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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 -
PloS One 2024Previous studies revealed that sleep disorders are potential risk factors for cardiovascular diseases, such as obstructive sleep apnea and rapid eye movement (REM) sleep...
BACKGROUND
Previous studies revealed that sleep disorders are potential risk factors for cardiovascular diseases, such as obstructive sleep apnea and rapid eye movement (REM) sleep behavior disorder (RBD). However, the causal associations between RBD and cardiovascular diseases remained unknown.
MATERIALS AND METHODS
We used the latest and largest summary-level genome-wide association studies of RBD, stroke and its subtypes, coronary artery disease (CAD), myocardial infarction (MI), and heart failure (HF) to select genetic variants as the instrumental variables. Mendelian randomization (MR) analysis was performed to test the causal associations between RBD and the cardiovascular diseases above. Inverse variance weighted method was used as the main analysis.
RESULTS
After multiple comparisons, genetically predicted RBD was significantly associated with the risk of HF [odds ratio (OR) = 1.033, 95% CI 1.013-1.052, p = 0.001]. Leave-one-out analysis further supported the robustness of the causal association. Furthermore, we identified a suggestive association between genetically predicted MI and RBD (OR = 0.716, 95% CI 0.546-0.940, p = 0.016). However, in our study no associations were identified of RBD with CAD or stroke and its subtypes.
CONCLUSION
Our study highlighted the potential associations between RBD and cardiovascular diseases at genetic level, including HF and MI. More studies were required to clarify the biological mechanisms involved the associations.
Topics: Humans; REM Sleep Behavior Disorder; Cardiovascular Diseases; Genome-Wide Association Study; Mendelian Randomization Analysis; Myocardial Infarction; Risk Factors; Polymorphism, Single Nucleotide; Genetic Predisposition to Disease; Heart Failure; Stroke
PubMed: 38771893
DOI: 10.1371/journal.pone.0301112 -
PloS One 2024Sleep problems are common in children with attention deficit hyperactivity disorder (ADHD). Children's sleep problem may influence, and be influenced by, parents' sleep...
Sleep problems are common in children with attention deficit hyperactivity disorder (ADHD). Children's sleep problem may influence, and be influenced by, parents' sleep problems as well as parents' ADHD symptoms. In the current study we examined the associations of parent-rated sleep quality and sleep timing of pre-adolescent children with parental insomnia symptoms, parental ADHD symptoms and dysfunctional attitudes and beliefs about sleep in a convenience sample recruited by advertisement (N = 120). Childhood sleep problems were common in the sample, with 82% of children exceeding the threshold for the presence of a paediatric sleep disorder. Children's sleep quality showed minimal association with their sleep timing and chronotype. Parental insomnia symptoms, ADHD symptoms and dysfunctional beliefs and attitudes about sleep all associated with their children's sleep quality, and with the sleep subdomains of sleep anxiety and parasomnias. In multiple regression analysis only parental insomnia score was a significant predictor of children's sleep quality. Children's bedtimes, wake times, sleep duration, chronotype or social jetlag did not associate with parents' ADHD or insomnia symptoms. Sleep quality was significantly poorer in children whose parents scored as both consistent for adult ADHD and probable for insomnia disorder compared to parents who scored as either ADHD consistent or insomnia probable, or those who parents scored as neither. We discuss the putative nature of the relationships between sleep quality of children with ADHD and parental ADHD and insomnia symptoms, and suggest that clinicians consider parental sleep when attending to children with ADHD.
Topics: Humans; Attention Deficit Disorder with Hyperactivity; Child; Male; Sleep Initiation and Maintenance Disorders; Female; Parents; Surveys and Questionnaires; Adult; Sleep Quality
PubMed: 38771841
DOI: 10.1371/journal.pone.0298377 -
BMC Oral Health May 2024The etiology of sleep bruxism in obstructive sleep apnea (OSA) patients is not yet fully clarified. This prospective clinical study aimed to investigate the connection...
