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Li FJ, Li JY, Zhang RY, Liu XJ, Lv BC, Zhang T, Liu YN, Zhang ZX, Zhang W, Cui GY, Xu CY. PTPRD pleiotropy, genetically driven childbirth timing, and corpus callosum microstructure as potential mechanisms underlying ADHD-RLS comorbidity. Sleep Med 2025; 133:106631. [PMID: 40561837 DOI: 10.1016/j.sleep.2025.106631] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2024] [Revised: 06/05/2025] [Accepted: 06/05/2025] [Indexed: 06/28/2025]
Abstract
OBJECTIVES To investigate the genetic mechanisms underlying the comorbidity of attention deficit hyperactivity disorder (ADHD) and restless legs syndrome (RLS). METHODS We conducted a three-stage study to investigate the genetic relationship between ADHD and RLS. In the first stage, we used linkage disequilibrium score regression (LDSC) and high-definition likelihood (HDL) to assess genome-wide genetic correlations. In the second stage, pleiotropic analysis under composite null hypothesis (PLACO) and functional mapping and annotation (FUMA) were applied to identify pleiotropic genes shared by both disorders. In the third stage, network Mendelian randomization (MR) was used to explore gene-driven causal pathways between ADHD and RLS. RESULTS Genome-wide analyses revealed a significant genetic correlation between ADHD and RLS. Fourteen potential pleiotropic genes were identified, six of which showed strong protein-protein interaction evidence. Colocalization analysis confirmed PTPRD as a likely causative gene. Pleiotropic loci were enriched in brain tissue, and functional annotation indicated involvement in pathways related to learning, memory, synaptic plasticity, and neural development. MR analysis demonstrated bidirectional gene-driven causality: ADHD may increase the risk of RLS by leading to an earlier age at first childbirth, whereas RLS may contribute to ADHD via reduced fractional anisotropy in the corpus callosum body, primarily driven by increased radial diffusivity. CONCLUSIONS Our findings suggest that the PTPRD gene may contribute to the comorbidity of ADHD and RLS through pleiotropic effects. Genetically influenced childbirth timing and alterations in corpus callosum white matter microstructure may represent potential neurodevelopmental pathways linking the two conditions.
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Affiliation(s)
- Fu-Jia Li
- Department of Neurology, The Eighth Affiliated Hospital, Sun Yat-Sen University, Shenzhen, Guangdong, China
| | - Jin-Yu Li
- Department of Neurology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Ru-Yu Zhang
- Department of Pulmonary and Critical Care Medicine, First People's Hospital of Zigong, Zigong, Sichuan, China
| | - Xuan-Jing Liu
- Department of Neurology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Bing-Chen Lv
- Department of Neurology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Tao Zhang
- Department of Neurology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Yu-Ning Liu
- Department of Neurology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Zi-Xuan Zhang
- Department of Neurology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Wei Zhang
- Department of Neurology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Gui-Yun Cui
- Department of Neurology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.
| | - Chuan-Ying Xu
- Department of Neurology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.
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Yoganathan S, Chakrabarty B. Epidemiology of Pediatric Restless Leg Syndrome. Sleep Med Clin 2025; 20:183-192. [PMID: 40348530 DOI: 10.1016/j.jsmc.2025.02.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/14/2025]
Abstract
Pediatric Restless Legs Syndrome (RLS)/Willis Ekbom Disease is prevalent at around 2% with onset around the end of first decade. There is a strong genetic predisposition and no gender preference till late adolescence, with a female preponderance beyond that. Insomnia-like symptoms, periodic limb movement disorder (PLMD), and excessive daytime sleepiness are significantly associated causing impaired cognition and behavior. RLS can be associated with chronic kidney disease, celiac disease, migraine, and pediatric-onset multiple sclerosis. A close clinical differential is growing pains. Case definitions need to be refined and prospective studies with relevant serum and radiologic biomarkers need planning.
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Affiliation(s)
- Sangeetha Yoganathan
- Pediatric Neurology Division, Department of Neurological Sciences, CMC, Vellore, Tamil Nadu, India
| | - Biswaroop Chakrabarty
- Child Neurology Division, Department of Pediatrics, All-India Institute of Medical Sciences (AIIMS), New Delhi, India.
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3
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Schormair B. Genetics of Restless Legs Syndrome: Insights from Genome-Wide Association Studies. Sleep Med Clin 2025; 20:193-202. [PMID: 40348531 DOI: 10.1016/j.jsmc.2025.02.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/14/2025]
Abstract
Genome-wide association studies (GWAS) of common and low-frequency variants have discovered 164 genetic risk loci for restless legs syndrome (RLS) in adult populations of European ancestry. Sex-specific GWAS meta-analyses revealed largely overlapping genetic risk profiles for women and men and are in line with a nongenetic risk factor driving the higher prevalence seen in women. Genetic investigations of pediatric RLS are limited, but the likely inclusion of early-onset cases in GWAS of adult populations and the similar phenotypic presentation of both forms suggest that genetic risk variants identified in adult populations transfer to pediatric RLS.
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Affiliation(s)
- Barbara Schormair
- Institute of Neurogenomics, Computational Health Department, Helmholtz Zentrum München - German Research Center for Environmental Health (GmbH), Ingolstaedter Landstrasse 1, Neuherberg 85764, Germany; Institute of Human Genetics, TUM School of Medicine and Health, Technical University Munich, Munich, Germany.
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4
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Mammarella V, Breda M, Esposito D, Orecchio S, Polese D, Bruni O. Psychiatric Comorbidities in Pediatric Restless Leg Syndrome. Sleep Med Clin 2025; 20:209-218. [PMID: 40348533 DOI: 10.1016/j.jsmc.2025.02.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/14/2025]
Abstract
Recent research reported an association between pediatric Restless Leg Syndrome (RLS) and psychiatric disorders, in particular attention-deficit hyperactivity disorder in which shared symptoms, such as restlessness and difficulty concentrating, can make differential diagnosis challenging. Comorbidities with depression and anxiety, present in adults, have to be considered in children. Behavioral and psychosomatic disorders and autism can be associated with RLS. Both neurobiologic mechanisms and clinical implication could explain the several comorbidities. In clinical practice, pediatric RLS patients should be evaluated for the presence of psychiatric disorders to tailor multidisciplinary intervention and integrated treatment.
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Affiliation(s)
- Valeria Mammarella
- Department of Psychology, Sapienza University of Rome, Via dei Marsi 78, Rome 00185
| | - Maria Breda
- Department of Psychology, Sapienza University of Rome, Via dei Marsi 78, Rome 00185
| | | | | | - Daniela Polese
- Department of Neuroscience, Mental Health and Sensory Organs NESMOS, Sapienza University of Rome, Sant'Andrea Hospital, Via di Grottarossa 1035-1039, Rome 00189, Italy
| | - Oliviero Bruni
- Department Developmental and Social Psychology, Sapienza University of Rome, Via dei Marsi 78, Rome 00185, Italy.
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Auerbach M, DeLoughery TG, Tirnauer JS. Iron Deficiency in Adults: A Review. JAMA 2025; 333:1813-1823. [PMID: 40159291 DOI: 10.1001/jama.2025.0452] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/02/2025]
Abstract
Importance Absolute iron deficiency, defined as low iron stores with or without anemia, affects approximately 2 billion people worldwide and 14% of adults in the US. Iron-deficiency anemia, defined as low hemoglobin due to low iron stores, affects approximately 1.2 billion people worldwide, including 10 million in the US. Observations Absolute iron deficiency progresses from low iron stores to iron-deficiency anemia. Individuals with nonanemic iron deficiency or iron-deficiency anemia may be asymptomatic or experience fatigue, irritability, depression, difficulty concentrating, restless legs syndrome (32%-40%), pica (40%-50%), dyspnea, lightheadedness, exercise intolerance, and worsening heart failure (HF). Symptom prevalences vary depending on age, comorbidities (eg, chronic kidney disease [CKD], HF), and severity and rate of development of iron deficiency. The most common causes of iron deficiency are bleeding (menstrual, gastrointestinal), impaired iron absorption (atrophic gastritis, celiac disease, bariatric surgical procedures), inadequate dietary iron intake, and pregnancy. In high-income countries, approximately 38% of nonpregnant, reproductive-age women have iron deficiency without anemia and about 13% have iron-deficiency anemia. During the third trimester of pregnancy, iron deficiency affects up to 84% of pregnant women, based on data from high-income countries. Additional risk factors include use of nonsteroidal anti-inflammatory drugs, inflammatory bowel disease (IBD [13%-90%]), and other chronic inflammatory conditions, such as CKD (24%-85%), HF (37%-61%), and cancer (18%-82%). Testing for iron deficiency is indicated for patients with anemia and/or symptoms of iron deficiency (fatigue, pica, or restless legs syndrome) and should be considered for those with risk factors such as heavy menstrual bleeding, pregnancy, or IBD. Iron deficiency is diagnosed by low serum ferritin (typically <30 ng/mL) in individuals without inflammatory conditions or by transferrin saturation (iron/total iron binding capacity × 100) less than 20%. Causes of iron deficiency should be identified and treated. Oral iron (ferrous sulfate 325 mg/d or on alternate days) is typically first-line therapy. Intravenous iron is indicated for patients with oral iron intolerance, poor absorption (celiac disease, post-bariatric surgical procedure), chronic inflammatory conditions (CKD, HF, IBD, cancer), ongoing blood loss, and during the second and third trimesters of pregnancy. Conclusions and Relevance Iron deficiency and iron-deficiency anemia are common conditions that may cause symptoms such as fatigue, exercise intolerance, and difficulty concentrating. Ferritin and/or transferrin saturation are required for diagnosis and screening. Oral iron is first-line therapy for most patients. Intravenous iron is used for individuals who do not tolerate or have impaired absorption of oral iron, those with ongoing blood loss, certain chronic inflammatory conditions (IBD, CKD, HF, cancer), and during the second and third trimesters of pregnancy.
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Affiliation(s)
- Michael Auerbach
- Auerbach Hematology and Oncology, Baltimore, Maryland
- Georgetown University School of Medicine, Washington, DC
| | - Thomas G DeLoughery
- Knight Cancer Institute, Division of Hematology and Medical Oncology, Oregon Health & Science University, Portland
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Anupama AV, Mehta A, Javali M, Eswarappa M, Rangaiah P, Acharya P. Prevalence, Risk Factors, and Psychosocial Impact of Restless Legs Syndrome in End-Stage Renal Disease Patients Undergoing Hemodialysis - A Cross-Sectional Study. Ann Indian Acad Neurol 2025; 28:387-391. [PMID: 40470664 PMCID: PMC12192391 DOI: 10.4103/aian.aian_1038_24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2024] [Revised: 02/19/2025] [Accepted: 03/15/2025] [Indexed: 06/16/2025] Open
Abstract
BACKGROUND AND OBJECTIVES Restless legs syndrome (RLS) is common but often underdiagnosed in patients with end-stage renal disease (ESRD) undergoing hemodialysis, significantly impacting their quality of life. This study investigates the prevalence, risk factors, and psychosocial effects of RLS in this population. METHODS A cross-sectional study was conducted among 308 hemodialysis patients at a tertiary care hospital. RLS was diagnosed based on the International Restless Legs Syndrome Study Group criteria. The severity of RLS, sleep quality, and mental health were assessed using the International Restless Legs Syndrome (IRLS) Severity Score, Pittsburgh Sleep Quality Index, and Hospital Anxiety and Depression Scale. Clinical and biochemical parameters were also analyzed. Statistical significance was determined using Chi-squared and unpaired t -tests ( P < 0.05). RESULTS RLS was identified in 46 patients (14.9%). Among them, 56.6% had mild symptoms, 41.3% had moderate symptoms, and 2.1% had severe symptoms. Patients with RLS were younger (50.15 ± 12.19 vs. 57.41 ± 13.43 years, P = 0.001) and had lower body weight (57.89 ± 9.64 vs. 62.78 ± 10.58 kg, P = 0.03). Anxiety and depression were significantly higher in the RLS group ( P = 0.001). Poor sleep quality was reported in 97.8% of RLS patients ( P = 0.001). Hemoglobin ( P = 0.02) and thyroid-stimulating hormone ( P = 0.03) levels also differed significantly between groups. CONCLUSIONS RLS is highly prevalent in ESRD patients undergoing hemodialysis and is associated with significant psychosocial burden and poor sleep quality.
