OBJECTIVE: To date, very few studies have focused on structural changes and their association with cognitive performance in isolated REM sleep behaviour disorder (iRBD). Moreover, the results of these studies are inconclusive. This study aims to evaluate differences in the associations between brain morphology and cognitive tests in iRBD and healthy controls. METHODS: Sixty-three patients with iRBD and thirty-six controls underwent MRI with a 3 T scanner. The cognitive performance was assessed by a comprehensive neuropsychological battery. Based on performance, the iRBD group was divided into two subgroups with (iRBD-MCI) and without mild cognitive impairment (iRBD-NC). The high-resolution T1-weighted images were analysed using an automated atlas segmentation tool, voxel-based (VBM) and deformation-based (DBM) morphometry to identify between-group differences and correlations with cognitive performance. RESULTS: VBM, DBM and the comparison of ROI volumes yielded no significant differences between iRBD and controls. In the iRBD group, significant correlations in VBM were found between several cortical and subcortical structures primarily located in the temporal, parietal, occipital lobe, cerebellum, and basal ganglia and three cognitive tests assessing psychomotor speed and one memory test. Between-group analysis of cognition revealed a significant difference between iRBD-MCI and iRBD-NC in tests including a processing speed component. CONCLUSIONS: iRBD shows deficits in several cognitive tests that correlate with morphological changes, the most prominent of which is in psychomotor speed and visual attention as measured by the TMT-A and associated with the volume of striatum, insula, cerebellum, temporal lobe, pallidum and amygdala.
Little attention has been paid to the long-term development of idiopathic hypersomnia symptoms and idiopathic hypersomnia comorbidities. The aim of this study was to describe the general health of patients with idiopathic hypersomnia years after the initial diagnosis, focusing on current subjective hypersomnolence and the presence of its other possible causes. Adult patients diagnosed with idiopathic hypersomnia ≥ 3 years ago at sleep centres in Prague and Kosice were invited to participate in this study. A total of 60 patients were examined (age 47.3 ± SD = 13.2 years, 66.7% women). In all participants, their hypersomnolence could not be explained by any other cause but idiopathic hypersomnia at the time of diagnosis. The mean duration of follow-up was 9.8 + 8.0 years. Fifty patients (83%) reported persisting hypersomnolence, but only 33 (55%) had no other disease that could also explain the patient's excessive daytime sleepiness and/or prolonged sleep. In two patients (3%), the diagnosis in the meantime had changed to narcolepsy type 2, and 15 patients (25%) had developed a disease or diseases potentially causing hypersomnolence since the initial diagnosis. Complete hypersomnolence resolution without stimulant treatment lasting longer than 6 months was reported by 10 patients (17%). To conclude, in a longer interval from the diagnosis of idiopathic hypersomnia, hypersomnolence may disappear or may theoretically be explained by another newly developed disease, or the diagnosis may be changed to narcolepsy type 2. Thus, after 9.8 years, only 55% of the examined patients with idiopathic hypersomnia had a typical clinical picture of idiopathic hypersomnia without doubts about the cause of the current hypersomnolence.
- MeSH
- dospělí MeSH
- idiopatická hypersomnie * diagnóza epidemiologie farmakoterapie MeSH
- komorbidita MeSH
- lidé středního věku MeSH
- lidé MeSH
- narkolepsie * diagnóza epidemiologie MeSH
- poruchy nadměrné spavosti * diagnóza epidemiologie komplikace MeSH
- pozornost MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- polysomnografie přístrojové vybavení MeSH
- poruchy spánku a bdění * diagnóza komplikace MeSH
- Publikační typ
- novinové články MeSH
- rozhovory MeSH
Narcolepsy type 1 (NT1) is caused by a loss of hypocretin/orexin transmission. Risk factors include pandemic 2009 H1N1 influenza A infection and immunization with Pandemrix®. Here, we dissect disease mechanisms and interactions with environmental triggers in a multi-ethnic sample of 6,073 cases and 84,856 controls. We fine-mapped GWAS signals within HLA (DQ0602, DQB1*03:01 and DPB1*04:02) and discovered seven novel associations (CD207, NAB1, IKZF4-ERBB3, CTSC, DENND1B, SIRPG, PRF1). Significant signals at TRA and DQB1*06:02 loci were found in 245 vaccination-related cases, who also shared polygenic risk. T cell receptor associations in NT1 modulated TRAJ*24, TRAJ*28 and TRBV*4-2 chain-usage. Partitioned heritability and immune cell enrichment analyses found genetic signals to be driven by dendritic and helper T cells. Lastly comorbidity analysis using data from FinnGen, suggests shared effects between NT1 and other autoimmune diseases. NT1 genetic variants shape autoimmunity and response to environmental triggers, including influenza A infection and immunization with Pandemrix®.
