Search Results (49)

Sleep disorders and stroke are intricately linked through a complex, bidirectional relationship. Sleep disturbances such as obstructive sleep apnea (OSA), insomnia, and restless legs syndrome (RLS) not only increase the risk of stroke but also frequently emerge as consequences of cerebrovascular events. OSA, in particular, is associated with a two- to three-fold increased risk of incident stroke, primarily through mechanisms involving intermittent hypoxia, systemic inflammation, endothelial dysfunction, and autonomic dysregulation. Conversely, stroke can disrupt sleep architecture and trigger or exacerbate sleep disorders, including insomnia, hypersomnia, circadian rhythm disturbances, and breathing-related sleep disorders. These post-stroke sleep disturbances are common and significantly impair rehabilitation, cognitive recovery, and quality of life, yet they remain underdiagnosed and undertreated. Early identification and management of sleep disorders in stroke patients are essential to optimize recovery and reduce the risk of recurrence. Therapeutic strategies include lifestyle modifications, pharmacological treatments, medical devices such as continuous positive airway pressure (CPAP), and emerging alternatives for CPAP-intolerant individuals. Despite growing awareness, significant knowledge gaps persist, particularly regarding non-OSA sleep disorders and their impact on stroke outcomes. Improved diagnostic tools, broader screening protocols, and greater integration of sleep assessments into stroke care are urgently needed. This narrative review synthesizes current evidence on the interplay between sleep and stroke, emphasizing the importance of personalized, multidisciplinary approaches to diagnosis and treatment. Advancing research in this field holds promise for reducing the global burden of stroke and improving long-term outcomes through targeted sleep interventions. Full article

The MAM domain-containing glycosylphosphatidylinositol anchor 1 (MDGA1) gene, which encodes a protein involved in synaptic inhibition, has been identified as a potential risk gene for restless legs syndrome. A recent study in the Chinese population described increased MDGA1 methylation levels in patients with idiopathic RLS (iRLS) compared to healthy controls. In this study, we investigated the possible association between the most common variants in the MDGA1 gene and the risk for iRLS in a Caucasian Spanish population. We assessed the frequencies of MDGA1 rs10947690, MDGA1 rs61151079, and MDGA1 rs79792089 genotypes and allelic variants in 263 patients with idiopathic RLS and 280 healthy controls using a specific TaqMan-based qPCR assay. We also analyzed the possible influence of the genotype frequencies on several variables, including age at the onset of RLS, gender, a family history of RLS, and response to drugs commonly used in the treatment of RLS. The frequencies of the genotypes and allelic variants of the three common missense SNVs studied did not differ significantly between RLS patients and controls, neither in the whole series nor when analyzing each gender separately; were not correlated with age at onset and the severity of RLS assessed by the International Restless Legs Syndrome Study Group Rating Scale (IRLSSGRS); and were not related to a family history of RLS or the pharmacological response to dopamine agonists, clonazepam, or gabaergic drugs. Our findings suggest that common missense SNVs in the MDGA1 gene are not associated with the risk of developing idiopathic RLS in Caucasian Spanish people. Full article

Background and Objectives: According to the literature, Restless Legs Syndrome (RLS) often remains underdiagnosed, with only a small proportion of individuals experiencing symptoms receiving an official diagnosis, highlighting the need for effective screening and diagnostic tools. The International Restless Legs Syndrome Study Group Rating Scale (IRLS) is a widely used tool for assessing the severity of Restless Legs Syndrome (RLS). However, a validated Lithuanian version has not yet been established. This study aimed to validate the Lithuanian version of the IRLS and assess its reliability, diagnostic performance, and correlation with clinical and demographic factors. Materials and Methods: This retrospective study included 136 patients who completed the Lithuanian version of the IRLS and underwent polysomnographic and clinical evaluations at the Department of Neurology of the Lithuanian University of Health Sciences between 2018 and 2024. A total of 134 patients were analyzed: 66 with clinically confirmed RLS and 68 controls without sleep disorders. Statistical analysis included the Mann–Whitney U test, chi-squared tests, Receiver Operating Characteristics (ROC) curve analysis, multivariate logistic regression, and Akaike Information Criterion (AIC). Results: The Lithuanian IRLS demonstrated good diagnostic accuracy with an Area Under the Curve (AUC) value of 0.843 (95% CI: 0.782–0.904), with an optimal cut-off score of 7.50, resulting in high sensitivity (92.4%) and moderate specificity (66.2%). Multivariate regression identified higher IRLS scores (OR = 1.212, 95% CI: 1.084–1.356, p < 0.001) and a higher periodic limb movements of sleep arousal index (PLMSAI) (OR = 1.961, 95% CI: 1.036–3.712, p = 0.039) as significant independent predictors of RLS. After adjustments for age and sex, both IRLS scores and PLMSAI remained statistically significant predictors. Conclusions: the Lithuanian version of IRLS is a valid and reliable instrument for assessing RLS severity. Its diagnostic performance supports its use in clinical and research settings for identifying and monitoring RLS in Lithuanian population. Full article