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Affiliation(s)
- Alamanda Venkata Anupama
- Department of Neurology, Ramaiah Medical College and Hospitals, Ramaiah University of Applied Sciences, Bengaluru, Karnataka, India
| | - Anish Mehta
- Department of Neurology, Ramaiah Medical College and Hospitals, Ramaiah University of Applied Sciences, Bengaluru, Karnataka, India
| | - Mahendra Javali
- Department of Neurology, Ramaiah Medical College and Hospitals, Ramaiah University of Applied Sciences, Bengaluru, Karnataka, India
| | - Mahesh Eswarappa
- Department of Neurology, Ramaiah Medical College and Hospitals, Ramaiah University of Applied Sciences, Bengaluru, Karnataka, India
| | - Pradeep Rangaiah
- Department of Neurology, Ramaiah Medical College and Hospitals, Ramaiah University of Applied Sciences, Bengaluru, Karnataka, India
| | - Purushottam Acharya
- Department of Neurology, Ramaiah Medical College and Hospitals, Ramaiah University of Applied Sciences, Bengaluru, Karnataka, India
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Vafaei A, Khorashadizadeh F, Saberi-Karimian M, Soflaei SS, Amini M, Rashid A, Yousefian S, Ferns GA, Esmaily H, Ghayour-Mobarhan M, Salaran R, Taherian F. Association of restless legs syndrome and obesity: A sub-population of the MASHAD cohort study. Neurobiol Sleep Circadian Rhythms 2025; 18:100113. [PMID: 40104670 PMCID: PMC11914754 DOI: 10.1016/j.nbscr.2025.100113] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2024] [Revised: 02/05/2025] [Accepted: 02/05/2025] [Indexed: 03/20/2025] Open
Abstract
Introduction Restless Legs Syndrome (RLS), as a relatively unknown sleep disorder, often associated with obesity. The purpose of this study was to examine the relationship between RLS and different definitions of obesity within the Mashhad stroke and heart atherosclerotic disorder (MASHAD) cohort study population. Methods A total of 1006 subjects, with an average age of 57 (51.75-63.00) years old, were randomly selected from the MASHAD cohort study phase II. This sample included 449 males and 557 females, who were contacted by phone to inquire about RLS. Anthropometric measurements such as weight, height, waist circumference (WC), and hip circumference (HC) were taken. Central obesity was defined as a WC > 90 cm for men and >85 cm for women, as well as a waist-to-hip ratio (WHR) greater than 0.90 for men and 0.85 for women. Statistical analyses were conducted using R version 4.3.2 for Windows, with a significance level set at a two-sided P-value<0.05. Chi-squared and Fisher's exact tests were used to compare the categorical variables between two study groups. Logistic models applied to evaluate the association between RLS and BMI while adjusting for age effects. Results The study found a significant relationship between RLS and employment status (p-value = 0.04), marital status (p-value = 0.05), and BMI (p-value<0.001). The results showed that in the total population, the OR of RLS in subjects having BMI>30 kg/m2 increased to 1.50(1.10-2.03) after adjusting for confounding factors (p-value<0.01). A BMI>30 kg/m2 increased odds of RLS by 1.72 times in males (95%CI: 1.03-2.84, p-value<0.05), however this association was diminished after adjustment (OR = 1.20, 95%CI: 0.64-2.17). There was no significant association between BMI and RLS in females. Moreover, there was no significant association between RLS and obesity based on WC and WHR in fully adjusted model respectively. Conclusion There was a significant association between BMI and RLS. A BMI>30 kg/m2 increased the odds of RLS by 1.50 times in the study population.
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Affiliation(s)
- Azam Vafaei
- Faculty of Veterinary Medicine, Ferdowsi University of Mashhad, Mashhad, Iran
| | - Fatemeh Khorashadizadeh
- Department of Epidemiology and Biostatistics, Neyshabur University of Medical Sciences, Neyshabur, Iran
| | - Maryam Saberi-Karimian
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, 99199-91766, Mashhad, Iran
| | - Sara Saffar Soflaei
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, 99199-91766, Mashhad, Iran
- International UNESCO Center for Health-Related Basic Sciences and Human Nutrition, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mahnaz Amini
- Department of Pulmonary Disease, Lung Diseases Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Division of Sleep Medicine, Psychiatry and Behavioral Sciences Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Abolfazl Rashid
- International UNESCO Center for Health-Related Basic Sciences and Human Nutrition, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Sara Yousefian
- International UNESCO Center for Health-Related Basic Sciences and Human Nutrition, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Gordon A Ferns
- Brighton and Sussex Medical School, Division of Medical Education, Brighton, UK
| | - Habibollah Esmaily
- Department of Biostatistics, School of Health, Mashhad University of Medical Sciences, Mashhad, Iran
- Social Determinants of Health Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Majid Ghayour-Mobarhan
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, 99199-91766, Mashhad, Iran
- International UNESCO Center for Health-Related Basic Sciences and Human Nutrition, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Reza Salaran
- International UNESCO Center for Health-Related Basic Sciences and Human Nutrition, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Fatemeh Taherian
- International UNESCO Center for Health-Related Basic Sciences and Human Nutrition, Mashhad University of Medical Sciences, Mashhad, Iran
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Dunbar C, Sansom K, Lovato N, Vakulin A, Loffler KA, Nguyen K, Fitton J, Rajaratnam SMW, Sletten TL, Micic G, Ferguson SA, Wanstall SE, Brown BWJ, Harvey G, Adams R, Reynolds AC. Protocol for a pilot hybrid type I effectiveness-implementation study to improve help-seeking for sleep disorders in the future healthcare workforce: The Sleep Check Before Shift Work trial. SLEEP ADVANCES : A JOURNAL OF THE SLEEP RESEARCH SOCIETY 2025; 6:zpaf020. [PMID: 40351549 PMCID: PMC12062959 DOI: 10.1093/sleepadvances/zpaf020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/11/2024] [Revised: 02/05/2025] [Indexed: 05/14/2025]
Abstract
Sleep disorders are prevalent in shift workers but are commonly undiagnosed and unmanaged. This poses considerable safety, productivity, and health risks. There is limited education or early intervention to encourage awareness of, and treatment for, sleep disorders in young adults who will transition into careers requiring shift work. This study aims to investigate (a) the clinical effectiveness of simulated shift work exposure and cognitive performance feedback for prompting help-seeking for sleep problems, and (b) the feasibility and acceptability of implementing this intervention for future healthcare workers. A hybrid type I effectiveness-implementation trial will be conducted from June 2024 to December 2025 with prospective healthcare workers currently enrolled in a medicine, paramedicine, or nursing degree. Ninety adults (18-39 years) who self-report sleep disturbances will be recruited and complete a combination of structured clinical interviews, screening questionnaires, remote monitoring technology, and overnight polysomnography (PSG). Participants will be randomized across three conditions, with varying exposure to a simulated transition to night shift without sleep, and cognitive performance feedback. All individuals will attend a diagnostic appointment with a sleep psychologist or sleep physician and discuss help-seeking pathways for their sleep. The primary outcomes will be help-seeking from a health professional for sleep (yes/no), time to help-seeking (days), and road safety-related events over 12 months. Process evaluation will explore the feasibility and acceptability of this approach from the participants' perspective.
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Affiliation(s)
- Claire Dunbar
- Flinders Health and Medical Research Institute: Sleep Health, Flinders University, Adelaide, SA, Australia
| | - Kelly Sansom
- Flinders Health and Medical Research Institute: Sleep Health, Flinders University, Adelaide, SA, Australia
- Centre for Healthy Ageing, Health Futures Institute, Murdoch University, Perth, WA, Australia
| | - Nicole Lovato
- Flinders Health and Medical Research Institute: Sleep Health, Flinders University, Adelaide, SA, Australia
| | - Andrew Vakulin
- Flinders Health and Medical Research Institute: Sleep Health, Flinders University, Adelaide, SA, Australia
| | - Kelly A Loffler
- Flinders Clinical Trials, Flinders University, Adelaide, SA, Australia
| | - Katrina Nguyen
- Flinders Health and Medical Research Institute: Sleep Health, Flinders University, Adelaide, SA, Australia
| | - Josh Fitton
- Flinders Health and Medical Research Institute: Sleep Health, Flinders University, Adelaide, SA, Australia
| | - Shantha M W Rajaratnam
- School of Psychological Sciences and Turner Institute for Brain and Mental Health, Monash University, Melbourne, VIC, Australia
| | - Tracey L Sletten
- School of Psychological Sciences and Turner Institute for Brain and Mental Health, Monash University, Melbourne, VIC, Australia
| | - Gorica Micic
- Flinders Health and Medical Research Institute: Sleep Health, Flinders University, Adelaide, SA, Australia
| | | | - Sian E Wanstall
- Flinders Health and Medical Research Institute: Sleep Health, Flinders University, Adelaide, SA, Australia
| | - Brandon W J Brown
- Flinders Health and Medical Research Institute: Sleep Health, Flinders University, Adelaide, SA, Australia
| | - Gillian Harvey
- Caring Futures Institute, College of Nursing and Health Sciences, Flinders University, Adelaide, SA, Australia
| | - Robert Adams
- Flinders Health and Medical Research Institute: Sleep Health, Flinders University, Adelaide, SA, Australia
| | - Amy C Reynolds
- Flinders Health and Medical Research Institute: Sleep Health, Flinders University, Adelaide, SA, Australia
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Sharma A, Rai NK, Singh R. Clinical profile of restless leg syndrome and its effect on sleep and quality of life. J Family Med Prim Care 2025; 14:1359-1367. [PMID: 40396061 PMCID: PMC12088570 DOI: 10.4103/jfmpc.jfmpc_1194_24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2024] [Revised: 10/17/2024] [Accepted: 10/28/2024] [Indexed: 05/22/2025] Open
Abstract
Background Restless leg syndrome is a sensorimotor disorder characterized by unpleasant sensations primarily involving lower limb but may involve trunk, neck and upper limb. The present study analyzed the clinical profile of RLS patients and explored its association with sleep and quality of life. Methods A cross-sectional study was conducted among adult patients diagnosed of RLS based on the IRLSSG (International RLS Study Group) diagnostic criteria. Severity of RLS was assessed using the IRLSSG rating scale. Sleep quality, daytime sleepiness, and quality of life were assessed using the Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, and RLS Quality Of Life Scale (RLSQOL). Results We enrolled 133 participants, of mean age 45.9 ± 15.2 years and 57.14% (76) being females. Different sensory-motor complaints were present, predominant sensory complaints being pain in 56.39% (75) and motor complaint being excessive movements (78.20% (104)). 80.45% (107) of individuals had sleep complaints including delayed onset sleep, repeated awakening, and nonrefreshing sleep. Excessive daytime sleepiness was present in 56.39% (75), and 78.2% (104) were poor sleepers. Upper limb was involved in 12.78% (17) of patients. Symptoms were majorly bilateral, but 6.02% (8) of patients had unilateral symptoms. RLSQOL score was 35.23 ± 10.3, and there was significant deterioration of sleep quality as well as quality of life with the increasing severity of RLS. Conclusion RLS remains an underdiagnosed, misdiagnosed, and undertreated clinical entity which has a negative effect on individuals' sleep as well as quality of life. Early detection of RLS by primary care physician will not only reduce the morbidity but also enhance the QOL of these individuals.
