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Nature and Science of Sleep 2024To investigate sleep problems in children with self-limited epilepsy with central temporal spiking (SeLECTS) and to assess the relationship between sleep problems and...
PURPOSE
To investigate sleep problems in children with self-limited epilepsy with central temporal spiking (SeLECTS) and to assess the relationship between sleep problems and attention network dysfunction.
PATIENTS AND METHODS
107 children 6-14 years of age with SeLECTS and 90 age- and sex-matched healthy controls were recruited for this study. The sleep status of these participants was evaluated using the Children's Sleep Habits Questionnaire (CSHQ), while attentional network function was assessed with the attention network function test (ANT).
RESULTS
Together, these analyses revealed that children with SeLECTS exhibited higher total CSHQ scores and sleep disorder incidence relative to healthy controls (P< 0.001). Children with SeLECTS had higher scores in delayed sleep onset, sleep duration, night awakenings, parasomnias, daytime sleepiness and sleep anxiety (P<0.01). Total CSHQ scores were negatively correlated with average ANT correct rates (= -0.253, P<0.01), while they were positively correlated with total reaction time (=0.367, P<0.01) and negatively correlated with the efficiency of the alerting and executive control networks (=-0.344 P<0.01; =-0.418 P<0.01).
CONCLUSION
Children with SeLECTS face a higher risk of experiencing sleep disorders relative to age-matched healthy children, while also demonstrating that the magnitude of the impairment of attentional network function in these children is positively correlated with sleep disorder severity. Thus, the prognosis and quality of life of children with SeLECTS can be improved by interventions addressing sleep disorders.
PubMed: 38894978
DOI: 10.2147/NSS.S460558 -
Nature Communications Jun 2024Parkinson's disease is increasingly prevalent. It progresses from the pre-motor stage (characterised by non-motor symptoms like REM sleep behaviour disorder), to the...
Parkinson's disease is increasingly prevalent. It progresses from the pre-motor stage (characterised by non-motor symptoms like REM sleep behaviour disorder), to the disabling motor stage. We need objective biomarkers for early/pre-motor disease stages to be able to intervene and slow the underlying neurodegenerative process. Here, we validate a targeted multiplexed mass spectrometry assay for blood samples from recently diagnosed motor Parkinson's patients (n = 99), pre-motor individuals with isolated REM sleep behaviour disorder (two cohorts: n = 18 and n = 54 longitudinally), and healthy controls (n = 36). Our machine-learning model accurately identifies all Parkinson patients and classifies 79% of the pre-motor individuals up to 7 years before motor onset by analysing the expression of eight proteins-Granulin precursor, Mannan-binding-lectin-serine-peptidase-2, Endoplasmatic-reticulum-chaperone-BiP, Prostaglaindin-H2-D-isomaerase, Interceullular-adhesion-molecule-1, Complement C3, Dickkopf-WNT-signalling pathway-inhibitor-3, and Plasma-protease-C1-inhibitor. Many of these biomarkers correlate with symptom severity. This specific blood panel indicates molecular events in early stages and could help identify at-risk participants for clinical trials aimed at slowing/preventing motor Parkinson's disease.
Topics: Humans; Parkinson Disease; Biomarkers; Male; Proteomics; Female; Aged; Middle Aged; Machine Learning; REM Sleep Behavior Disorder; Case-Control Studies; Mass Spectrometry
PubMed: 38890280
DOI: 10.1038/s41467-024-48961-3 -
Frontiers in Psychiatry 2024Sleep-related eating disorder (SRED) is a non-REM parasomnia with potentially significant negative effects on general health (dangerous activities during night eating...
Sleep-related eating disorder (SRED) is a non-REM parasomnia with potentially significant negative effects on general health (dangerous activities during night eating episodes, obesity, or metabolic syndrome, for example). Although the history of SRED encompasses more than six decades, public awareness and even the awareness of the mental health specialists of this disorder is very limited, a phenomenon that hinders the development of research in this field. Therefore, a systematic review based on PRISMA 2020 guidelines explored the available evidence for SRED found in four electronic databases (PubMed, Cochrane Collaboration, Google Scholar, and Clarivate/Web of Science). A number of 94 primary and secondary reports were retrieved, investigating aspects regarding the risk factors, epidemiology, clinical data and differential diagnosis, epidemiology, structured evaluation, and treatment of SRED. Based on the results of these reports, Z-drugs, but also certain benzodiazepines, antidepressants, antipsychotics, and psychostimulants may trigger the onset of SRED. Psychiatric and neurologic disorders have also been associated with SRED, either as risk factors or comorbid conditions. Cerebral glucose metabolism dysfunctions, neurotransmitter dysfunctions, and genetic factors have been invoked as pathogenetic contributors. Structured assessment of SRED is possible, but there is a dearth of instruments dedicated to this purpose. Data on the prevalence and treatment of SRED exist, but good-quality epidemiological studies and clinical trials are still missing. In conclusion, future research is expected to address the shortcomings of SRED exploration by creating the conditions for better quality and larger group clinical research. The need for such investigation is granted by the importance of this pathology and its negative functional consequences.
