OBJECTIVE: This study assessed the relationship between speech and language impairment and outcome in a multicenter cohort of isolated/idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD). METHODS: Patients with iRBD from 7 centers speaking Czech, English, German, French, and Italian languages underwent a detailed speech assessment at baseline. Story-tale narratives were transcribed and linguistically annotated using fully automated methods based on automatic speech recognition and natural language processing algorithms, leading to the 3 distinctive linguistic and 2 acoustic patterns of language deterioration and associated composite indexes of their overall severity. Patients were then prospectively followed and received assessments for parkinsonism or dementia during follow-up. The Cox proportional hazard was performed to evaluate the predictive value of language patterns for phenoconversion over a follow-up period of 5 years. RESULTS: Of 180 patients free of parkinsonism or dementia, 156 provided follow-up information. After a mean follow-up of 2.7 years, 42 (26.9%) patients developed neurodegenerative disease. Patients with higher severity of linguistic abnormalities (hazard ratio [HR = 2.35]) and acoustic abnormalities (HR = 1.92) were more likely to develop a defined neurodegenerative disease, with converters having lower content richness (HR = 1.74), slower articulation rate (HR = 1.58), and prolonged pauses (HR = 1.46). Dementia-first (n = 16) and parkinsonism-first with mild cognitive impairment (n = 9) converters had higher severity of linguistic abnormalities than parkinsonism-first with normal cognition converters (n = 17). INTERPRETATION: Automated language analysis might provide a predictor of phenoconversion from iRBD into synucleinopathy subtypes with cognitive impairment, and thus can be used to stratify patients for neuroprotective trials. ANN NEUROL 2024;95:530-543.
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
OBJECTIVES: To analyze REM sleep without atonia (RWA) metrics in patients with isolated REM sleep behavior disorder (iRBD), Parkinson's disease (PD) and healthy subjects and compare them in terms of degree of presumed brainstem damage. METHODS: Forty-nine iRBD patients, 62 PD patients and 38 healthy controls were included into the analysis. Detailed polysomnographic and clinical data including motor, olfactory, autonomic, and cognitive assessment were obtained in all participants and subsequently compared within groups without RBD (i.e., healthy controls, PD-RBD-) and with RBD (i.e., iRBD, PD-RBD+). SINBAR criteria were used to score RWA. RESULTS: Twenty-one PD patients (33.8 %) had RBD. When comparing PD-RBD-patients and controls, RWA tonic (p = 0.001) and RWA mixed (p = 0.03) were higher in PD-RBD-group. PD-RBD-patients had worse olfactory function than controls (p < 0.001); no significant difference in autonomic or cognitive function was registered. There were no significant differences in RWA parameters when comparing iRBD and PD-RBD + groups. iRBD patients had better olfactory function than PD-RBD+ (p = 0.006); no significant difference in autonomic or cognitive function was registered. PD-RBD + had worse autonomic (p = 0.006) and olfactory (p = 0.001) but not motor and cognitive function compared to PD-RBD-. CONCLUSIONS: Untreated de-novo PD patients without RBD have increased RWA metrics compared to healthy subjects indicating subclinical degeneration of brainstem nuclei responsible for RWA. iRBD patients do not differ in RWA metrics from untreated de-novo PD patients with premotor RBD suggesting a similar level of brainstem degeneration caudal to substantia nigra in both groups. Groups with RBD are associated with autonomic dysfunction.
- MeSH
- kognice MeSH
- lidé MeSH
- Parkinsonova nemoc * komplikace MeSH
- polysomnografie MeSH
- porucha chování v REM spánku * MeSH
- svalová hypotonie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
INTRODUCTION: Obstructive sleep apnoea (OSA) is more prevalent in men. Several studies suggested that higher testosterone levels were associated with a greater risk of OSA. We aimed to determine whether testosterone administration in transgender men would accentuate symptoms of OSA. METHODS: The study involved 94 adult people undergoing a female-to-male transition with testosterone administration. The participants answered the Berlin Questionnaire (BQ) and a separate question on snoring before starting testosterone treatment and after at least 1 year of being on testosterone treatment. RESULTS: A higher proportion of participants at the follow-up answered positively to the first category of BQ devoted to snoring. A lower proportion of participants at follow-up answered positively to the second category of BQ devoted to tiredness. The percentage of subjects with a high risk of sleep apnoea, according to BQ, and of those who answered the question on snoring positively did not change significantly. CONCLUSION: An increased number of transgender men who reported snoring in BQ after testosterone administration indicate a higher risk of OSA development.
