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Sleep Medicine: X Dec 2023NREM parasomnias also known as disorders of arousal (DOA) are characterised by abnormal motor and autonomic activation during arousals primarily from slow wave sleep....
OBJECTIVES
NREM parasomnias also known as disorders of arousal (DOA) are characterised by abnormal motor and autonomic activation during arousals primarily from slow wave sleep. Dissociative state between sleep and wake is likely responsible for clinical symptoms of DOA. We therefore investigated potential dissociation outside of parasomnic events by using simultaneous 256-channel EEG (hdEEG) and functional magnetic resonance imaging (fMRI).
METHODS
Eight DOA patients (3 women, mean age = 27.8; SD = 4.2) and 8 gender and age matched healthy volunteers (3 women, mean age = 26,5; SD = 4.0) were included into the study. They underwent 30-32 h of sleep deprivation followed by hdEEG and fMRI recording. We determined 2 conditions: falling asleep (FA) and arousal (A), that occurred outside of deep sleep and/or parasomnic event. We used multimodal approach using data obtained from EEG, fMRI and EEG-fMRI integration approach.
RESULTS
DOA patients showed increase in delta and beta activity over postcentral gyrus and cuneus during awakening period. This group expressed increased connectivity between motor cortex and cingulate during arousals unrelated to parasomnic events in the beta frequency band. They also showed lower connectivity between different portions of cingulum. In contrast, the greater connectivity was found between thalamus and some cortical areas, such as occipital cortex.
CONCLUSION
Our findings suggest a complex alteration in falling asleep and arousal mechanisms at both subcortical and cortical levels in response to sleep deprivation. As this alteration is present also outside of slow wave sleep and/or parasomnic episodes we believe this could be a trait factor of DOA.
PubMed: 37745863
DOI: 10.1016/j.sleepx.2023.100086 -
International Journal of Environmental... Apr 2024Sleep bruxism (SB) can be determined with different diagnostic procedures. The relationship between psychometric variables and SB varies depending on the diagnostic...
Sleep bruxism (SB) can be determined with different diagnostic procedures. The relationship between psychometric variables and SB varies depending on the diagnostic method. The aim of the study was to compare the association between SB and oral health-related quality of life (OHRQoL; measured by the Oral Health Impact Profile, OHIP), anxiety (measured by the State-Trait anxiety inventory, STAI), and stress (single scale variable) depending on the diagnostic method in the same sample. N = 45 participants were examined by non-instrumental (possible/probable SB) and instrumental methods (definite SB). The OHIP differed significantly between possible SB (median = 4) and non-SB (median = 0) with W = 115, = 0.01, and probable SB (median = 6) and non-SB (median = 0) with W = 101, = 0.01). There was no significant difference in the OHIP score between definite SB and non-SB. For the other psychometric variables, the analyses revealed no significant differences between SB and non-SB in all diagnostic procedures. The results suggest that there is a difference between possible/probable and definite SB with respect to the association with OHRQoL. Certain aspects of possible/probable SB might be responsible for the poor OHRQoL, which are not measured in definite SB.
Topics: Humans; Sleep Bruxism; Female; Male; Psychometrics; Adult; Quality of Life; Young Adult; Anxiety; Middle Aged; Stress, Psychological; Oral Health; Surveys and Questionnaires
PubMed: 38791756
DOI: 10.3390/ijerph21050543 -
Parkinsonism & Related Disorders May 2024Olfactory dysfunction and REM sleep behavior disorder (RBD) are associated with distinct cognitive trajectories in the course of Parkinson's disease (PD). The underlying...
INTRODUCTION
Olfactory dysfunction and REM sleep behavior disorder (RBD) are associated with distinct cognitive trajectories in the course of Parkinson's disease (PD). The underlying neurobiology for this relationship remains unclear but may involve distinct patterns of neurodegeneration. This study aimed to examine longitudinal cortical atrophy and thinning in early-stage PD with severe olfactory deficit (anosmia) without and with concurrent probable RBD.