Background/Objectives: Sleep disorders (SDs) and Restless Legs Syndrome (RLS) have been reported with high prevalence in Multiple Sclerosis (MS), but data on Pediatric-Onset MS (POMS) are scarce. This study aims to assess the prevalence of SDs, particularly RLS, in a POMS cohort and examine associated clinical features. Methods: We recruited POMS patients who attended the POMS Center of the Bambino Gesù Children’s Hospital between September 2021 and February 2023; they were evaluated for SDs using the Pittsburgh Sleep Quality Index (PSQI) or the Sleep Disturbance Scale for Children (SDSC) and screened for RLS. Correlations with demographical, clinical, neuroradiological, and laboratory findings were analyzed. Results: We recruited 44 POMS patients, of whom 39% were classified as “good sleepers” and 61% were identified as “poor sleepers.” RLS was diagnosed in 10 patients (22.7%). Those with RLS were older and had higher Expanded Disability Status Scale (EDSS) scores compared to non-RLS patients (p = 0.028; p = 0.03). The presence of RLS did not show any significant correlation with MRI lesion load or laboratory data. Conclusions: Our findings suggest an increased rate of SDs and RLS in pediatric MS patients compared to the general pediatric population. Clinical data could support a secondary form of RLS in this population, but results need further confirmation. Full article

Background: Restless legs syndrome (RLS) is a common sensorimotor sleep disorder that affects sleep quality of life. Much effort has been made to make progress in RLS pharmacotherapy; however, patients with RLS still report poor long-term symptom control. Methods: Comprehensive Mendelian randomization (MR) was performed to search for potential causal genes and drug targets using the cis-pQTL and RLS GWAS data. Robustness was validated using the summary-based Mendelian randomization (SMR) method and co-localization analysis. Further evidence of pleiotropy of the target genes and their potential side effects was provided by phenome-wide MR analysis (MR-PheWAS). Finally, molecular docking simulations were conducted on drug candidates corresponding to these targets, which revealed promising binding affinities and interaction patterns and underscored the druggable potential of the target gene. All of the analyses above were conducted in the context of Homo sapiens. Results: MAN1A2 showed a statistically significant result in the MR analysis, which was validated through SMR and co-localization analysis. The MR-PheWAS showed a low probability of pleiotropy and prospective side effects. Molecular docking was used to visualize the binding structure and fine affinity for MAN1A2 and the drugs predicted by DSigDB. Conclusions: Our study provides comprehensive evidence supporting MAN1A2 as a promising causal gene and therapeutic target for RLS, offering insights into the underlying molecular mechanisms and paving the way for future drug development efforts. Full article