- Publikační typ
- časopisecké články MeSH
STUDY OBJECTIVES: Microbial antigens can elicit an immune response leading to the production of autoantibodies cross-reacting with autoantigens. Still, their clinical significance in human sera in the context of brain diseases is unclear. Therefore, assessment of natural autoantibodies reacting with their neuropeptides may elucidate the autoimmune etiology of central hypersomnias. The study aims to determine whether serum autoantibody levels differ in patients with different types of central hypersomnias (narcolepsy type 1 and 2, NT1 and NT2; idiopathic hypersomnia, IH) and healthy controls and if the differences could suggest the participation of autoantibodies in disease pathogenesis. METHODS: Sera from 91 patients with NT1, 27 with NT2, 46 with IH, and 50 healthy controls were examined for autoantibodies against assorted neuropeptides. Participants were screened using questionnaires related to sleep disorders, quality of life, and mental health conditions. In addition, serum biochemical parameters and biomarkers of microbial penetration through the intestinal wall were determined. RESULTS: A higher prevalence of autoantibodies against neuropeptides was observed only for alpha-melanocytes-stimulating hormone (α-MSH) and neuropeptide glutamic acid-isoleucine (NEI), which differed slightly among diagnoses. Patients with both types of narcolepsy exhibited signs of microbial translocation through the gut barrier. According to the questionnaires, patients diagnosed with NT2 or IH had subjectively worse life quality than patients with NT1. Patients displayed significantly lower levels of bilirubin and creatinine and slightly higher alkaline phosphatase values than healthy controls. CONCLUSIONS: Overall, serum anti-neuronal antibodies prevalence is rare, suggesting that their participation in the pathophysiology of concerned sleep disorders is insignificant. Moreover, their levels vary slightly between diagnoses indicating no major diagnostic significance.
- MeSH
- autoprotilátky MeSH
- kvalita života MeSH
- lidé MeSH
- narkolepsie * epidemiologie MeSH
- neuropeptidy * MeSH
- poruchy nadměrné spavosti * epidemiologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
In recent years, there has been an increased interest in elucidating the influence of the gut microbiota on sleep physiology. The gut microbiota affects the central nervous system by modulating neuronal pathways through the neuroendocrine and immune system, the hypothalamus-pituitary-adrenal axis, and various metabolic pathways. The gut microbiota can also influence circadian rhythms. In this study, we observed the gut microbiota composition of patients suffering from narcolepsy type 1, narcolepsy type 2, and idiopathic hypersomnia. We did not observe any changes in the alpha diversity of the gut microbiota among patient groups and healthy controls. We observed changes in beta diversity in accordance with Jaccard dissimilarities between the control group and groups of patients suffering from narcolepsy type 1 and idiopathic hypersomnia. Our results indicate that both these patient groups differ from controls relative to the presence of rare bacterial taxa. However, after adjustment for various confounding factors such as BMI, age, and gender, there were no statistical differences among the groups. This indicates that the divergence in beta diversity in the narcolepsy type 1 and idiopathic hypersomnia groups did not arise due to sleep disturbances. This study implies that using metabolomics and proteomics approaches to study the role of microbiota in sleep disorders might prove beneficial.