METHODS
Longitudinal MRI data over four years of 134 de novo PD and 49 healthy controls (HC) from the Parkinson Progression Marker Initiative (PPMI) cohort were analyzed using a linear mixed-effects model. Patients were categorized into those with anosmia by the University of Pennsylvania Smell Identification Test (UPSIT) score ≤ 18 (AO+) and those without (UPSIT score > 18, AO-). The AO+ group was further subdivided into AO+ with probable RBD (AO+RBD+) and without (AO+RBD-) for subanalysis.
RESULTS
Compared to subjects without baseline anosmia, the AO+ group exhibited greater longitudinal declines in both volume and thickness in the bilateral parahippocampal gyri and right transverse temporal gyrus. Patients with concurrent anosmia and RBD showed more extensive longitudinal declines in cortical volume and thickness, involving additional brain regions including the bilateral precuneus, left inferior temporal gyrus, right paracentral gyrus, and right precentral gyrus.
CONCLUSIONS
The atrophy/thinning patterns in early-stage PD with severe olfactory dysfunction include regions that are critical for cognitive function and could provide a structural basis for previously reported associations between severe olfactory deficit and cognitive decline in PD. Concurrent RBD might enhance the dynamics of cortical changes.
Topics: Humans; Parkinson Disease; Male; Female; Aged; Middle Aged; Longitudinal Studies; Magnetic Resonance Imaging; REM Sleep Behavior Disorder; Olfaction Disorders; Atrophy; Anosmia; Disease Progression; Brain
PubMed: 38430690
DOI: 10.1016/j.parkreldis.2024.106072 -
Neurology Dec 2023To evaluate the prevalence of REM sleep behavior disorder (RBD) and its possible prodromal conditions, isolated dream enactment behavior (DEB) and isolated REM without...
BACKGROUND AND OBJECTIVES
To evaluate the prevalence of REM sleep behavior disorder (RBD) and its possible prodromal conditions, isolated dream enactment behavior (DEB) and isolated REM without atonia (RWA), in a general population sample, and the factors associated with diagnosis and symptom frequency.
METHODS
From a population-based prospective cohort in Korea, 1,075 participants (age 60.1 ± 7.0 years; range 50-80 years; men 53.7%) completed the RBD screening questionnaire (RBDSQ), a structured telephone interview for the presence and characteristics of repeated DEB, and home polysomnography (PSG). RWA was measured on submentalis EMG, including 30-second epoch-based tonic and phasic activity as well as 3-second mini-epoch-based phasic and any EMG activities. Based on the presence of repeated DEB and any EMG activity of ≥22.3%, we categorized the participants into no RBD, isolated RWA, isolated DEB, and RBD groups.
RESULTS
RBD was diagnosed in 20 participants, isolated RWA in 133 participants, and isolated DEB in 48 participants. Sex and DEB frequency-adjusted prevalence of RBD was 1.4% (95% CI 1.0%-1.8%), isolated RWA was 12.5% (95% CI 11.3%-13.6%), and isolated DEB was 3.4% (95% CI 2.7%-4.1%). Total RBDSQ score was higher in the RBD and isolated DEB groups than in the isolated RWA and no RBD group (median 5 [interquartile range (IQR) 4-6] for RBD, median 4 [IQR 3-6] for isolated DEB, median 2 [IQR 1-3] for isolated RWA, and median 2 [IQR 1-4] for no RBD groups, < 0.001). RBDSQ score of ≥5 had good specificity but poor positive predictive value (PPV) for RBD (specificity 84.1% and PPV 7.7%) and its prodromal conditions (specificity 85.2% and PPV 29.1%). Among the RWA parameters, any EMG activity showed the best association with the RBD and its possible prodromes (area under the curve, 0.917). Three-second mini-epoch-based EMG activity and phasic EMG activity were correlated with the frequency of DEB (standardized Jonckheere-Terpstra statistic [std. J-T static] for trend = 0.488, < 0.001, and std. J-T static = 3.265, = 0.001, respectively).