Iron deficiency (ID) and restlessness are associated with sleep/wake-disorders (e.g., restless legs syndrome (RLS)) and neurodevelopmental disorders (attention deficit/hyperactivity and autism spectrum disorders (ADHD; ASD)). However, a standardized approach to assessing ID and restlessness is missing. We reviewed iron status and family sleep/ID history data collected at a sleep/wake behavior clinic under a quality improvement/quality assurance project. Restlessness was explored through patient and parental narratives and a ‘suggested clinical immobilization test’. Of 199 patients, 94% had ID, with 43% having a family history of ID. ADHD (46%) and ASD (45%) were common conditions, along with chronic insomnia (61%), sleep-disordered breathing (50%), and parasomnias (22%). In unadjusted analysis, a family history of ID increased the odds (95% CI) of familial RLS (OR: 5.98, p = 0.0002, [2.35–15.2]), insomnia/DIMS (OR: 3.44, p = 0.0084, [1.37–8.64]), and RLS (OR: 7.00, p = 0.01, [1.49–32.93]) in patients with ADHD, and of insomnia/DIMS (OR: 4.77, p = 0.0014, [1.82–12.5]), RLS/PLMS (OR: 5.83, p = 0.009, [1.54–22.1]), RLS (OR: 4.05, p = 0.01, [1.33–12.3]), and familial RLS (OR: 2.82, p = 0.02, [1.17–6.81]) in patients with ASD. ID and restlessness were characteristics of ADHD and ASD, and a family history of ID increased the risk of sleep/wake-disorders. These findings highlight the need to integrate comprehensive blood work and family history to capture ID in children and adolescents with restless behaviors. Full article

Many drastic actions are taken by cocaine users for the sake of experiencing high levels of dopamine, which depends on iron for its synthesis. Dopamine depletion and iron deficiency are also involved in the symptoms of restless leg syndrome (RLS). The intersecting biochemical pathways of cocaine use, iron deficiency, and RLS have not been adequately investigated. This case report reveals the successful treatment of a patient experiencing these conditions. A 63-year-old male with a history of cocaine use disorder, insomnia, and RLS sought emergency care for suicidality. Upon admission, he was also found to be iron deficient. He revealed that his RLS worsened when he attempted to abstain from cocaine. He also used alcohol to sustain the effects of cocaine when the cost of cocaine was too high. During hospitalization, his mood, cravings, and RLS were resolved with adjunctive iron supplementation, as well as treatment with 300 mg of Wellbutrin (bupropion hydroxychloride). If iron deficiency is present, the replenishment of the adequate dopaminergic receptor density and function via supplementation may play an essential role in the prevention of cocaine use and the cessation of cocaine withdrawal symptoms. Further research is warranted to validate these findings and to investigate the implications of iron supplementation in addiction medicine. Full article

Current evidence suggests that iron deficiency (ID) plays a key role in the pathogenesis of conditions presenting with restlessness such as attention deficit hyperactivity disorder (ADHD) and restless legs syndrome (RLS). In clinical practice, ID and iron supplementation are not routinely considered in the diagnostic work-up and/or as a treatment option in such conditions. Therefore, we conducted a scoping literature review of ID guidelines. Of the 58 guidelines included, only 9 included RLS, and 3 included ADHD. Ferritin was the most frequently cited biomarker, though cutoff values varied between guidelines and depending on additional factors such as age, sex, and comorbidities. Recommendations surrounding measurable iron biomarkers and cutoff values varied between guidelines; moreover, despite capturing the role of inflammation as a concept, most guidelines often did not include recommendations for how to assess this. This lack of harmonization on the interpretation of iron and inflammation biomarkers raises questions about the applicability of current guidelines in clinical practice. Further, the majority of ID guidelines in this review did not include the ID-associated disorders, ADHD and RLS. As ID can be associated with altered movement patterns, a novel consensus is needed for investigating and interpreting iron status in the context of different clinical phenotypes. Full article

Restless legs syndrome (RLS) is a common neurological disorder. It disrupts sleep and well-being and is often associated with other conditions. This review examines the potential of dietary supplements to manage RLS symptoms and reduce reliance on medications. A total of 10 randomized clinical trials involving 482 participants were analyzed, focusing on the impact of various supplements on symptom severity, sleep quality, and daytime sleepiness. Findings suggest some supplements may have positive results. Magnesium oxide and vitamin B6 significantly improved sleep quality and RLS symptoms, with magnesium showing greater effectiveness. Vitamin D supplementation did not show significant benefits. Oral iron has promising results, indicating potential efficacy but issues related to compliance and absorption. Both vitamins C and E positively affect RLS symptoms, likely due to their antioxidant properties. Valerian improved RLS and sleep but did not show a statistically significant improvement. Despite these encouraging results, a high risk of bias was noted in half of the studies, emphasizing the need for more rigorous research. Overall, this review suggests that dietary supplements may be a promising approach to managing RLS. However, further investigation is required to confirm the efficacy and safety. Full article