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Affiliation(s)
- Agrata Sharma
- Department of Neurology, AIIMS, Bhopal, Madhya Pradesh, India
| | | | - Ruchi Singh
- Department of Physiology, AIIMS, Bhopal, Madhya Pradesh, India
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10
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Prakash S, Vadodaria V, Chawda N, Shah CS, Prakash A. Restless head syndrome: A retrospective study. World J Methodol 2025; 15:97171. [PMID: 40115407 PMCID: PMC11525892 DOI: 10.5662/wjm.v15.i1.97171] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2024] [Revised: 07/07/2024] [Accepted: 07/15/2024] [Indexed: 09/29/2024] Open
Abstract
BACKGROUND Restless legs syndrome (RLS) is characterized by an urge to move with an unpleasant sensation in the lower limbs. RLS typically affects the legs. However, it can also affect several other body regions, such as the arms, abdomen, face, neck, head, and genital area. There are only a few reports of the RLS variant affecting the head. AIM To assess the epidemiological, clinical, and other aspects of the RLS variant affecting the head. METHODS We conducted a retrospective study of 17 adult patients (> 18 years) who met the RLS criteria and simultaneously experienced RLS-like symptoms in the head. RESULTS The median age at which symptoms appeared was 41.6 years. Males and females were equally affected (1.1:1). All 17 patients had uncomfortable sensations in the lower legs. Insomnia or disturbed sleep was the most common comorbidity (n = 16, 88.2%). However, headache was the most common presenting or primary symptom (n = 10, 70.5%). Dizziness or an abnormal sensation in the head was the second most common presenting symptom (5 patients, 29.4%). Other presenting features were leg pain, backache, and generalized body pain. All patients responded favorably to dopaminergic medications. CONCLUSION If RLS-related unpleasant sensations and pain are felt in the head, they may be misinterpreted as headache, dizziness, or psychosomatic symptoms. RLS and headaches in a subset of patients may be two phenotypic manifestations of the same disorder.
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Affiliation(s)
- Sanjay Prakash
- Department of Neurology, Smt. B. K. Shah Medical Institute and Research Centre, Sumandeep Vidyapeeth, Vadodara 391760, Gujarāt, India
| | - Varoon Vadodaria
- Department of Neurology, Smt. B. K. Shah Medical Institute and Research Centre, Sumandeep Vidyapeeth, Vadodara 391760, Gujarāt, India
| | - Niraj Chawda
- Department of Medicine, Smt. B. K. Shah Medical Institute and Research Centre, Sumandeep Vidyapeeth, Vadodara 391760, Gujarāt, India
| | - Chetsi S Shah
- Department of Neurology, Smt. B. K. Shah Medical Institute and Research Centre, Sumandeep Vidyapeeth, Vadodara 391760, Gujarāt, India
| | - Anurag Prakash
- Department of Medicine, Parul Institute of Medical Sciences and Research Centre, Parul University Waghodia, Vadodara 391760, India
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11
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Nguyen CTH, Nguyen NHM, Van TT. Restless Legs Syndrome in Psoriasis: A Multicenter Study on Its Prevalence, Severity, and Impact on Patients. Clin Cosmet Investig Dermatol 2025; 18:367-378. [PMID: 39968328 PMCID: PMC11832437 DOI: 10.2147/ccid.s502902] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2024] [Accepted: 02/04/2025] [Indexed: 02/20/2025]
Abstract
Purpose Psoriasis is a chronic inflammatory skin disease often associated with multiple comorbidities, including restless leg syndrome (RLS). However, the prevalence and impact of RLS on quality of life and clinical outcomes in patients with psoriasis remain underexplored, particularly in Asian populations. In this study, we compared the prevalence of RLS in patients with psoriasis and healthy controls and evaluated the association between RLS and quality of life, sleep disturbances, and clinical severity of psoriasis. Patients and Methods This multicenter, cross-sectional study involved 212 participants (106 patients with psoriasis and 106 healthy controls) and was conducted from March to July 2024 at three major hospitals in Ho Chi Minh City, Vietnam. RLS was diagnosed according to the International Restless Leg Syndrome Study Group (IRLSSG) criteria. The RLS severity, sleep quality, quality of life, and psoriasis severity were assessed using the Restless Legs Syndrome Rating Scale, Pittsburgh Sleep Quality Index, Dermatology Life Quality Index, and Psoriasis Area and Severity Index (PASI), respectively. Results The prevalence of RLS was significantly higher in patients with psoriasis than in healthy controls. Patients with psoriasis and RLS exhibited significantly poorer sleep quality and a greater impact on quality of life than those without RLS. The RLS group exhibited a higher PASI score, indicating more severe psoriasis. A strong positive correlation was observed between PASI and RLS severity. Conclusion RLS is significantly more prevalent in patients with psoriasis and is associated with worse sleep quality, greater impairment of quality of life, and increased psoriasis severity. Early screening for RLS in patients with psoriasis using the IRLSSG criteria may facilitate timely intervention and improve outcomes.
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Affiliation(s)
- Chuyen Thi Hong Nguyen
- Department of Dermatology, University of Medicine and Pharmacyat Ho Chi Minh City, 700000, Vietnam
| | - Nguyet Huu Minh Nguyen
- Department of Dermatology, University of Medicine and Pharmacyat Ho Chi Minh City, 700000, Vietnam
| | - Trung The Van
- Department of Dermatology, University of Medicine and Pharmacyat Ho Chi Minh City, 700000, Vietnam
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12
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Gokdeniz Yildirim A, Kaya D, Dost FS, Ontan MS, Isik AT. Sarcopenia Seems to Be Common in Older Patients With Restless Legs Syndrome. J Cachexia Sarcopenia Muscle 2025; 16:e13637. [PMID: 39568327 DOI: 10.1002/jcsm.13637] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2024] [Revised: 09/27/2024] [Accepted: 10/11/2024] [Indexed: 11/22/2024] Open
Abstract
BACKGROUND Restless legs syndrome (RLS) is a disorder characterized by nocturnally exacerbating pain that leads to significant sleep disturbances. The hormonal and metabolic changes caused by sleep disruption may increase the incidence of muscle-related diseases like sarcopenia in older adults, which is defined by a progressive loss of muscle strength and mass. This study aimed to investigate the relationship between RLS and sarcopenia, which may affect each other through common pathophysiological pathways in older adults. METHODS This was a cross-sectional study including 109 patients with RLS and 220 without RLS who applied to the geriatric clinic. RLS was assessed using the Turkish version of the International Restless Legs Syndrome Study Group (IRLSSG). Sarcopenia was diagnosed according to the European Working Group on Sarcopenia in Older People-2 criteria. All the demographics, comorbid conditions, medications and findings of comprehensive geriatric assessments were recorded. The association between RLS and sarcopenia was examined by logistic regression. RESULTS The mean age was 75 ± 7.4 and 73.8 ± 7 years for the RLS and the control groups, respectively (p > 0.05) and the ratio of females was higher in the RLS group (69.7% vs. 57.9%) (p = 0.035). The frequencies of coronary artery disease (CAD), hypertension (HT) and peripheral artery disease (PAD) were significantly higher in RLS patients (p = 0.020, p = 0.047, p = 0.010, respectively), while the prevalence of anaemia was 41% and 25-OH Vitamin D levels (25[OH]D) were higher than in the control group (p < 0.001). The frequency of probable sarcopenia and sarcopenia was higher in patients with RLS than in controls (20% vs. 11%, p = 0.037 and 8% vs. 2.3%, p = 0.047, respectively). A significant association between RLS and an increased likelihood of probable sarcopenia, sarcopenia and slow gait speed (odds ratio [OR]: 2.621, 95% confidence interval [CI] [1.265, 5.431]; OR: 4.542, 95% CI [1.284, 16.071]; OR: 2.663, 95% CI [1.432, 4.951], respectively) was found after adjusting for factors such as gender, HT, CAD, PAD, serum 25(OH)D levels, anaemia, chronic kidney disease (CKD) and nutritional status. However, the significance of low muscle mass disappeared (p > 0.05). CONCLUSION This study demonstrated that sarcopenia is prevalent among older patients with RLS, which seems to be associated with low muscle strength and slow gait speed. Given the negative health outcomes related to sarcopenia, interventions aimed at preventing its development could be significantly beneficial for patients with RLS in older adults as well.
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Affiliation(s)
- Açelya Gokdeniz Yildirim
- Department of Geriatric Medicine, Faculty of Medicine, Dokuz Eylul University, Izmir, Turkey
- Geriatric Sciences Association, Izmir, Turkey
| | - Derya Kaya
- Department of Geriatric Medicine, Faculty of Medicine, Dokuz Eylul University, Izmir, Turkey
- Geriatric Sciences Association, Izmir, Turkey
| | - Fatma Sena Dost
- Department of Geriatric Medicine, Faculty of Medicine, Dokuz Eylul University, Izmir, Turkey
- Geriatric Sciences Association, Izmir, Turkey
| | - Mehmet Selman Ontan
- Department of Geriatric Medicine, Faculty of Medicine, Dokuz Eylul University, Izmir, Turkey
- Geriatric Sciences Association, Izmir, Turkey
| | - Ahmet Turan Isik
- Department of Geriatric Medicine, Faculty of Medicine, Dokuz Eylul University, Izmir, Turkey
- Geriatric Sciences Association, Izmir, Turkey
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Tahanis A, Hashem V, Ondo W. Serum alpha-synuclein in restless legs syndrome. Sleep 2025; 48:zsae217. [PMID: 39283300 DOI: 10.1093/sleep/zsae217] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2024] [Revised: 08/16/2024] [Indexed: 01/14/2025] Open
Abstract
STUDY OBJECTIVES To determine any correlation between serum alpha-synuclein (α-syn) concentrations and restless legs syndrome (RLS), and to explore the impact of intravenous iron supplementation on serum α-syn levels. METHODS We collected clinical data on 113 RLS patients in whom serum α-syn levels were quantified using an ELISA kit and compared to a group of 45 age-matched controls. A subset of nine RLS patients who received intravenous (IV) iron underwent pre- and post-treatment blood sampling to assess α-syn and ferritin response. RESULTS A family history of RLS was reported by 62.8% of patients, and current dopaminergic augmentation was observed in 31.0%. Low serum ferritin levels below 75 μg/L were seen in 39.8%. Serum α-syn levels were found to be significantly decreased in RLS patients (mean: 7.7 ng/mL) compared to controls (mean: 10.7 ng/mL), p < .05. Stratification based on sex, age, and age of onset, did not reveal significant differences in α-syn levels. In nine RLS patients who received IV iron treatment, a linear correlation between fold change in α-syn and ferritin was observed (R: 0.7, p < .05). The temporal relation between serum α-syn and IV iron treatment showed a gradual decline of α-syn and ferritin by time correlation (p = .023, R: -.739). CONCLUSION In our study of 113 RLS participants, serum α-syn levels were decreased in RLS patients compared to healthy controls, and increased in the nine patients who received IV iron treatment in correlation with ferritin. This correlation could suggest a mechanism for reduced dopamine transmission in RLS.