DISCUSSION
This study provides prevalence estimates of RBD and its possible prodromal conditions based on a structured telephone interview and RWA measurement on PSG from the general population.
Topics: Male; Humans; Middle Aged; Aged; REM Sleep Behavior Disorder; Polysomnography; Prevalence; Prospective Studies; Sleep, REM; Electromyography
PubMed: 37816644
DOI: 10.1212/WNL.0000000000207947 -
Tidsskrift For Den Norske Laegeforening... Mar 2024In some forms of epilepsy, the seizures occur almost exclusively during sleep. This is particularly the case with hypermotor frontal lobe seizures. Clinically it can be... (Review)
Review
In some forms of epilepsy, the seizures occur almost exclusively during sleep. This is particularly the case with hypermotor frontal lobe seizures. Clinically it can be difficult to distinguish such seizures from parasomnias and psychogenic non-epileptic seizures. This clinical review article aims to highlight the importance of making the correct diagnosis, as these conditions require completely different treatment.
Topics: Humans; Epilepsy, Frontal Lobe; Electroencephalography; Parasomnias; Seizures; Sleep
PubMed: 38506017
DOI: 10.4045/tidsskr.23.0579 -
Nature Genetics Jun 2024Restless legs syndrome (RLS) affects up to 10% of older adults. Their healthcare is impeded by delayed diagnosis and insufficient treatment. To advance disease... (Meta-Analysis)
Meta-Analysis
Restless legs syndrome (RLS) affects up to 10% of older adults. Their healthcare is impeded by delayed diagnosis and insufficient treatment. To advance disease prediction and find new entry points for therapy, we performed meta-analyses of genome-wide association studies in 116,647 individuals with RLS (cases) and 1,546,466 controls of European ancestry. The pooled analysis increased the number of risk loci eightfold to 164, including three on chromosome X. Sex-specific meta-analyses revealed largely overlapping genetic predispositions of the sexes (r = 0.96). Locus annotation prioritized druggable genes such as glutamate receptors 1 and 4, and Mendelian randomization indicated RLS as a causal risk factor for diabetes. Machine learning approaches combining genetic and nongenetic information performed best in risk prediction (area under the curve (AUC) = 0.82-0.91). In summary, we identified targets for drug development and repurposing, prioritized potential causal relationships between RLS and relevant comorbidities and risk factors for follow-up and provided evidence that nonlinear interactions are likely relevant to RLS risk prediction.
Topics: Restless Legs Syndrome; Humans; Genome-Wide Association Study; Genetic Predisposition to Disease; Risk Factors; Female; Male; Polymorphism, Single Nucleotide; Mendelian Randomization Analysis; Machine Learning
PubMed: 38839884
DOI: 10.1038/s41588-024-01763-1 -
Brazilian Oral Research 2024Occlusal stabilization splints are the most common treatment for controlling the deleterious effects of sleep bruxism. This study aimed to evaluate the effectiveness of... (Randomized Controlled Trial)
Randomized Controlled Trial
Occlusal stabilization splints are the most common treatment for controlling the deleterious effects of sleep bruxism. This study aimed to evaluate the effectiveness of a low-cost, mixed occlusal splint (MOS) compared to that of a rigid splint. A randomized clinical trial was performed on 43 adults of both sexes with possible sleep bruxism and satisfactory dental conditions. They were divided into rigid occlusal splint (ROS) (n = 23) and MOS (n = 20) groups. Masticatory muscle and temporomandibular joint (TMJ) pain intensity (visual analog scale), quality of life (WHOQOL-BREF), indentations in the oral mucosa, anxiety, and depression (HADS), number of days of splint use, and splint wear were evaluated. All variables were evaluated at baseline (T0), 6 months (T6), and 12 months (T12) after splint installation (T0), and splint wear was evaluated at T6 and T12. Student's t-test, Mann-Whitney U test, non-parametric Friedman's analysis of variance for paired samples and pairwise multiple comparisons, Pearson's chi-square test, two-proportion z-test, non-parametric McNemar's and Cochran's Q, and Wilcoxon tests were used (p < 0.05). In both groups, there was a decrease in TMJ pain and pain intensity over time and improvements in the quality of life scores. At T6, there was a higher rate of splint wear in the MOS group than in the ROS group (p = 0.023). The MOS showed a higher rate of wear than the rigid splint but had similar results for the other variables. Therefore, the use of a mixed splint appears to be effective in controlling the signs and symptoms of sleep bruxism.