BACKGROUND
The etiology of sleep bruxism in obstructive sleep apnea (OSA) patients is not yet fully clarified. This prospective clinical study aimed to investigate the connection between probable sleep bruxism, electromyographic muscle tone, and respiratory sleep patterns recorded during polysomnography.
METHODS
106 patients with OSA (74 males, 31 females, mean age: 56.1 ± 11.4 years) were divided into two groups (sleep bruxism: SB; no sleep bruxism: NSB). Probable SB were based on the AASM criteria: self-report of clenching/grinding, orofacial symptoms upon awakening, abnormal tooth wear and hypertrophy of the masseter muscle. Both groups underwent clinical examination for painful muscle symptoms aligned with Temporomandibular Disorders Diagnostic Criteria (DC/TMD), such as myalgia, myofascial pain, and headache attributed to temporomandibular disorder. Additionally, non-complaint positive muscle palpation and orofacial-related limitations (Jaw Functional Limited Scale-20: JFLS-20) were assessed. A one-night polysomnography with electromyographic masseter muscle tone (EMG) measurement was performed. Descriptive data, inter-group comparisons and multivariate logistic regression were calculated.
RESULTS
OSA patients had a 37.1% prevalence of SB. EMG muscle tone (N1-N3, REM; P = 0.001) and the number of hypopneas (P = 0.042) were significantly higher in the sleep bruxism group. While measures like apnea-hypopnea-index (AHI), respiratory-disturbance-index (RDI), apnea index (AI), hypopnea-index (HI), number of arousals, and heart rate (1/min) were elevated in sleep bruxers, the differences were not statistically significant. There was no difference in sleep efficiency (SE; P = 0.403). Non-complaint masseter muscle palpation (61.5%; P = 0.015) and myalgia (41%; P = 0.010) were significant higher in SB patients. Multivariate logistic regression showed a significant contribution of EMG muscle tone and JFLS-20 to bruxism risk.
CONCLUSION
Increased EMG muscle tone and orofacial limitations can predict sleep bruxism in OSA patients. Besides, SB patients suffer more from sleep disorder breathing. Thus, sleep bruxism seems to be not only an oral health related problem in obstructive apnea. Consequently, interdisciplinary interventions are crucial for effectively treating these patients.
TRIAL REGISTRATION
The study was approved by the Ethics Committee of Philipps-University Marburg (reg. no. 13/22-2022) and registered at the "German Clinical Trial Register, DRKS" (DRKS0002959).
Topics: Humans; Male; Female; Sleep Apnea, Obstructive; Sleep Bruxism; Middle Aged; Electromyography; Prospective Studies; Polysomnography; Masseter Muscle; Oral Health; Adult; Muscle Tonus
PubMed: 38745301
DOI: 10.1186/s12903-024-04351-1 -
International Journal of Qualitative... Dec 2024Restless Legs Syndrome (RLS) is a widespread condition that affects sleep leading to daytime sleepiness, depression, and reduced quality of life. This study aims to...
PURPOSE
Restless Legs Syndrome (RLS) is a widespread condition that affects sleep leading to daytime sleepiness, depression, and reduced quality of life. This study aims to determine and describe how patients with RLS experience their everyday life, with a focus on facilitators and barriers related to Maslow's hierarchical theory of human needs.
METHOD
Semi-structured interviews were analysed with qualitative content analysis resulting in facilitators and barriers affecting the fulfilment of the five human needs.
RESULTS
Addressing RLS symptoms through medications and a quiet sleep environment fulfils psychological needs. Control over RLS symptoms, engagement in activities, trust in treatments, and social support meet safety and security needs. Social inclusion, close relationships, and meaningful interactions fulfil a sense of belongingness and love needs despite RLS. Competence in managing RLS, effective self-care strategies, confident communication, and trust-building support esteem needs. Finally, comprehensive understanding through person-centred interventions and coping fulfils the self-actualization needs in managing RLS.
CONCLUSION
Holistic and person-centred interventions, including facilitators for the fulfilment of physiological, psychological, and social needs could help healthcare professionals to provide holistic care.