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Affiliation(s)
- Aboud Tahanis
- Department of Neurosurgery, Center for Neuroregeneration, Houston Methodist Research Institute, Houston, TX, USA
| | - Vera Hashem
- Department of Neurology, Methodist Neurological Institute, Houston, TX, USA
| | - William Ondo
- Department of Neurology, Methodist Neurological Institute, Houston, TX, USA
- Department of Neurology, Weill Cornell Medical School, New York, NY, USA
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14
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Mitterling T, Riffert V, Heimel S, Leibetseder A, Kaindlstorfer A, Heidbreder A, Pichler J, von Oertzen TJ. Beyond sleep disturbance: Structured analysis of sleep habits, chronotype and sleep disorders in adults with glioma. A cross-sectional exploratory study. Sleep Med 2025; 125:146-154. [PMID: 39608186 DOI: 10.1016/j.sleep.2024.11.033] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2024] [Revised: 10/23/2024] [Accepted: 11/20/2024] [Indexed: 11/30/2024]
Abstract
OBJECTIVE To evaluate the prevalence of the whole spectrum of sleep disorders as well as sleep related motor phenomena and chronotype in adults with glioma and to analyze their link with tumor localization and grade. METHODS This prospective cross-sectional exploratory study included 79 patients with glioma irrespective of localization and type. Sleep habits, sleep disorders of any kind and chronotype were evaluated in structured interviews using validated disease specific scales. RESULTS For the whole sample the PSQI score was not increased, and specific insomnia severity was low. Patients with frontal tumors had worse sleep quality according to the PSQI and were more often allocated to worse ISI categories. The prevalence of EDS was markedly increased (ESS >10 in 17.7 % of patients), and 43 % scored ≥3 on STOPBANG. The predominant chronotype was a moderate morning type (54.4 %). Seven patients fulfilled RLS criteria and 9 fulfilled criteria for probable RBD, a self-report of hypnic jerks and nightmares were most common (45.6 % and 31.6 % respectively). According to regression analyses tumor relapse, depressive symptoms and fatigue determined poor sleep quality (Nagelkerke's R2: 0.511 p < 0.001), while performance-status, fatigue and anti-seizure medication contributed to excessive daytime sleepiness (Nagelkerke's R2: 0.600, p < 0.001), and age, BMI, and tumor localization contributed to the risk of sleep apnea (Nagelkerke's R2: 0.556, p < 0.001). CONCLUSIONS This study shows the broad range of sleep symptoms in glioma patients, and a complex association with tumor grade and localization. This underlines the need for a comprehensive evaluation of sleep related symptoms in glioma patients.
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Affiliation(s)
- Thomas Mitterling
- Department of Neurology, Kepler University Hospital, Johannes Kepler University Linz, Linz, Austria; Clinical Research Institute for Neuroscience, Johannes Kepler University Linz, Linz, Austria.
| | - Vivien Riffert
- Department of Neurology, Kepler University Hospital, Johannes Kepler University Linz, Linz, Austria
| | - Sophie Heimel
- Department of Neurology, Kepler University Hospital, Johannes Kepler University Linz, Linz, Austria
| | - Annette Leibetseder
- Department of Neurology, Kepler University Hospital, Johannes Kepler University Linz, Linz, Austria; Clinical Research Institute for Neuroscience, Johannes Kepler University Linz, Linz, Austria; Department of Internal Medicine and Neurooncology, Kepler University Hospital, Neuromed Campus, Linz, Austria
| | - Andreas Kaindlstorfer
- Department of Neurology, Kepler University Hospital, Johannes Kepler University Linz, Linz, Austria; Clinical Research Institute for Neuroscience, Johannes Kepler University Linz, Linz, Austria
| | - Anna Heidbreder
- Department of Neurology, Kepler University Hospital, Johannes Kepler University Linz, Linz, Austria; Clinical Research Institute for Neuroscience, Johannes Kepler University Linz, Linz, Austria
| | - Josef Pichler
- Department of Internal Medicine and Neurooncology, Kepler University Hospital, Neuromed Campus, Linz, Austria
| | - Tim J von Oertzen
- Department of Neurology, Kepler University Hospital, Johannes Kepler University Linz, Linz, Austria
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15
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Lillo-Triguero L, Del Castillo-Rueda A, Bellón JM, Peraita-Adrados R. Prospective study of restless legs syndrome in a blood donors' sample. Rev Clin Esp 2025; 225:9-15. [PMID: 39488246 DOI: 10.1016/j.rceng.2024.10.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2024] [Accepted: 07/22/2024] [Indexed: 11/04/2024]
Abstract
BACKGROUND AND OBJECTIVES Blood donation is suggested to increase the risk of restless legs syndrome (RLS). This study aims to assess the prevalence of RLS in Spanish blood donors and determined its potential correlation with iron metabolism parameters. MATERIALS AND METHODS Prospective cohort study of 129 blood donors (54.3% men, 39.44 years ± 11.0) that underwent a physical examination, blood analysis (hemoglobin, ferritin, transferrin saturation index and soluble transferrin receptor) and a RLS screening questionnaire followed by a prospective follow-up study including a clinical phone interview. A multivariate logistic regression model was performed to examine the association between RLS and other variables. RESULTS Eighty-four (65.1%) participants were repeat blood donors (mean of 2.11 donations/year) at inclusion and 61 (47.4%) at follow-up (mean of 2.09 donations/year). Non-anemic iron deficiency (ferritin < 50 µg/l) was high in women p < 0.001 and in repeat donors (p = 0.003). The prevalence of RLS was 14.1% at inclusion increasing prospectively (19.5%; p = 0.065). On multivariate analysis, gender was the only variable significantly associated with a RLS diagnosis, being higher in women (OR 5.1; 95% CI 1.71-15.3; p = 0.003). CONCLUSIONS Despite the high prevalence of non-anemic iron deficiency there was no association between ferritin, transferrin saturation index, soluble transferrin receptor concentration values and RLS diagnosis. Gender was associated with RLS diagnosis regardless of other variables.
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Affiliation(s)
- L Lillo-Triguero
- Neurology and Sleep Unit, Ruber International Hospital, Madrid, Spain
| | - A Del Castillo-Rueda
- Internal Medicine Department, University General Hospital and Research Institute Gregorio Marañón, University Complutense of Madrid (UCM), Madrid, Spain
| | - J M Bellón
- Biostatistics, Research Institute Gregorio Marañón, University Complutense of Madrid (UCM), Madrid, Spain
| | - R Peraita-Adrados
- Sleep and Epilepsy Unit-Clinical Neurophysiology Service, University General Hospital and Research Institute Gregorio Marañón, University Complutense of Madrid (UCM), Madrid, Spain.
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Teng L, Li H, Han Y, Yuan T, Xu C, Tan T, Chang W. Association between Restless Legs Syndrome and Sleep Disturbance and 3-Year Mortality in Hemodialysis Patients. KIDNEY DISEASES (BASEL, SWITZERLAND) 2025; 11:160-169. [PMID: 40191764 PMCID: PMC11970879 DOI: 10.1159/000545008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/02/2024] [Accepted: 02/23/2025] [Indexed: 04/09/2025]
Abstract
Introduction Whether restless legs syndrome (RLS) and sleep disturbance (SD) in hemodialysis (HD) patients influence all-cause and cardiovascular mortality remains controversial. The aim of this study was to evaluate the association between RLS or SD and 3-year mortality in HD patients. Methods A total of 301 patients who underwent HD were examined in April 2021 and were followed up for 3 years. The median follow-up time was 36.0 [33.3, 36.0] months. Fifty-four patients fulfilled the diagnosis of RLS (17.9%), 126 patients complained of SD (41.9%). Demographic parameters, clinical features, laboratory indices, and two questionnaires to assess the diagnosis of RLS and sleep status were collected. All-cause mortality and cardiovascular mortality in this population were evaluated. Cox regression analyses and Kaplan-Meier curves were performed to determine the effect of RLS or SD on 3-year mortality. Results The RLS group reported that 29 patients (53.8%) exhibited concurrent symptoms of SD. The presence of RLS or SD alone did not significantly elevate the risk of all-cause mortality (p = 0.053 and p = 0.193). However, the coexistence of RLS and SD was identified as an independent risk factor for all-cause mortality (p = 0.011). Furthermore, the various combinations associated with RLS or SD were found to be independently correlated with the risk of cardiovascular death (p < 0.05). Conclusion The combination of RLS and SD in HD patients is associated with an increased risk of cardiovascular and all-cause mortality, underscoring the clinical significance of this association.
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Affiliation(s)
- Lanbo Teng
- Department of Nephrology, Tianjin First Center Hospital, Tianjin, China
| | - Huanan Li
- Department of Tuina, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, China
| | - Yingying Han
- Department of Nephrology, Tianjin First Center Hospital, Tianjin, China
| | - Tao Yuan
- Tianjin Medical University, Tianjin, China
| | - Chuhan Xu
- Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Tao Tan
- Department of Tuina, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, China
| | - Wenxiu Chang
- Department of Nephrology, Tianjin First Center Hospital, Tianjin, China
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Beaudin AE, Younes M, Gerardy B, Raneri JK, Hirsch Allen AJM, Gomes T, Gakwaya S, Sériès F, Kimoff J, Skomro RP, Ayas NT, Smith EE, Hanly PJ. Association between sleep microarchitecture and cognition in obstructive sleep apnea. Sleep 2024; 47:zsae141. [PMID: 38943546 PMCID: PMC11632191 DOI: 10.1093/sleep/zsae141] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2024] [Revised: 05/21/2024] [Indexed: 07/01/2024] Open
Abstract
STUDY OBJECTIVES Obstructive sleep apnea (OSA) increases the risk of cognitive impairment. Measures of sleep microarchitecture from EEG may help identify patients at risk of this complication. METHODS Participants with suspected OSA (n = 1142) underwent in-laboratory polysomnography and completed sleep and medical history questionnaires, and tests of global cognition (Montreal Cognitive Assessment, MoCA), memory (Rey Auditory Verbal Learning Test, RAVLT) and information processing speed (Digit-Symbol Coding, DSC). Associations between cognitive scores and stage 2 non-rapid eye movement (NREM) sleep spindle density, power, frequency and %-fast (12-16Hz), odds-ratio product (ORP), normalized EEG power (EEGNP), and the delta:alpha ratio were assessed using multivariable linear regression (MLR) adjusted for age, sex, education, and total sleep time. Mediation analyses were performed to determine if sleep microarchitecture indices mediate the negative effect of OSA on cognition. RESULTS All spindle characteristics were lower in participants with moderate and severe OSA (p ≤ .001, vs. no/mild OSA) and positively associated with MoCA, RAVLT, and DSC scores (false discovery rate corrected p-value, q ≤ 0.026), except spindle power which was not associated with RAVLT (q = 0.185). ORP during NREM sleep (ORPNREM) was highest in severe OSA participants (p ≤ .001) but neither ORPNREM (q ≥ 0.230) nor the delta:alpha ratio were associated with cognitive scores in MLR analyses (q ≥ 0.166). In mediation analyses, spindle density and EEGNP (p ≥ .048) mediated moderate-to-severe OSA's negative effect on MoCA scores while ORPNREM, spindle power, and %-fast spindles mediated OSA's negative effect on DSC scores (p ≤ .018). CONCLUSIONS Altered spindle activity, ORP and normalized EEG power may be important contributors to cognitive deficits in patients with OSA.