Background: Restless legs syndrome/Willis–Ekbom disease (RLS/WED) has occasionally but not consistently been associated with cognitive and most notably language and executive impairment. The present study was conducted to investigate the cognitive trajectories of older individuals with RLS/WED. Methods: Participants were drawn from the randomly selected, older (>64 years), population-based HELIAD cohort. Individuals without dementia and with available neuropsychological evaluations at baseline and follow-up were considered for potential eligibility. A comprehensive assessment examining five principal components of cognition (memory, visuo-spatial ability, attention, executive function, and language) was administered to the participants. Generalized estimating equation analyses were used to examine the unadjusted and adjusted (for critical factors and covariates) effects of RLS/WED on cognition over time. Results: A total of 1003 predominantly female (59.5%), older (72.9 ± 4.9 years) participants with follow-up evaluations after a mean of 3.09 ± 0.85 years and without dementia at baseline and follow-up were included in the present study. Among them, 81 were diagnosed with RLS/WED at baseline. Global cognition, memory, attention, and executive and visuo-perceptual skills did not differ between those with and without RLS/WED. However, the RLS/WED group performed worse on language at baseline by a standard deviation of 0.249, while demonstrating a mitigated language decline over time, by a standard deviation of 0.063. The unadjusted models yielded similar results. Conclusions: Our findings were indicative of a baseline language disadvantage among older individuals with RLS/WED, but the initial discrepancy tends to dissolve over time. Full article

Background: We examined the association between restless legs syndrome (RLS) and comprehensive geriatric assessment (CGA) data in two older European populations. The second goal was to evaluate correlates of their quality of life (QoL). Methods: Diagnostic criteria of the International RLS Study Group (IRLSSG) and elements of CGA were used in this study. Results: Among the examined 246 participants, 77 (31.3%) suffered from RLS, more often in the UK (39.4%) than in Poland (25.4%) (p = 0.019). In the multivariate logistic regression model, female sex [OR (CI) = 3.29 (1.51–7.21); p = 0.0014], the number of medications per day [OR (CI) = 1.11 (1.02–1.20); p = 0.011] and alcohol consumption [OR (CI) = 5.41 (2.67–10.95); p < 0.001] increased the probability of RLS. Residing in Poland [OR (CI) = 3.06 (1.36–6.88); p = 0.005], the presence of RLS [OR (CI) = 2.90 (1.36–6.17); p = 0.004], chronic heart failure, [OR (CI) = 3.60 (1.75–7.41); p < 0.001], osteoarthritis [OR (CI) = 2.85 (1.47–5.49); p = 0.0016], and urinary incontinence [OR (CI) = 4.74 (1.87–11.9); p < 0.001] were associated with a higher probability of mobility dimension problems in the QoL. Higher physical activity was related to a lower probability of mobility problems [OR (CI) = 0.85 (0.78–0.92); p < 0.001]. Conclusions: female sex, the number of medications and alcohol consumption are independent correlates of RLS in older adults. RLS together with several chronic medical conditions and a low physical activity level were independent correlates of the mobility dimension of the QoL. Full article

Parknson’s disease (PD) is the second most common neurodegenerative disease, affecting 1% of people aged over 60. PD is characterized by a wide range of motor symptoms, however the clinical spectrum of PD covers a wide range of non-motor symptoms, as well. Sleep disorders are among the most common non-motor symptoms of PD, can occur at any stage of the disease and significantly affect quality of life. These include rapid eye movement sleep behavior disorder (RBD), restless legs syndrome (RLS), excessive daytime sleepiness (EDS), insomnia, obstructive sleep apnea (OSA) and circadian rhythm disturbances. One of the main challenges in PD research is identifying individuals during the prodromal phase of the disease. Combining genetic and prodromal data may aid the early identification of individuals susceptible to PD. This review highlights current data regarding the genetic component of sleep disorders in PD patients, focusing on genes that have currently been associated with this PD co-morbidity. Full article

