated with the incidence of MRD in NSDs. Age and BMI in NT1, BMI and human leukocyte antigen (HLA)-DQB1*06:02 positivity in NT2, and only age in IH were factors associated with the incidence of MRD. Obesity should be carefully monitored in narcolepsy; however, NT2 with HLA-DQB1*06:02 positive should be followed up for the development of MRD even without obesity. Full article

Introduction: Narcolepsy is a chronic neurological sleep disorder, the diagnosis of which is based upon clinical evaluation and additional paraclinical assessments. Awareness of narcolepsy is low and screening tools needed. The Epworth Sleepiness Scale (ESS), the Ullanlinna Narcolepsy Scale (UNS), and more recently the Swiss Narcolepsy Scale (SNS) were used as screening tools for narcolepsy. The aims of the present study are (1) to assess the value of the SNS in a new series of patients with narcolepsy with cataplexy (NC), and (2) to compare its sensitivity and specificity with the ESS and UNS. Patients and Methods: We prospectively assessed by questionnaire patients with NC (n = 80, all with assessment of cerebrospinal fluid (CSF) hypocretin-1 levels) and patients with excessive daytime sleepiness (EDS) of other origin (n = 111) in Zurich and Leiden. Causes of EDS included idiopathic hypersomnia (n = 12), behaviorally induced sleep insufficiency syndrome (n = 32), restless legs syndrome (n = 7), sleep-disordered breathing (n = 22), and hypersomnia due to medical disorders (n = 9). Diagnoses were made according to the International Classification of Sleep Disorders (third edition). Cutoff values of UNS and SNS for diagnosis of narcolepsy were those suggested in the literature. Results: For the diagnosis of narcolepsy, the following sensitivities and specificities were found: SNS (89% and 88%), UNS (100% and 62%), and ESS (91% and 54%). For the diagnosis of narcolepsy with low or non-detectable CSF hypocretin-1, the sensitivities and specificities were: SNS (93% and 88%), UNS (100% and 62%), and ESS (93% and 54%). Discussion: In conclusion, the SNS is accurate and superior to the ESS and the UNS for the screening/diagnosis of NC and allows, in addition, the identification of hypocretin-1 deficient patients. Full article