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Affiliation(s)
- Andrew E Beaudin
- Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
- Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
| | - Magdy Younes
- Sleep Disorders Center, Misericordia Health Center, University of Manitoba, Winnipeg, Canada
- YRT Limited, Winnipeg, Manitoba, Canada
| | | | - Jill K Raneri
- Sleep Centre, Foothills Medical Centre, Calgary AB, Canada
| | - A J Marcus Hirsch Allen
- Department of Medicine, Respiratory and Critical Care Divisions, University of British Columbia, Vancouver, BC, Canada
| | - Teresa Gomes
- Respiratory Division and Sleep Laboratory, McGill University Health Centre, Montreal, QC, Canada
| | - Simon Gakwaya
- Unité de recherche en pneumologie, Centre de recherche, Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Québec, QC, Canada
| | - Frédéric Sériès
- Unité de recherche en pneumologie, Centre de recherche, Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Québec, QC, Canada
| | - John Kimoff
- Respiratory Division and Sleep Laboratory, McGill University Health Centre, Montreal, QC, Canada
| | - Robert P Skomro
- Division of Respirology, Critical Care and Sleep Medicine, University of Saskatchewan, Saskatoon, SK, Canada
| | - Najib T Ayas
- Department of Medicine, Respiratory and Critical Care Divisions, University of British Columbia, Vancouver, BC, Canada
| | - Eric E Smith
- Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
- Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
| | - Patrick J Hanly
- Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
- Sleep Centre, Foothills Medical Centre, Calgary AB, Canada
- Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
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18
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Nam S, Jeon S, Ordway M, Mazure C, Sinha R, Yau L, Iennaco J. Mindfulness-based therapy for insomnia in Black women: a pilot randomized controlled trial. J Behav Med 2024; 47:1094-1106. [PMID: 39306634 DOI: 10.1007/s10865-024-00521-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2024] [Accepted: 09/05/2024] [Indexed: 10/25/2024]
Abstract
The purpose of the study was to evaluate the feasibility, acceptability, and preliminary efficacy of mindfulness-based therapy for insomnia (MBT-I) among Black women. The MBT-I group received weekly sessions that included mindfulness meditation and behavioral sleep strategies. The time and attention control group received lifestyle health education (HE) that included healthy eating, physical activity, and sleep hygiene. The primary outcome was post-intervention changes in insomnia severity score by the Insomnia Severity Index (ISI) at week 10. Other measures included: Pittsburgh Sleep Quality Index, Sleep Hygiene Practice, Spielberger State-Trait Anxiety Inventory (STAI), and Patient Health Questionnaire-9 (PHQ-9). Objective sleep was measured by Actiwatch™ at baseline and week 10. Thirty Black women completed the interventions with no attrition. About 97% of all participants attended 6-8 out of 8 sessions. The ISI scores were reduced at week 10 (MBT-I vs. HE: -7.67 vs. -7.22, p < .05). Anxiety and depression symptoms were significantly improved only in the MBT-I group. This is the first MBT-I for Black women with insomnia. Online MBT-I may be feasible and acceptable for Black women. The MBT-I and HE showed a clinically significant improvement in insomnia symptoms (ISI reduction > 7). MBT-I may be more effective in improving anxiety and depression symptoms than HE. Our findings encourage further study efforts with a longer follow-up and larger sample size to address sleep health disparities among Black women.
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Affiliation(s)
- Soohyun Nam
- School of Nursing, Yale University, 400 West Campus Dr, Orange, Connecticut, 06477, USA.
| | - Sangchoon Jeon
- School of Nursing, Yale University, 400 West Campus Dr, Orange, Connecticut, 06477, USA
| | - Monica Ordway
- School of Nursing, Yale University, 400 West Campus Dr, Orange, Connecticut, 06477, USA
| | - Carolyn Mazure
- School of Medicine, Yale University, 333 Cedar St, New Haven, Connecticut, 06510, USA
| | - Rajita Sinha
- School of Medicine, Yale University, 333 Cedar St, New Haven, Connecticut, 06510, USA
| | - Lauren Yau
- School of Nursing, Stony Brook University, 101 Nicolls Rd, Stony Brook, NY, 11794, USA
| | - Joanne Iennaco
- School of Nursing, Yale University, 400 West Campus Dr, Orange, Connecticut, 06477, USA
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Cole M, Simakajornboon N. Sleep-related movement disorders in children: recent updates. World J Pediatr 2024:10.1007/s12519-024-00856-5. [PMID: 39604768 DOI: 10.1007/s12519-024-00856-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2024] [Accepted: 10/23/2024] [Indexed: 11/29/2024]
Abstract
BACKGROUND Sleep-related movement disorders (SRMDs), such as restless legs syndrome (RLS) and periodic limb movement disorder (PLMD), are common in pediatric sleep practice. There is increasing literature on RLS, PLMD, and a newly described sleep disorder called "restless sleep disorder (RSD)". We aimed to review and provide recent updates on SRMDs. DATA SOURCES A comprehensive search for relevant English-language peer-reviewed publications focused on three common SRMDs, namely, RLS, PLMD and RSD, in a variety of indices in PubMed and SCOPUS. Both relevant databases and systematic reviews are included. RESULTS SRMDs, especially RLS and PLMD, are common in children and adolescents. However, they are underrecognized. Genetics, abnormal dopaminergic functions, and iron deficiency are the main pathophysiologies of RLS and PLMD. RLS and RSD may share common pathophysiologic mechanisms, as evidenced by low iron stores in both conditions. The diagnoses of RLS, PLMD, and RSD require specific clinical criteria and polysomnographic features. Several comorbid conditions have been associated with RLS, PLMD, and RSD. Iron therapy has been shown to be effective for treating RLS, PLMD, and RSD. There is increasing evidence on the effectiveness of specific medications in children with RLS and PLMD, but the data are still limited. CONCLUSIONS This review summarizes the pathophysiology, clinical manifestations, diagnostic criteria, and management of RLS, PLMD, and RSD in children based on relevant and recent literature. It is important for pediatricians to recognize the clinical presentation of RLS, PLMD, and RSD to facilitate early diagnosis. Further studies are needed to examine the pathogenesis, long-term consequences, and pharmacologic therapy of RSD in children.
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Affiliation(s)
- Melissa Cole
- Sleep Center, Division of Pulmonary and Sleep Medicine, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, MLC 7041, Cincinnati, OH, USA
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Narong Simakajornboon
- Sleep Center, Division of Pulmonary and Sleep Medicine, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, MLC 7041, Cincinnati, OH, USA.
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
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20
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Evans M, Crowther ME, Brown BWJ, Wanstall S, Rayner T, Vakulin A, Adams RJ, Reynolds AC. Sleep disorder risk, perceived control over sleep, and mental health symptoms in paramedicine students. INDUSTRIAL HEALTH 2024; 62:408-416. [PMID: 38735733 PMCID: PMC11611534 DOI: 10.2486/indhealth.2023-0135] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/07/2023] [Accepted: 04/27/2024] [Indexed: 05/14/2024]
Abstract
Paramedics commonly experience both poor sleep and mental health symptoms. Clarifying whether sleep or mental health symptoms are a challenge prior to commencement of employment is important, as early prevention and intervention initiatives during training could support these workers. Paramedicine students (n=53) were included, with sleep disorder screening (obstructive sleep apnea, insomnia and restless legs syndrome), and mental health outcomes (depressive symptoms: Patient Health Questionnaire-9, and anxiety symptoms: General Anxiety Disorder-7). Data were analysed using robust regression models, adjusted for age, sex, and shift work status. Meeting criteria for a sleep disorder (n=21) was associated with higher scores for anxiety (8.2 [95% CI: 5.9-10.5] v 4.6, [3.4-5.8]) and depressive symptoms (11.1 [8.6-13.6] v 4.4 [3.1-5.7)] compared to those who did not meet the criteria for a sleep disorder (n=32). Depressive symptoms were lower in those with perceived control over sleep (5.2 [3.2-7.2] v 9.8 [7.7-11.8]). There was no interaction between sleep disorder risk and perceived control over sleep on mental health symptoms. Investigation and management of factors contributing to low perceived control over sleep, together with early screening and management of sleep disorders, are likely to be important priorities to support paramedic student wellbeing prior to commencing shift work.
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Affiliation(s)
- Madeline Evans
- Flinders Health and Medical Research Institute (Sleep Health), Flinders University, Australia
| | - Meagan E Crowther
- Flinders Health and Medical Research Institute (Sleep Health), Flinders University, Australia
| | - Brandon W J Brown
- Flinders Health and Medical Research Institute (Sleep Health), Flinders University, Australia
| | - Sian Wanstall
- Flinders Health and Medical Research Institute (Sleep Health), Flinders University, Australia
| | - Tim Rayner
- Flinders Health and Medical Research Institute (Sleep Health), Flinders University, Australia
| | - Andrew Vakulin
- Flinders Health and Medical Research Institute (Sleep Health), Flinders University, Australia
| | - Robert J Adams
- Flinders Health and Medical Research Institute (Sleep Health), Flinders University, Australia
| | - Amy C Reynolds
- Flinders Health and Medical Research Institute (Sleep Health), Flinders University, Australia
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Lv Y, Zou K, Zhuang S, Zhou Y, Weng Y, Mi E, Xie M, Wang L. Restless Legs Syndrome in Hemodialysis Patients: Clinical and Electrophysiological Study. J Multidiscip Healthc 2024; 17:5251-5258. [PMID: 39558927 PMCID: PMC11572432 DOI: 10.2147/jmdh.s483327] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2024] [Accepted: 10/31/2024] [Indexed: 11/20/2024] Open
Abstract
Background Hemodialysis-related restless legs syndrome (HD-RLS) is a common sensorial and motor disorder. The diagnosis of this disease is based on clinical criteria, and it has recently been proposed to use physiological parameters of the nerves related to the duration of the F wave as a supplementary diagnostic modality. The aim of the study is to determine the value of these parameters in the diagnosis of HD-RLS by comparing the differences between patients with HD-RLS and hemodialysis patients without RLS (HD-nRLS). Methods A total of 20 HD-RLS patients, 33 HD-nRLS patients, and 30 age-and gender-matched healthy controls (HCs) were included in the study. The motor nerve conduction of the median and ulnar nerves in the upper limbs, as well as the tibial and peroneal nerves in the bilateral lower limbs, and the sensory nerve conduction of the sural nerve bilaterally and the superficial peroneal nerve, along with the F waves of the ulnar nerves, median nerve, and bilateral tibial nerve, were assessed. Results Both groups of HD patients had variable levels of axonal degeneration and demyelination, with the HD-RLS patients having more severe lower limb involvement. The HD-RLS patients showed an extension of the F-wave duration (FWD) of the bilateral tibial, median, and ulnar nerves, along with an increased ratio between FWD and compound muscle action potential duration (CMAPD). Conclusion Peripheral neuropathy occurs in patients with HD-RLS, and the FWD/CMAPD ratio could potentially serve as an adjunctive diagnostic tool for HD-RLS.