Topics: Adult; Female; Male; Humans; Occlusal Splints; Splints; Quality of Life; Reactive Oxygen Species; Sleep Bruxism
PubMed: 38477803
DOI: 10.1590/1807-3107bor-2024.vol38.0017 -
EBioMedicine Apr 2024Idiopathic rapid eye movement (REM) sleep behaviour disorder (IRBD) represents the prodromal stage of Lewy body disorders (Parkinson's disease (PD) and dementia with...
BACKGROUND
Idiopathic rapid eye movement (REM) sleep behaviour disorder (IRBD) represents the prodromal stage of Lewy body disorders (Parkinson's disease (PD) and dementia with Lewy bodies (DLB)) which are linked to variations in circulating cell-free mitochondrial DNA (cf-mtDNA). Here, we assessed whether altered cf-mtDNA release and integrity are already present in IRBD.
METHODS
We used multiplex digital PCR (dPCR) to quantify cf-mtDNA copies and deletion ratio in cerebrospinal fluid (CSF) and serum in a cohort of 71 participants, including 1) 17 patients with IRBD who remained disease-free (non-converters), 2) 34 patients initially diagnosed with IRBD who later developed either PD or DLB (converters), and 3) 20 age-matched controls without IRBD or Parkinsonism. In addition, we investigated whether CD9-positive extracellular vesicles (CD9-EVs) from CSF and serum samples contained cf-mtDNA.
FINDINGS
Patients with IRBD, both converters and non-converters, exhibited more cf-mtDNA with deletions in the CSF than controls. This finding was confirmed in CD9-EVs. The high levels of deleted cf-mtDNA in CSF corresponded to a significant decrease in cf-mtDNA copies in CD9-EVs in both IRBD non-converters and converters. Conversely, a significant increase in cf-mtDNA copies was found in serum and CD9-EVs from the serum of patients with IRBD who later converted to a Lewy body disorder.
INTERPRETATION
Alterations in cf-mtDNA copy number and deletion ratio known to occur in Lewy body disorders are already present in IRBD and are not a consequence of Lewy body disease conversion. This suggests that mtDNA dysfunction is a primary molecular mechanism of the pathophysiological cascade that precedes the full clinical motor and cognitive manifestation of Lewy body disorders.
FUNDING
Funded by Michael J. Fox Foundation research grant MJFF-001111. Funded by MICIU/AEI/10.13039/501100011033 "ERDF A way of making Europe", grants PID2020-115091RB-I00 (RT) and PID2022-143279OB-I00 (ACo). Funded by Instituto de Salud Carlos III and European Union NextGenerationEU/PRTR, grant PMP22/00100 (RT and ACo). Funded by AGAUR/Generalitat de Catalunya, grant SGR00490 (RT and ACo). MP has an FPI fellowship, PRE2018-083297, funded by MICIU/AEI/10.13039/501100011033 "ESF Investing in your future".
Topics: Humans; REM Sleep Behavior Disorder; Parkinson Disease; Parkinsonian Disorders; Forecasting; DNA, Mitochondrial
PubMed: 38502973
DOI: 10.1016/j.ebiom.2024.105065 -
European Journal of Neurology Dec 2023Idiopathic/isolated rapid eye movement (REM) sleep behavior disorder (iRBD) is considered the prodromal stage of alpha-synucleinopathies. Thus, iRBD patients are the... (Observational Study)
Observational Study
INTRODUCTION
Idiopathic/isolated rapid eye movement (REM) sleep behavior disorder (iRBD) is considered the prodromal stage of alpha-synucleinopathies. Thus, iRBD patients are the ideal target for disease-modifying therapy. The risk FActoRs PREdictive of phenoconversion in iRBD Italian STudy (FARPRESTO) is an ongoing Italian database aimed at identifying risk factors of phenoconversion, and eventually to ease clinical trial enrollment of well-characterized subjects.
