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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 -
Drugs in R&D Jun 2024A prospective, postmarketing observational study was conducted to evaluate the safety and efficacy of lemborexant (LEM) tablets in daily clinical practice in Japan. No...
BACKGROUND AND OBJECTIVE
A prospective, postmarketing observational study was conducted to evaluate the safety and efficacy of lemborexant (LEM) tablets in daily clinical practice in Japan. No other studies of a similar size have been conducted since the marketing approval of LEM, making this the first report of its kind.
METHODS
Insomnia patients (n = 550) administered LEM (5-10 mg daily) for the first time were enrolled. Adverse events were collected for target events (somnolence, parasomnia, narcolepsy and associated conditions, suicidal ideation and suicidal behavior). Overall improvement of insomnia symptoms was assessed by the investigator based on the patient's complaint. Subjective sleep onset latency (sSOL) and subjective total sleep time (sTST) were investigated as sleep parameters.
RESULTS
A case report form was obtained from 539 patients. The incidence of adverse drug reactions (ADRs) was 7.65% for somnolence, 1.76% for nightmares, 0.59% for abnormal dreams, and 0.20% for sleep paralysis. No serious ADRs or ADRs related to suicidal ideation or suicidal behavior were observed. The efficacy rate at the final evaluation was 80.83%. Decreased sSOL and increased sTST were observed as assessed starting from Week 8 of treatment.
CONCLUSION
Based on the results of this study, the safety result was consistent with the safety profile described in the current package insert. Efficacy results also indicated that LEM is clinically useful.
PubMed: 38839690
DOI: 10.1007/s40268-024-00462-w -
Current Opinion in Neurology May 2024This review aimed to comprehensively outline sleep and circadian rhythm abnormalities in hyperkinetic movement disorders beyond Parkinson's disease and atypical...
PURPOSE OF REVIEW
This review aimed to comprehensively outline sleep and circadian rhythm abnormalities in hyperkinetic movement disorders beyond Parkinson's disease and atypical parkinsonisms, including tremor, dystonia, choreiform movements, tics, and ataxia disorders.
RECENT FINDINGS
Insomnia, poor sleep quality, and excessive daytime sleepiness (EDS) are commonly reported in essential tremor, Wilson's disease, tics or Tourette's syndrome, and spinocerebellar ataxia (SCA). REM sleep behavior disorder (RBD) have been observed in Wilson's disease and SCA. A combination of REM and non-REM parasomnias, along with nocturnal stridor with the initiation of sleep and re-entering after awakening, are characterized by undifferentiated Non-REM and poorly structured N2 in anti-IgLON5 disease. Restless legs syndrome (RLS) has been reported commonly in SCAs. Sleep-related dyskinesia has been reported in ADCY5-related disease and GNAO1-related movement disorder.
SUMMARY
Sleep problems can manifest as a result of movement disorders, either through direct motor disturbances or secondary nonmotor symptoms. Medication effects must be considered, as certain medications for movement disorders can exacerbate or alleviate sleep disturbances. Distinguishing sleep problems in some diseases might involve pathognomonic symptoms and signs, aiding in the diagnosis of movement disorders.
PubMed: 38809245
DOI: 10.1097/WCO.0000000000001286 -
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 -
Sleep Medicine Jul 2024Excessive fragmentary myoclonus (EFM) is a frequent finding in patients undergoing video-polysomnography (VPSG). We aimed to evaluate the potential effect of...
STUDY OBJECTIVES
Excessive fragmentary myoclonus (EFM) is a frequent finding in patients undergoing video-polysomnography (VPSG). We aimed to evaluate the potential effect of sleep-related breathing disorder's treatment with positive airway pressure (PAP) therapy on EFM.
METHODS
One hundred consecutive patients with EFM and sleep-related breathing disorder subsequently treated with PAP at the sleep lab of the Medical University of Innsbruck, Department of Neurology, Austria, were included. Each patient underwent two nights of VPSG: the first night without and the second night with PAP therapy. Fragmentary myoclonus was automatically scored with validated software, and fragmentary myoclonus index (FMI) and minutes of non-rapid eye movement (NREM) sleep with EFM (min) were calculated.
RESULTS
Under PAP therapy there was a significant decrease in the min - 60.5 (9.5-161.8) at baseline vs. 37.5 (6.3-168.8) minutes under PAP, p = 0.025. No significant differences were observed for FMI between the two nights. Sleep variables, sleep diagnoses, comorbidities, and medication did not influence FMI or the min.
CONCLUSIONS
The initiation of PAP treatment led to a significant reduction of min, but not of FMI. The results suggest that PAP therapy might influence the distribution of FM potentials.
Topics: Humans; Male; Female; Middle Aged; Polysomnography; Continuous Positive Airway Pressure; Sleep Apnea Syndromes; Adult; Nocturnal Myoclonus Syndrome; Aged; Myoclonus
PubMed: 38796980
DOI: 10.1016/j.sleep.2024.05.044 -
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 -
Brain Sciences May 2024The COVID-19 pandemic increased symptoms of stress and anxiety and induced changes in sleep quality, dream activity, and parasomnia episodes. It has been shown that...
BACKGROUND
The COVID-19 pandemic increased symptoms of stress and anxiety and induced changes in sleep quality, dream activity, and parasomnia episodes. It has been shown that stressful factors and/or bad sleep habits can affect parasomnia behaviors. However, investigations on how COVID-19 has affected sleep, dreams, and episode frequency in parasomnias are rare. The current study focuses on the impact of the pandemic on a specific parasomnia characterized by speech production (sleep talking, ST).
METHODS
We selected 27 participants with frequent ST episodes (STs) during the pandemic and compared them with 27 participants with frequent STs from a previous study conducted during a pre-pandemic period. All participants performed home monitoring through sleep logs and recorded their nocturnal STs for one week.
RESULTS
We observed a higher frequency of STs in the pandemic group. Moreover, STs were related to the emotional intensity of dreams, independent of the pandemic condition. The pandemic was associated with lower bizarreness of dreams in the pandemic group. There were no differences in sleep variables between the two groups.
CONCLUSION
Overall, these results suggest a stressful effect of COVID-19 on the frequency of STs. Both the pandemic and the frequency of STs affect qualitative characteristics of dreams in this population.
PubMed: 38790464
DOI: 10.3390/brainsci14050486