- MeSH
- autoimunita genetika MeSH
- autoimunitní nemoci * epidemiologie genetika MeSH
- chřipka lidská * epidemiologie genetika MeSH
- lidé MeSH
- narkolepsie * chemicky indukované genetika MeSH
- vakcíny proti chřipce * škodlivé účinky MeSH
- virus chřipky A, podtyp H1N1 * genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
Cíl: Studie si kladla za cíl ověřit vhodnost použití Škály tíže narkolepsie (Narcolepsy Severity Scale; NSS) jako základního klinického nástroje pro stanovení subjektivní tíže onemocnění u pacientů s narkolepsií typu 1 (NT1) v ČR. Soubor a metodika: Celkem 78 pacientů ze 2 spánkových center s diagnózou NT1 (29 mužů, 49 žen, průměrný věk 36,1 ± 11,7 let, rozmezí 18–71 let, z toho léčených n = 51) vyplnilo škálu NSS sestávající z 15 otázek zaměřených na výskyt, frekvenci a dopad na denní aktivity všech hlavních narkoleptických příznaků. Současně byli instruováni vyplnit Epworthskou škálu spavosti (Epworth Sleepiness Scale; ESS), Škálu tíže únavy (Fatigue Severity Scale; FSS), Škálu hodnocení úzkosti a deprese při hospitalizaci (Hospital Anxiety and Depression Rating Scale; HADS) a zkrácenou verzi Dotazníku kvality života (Quality of Life Questionnaire; SF-36). Výsledky: Škála NSS vykazuje dobrou vnitřní konzistenci dotazníku pomocí koeficientu Cronbachova a, která je pro celou kohortu pacientů s NT1 0,80, pro skupinu léčených pacientů 0,79 a pro skupinu neléčených pacientů 0,82. Keiser-Meyer-Olkinův index pro celou kohortu je 0,73, což potvrzuje dostatečnou strukturální validitu dotazníku. Nebyl zjištěn signifikantní rozdíl ve skóre NSS léčených a neléčených pacientů, nicméně byla potvrzena korelace celkového skóre NSS s ESS (ρ = 0,61; p < 0,0001) a FSS (ρ = 0,4438; p < 0,0001). Závěr: NSS představuje vhodný a snadno aplikovatelný klinický nástroj ke stanovení subjektivní tíže onemocnění, dobře vystihuje hlavní narkoleptické příznaky a hodnotí jejich vliv na denní aktivity.
Aim: The aim of the study was to verify the applicability of the Narcolepsy Severity Scale (NSS) as a basic clinical tool for determining the subjective severity of the disease in patients with narcolepsy type 1 (NT1) in the Czech Republic. Patients and methods: A total of 78 patients from 2 sleep centers with a diagnosis of NT1 (29 men, 49 women, mean age 36.1 ± 11.7 years, range 18–71 years, N = 51 were treated) completed the NSS scale consisting of 15 questions focusing on the occurrence, frequency, and impact on daily activities of all major narcoleptic symptoms. At the same time, they were instructed to complete the Epworth Sleepiness Scale (ESS), the Fatigue Severity Scale (FSS), the Hospital Anxiety and Depression Rating Scale (HADS) and a short version of the Quality of Life Questionnaire (SF-36). Results: The NSS scale shows good internal consistency of the questionnaire using Cronbach‘s a, which is 0.80 for the whole cohort of NT1 patients, 0.79 for the treated group and 0.82 for the untreated group. The Keiser-Meyer-Olkin index for the entire cohort is 0.73, confirming sufficient structural validity of the questionnaire. There was no significant difference in the NSS scores of treated and untreated patients; however, the correlation of the total NSS score with ESS (ρ = 0.61; P < 0.0001) and FSS (ρ = 0.4438; P < 0.0001) was confirmed. Conclusions: The NSS is a convenient and practical clinical tool for determining the subjective severity of the disease, well capturing the main narcoleptic symptoms and assessing their impact on daily activities.