METHODS
Polysomnography-confirmed iRBD patients were retrospectively and prospectively enrolled. Baseline harmonized clinical and nigrostriatal functioning data were collected at baseline. Nigrostriatal functioning was evaluated by dopamine transporter-single-photon emission computed tomography (DaT-SPECT) and categorized with visual semi-quantification. Longitudinal data were evaluated to assess phenoconversion. Cox regressions were applied to calculate hazard ratios.
RESULTS
365 patients were enrolled, and 289 patients with follow-up (age 67.7 ± 7.3 years, 237 males, mean follow-up 40 ± 37 months) were included in this study. At follow-up, 97 iRBD patients (33.6%) phenoconverted to an overt synucleinopathy. Older age, motor and cognitive impairment, constipation, urinary and sexual dysfunction, depression, and visual semi-quantification of nigrostriatal functioning predicted phenoconversion. The remaining 268 patients are in follow-up within the FARPRESTO project.
CONCLUSIONS
Clinical data (older age, motor and cognitive impairment, constipation, urinary and sexual dysfunction, depression) predicted phenoconversion in this multicenter, longitudinal, observational study. A standardized visual approach for semi-quantification of DaT-SPECT is proposed as a practical risk factor for phenoconversion in iRBD patients. Of note, non-converted and newly diagnosed iRBD patients, who represent a trial-ready cohort for upcoming disease-modification trials, are currently being enrolled and followed in the FARPRESTO study. New data are expected to allow better risk characterization.
Topics: Male; Humans; Middle Aged; Aged; Dopaminergic Imaging; Retrospective Studies; Sleep, REM; REM Sleep Behavior Disorder; Dopamine; Constipation
PubMed: 37498611
DOI: 10.1111/ene.16001 -
Brain : a Journal of Neurology Jan 2024Restless legs syndrome (RLS) is responsive to opioid, dopaminergic and iron-based treatments. Receptor blocker studies in RLS patients suggest that the therapeutic...
Restless legs syndrome (RLS) is responsive to opioid, dopaminergic and iron-based treatments. Receptor blocker studies in RLS patients suggest that the therapeutic efficacy of opioids is specific to the opioid receptor and mediated indirectly through the dopaminergic system. An RLS autopsy study reveals decreases in endogenous opioids, β-endorphin and perhaps Met-enkephalin in the thalamus of RLS patients. A total opioid receptor knock-out (mu, delta and kappa) and a mu-opioid receptor knock-out mouse model of RLS show circadian motor changes akin to RLS and, although both models show sensory changes, the mu-opioid receptor knock mouse shows circadian sensory changes closest to those seen in idiopathic RLS. Both models show changes in striatal dopamine, anaemia and low serum iron. However, only in the total receptor knock-out mouse do we see the decreases in serum ferritin that are normally found in RLS. There are also decreases in serum iron when wild-type mice are administered a mu-opioid receptor blocker. In addition, the mu-opioid receptor knock-out mouse also shows increases in striatal zinc paralleling similar changes in RLS. Adrenocorticotropic hormone and α-melanocyte stimulating hormone are derived from pro-opiomelanocortin as is β-endorphin. However, they cause RLS-like symptoms and periodic limb movements when injected intraventricularly into rats. These results collectively suggest that an endogenous opioid deficiency is pathogenetic to RLS and that an altered melanocortin system may be causal to RLS as well.
Topics: Humans; Rats; Mice; Animals; Analgesics, Opioid; Restless Legs Syndrome; Melanocortins; beta-Endorphin; Iron; Dopamine
PubMed: 37633259
DOI: 10.1093/brain/awad283