PubMed: 38873533
DOI: 10.3389/fpsyt.2024.1393337 -
Sleep Science (Sao Paulo, Brazil) Jun 2024In adults, nightmare disorder is related to sleep deprivation, drug consumption or abuse, or other comorbid sleep disorders such as insomnia or insufficient sleep...
In adults, nightmare disorder is related to sleep deprivation, drug consumption or abuse, or other comorbid sleep disorders such as insomnia or insufficient sleep syndrome. Behavioral treatment has solid scientific evidence in disorders such as insomnia and, more recently, parasomnias. The aim of the present study was to investigate the clinical effectiveness of a Brief Behavioral Telemedicine Therapy in Nightmare Disorder in a 23-year-old female patient. The procedure consisted of the case study, with pre and posttreatment measures as well as follow-up after 1 month; and the Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index, Paris Arousal Disorders Severity Scale, and a sleep diary were applied. In parallel with changes recorded in the sleep diary, a decrease in nightmares, sleepiness, and insomnia symptoms was observed when the intervention was finished. The behavioral intervention was clinically effective; therefore, the present case report provides information on behavioral treatments for nightmare disorder.
PubMed: 38846595
DOI: 10.1055/s-0043-1777707 -
Clinical Parkinsonism & Related... 2024Nocturnal and sleep-related motor disorders in people with Parkinson's disease (PD) have a wide spectrum of manifestations and present a complex clinical picture....
Nocturnal and sleep-related motor disorders in people with Parkinson's disease (PD) have a wide spectrum of manifestations and present a complex clinical picture. Problems can arise due to impaired movement ability (hypokinesias), e.g. nocturnal hypokinesia or early-morning akinesia, or to excessive movement (hyperkinesias), e.g. end-of-the-day dyskinesia, parasomnias, periodic limb movement during sleep and restless legs syndrome. These disorders can have a significant negative impact on the sleep, daytime functional ability, and overall quality of life of individuals with PD and their carers. The debilitating motor issues are often accompanied by a combination of non-motor symptoms, including pain and cramping, which add to the overall burden. Importantly, nocturnal motor disorders encompass a broader timeline than just the period of sleep, often starting in the evening, as well as occurring throughout the night and on awakening, and are not just limited to problems of insomnia or sleep fragmentation. Diagnosis can be challenging as, in many cases, the 'gold standard' assessment method is video polysomnography, which may not be available in all settings. Various validated questionnaires are available to support evaluation, and alternative approaches, using wearable sensors and digital technology, are now being developed to facilitate early diagnosis and monitoring. This review sets out the parameters of what can be considered normal nocturnal movement and describes the clinical manifestations, usual clinical or objective assessment methods, and evidence for optimal management strategies for the common nocturnal motor disorders that neurologists will encounter in people with PD in their clinical practice.
PubMed: 38845753
DOI: 10.1016/j.prdoa.2024.100258 -
Journal of Global Health Jun 2024Restless legs syndrome (RLS) is a prevalent neuro-sensory disorder that impairs quality of life. In this systematic review and modelling study, we estimated the global...
BACKGROUND
Restless legs syndrome (RLS) is a prevalent neuro-sensory disorder that impairs quality of life. In this systematic review and modelling study, we estimated the global and regional prevalence of RLS and its associated factors.
METHODS
We searched PubMed, Embase, and Medline for population-based studies on RLS prevalence published up to 12 November 2023. The included studies reported prevalence using the International Restless Leg Syndrome Study Group's (IRLSSG) minimal diagnostic criteria without limitations on frequency, duration, or severity. We applied a multilevel multivariable mixed-effects meta-regression to generate the age-specific and sex-specific prevalence of RLS for high socio-demographic index (H-SDI) and low and middle socio-demographic index (LM-SDI) regions. We pooled odds ratios (ORs) for RLS associated factors using random-effects models. Finally, we derived the regional prevalence and cases of RLS based on an associated factor-based model.