This prospective study investigated white matter tracts associated with restless legs syndrome (RLS) severity in 69 patients with primary RLS using correlational tractography based on diffusion tensor imaging. Fractional anisotropy (FA) and quantitative anisotropy (QA) were analyzed separately to understand white matter abnormalities in RLS patients. Connectometry analysis revealed positive correlations between RLS severity and FA values in various white matter tracts, including the left and right cerebellum, corpus callosum forceps minor and major, corpus callosum body, right cingulum, and frontoparietal tract. In addition, connectometry analysis revealed that the FA of the middle cerebellar peduncle, left inferior longitudinal fasciculus, left corticospinal tract, corpus callosum forceps minor, right cerebellum, left frontal aslant tract, left dentatorubrothalamic tract, right inferior longitudinal fasciculus, left corticostriatal tract superior, and left cingulum parahippocampoparietal tract was negatively correlated with RLS severity in patients with RLS. However, there were no significant correlations between QA values and RLS severity. It is implied that RLS symptoms may be potentially reversible with appropriate treatment. This study highlights the importance of considering white matter alterations in understanding the pathophysiology of RLS and in developing effective treatment strategies. Full article

Background and Objectives: Chronic kidney disease (CKD) is a global public health issue with rising incidence linked to substantial morbidity and mortality. Selenium, an antioxidant trace element, has been linked to low serum levels in end-stage renal disease. Restless Leg Syndrome (RLS), a sleep disorder, is prevalent in CKD patients and significantly impacts their quality of life. The objective of this study was to examine the correlation between serum selenium levels and the prevalence of restless leg syndrome in individuals with chronic kidney disease. Materials and Methods: Forty-six CKD patients undergoing serum selenium level assessments between 1 January 2020 and 28 February 2022, at the Hitit University Faculty of Medicine Department of Nephrology Outpatient Clinic or Hemodialysis Unit, were included. Patients over 18 years of age with no history of hematological or oncological diseases or acute or chronic inflammatory conditions were included in the study groups. Patients taking selenium supplements were excluded. Demographic data, comorbidities, and laboratory values were collected, and RLS presence and severity were evaluated. Statistical analyses include descriptive statistics, correlation analysis, the Mann–Whitney U test, Student’s t test, and Chi-square test. Results: Among the 46 patients, 16 (34.78%) had RLS symptoms. The patient group included 34.78% predialysis, 34.78% peritoneal dialysis, and 30.44% hemodialysis patients, with a median age of 47.98 years. There was no difference in age, gender, and Charlson comorbidity between patients with or without RLS (p = 0.881, p = 0.702, p = 0.650). RLS prevalence varied across CKD subgroups, with hemodialysis patients having a higher prevalence (p = 0.036). Clinical parameters such as blood urea nitrogen, creatinine, calcium, phosphorus, platelet counts, and parathyroid hormone levels exhibited significant differences between patients with and without RLS (p < 0.05). Serum selenium levels were not significantly different between patients with and without RLS (p = 0.327). Conclusions: With an increased comorbidity burden, CKD poses a significant healthcare challenge. When accompanied by RLS, this burden can be debilitating. The difference in CKD stages between groups has shed light on a critical determinant of RLS in this population, emphasizing the role of the chronic kidney disease stage. In our study, serum selenium levels were not associated with the presence and severity of RLS. However, prospective studies with larger numbers of participants are needed to draw a definitive conclusion. Full article

Sleep disturbances are common in various neurological pathologies, including amyotrophic lateral sclerosis (ALS), multiple system atrophy (MSA), hereditary ataxias, Huntington’s disease (HD), progressive supranuclear palsy (PSP), and dementia with Lewy bodies (DLB). This article reviews the prevalence and characteristics of sleep disorders in these conditions, highlighting their impact on patients’ quality of life and disease progression. Sleep-related breathing disorders, insomnia, restless legs syndrome (RLS), periodic limb movement syndrome (PLMS), and rapid eye movement sleep behavior disorder (RBD) are among the common sleep disturbances reported. Both pharmacological and non-pharmacological interventions play crucial roles in managing sleep disturbances and enhancing overall patient care. Full article