Topics: Humans; Restless Legs Syndrome; Qualitative Research; Female; Male; Middle Aged; Social Support; Quality of Life; Aged; Adaptation, Psychological; Adult; Self Care; Trust
PubMed: 38735061
DOI: 10.1080/17482631.2024.2348884 -
BMC Psychiatry May 2024Restless arms syndrome (RAS) is the most common variant of restless legs syndrome (RLS), which is easy to be ignored in clinical practice due to the lack of specific...
BACKGROUND
Restless arms syndrome (RAS) is the most common variant of restless legs syndrome (RLS), which is easy to be ignored in clinical practice due to the lack of specific diagnostic criteria. When effective therapeutic agents induced RAS and symptoms persisted after briefly observation, clinicians will face the challenge of weighing efficacy against side effects.
CASE PRESENTATION
A 67-year-old woman was admitted to a geriatric psychiatric ward with depression. Upon admission, the escitalopram dose was reduced from 15 mg to 10 mg per day, and the duloxetine dose was increased from 60 mg to 80 mg per day. The next night before bedtime, she developed itching and creeping sensations deep inside bilateral shoulders and arms, with the urge to move, worsening at rest, and alleviation after hammering. The symptoms persisted when escitalopram was discontinued. A history of RLS was confirmed. Treatment with 40 mg of duloxetine and 0.125 mg of pramipexole significantly improved depression, and the paresthesia disappeared, with no recurrence occurring 6 months after discharge.
DISCUSSION AND CONCLUSIONS
This case suggests that psychiatrists should pay attention to RLS variants when increasing doses of duloxetine. Long-term improvement can be achieved through dosage reduction combined with dopaminergic drugs instead of immediate discontinuation.
Topics: Aged; Female; Humans; Antidepressive Agents; Duloxetine Hydrochloride; Phenotype; Pramipexole; Restless Legs Syndrome; Serotonin and Noradrenaline Reuptake Inhibitors
PubMed: 38730422
DOI: 10.1186/s12888-024-05763-7 -
PloS One 2024Restless Legs Syndrome (RLS) is a common sleep disorder characterized by an urge to move the legs that is responsive to movement (particularly during rest), periodic leg...
Restless Legs Syndrome (RLS) is a common sleep disorder characterized by an urge to move the legs that is responsive to movement (particularly during rest), periodic leg movements during sleep, and hyperarousal. Recent evidence suggests that the involvement of the adenosine system may establish a connection between dopamine and glutamate dysfunction in RLS. Transcranial magnetic stimulation (TMS) is a non-invasive electrophysiological technique widely applied to explore brain electrophysiology and neurochemistry under different experimental conditions. In this pilot study protocol, we aim to investigate the effects of dipyridamole (a well-known enhancer of adenosinergic transmission) and caffeine (an adenosine receptor antagonist) on measures of cortical excitation and inhibition in response to TMS in patients with primary RLS. Initially, we will assess cortical excitability using both single- and paired-pulse TMS in patients with RLS. Then, based on the measures obtained, we will explore the effects of dipyridamole and caffeine, in comparison to placebo, on various TMS parameters related to cortical excitation and inhibition. Finally, we will evaluate the psycho-cognitive performance of RLS patients to screen them for cognitive impairment and/or mood-behavioral dysfunction, thus aiming to correlate psycho-cognitive findings with TMS data. Overall, this study protocol will be the first to shed lights on the neurophysiological mechanisms of RLS involving the modulation of the adenosine system, thus potentially providing a foundation for innovative "pharmaco-TMS"-based treatments. The distinctive TMS profile observed in RLS holds indeed the potential utility for both diagnosis and treatment, as well as for patient monitoring. As such, it can be considered a target for both novel pharmacological (i.e., drug) and non-pharmacological (e.g., neuromodulatory), "TMS-guided", interventions.
Topics: Humans; Restless Legs Syndrome; Transcranial Magnetic Stimulation; Caffeine; Pilot Projects; Dipyridamole; Male; Adenosine; Adult; Female; Purinergic P1 Receptor Antagonists; Middle Aged; Proof of Concept Study
PubMed: 38728342
DOI: 10.1371/journal.pone.0302829