RESULTS
From 52 articles across 23 countries, the global RLS prevalence in 2019 was estimated to be 7.12% (95% confidence interval (CI) = 5.15-9.76) among adults 20-79 years of age, equating to 356.07 million (95% CI = 257.61-488.09) affected individuals. Prevalence was similar in H-SDI (7.29%; 95% CI = 5.04-10.41) and LM-SDI (7.10%; 95% CI = 5.16-9.70) regions, with the majority of cases in LM-SDI countries (323.06 million; 90.73%). Europe had the highest (7.60%; 95% CI = 5.44-10.52) and Africa the lowest regional prevalence (6.48%; 95% CI = 4.70-8.87). The Western Pacific Region, meanwhile, had the most cases (111.91 million; 95% CI = 80.93-153.42). Factors positively associated with RLS included advanced age (OR = 1.13; 95% CI = 1.04-1.24), smoking (OR = 1.46; 95% CI = 1.29-1.64), depression (OR = 1.71; 95% CI = 1.26-2.32), and diabetes (OR = 1.54; 95% CI = 1.19-1.97).
CONCLUSIONS
A considerable global burden of RLS exists. Effective strategies are needed to increase awareness and optimise resource allocation to address this often-overlooked condition. High-quality epidemiological investigations employing standardised and rigorous criteria for RLS are essential for addressing RLS burden more effectively.
REGISTRATION
PROSPERO: CRD42020161860.
Topics: Adult; Humans; Middle Aged; Global Health; Prevalence; Restless Legs Syndrome; Aged
PubMed: 38843039
DOI: 10.7189/jogh.14.04113 -
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 -
Brain : a Journal of Neurology Jun 2024The LRRK2 G2019S variant is the most common cause of monogenic Parkinson's disease (PD); however, questions remain regarding the penetrance, clinical phenotype and...
The LRRK2 G2019S variant is the most common cause of monogenic Parkinson's disease (PD); however, questions remain regarding the penetrance, clinical phenotype and natural history of carriers. We performed a 3.5-year prospective longitudinal online study in a large number of 1286 genotyped LRRK2 G2019S carriers and 109 154 controls, with and without PD, recruited from the 23andMe Research Cohort. We collected self-reported motor and non-motor symptoms every 6 months, as well as demographics, family histories and environmental risk factors. Incident cases of PD (phenoconverters) were identified at follow-up. We determined lifetime risk of PD using accelerated failure time modelling and explored the impact of polygenic risk on penetrance. We also computed the genetic ancestry of all LRRK2 G2019S carriers in the 23andMe database and identified regions of the world where carrier frequencies are highest. We observed that despite a 1 year longer disease duration (P = 0.016), LRRK2 G2019S carriers with PD had similar burden of motor symptoms, yet significantly fewer non-motor symptoms including cognitive difficulties, REM sleep behaviour disorder (RBD) and hyposmia (all P-values ≤ 0.0002). The cumulative incidence of PD in G2019S carriers by age 80 was 49%. G2019S carriers had a 10-fold risk of developing PD versus non-carriers. This rose to a 27-fold risk in G2019S carriers with a PD polygenic risk score in the top 25% versus non-carriers in the bottom 25%. In addition to identifying ancient founding events in people of North African and Ashkenazi descent, our genetic ancestry analyses infer that the G2019S variant was later introduced to Spanish colonial territories in the Americas. Our results suggest LRRK2 G2019S PD appears to be a slowly progressive predominantly motor subtype of PD with a lower prevalence of hyposmia, RBD and cognitive impairment. This suggests that the current prodromal criteria, which are based on idiopathic PD, may lack sensitivity to detect the early phases of LRRK2 PD in G2019S carriers. We show that polygenic burden may contribute to the development of PD in the LRRK2 G2019S carrier population. Collectively, the results should help support screening programmes and candidate enrichment strategies for upcoming trials of LRRK2 inhibitors in early-stage disease.
Topics: Humans; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; Parkinson Disease; Female; Male; Middle Aged; Aged; Longitudinal Studies; Genetic Predisposition to Disease; Adult; Prospective Studies; Heterozygote; Penetrance; Aged, 80 and over; REM Sleep Behavior Disorder; Mutation
PubMed: 38804604
DOI: 10.1093/brain/awae073