Rapid-eye movement (REM) sleep behavior disorder (RBD), enactment of dreams during REM sleep, is an early clinical symptom of alpha-synucleinopathies and defines a more severe subtype. The genetic background of RBD and its underlying mechanisms are not well understood. Here, we perform a genome-wide association study of RBD, identifying five RBD risk loci near SNCA, GBA, TMEM175, INPP5F, and SCARB2. Expression analyses highlight SNCA-AS1 and potentially SCARB2 differential expression in different brain regions in RBD, with SNCA-AS1 further supported by colocalization analyses. Polygenic risk score, pathway analysis, and genetic correlations provide further insights into RBD genetics, highlighting RBD as a unique alpha-synucleinopathy subpopulation that will allow future early intervention.
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.
- Publikační typ
- časopisecké články MeSH
PURPOSE: To report the efficacy and safety of lower-sodium oxybate (LXB; Xywav®) during the open-label titration and optimization period (OLT) and stable-dose period (SDP) in a clinical study for the treatment of idiopathic hypersomnia. PATIENTS AND METHODS: Data were collected during treatment titration and optimization in a phase 3 randomized withdrawal trial in adults (18-75 years of age) with idiopathic hypersomnia who took LXB treatment (once, twice, or thrice nightly, administered orally) in the OLT (10-14 weeks), followed by the 2-week, open-label SDP. Endpoints included the Epworth Sleepiness Scale (ESS), Idiopathic Hypersomnia Severity Scale (IHSS), Patient Global Impression of Change, Clinical Global Impression of Change, Functional Outcomes of Sleep Questionnaire (FOSQ)-10, and Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI:SHP). RESULTS: The safety population included 154 participants; the modified intent-to-treat population comprised 115 participants. During open-label treatment, mean (SD) ESS scores improved (decreased) from 15.7 (3.8) at baseline to 6.1 (4.0) at end of SDP, and IHSS scores improved (decreased) from 31.6 (8.3) to 15.3 (8.5). Improvements were also observed during OLT in each individual IHSS item and in FOSQ-10 and WPAI:SHP scores. Thirty-five (22.7%) participants discontinued during OLT and SDP, 22 (14.3%) due to treatment-emergent adverse events (TEAEs) during OLT and SDP. The most frequent TEAEs in the first 4 weeks were nausea, headache, dizziness, and dry mouth; TEAE incidence decreased throughout OLT and SDP (weeks 1-4, n = 87 [56.5%]; weeks 13-16, n = 39 [31.7%]). CONCLUSION: During open-label treatment with LXB, participants showed clinically meaningful improvements in idiopathic hypersomnia symptoms and in quality of life and functional measures. TEAE incidence declined over LXB titration and optimization.
- Publikační typ
- časopisecké články MeSH
- MeSH
- lidé MeSH
- nemoci nervového systému * komplikace MeSH
- poruchy spánku a bdění * etiologie komplikace MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- úvodní články MeSH
Trvalý přetlak v dýchacích cestách (CPAP) je efektivní léčba střední a těžké obstrukční spánkové apnoe (OSA), která zlepšuje symptomy OSA, snižuje zdravotní důsledky OSA a zlepšuje kvalitu života nemocného. Pro dosažení terapeutického efektu CPAP je nutná dostatečná compliance a správné nastavení CPAP. Tuto léčbu je vhodné doplnit dalšími metodami léčení OSA zejména redukcí hmotnosti. Princip CPAP byl popsán Colinem Sullivanem v roce 1981 a následně došlo k mnoha technickým zlepšením, která usnadňují jeho použití a zlepšují compliance. Objev CPAP je jedním z milníků moderní medicíny.
Continuous positive airway pressure (CPAP) is an effective treatment for moderate and severe obstructive sleep apnea (OSA) that improves OSA symptoms, reduces the health consequences of OSA, and improves the patient's quality of life. Sufficient compliance and proper CPAP settings are required to achieve the therapeutic effect of CPAP. This treatment should be supplemented with other methods of OSA treatment, especially weight reduction. The principle of CPAP was described by Colin Sullivan in 1981, and many technical improvements have subsequently been made to facilitate its application and improve compliance. The discovery of CPAP is one of the milestones of modern medicine.