- MeSH
- idiopatická hypersomnie * MeSH
- lidé MeSH
- narkolepsie * MeSH
- poruchy nadměrné spavosti * MeSH
- poruchy spánku a bdění * MeSH
- spánek MeSH
- střevní mikroflóra * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
The neurodegenerative synucleinopathies, including Parkinson's disease and dementia with Lewy bodies, are characterized by a typically lengthy prodromal period of progressive subclinical motor and non-motor manifestations. Among these, idiopathic REM sleep behaviour disorder is a powerful early predictor of eventual phenoconversion, and therefore represents a critical opportunity to intervene with neuroprotective therapy. To inform the design of randomized trials, it is essential to study the natural progression of clinical markers during the prodromal stages of disease in order to establish optimal clinical end points. In this study, we combined prospective follow-up data from 28 centres of the International REM Sleep Behavior Disorder Study Group representing 12 countries. Polysomnogram-confirmed REM sleep behaviour disorder subjects were assessed for prodromal Parkinson's disease using the Movement Disorder Society criteria and underwent periodic structured sleep, motor, cognitive, autonomic and olfactory testing. We used linear mixed-effect modelling to estimate annual rates of clinical marker progression stratified by disease subtype, including prodromal Parkinson's disease and prodromal dementia with Lewy bodies. In addition, we calculated sample size requirements to demonstrate slowing of progression under different anticipated treatment effects. Overall, 1160 subjects were followed over an average of 3.3 ± 2.2 years. Among clinical variables assessed continuously, motor variables tended to progress faster and required the lowest sample sizes, ranging from 151 to 560 per group (at 50% drug efficacy and 2-year follow-up). By contrast, cognitive, olfactory and autonomic variables showed modest progression with higher variability, resulting in high sample sizes. The most efficient design was a time-to-event analysis using combined milestones of motor and cognitive decline, estimating 117 per group at 50% drug efficacy and 2-year trial duration. Finally, while phenoconverters showed overall greater progression than non-converters in motor, olfactory, cognitive and certain autonomic markers, the only robust difference in progression between Parkinson's disease and dementia with Lewy bodies phenoconverters was in cognitive testing. This large multicentre study demonstrates the evolution of motor and non-motor manifestations in prodromal synucleinopathy. These findings provide optimized clinical end points and sample size estimates to inform future neuroprotective trials.
- MeSH
- biologické markery MeSH
- demence s Lewyho tělísky * diagnóza MeSH
- lidé MeSH
- Parkinsonova nemoc * komplikace diagnóza MeSH
- porucha chování v REM spánku * diagnóza MeSH
- prodromální symptomy MeSH
- progrese nemoci MeSH
- prospektivní studie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
REM sleep without atonia (RWA) is the hallmark of isolated REM sleep behavior disorder (iRBD) and is caused by neurodegeneration of brainstem structures. Previously, quantitative susceptibility mapping (QSM) was shown to detect microstructural tissue changes in neurodegenerative diseases. The goal of the study was to compare brainstem magnetic susceptibility (MS) in iRBD and controls using the voxel-based QSM approach and to examine the association between brainstem MS and severity of RWA in iRBD. Sixty iRBD patients and 41 healthy controls were included in the study. Phasic, tonic, mixed RWA and SINBAR score was quantified. QSM maps were reconstructed with QSMbox software from a multi-gradient-echo sequence acquired at 3T MRI system and normalized using a custom T1 template. Voxel-based analysis with age and gender as covariates was performed using a two-sample t-test model for between-group comparison and using a linear regression model for association with the RWA parameters. Statistical maps were generated using threshold free cluster enhancement with p-value p < 0.05, corrected for family wise error. Compared to controls, the iRBD group had higher MS in bilateral substantia nigra (SN), red nucleus and the ventral tegmental area. MS positively correlated with iRBD duration in the right pedunculotegmental nucleus and white matter of caudal mesencephalic and pontine tegmentum and with phasic RWA in bilateral SN. QSM was able to detect MS abnormalities in several brainstem structures in iRBD. Association of MS levels in the brainstem with the intensity of RWA suggests that increased iron content in SN is related to RWA severity.
- Publikační typ
- časopisecké články MeSH
Synucleinopathies-related disorders such as Lewy body dementia (LBD) and isolated/idiopathic REM sleep behavior disorder (iRBD) have been associated with neuroinflammation. In this study, we examined whether the human leukocyte antigen (HLA) locus plays a role in iRBD and LBD. In iRBD, HLA-DRB1*11:01 was the only allele passing FDR correction (OR = 1.57, 95% CI = 1.27-1.93, p = 2.70e-05). We also discovered associations between iRBD and HLA-DRB1 70D (OR = 1.26, 95%CI = 1.12-1.41, p = 8.76e-05), 70Q (OR = 0.81, 95%CI = 0.72-0.91, p = 3.65e-04) and 71R (OR = 1.21, 95%CI = 1.08-1.35, p = 1.35e-03). Position 71 (pomnibus = 0.00102) and 70 (pomnibus = 0.00125) were associated with iRBD. Our results suggest that the HLA locus may have different roles across synucleinopathies.