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Affiliation(s)
- Ying Lv
- Department of Nephrology, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang,People’s Republic of China
| | - Kun Zou
- Department of Neurology, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, People’s Republic of China
| | - Shanshan Zhuang
- Department of Hemodialysis Center, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, People’s Republic of China
| | - Yang Zhou
- Department of Nephrology, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang,People’s Republic of China
| | - Yaping Weng
- Department of Hemodialysis Center, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, People’s Republic of China
| | - Enna Mi
- Department of Nephrology, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang,People’s Republic of China
| | - Minzhu Xie
- Department of Nephrology, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang,People’s Republic of China
| | - Long Wang
- Department of Nephrology, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang,People’s Republic of China
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22
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Akçimen F, Chia R, Saez-Atienzar S, Ruffo P, Rasheed M, Ross JP, Liao C, Ray A, Dion PA, Scholz SW, Rouleau GA, Traynor BJ. Genomic Analysis Identifies Risk Factors in Restless Legs Syndrome. Ann Neurol 2024; 96:994-1005. [PMID: 39078117 PMCID: PMC11496024 DOI: 10.1002/ana.27040] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2024] [Revised: 07/11/2024] [Accepted: 07/12/2024] [Indexed: 07/31/2024]
Abstract
OBJECTIVE Restless legs syndrome (RLS) is a neurological condition that causes uncomfortable sensations in the legs and an irresistible urge to move them, typically during periods of rest. The genetic basis and pathophysiology of RLS are incompletely understood. We sought to identify additional novel genetic risk factors associated with RLS susceptibility. METHODS We performed a whole-genome sequencing and genome-wide association meta-analysis of RLS cases (n = 9,851) and controls (n = 38,957) in 3 population-based biobanks (All of Us, Canadian Longitudinal Study on Aging, and CARTaGENE). RESULTS Genome-wide association analysis identified 9 independent risk loci, of which 8 had been previously reported, and 1 was a novel risk locus (LMX1B, rs35196838, OR 1.14, 95% CI 1.09-1.19, p value = 2.2 × 10-9). Furthermore, a transcriptome-wide association study also identified GLO1 and a previously unreported gene, ELFN1. A genetic correlation analysis revealed significant common variant overlaps between RLS and neuroticism (rg = 0.40, se = 0.08, p value = 5.4 × 10-7), depression (rg = 0.35, se = 0.06, p value = 2.17 × 10-8), and intelligence (rg = -0.20, se = 0.06, p value = 4.0 × 10-4). INTERPRETATION Our study expands the understanding of the genetic architecture of RLS, and highlights the contributions of common variants to this prevalent neurological disorder. ANN NEUROL 2024;96:994-1005.
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Affiliation(s)
- Fulya Akçimen
- Neuromuscular Diseases Research Section, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA
| | - Ruth Chia
- Neuromuscular Diseases Research Section, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA
| | - Sara Saez-Atienzar
- Neuromuscular Diseases Research Section, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA
| | - Paola Ruffo
- Neuromuscular Diseases Research Section, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA
- Medical Genetics Laboratory, Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Rende, Italy
| | - Memoona Rasheed
- Neuromuscular Diseases Research Section, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA
| | - Jay P. Ross
- Department of Human Genetics, McGill University, Montréal, QC, Canada
- Montreal Neurological Institute-Hospital, McGill University, Montréal, QC, Canada
| | - Calwing Liao
- Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA
- Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA
- Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA
| | - Anindita Ray
- Neurodegenerative Diseases Research Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA
| | - Patrick A. Dion
- Montreal Neurological Institute-Hospital, McGill University, Montréal, QC, Canada
- Department of Neurology and Neurosurgery, McGill University, Montréal, QC, Canada
| | - Sonja W. Scholz
- Neurodegenerative Diseases Research Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA
- Department of Neurology, Johns Hopkins University Medical Center, Baltimore, MD, USA
| | - Guy A. Rouleau
- Department of Human Genetics, McGill University, Montréal, QC, Canada
- Montreal Neurological Institute-Hospital, McGill University, Montréal, QC, Canada
- Department of Neurology and Neurosurgery, McGill University, Montréal, QC, Canada
| | - Bryan J. Traynor
- Neuromuscular Diseases Research Section, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA
- Department of Neurology, Johns Hopkins University Medical Center, Baltimore, MD, USA
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23
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Miyaguchi R, Masuda F, Sumi Y, Kadotani H, Ozeki Y, Banno M, Kuniyoshi Y. Prevalence of depression or depressive state in patients with restless legs syndrome: A systematic review and meta-analysis. Sleep Med Rev 2024; 77:101975. [PMID: 39024776 DOI: 10.1016/j.smrv.2024.101975] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2024] [Revised: 06/19/2024] [Accepted: 07/09/2024] [Indexed: 07/20/2024]
Abstract
Restless legs syndrome (RLS) is a common sleep-related disorder characterized by limb discomfort and the urge to move them when at rest, especially in the evening or at night. Although depression is often linked to various conditions, no systematic review has assessed depression prevalence in patients with RLS after the latest diagnostic criteria revision. This systematic review and meta-analysis aimed to investigate the depression and depressive state prevalence among patients with RLS. We systematically searched databases up to November 2022 and performed meta-analyses of the depression prevalence using a random-effects model and a meta-regression analysis to explore the relationship between the prevalence and severity of depression and factors such as age and RLS severity. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we analyzed 24 studies with 2039 patients. The pooled depression or depressive state prevalence, mostly defined by questionnaire scores, was 30.39 %. Nine studies reported the proportion of patients taking antidepressants (pooled rate: 3.41 %). No specific factors related to the prevalence or severity of depression were identified in patients with RLS. These findings highlight the significant prevalence of depression and underscore the need for future research with standardized diagnostic interviews and consistent methodologies across multi-site studies.
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Affiliation(s)
- Rin Miyaguchi
- Faculty of Medicine, Shiga University of Medical Science, Shiga, Japan
| | - Fumi Masuda
- Department of Psychiatry, Shiga University of Medical Science, Shiga, Japan
| | - Yukiyoshi Sumi
- Department of Psychiatry, Shiga University of Medical Science, Shiga, Japan; Department of Psychiatry, Nagahama Red Cross Hospital, Shiga, Japan
| | - Hiroshi Kadotani
- Department of Psychiatry, Shiga University of Medical Science, Shiga, Japan.
| | - Yuji Ozeki
- Department of Psychiatry, Shiga University of Medical Science, Shiga, Japan
| | - Masahiro Banno
- Scientific Research Works Peer Support Group (SRWS-PSG), Osaka, Japan; Department of Psychiatry, Seichiryo Hospital, Nagoya, Japan
| | - Yasutaka Kuniyoshi
- Scientific Research Works Peer Support Group (SRWS-PSG), Osaka, Japan; Department of Pediatrics, Tsugaruhoken Medical COOP Kensei Hospital, Aomori, Japan
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24
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Gülçiçek A, Şanlı E, Şenel GB, Karadeniz D, Timirci-Kahraman Ö, Küçükali Cİ, Tüzün E. Patients with restless legs syndrome exhibit reduced serum colony-stimulating factor-1, humanin-like 3 and 10 levels. Acta Neurol Belg 2024; 124:1561-1568. [PMID: 38630326 DOI: 10.1007/s13760-024-02549-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2024] [Accepted: 03/23/2024] [Indexed: 12/05/2024]
Abstract
OBJECTIVE The main pathophysiological mechanisms in restless legs syndrome (RLS) are known as genetic predisposition, brain iron deficiency, and dopaminergic dysfunction. While some genetic variants and polymorphisms were defined, the genetic basis and etiopathogenesis of RLS remain unclear. We aimed to identify new candidate genes and/or potential biomarkers associated with increased RLS risk. METHODS Twenty-three patients with RLS, 30 patients with Parkinson's disease (PD), and 27 healthy controls were enrolled. Agilent Human 8X60K Oligo Microarray was used for the identification of gene expression levels in peripheral blood cells. Gene ontology (GO) analysis was used for functional annotation of differentially expressed genes (DEGs). Serum levels of selected DEGs were measured by ELISA for validation. RESULTS Patients with RLS showed 30 downregulated DEGs compared to healthy controls. Two genes, MTRNR2L10 and MTRNR2L3, involved negative regulation of the execution phase of apoptosis were highlighted in GO analysis. These genes encode humanin-like 10 and 3, respectively, were encoded by these genes, and their levels, along with CSF-1, linked to neurodegeneration, were reduced in RLS patients. Humanin-like 10 and CSF-1 levels correlated with sleep efficiency and N2 sleep duration, while humanin-like 3 levels correlated with mean sleep oxygen saturation during sleep. CONCLUSION Our study showed that several neuroprotective genes were downregulated in RLS, which may confer susceptibility to neuronal death associated with decreased sleep efficiency. Microarray results differed between RLS and PD patients, suggesting diverse pathogenetic mechanisms. CSF-1, which is involved in iron, dopamine metabolism, and blood oxygenation, appears to partake in RLS pathophysiology.
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Affiliation(s)
- Asena Gülçiçek
- Department of Neuroscience, Institute of Graduate Studies in Health Sciences, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey.
| | - Elif Şanlı
- Department of Neuroscience, Institute of Graduate Studies in Health Sciences, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey
| | - Gülçin Benbir Şenel
- Sleep and Disorders Unit, Division of Clinical Neurophysiology, Department of Neurology, Cerrahpasa Faculty of Medicine, Istanbul University-Cerrahpasa, Istanbul, Türkiye
| | - Derya Karadeniz
- Sleep and Disorders Unit, Division of Clinical Neurophysiology, Department of Neurology, Cerrahpasa Faculty of Medicine, Istanbul University-Cerrahpasa, Istanbul, Türkiye
| | - Özlem Timirci-Kahraman
- Department of Molecular Medicine, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey
| | - Cem İsmail Küçükali
- Department of Neuroscience, Institute of Graduate Studies in Health Sciences, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey
| | - Erdem Tüzün
- Department of Neuroscience, Institute of Graduate Studies in Health Sciences, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey
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Singh H, Baker FC, Ojile J, Adlou B, Kolotovska V, Rigot SK, Charlesworth JD. Efficacy and safety of TOMAC for treatment of medication-naïve and medication-refractory restless legs syndrome: A randomized clinical trial and meta-analysis. Sleep Med 2024; 122:141-148. [PMID: 39173210 PMCID: PMC11414842 DOI: 10.1016/j.sleep.2024.08.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2024] [Revised: 07/29/2024] [Accepted: 08/16/2024] [Indexed: 08/24/2024]
Abstract
OBJECTIVE/BACKGROUND There is a significant unmet need for safe and effective nonpharmacological therapies for restless legs syndrome (RLS). The objective was to evaluate the efficacy and safety of tonic motor activation (TOMAC) in patients with RLS. PATIENTS/METHODS A multicenter, randomized, participant-blinded, sham-controlled trial enrolled 45 adults with primary moderate-to-severe RLS who were either medication-naïve (n = 20) or medication-refractory (n = 25). Participants were 1:1 randomized to TOMAC (n = 22) or sham (n = 23) for two weeks and instructed to self-administer 30-min TOMAC sessions when they experienced RLS symptoms. The primary outcome was mean change in International RLS Study Group Rating Scale (IRLS) total score. A subsequent meta-analysis included the present trial and a previous randomized clinical trial that enrolled medication-naïve RLS patients. RESULTS IRLS reduction was significantly greater for TOMAC than sham (TOMAC -6.59 vs. sham -2.17; mean difference (MD) = -4.42; 95 % confidence interval [CI] -1.57 to -7.26; p = 0.0040). Subgroup analysis showed similar IRLS mean difference for medication-refractory (MD = -4.50; p = 0.02) and medication-naïve (MD = -4.40; p = 0.08) cohorts, which was significantly different from sham only for the medication-refractory cohort. Meta-analysis of combined data from 33 medication-naïve RLS patients showed a significant reduction in mean IRLS score after two weeks for TOMAC compared to sham (MD = -4.30; 95 % CI -1.36 to -7.24; p = 0.004). CONCLUSIONS The present trial confirmed previous reports documenting efficacy and safety of TOMAC in refractory RLS and indicated similar effect sizes in refractory versus naïve subgroups. The meta-analysis demonstrated that TOMAC significantly improves RLS symptoms in naïve participants.
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Affiliation(s)
- Haramandeep Singh
- Sleep Medicine Specialists of California, 5201 Norris Canyon Rd, Suite 120, San Ramon, CA 94583, USA.
| | - Fiona C Baker
- Center for Health Sciences, SRI International, 333 Ravenswood Ave, Menlo Park, CA 94025, USA.
| | - Joseph Ojile
- Clayton Sleep Institute, LLC, 11188 Tesson Ferry Road, Suite 100, St. Louis, MO 63123 USA.
| | - Bahman Adlou
- Noctrix Health, Inc., 6700 Koll Center Pkwy, Suite 310, Pleasanton, CA, USA
| | | | - Stephanie K Rigot
- Noctrix Health, Inc., 6700 Koll Center Pkwy, Suite 310, Pleasanton, CA, USA
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Burini A, Pellitteri G, Merlino G, Nilo A, Tereshko Y, Dolso P, Gigli GL, Valente M. Current and emerging pharmaceutical strategies for the treatment and management of restless legs syndrome. Expert Rev Neurother 2024; 24:997-1009. [PMID: 39082506 DOI: 10.1080/14737175.2024.2385947] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2024] [Accepted: 07/25/2024] [Indexed: 09/21/2024]
Abstract
INTRODUCTION Restless legs syndrome (RLS) is a sensory-motor sleep disorder that affects up to 13% of adults in the Western world and 2-4% of children. It impairs night sleep with an impact on daily performances and life quality. Thus, moderate-to-severe RLS requires pharmacological treatment. AREAS COVERED In the present review, which is based on PubMed searches with no time limits, the authors discuss the recommended pharmacotherapy for RLS in addition to other emerging treatment options. The authors provide coverage to the current recommendations for both adults and pediatric patients with RLS. EXPERT OPINION Current evidence suggests removing all causes of secondary RLS, including iron deficiency, chronic renal failure, drugs, and treating other sleep disorders that may worsen symptoms. Also, intermittent RLS should be addressed with behavioral measures and on-demand therapy. For chronic persistent RLS, α2δ calcium channel ligands are a first-line pharmacological approach, whereas dopamine agonists are associated with increased risk and should be spared. When RLS is refractory to first-line treatment, polytherapy, or opioid monotherapy should be considered. Nonetheless, some patients may not reach sustained symptom relief. Further research is needed to better understand the pathophysiology of RLS and to develop newer more effective drugs.
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Affiliation(s)
- Alessandra Burini
- Clinical Neurology, Department of Medicine (DMED), University of Udine, Udine, Italy
- Clinical Neurology, Department of Head-Neck and Neuroscience, Azienda Sanitaria Universitaria Friuli Centrale (ASU FC), Udine, Italy
| | - Gaia Pellitteri
- Clinical Neurology, Department of Head-Neck and Neuroscience, Azienda Sanitaria Universitaria Friuli Centrale (ASU FC), Udine, Italy
| | - Giovanni Merlino
- Clinical Neurology, Department of Head-Neck and Neuroscience, Azienda Sanitaria Universitaria Friuli Centrale (ASU FC), Udine, Italy
- SOSD Stroke Unit, Department of Head-Neck and Neuroscience, Azienda Sanitaria Universitaria Friuli Centrale (ASU FC), Udine, Italy
| | - Annacarmen Nilo
- Clinical Neurology, Department of Medicine (DMED), University of Udine, Udine, Italy
- Clinical Neurology, Department of Head-Neck and Neuroscience, Azienda Sanitaria Universitaria Friuli Centrale (ASU FC), Udine, Italy
| | - Yan Tereshko
- Clinical Neurology, Department of Head-Neck and Neuroscience, Azienda Sanitaria Universitaria Friuli Centrale (ASU FC), Udine, Italy
| | - Pierluigi Dolso
- Clinical Neurology, Department of Head-Neck and Neuroscience, Azienda Sanitaria Universitaria Friuli Centrale (ASU FC), Udine, Italy
| | - Gian Luigi Gigli
- Clinical Neurology, Department of Medicine (DMED), University of Udine, Udine, Italy
| | - Mariarosaria Valente
- Clinical Neurology, Department of Medicine (DMED), University of Udine, Udine, Italy
- Clinical Neurology, Department of Head-Neck and Neuroscience, Azienda Sanitaria Universitaria Friuli Centrale (ASU FC), Udine, Italy
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Guan XR, Chen YH, Li JF, Su XQ, Sun W. Effect of "He Tiao Du Ren An Shen Acupuncture" on restless leg syndrome: A randomized trial. Medicine (Baltimore) 2024; 103:e39926. [PMID: 39331896 PMCID: PMC11441916 DOI: 10.1097/md.0000000000039926] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2024] [Accepted: 09/13/2024] [Indexed: 09/29/2024] Open
Abstract
BACKGROUND This study aimed to observe the clinical effects of "He Tiao Du Ren An Shen Acupuncture" (HTDRAS Acupuncture) for treating restless leg syndrome (RLS). METHODS We randomly divided 66 RLS patients into 2 groups: the observation group received "He Tiao Du Ren An Shen Acupuncture" and the control group received conventional acupuncture. All participants were treated once a day, 6 days a week, with 1 day off, for a total of 1 month. Clinical effectiveness of the 2 groups was compared, neurotransmitter levels, the International Restless Leg Syndrome Scale and the Hamilton Anxiety Scale were assessed in both groups. RESULTS The curative effect in the observation group was better than that in the control group (P < .05). After treatment, the expression of 5-hydroxytryptamine in the observation group was higher than in the control group (P < .05). The International Restless Leg Syndrome Scale and Hamilton Anxiety Scale scores in observation group were lower than those in control group (P < .05). CONCLUSION "He Tiao Du Ren An Shen Acupuncture" for RLS is significantly effective and safe. It can effectively improve the levels of 5-hydroxytryptamine in RLS patients, alleviate clinical symptoms and reduce anxiety. This treatment has a high clinical application value and is worthy of clinical promotion.
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Affiliation(s)
- Xin-Rui Guan
- Heilongjiang University of Chinese Medicine, Harbin, China
| | - Ying-Hua Chen
- First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Jun-Feng Li
- First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Xiao-Qing Su
- First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Wei Sun
- Heilongjiang University of Chinese Medicine, Harbin, China
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28
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Kaya SP, Özçoban FA, Dilbaz B. Factors affecting poor sleep quality in last trimester pregnant women: a cross-sectional research from Turkey. REVISTA DA ASSOCIACAO MEDICA BRASILEIRA (1992) 2024; 70:e20240180. [PMID: 39292081 DOI: 10.1590/1806-9282.20240180] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/31/2024] [Accepted: 06/26/2024] [Indexed: 09/19/2024]
Abstract
OBJECTIVE The aim of the study was to determine the factors affecting poor sleep quality in the last trimester pregnant women. METHODS A cross-sectional study was conducted at a tertiary care maternity hospital in Ankara, Turkey. The research was conducted between May and September 2019 with 570 pregnant women in the last trimester. The data were collected through the Personal Information Form, Pittsburgh Sleep Quality Index, International Physical Activity Questionnaire Short Form, Restless Legs Syndrome Form, Brief Fatigue Inventory, and Perceived Stress Scale. RESULTS The mean Pittsburgh Sleep Quality Index score of the pregnant women was 5.98±3.31, and 48.9% of them were found to have over five Pittsburgh Sleep Quality Index scores. Hemoglobin levels, income perceptions, smoking habits, attending pregnant schools, experiencing leg pains or cramping, experiencing back, waist, or neck pains, Restless Legs Syndrome, fatigue levels, and perceived stress levels of the pregnant women were found to be important determinants of sleep quality (p<0.05). CONCLUSION According to the findings, increasing hemogram levels, attending antenatal education programs, and improving the ability of pregnant women to manage stress are opportunities to improve sleep quality during pregnancy. Careful evaluation of pregnant women in terms of insomnia and affecting factors can be suggested during antenatal follow-up.
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Affiliation(s)
- Sibel Peksoy Kaya
- Ankara Yıldırım Beyazıt University, Faculty of Health Sciences, Department of Nursing - Ankara, Turkey
| | | | - Berna Dilbaz
- University of Heath Sciences, Ankara Etlik Zübeyde Hanım Women's Health Training and Research Hospital - Ankara, Turkey
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29
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Giannaki CD, Sakkas GK, Hadjigeorgiou GM, Manconi M, Bargiotas P. Unfolding the role of exercise in the management of sleep disorders. Eur J Appl Physiol 2024; 124:2547-2560. [PMID: 39031176 PMCID: PMC11365864 DOI: 10.1007/s00421-024-05556-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2024] [Accepted: 06/28/2024] [Indexed: 07/22/2024]
Abstract
Sleep disorders are prevalent among the general population and even more in individuals suffering from chronic diseases. Recent data reveal promising effects of physical exercise as a non-pharmacological approach for improving sleep and managing various sleep disorders. However, more studies with proper design and methodology should be conducted in the future to obtain a clearer understanding of the subject. The role of exercise in preventing and improving sleep disorders is probably much higher than what is currently exploited. To fully exploit the potential benefit of physical activity on sleep disorders in the future, it is necessary to identify the relevant tools to assess sleep-wake disorders and establish specific exercise protocols tailored to different sleep disorders. The present manuscript aims to review the literature on the use of exercise in managing selected sleep disorders. Regular exercise, including short-term aerobic activity, resistance training, and mind-body exercises, can effectively improve sleep quality, particularly in cases of insomnia and sleep-disordered breathing. Additionally, increasing evidence supports the effectiveness of aerobic and strength training, and body-mind exercises such as yoga in managing sleep-related movement disorders. Exercise can be a safe, affordable, and efficient tool in enhancing sleep quality and improving sleep disorders. Per se, regular exercise could play an adjuvant role alongside with established therapies, or a valid alternative when the pharmacological approach is limited by side effects, interactions, or inefficacy. More research is needed to define how exercise affects the physiology of sleep, and consequently how to use exercise in patients with sleep disorders.
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Affiliation(s)
- Christoforos D Giannaki
- Department of Life Sciences, School of Life and Health Sciences, University of Nicosia, 46 Makedonitisas Avenue, 1700, Nicosia, Cyprus.
| | - Giorgos K Sakkas
- School of Physical Education, Sport Science and Dietetics, University of Thessaly, Trikala, Greece
| | | | - Mauro Manconi
- Sleep Medicine Unit, Regional Hospital of Lugano, Neurocenter of Southern Switzerland, Lugano, Switzerland
| | - Panagiotis Bargiotas
- Department of Neurology, Medical School, University of Cyprus, Nicosia, Cyprus
- Sleep and Motion Laboratory, Medical School, University of Cyprus, Nicosia, Cyprus
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30
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Kristófersdóttir KH, Kristjánsdóttir H, Asgeirsdottir RL, Karlsson T, Vésteinsdóttir V, Thorsdottir F. Investigating the PHQ-9 With Mokken Scale Analysis and Cognitive Interviews. Assessment 2024; 31:1332-1355. [PMID: 38159031 DOI: 10.1177/10731911231216961] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2024]
Abstract
Scores on the Patient Health Questionnaire-9 (PHQ-9) are frequently used to assess depression both in research and in clinical practice. The aim was to examine the validity of the PHQ-9 sum score by using Mokken scale analysis (Study I) and cognitive interviews (Study II) on the Icelandic version of PHQ-9. A primary care sample of 618 individuals was used in Study I. The results indicate that the PHQ-9 items are not close enough to perfectly unidimensional for their sum score to accurately order people on the depression severity dimension. In Study II, the sample consisted of 53 individuals, with 28 having a history of depression and 25 not. The findings reveal a number of issues concerning respondents' use of the PHQ-9. No systematic differences were found in the results of the two groups. The PHQ-9 sum score should thus be interpreted and used with great care. We provide scale revision recommendations to improve the quality of PHQ-9.
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Brown BWJ, Adams RJ, Wanstall S, Crowther ME, Rawson G, Vakulin A, Rayner T, McEvoy RD, Eastwood P, Reynolds AC. Introducing a sleep disorder screening and management strategy for workers with future shift work requirements: a feasibility and acceptability study. Sci Rep 2024; 14:19964. [PMID: 39198594 PMCID: PMC11358459 DOI: 10.1038/s41598-024-69479-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2023] [Accepted: 08/05/2024] [Indexed: 09/01/2024] Open
Abstract
Sleep disorders are common, and largely undiagnosed in early-career workers. The combination of sleep disorders and shift work has implications for mental health, workplace safety, and productivity. Early identification and management of sleep disorders is likely to be beneficial to workers, employers and the community more broadly. We assessed the feasibility and acceptability of a tailored sleep disorder screening and management pathway for individuals with future shift work requirements. Paramedic students were invited to complete an online sleep health survey, which included validated sleep disorder screening questionnaires for insomnia, obstructive sleep apnea and restless legs syndrome. Participants were able to express interest in participating in a sleep monitoring and management study. Participants at risk for a sleep disorder were identified, contacted by the study physician (RJA), notified of their sleep disorder screening results and provided with information regarding management options. Feasibility of the screening and management pathways were determined by completion of the 12 week follow-up, and ability to engage with health services for diagnostic testing or treatment. Acceptability of these pathways was assessed with a semi-structured interview on completion of the study at 12 weeks. Screening was completed in thirty participants (mean age 22.5 ± 6.7, 63% female), 17 of whom were 'at-risk' for a sleep disorder and offered a management pathway. All participants engaged with the study physician (RJA), with 16 completing the study (94% completion rate). Three participants with excessive daytime sleepiness received feedback from the study physician (RJA) and no further care required. Of the remaining 14 participants, 11 (78%) engaged with health services after speaking with the study physician (RJA). Those who engaged with diagnostic and management services reported that a structured pathway with online screening was convenient and easy to follow. Facilitating screening and management of sleep disorders in students with future shift work requirements is both feasible and acceptable. These findings can inform the development of a preventive strategy for sleep disorders and ideally, a health services feasibility trial for future shift workers.
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Affiliation(s)
- Brandon W J Brown
- Flinders Health and Medical Research Institute (Sleep Health), Flinders University, Adelaide, Australia.
| | - Robert J Adams
- Flinders Health and Medical Research Institute (Sleep Health), Flinders University, Adelaide, Australia
| | - Sian Wanstall
- Flinders Health and Medical Research Institute (Sleep Health), Flinders University, Adelaide, Australia
| | - Meagan E Crowther
- Flinders Health and Medical Research Institute (Sleep Health), Flinders University, Adelaide, Australia
| | - Georgina Rawson
- Flinders Health and Medical Research Institute (Sleep Health), Flinders University, Adelaide, Australia
| | - Andrew Vakulin
- Flinders Health and Medical Research Institute (Sleep Health), Flinders University, Adelaide, Australia
| | - Tim Rayner
- College of Medicine and Public Health, Flinders University, Adelaide, Australia
| | - R Doug McEvoy
- Flinders Health and Medical Research Institute (Sleep Health), Flinders University, Adelaide, Australia
| | - Peter Eastwood
- Health Futures Institute, Murdoch University, Perth, Australia
| | - Amy C Reynolds
- Flinders Health and Medical Research Institute (Sleep Health), Flinders University, Adelaide, Australia
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Kaplan Ö, Başer M, Özgün MT. The effect of compression stockings on the complaints well-being and sleep quality of pregnant women with restless legs syndrome: a randomized controlled study. REVISTA DA ASSOCIACAO MEDICA BRASILEIRA (1992) 2024; 70:e20240145. [PMID: 39166663 PMCID: PMC11329251 DOI: 10.1590/1806-9282.20240145] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/05/2024] [Accepted: 03/24/2024] [Indexed: 08/23/2024]
Abstract
OBJECTIVE The aim of this study was to determine the effect of compression stockings on complaints, well-being, and sleep quality in pregnant women with restless legs syndrome. METHODS This randomized placebo-controlled study was conducted on 63 pregnant women (placebo group [PG]=31; experimental group [EG]=32) at the Perinatology Outpatient Clinic of a Health Research and Application Centre in Turkey. Pregnant women in the experimental group wore compression stockings when they got up in the morning for 3 weeks and took them off at bedtime. Placebo group women wore a placebo stocking. Data were collected using the restless legs syndrome Severity Rating Scale, the Pittsburgh Sleep Quality Index, the World Health Organization-5 Well-Being Index, and the Application Satisfaction Form on the 22nd day of the first interview. Statistical significance was accepted as p<0.05. RESULTS Post-test mean scores of both the experimental group and placebo group in the restless legs syndrome Severity Rating Scale (post-test:;8.87±5.27, 12.19±5.60; pre-test:;21.28±5.63, 21.0±5.61; p<0.05), the Pittsburgh Sleep Quality Index (post-test:;5.34±3.28, 6.12±3.12; pre-test:;10.15±4.23, 9.61±4.59; p<0.05), and Well-Being Index (post-test:;18.06±4.59, 19.00±4.47; pre-test:;12.71±5.85, 15.09±5.62; p<0.05) showed recovery according to the pre-tests. However, the post-test restless legs syndrome Severity Rating Scale of the experimental group was lower than that of the placebo group (p<0.05). The effect of their application started in 3.93±1.74 days on average in the experimental group, while it started in 5.09±1.55 days in the placebo group (p<0.05). CONCLUSION Both applications reduced the severity of restless legs syndrome in pregnant women and increased sleep quality and well-being. However, compression stockings were more effective in reducing restless legs syndrome severity. Nurses can use compression and placebo stockings in the care of pregnant women with restless legs syndrome. CLINICAL TRIAL REGISTRATION NUMBER NCT05795868.
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Affiliation(s)
- Özlem Kaplan
- Erciyes University, Faculty of Health Sciences, Department of Obstetrics and Gynecology – Kayseri, Turkey
| | - Mürüvvet Başer
- Erciyes University, Faculty of Health Sciences, Department of Obstetrics and Gynecology – Kayseri, Turkey
| | - Mahmut Tuncay Özgün
- Erciyes University, Faculty of Medicine, Department of Obstetrics and Gynecology – Kayseri, Turkey
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Na M, Shetty SS, Niu X, Hinkle SN, Zhang C, Gao X. Sleep duration, napping behaviors and restless legs syndrome during pregnancy and the trajectories of ultrasonographic measures of fetal growth: Findings from the NICHD Fetal Growth Studies-Singletons. Sleep Health 2024; 10:462-469. [PMID: 38862351 DOI: 10.1016/j.sleh.2024.04.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2023] [Revised: 04/15/2024] [Accepted: 04/18/2024] [Indexed: 06/13/2024]
Abstract
OBJECTIVES Given the plausible mechanisms and the lacking of empirical evidence, the study aims to investigate how gestational sleep behaviors and the development of sleep disorders, such as restless legs syndrome, influence ultrasonographic measures of fetal growth. METHODS The study included 2457 pregnant women from the NICHD Fetal Growth Studies - Singletons (2009-2013), who were recruited between 8-13 gestational weeks and followed up to five times during pregnancy. Women were categorized into six groups based on their total sleep hours and napping frequency. The trajectory of estimated fetal weight from 10-40weeks was derived from three ultrasonographic measures. Linear mixed effect models were applied to model the estimated fetal weight in relation to self-reported sleep-napping behaviors and restless legs syndrome status, adjusting for age, race and ethnicity, education, parity, prepregnancy body mass index category, infant sex, and prepregnancy sleep-napping behavior. RESULTS From enrollment to near delivery, pregnant women's total sleep duration and nap frequency declined and restless legs syndrome symptoms frequency increased generally. No significant differences in estimated fetal weight were observed by sleep-napping group or by restless legs syndrome status. Results remained similar in sensitivity analyses and stratified analyses by women's prepregnancy body mass index category (normal vs. overweight/obese) or by infant sex. CONCLUSIONS Our data indicate that there is no association between sleep during pregnancy-assessed as total sleep duration and napping frequency, nor restless legs syndrome symptoms-and fetal growth from weeks 10 to 40 in healthy pregnant women.
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Affiliation(s)
- Muzi Na
- Department of Nutritional Sciences, College of Health and Human Development, The Pennsylvania State University, University Park, Pennsylvania, USA
| | - Samidha Sudhakar Shetty
- Department of Mathematical Sciences, College of Letters and Science, Montana State University, Bozeman, Montana, USA
| | - Xiaoyue Niu
- Department of Statistics, Eberly College of Science, The Pennsylvania State University, University Park, Pennsylvania, USA
| | - Stefanie N Hinkle
- Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Cuilin Zhang
- Global Center for Asian Women's Health (GloW) and Bia-Echo Asia Centre for Reproductive Longevity and Equality (ACRLE), National University of Singapore, Singapore, Singapore; Department of Obstetrics and Gynecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
| | - Xiang Gao
- Department of Nutrition and Food Hygiene, School of Public Health, Institute of Nutrition, Fudan University, Shanghai, China.
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DelRosso LM, Picchietti DL, Sharon D, Spruyt K, Owens JA, Walters AS, Zucconi M, Ferri R. Periodic limb movement disorder in children: A systematic review. Sleep Med Rev 2024; 76:101935. [PMID: 38652932 DOI: 10.1016/j.smrv.2024.101935] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2024] [Revised: 03/09/2024] [Accepted: 04/07/2024] [Indexed: 04/25/2024]
Abstract
This systematic review evaluates the scientific literature on pediatric periodic limb movement disorder (PLMD), adhering to PRISMA guidelines and utilizing PICOS criteria. The search across PubMed, EMBASE, and Scopus yielded 331 articles, with 17 meeting inclusion criteria. Diagnostic criteria evolved, with polysomnography and PLMS index ≥5 required since 2003. Also, PLMD diagnosis mandates clinical consequences like insomnia, hypersomnia, and fatigue, excluding comorbidities causing sleep disruption. Prevalence in children is low (0.3%), emphasizing the need for meticulous investigation. Comorbidities, particularly the bidirectional relationship with ADHD, were explored. Challenges in diagnosis and understanding arise from overlapping conditions such as sleep disordered breathing, psychotropic medication, and criteria non-adherence. Despite generally good study quality, weaknesses include sample size justification and biases. The periodic leg movement index shows high sensitivity but low specificity, underscoring strict diagnostic criteria adherence. Diverse metrics for symptoms necessitate standardized approaches. Family history of RLS in children with PLMD suggests unexplored aspects. Treatment, mainly iron supplementation, lacks standardized assessment metrics. The review emphasizes diagnostic and treatment challenges, recommending unbiased studies with precise techniques. Comprehensive research, quantifying PLMS and objectively assessing sleep parameters, is crucial for advancing understanding in pediatric PLMD. PROSPERO REGISTRATION NUMBER: CRD42021251406.
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Affiliation(s)
| | - Daniel L Picchietti
- University of Illinois School of Medicine, Carle Illinois College of Medicine, and Carle Health, Urbana, IL, USA.
| | - Denise Sharon
- Pomona Valley Hospital and Medical Center, Claremont, CA, USA.
| | - Karen Spruyt
- Université de Paris, NeuroDiderot, INSERM, Paris, 75019, France.
| | - Judith A Owens
- Division of Neurology, Boston Children's Hospital, Harvard Medical School, Waltham, MA, USA.
| | - Arthur S Walters
- Division of Sleep Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA.
| | - Marco Zucconi
- Sleep Disorders Center, Department of Neurology, Scientific Institute and University Ospedale San Raffaele, Vita-Salute University, Institute and Ospedale San Raffaele, Milan, Italy.
| | - Raffaele Ferri
- Sleep Research Centre, Oasi Research Institute - IRCCS, Troina, Italy.
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González-Parejo P, Martín-Núñez J, Cabrera-Martos I, Valenza MC. Effects of Dietary Supplementation in Patients with Restless Legs Syndrome: A Systematic Review. Nutrients 2024; 16:2315. [PMID: 39064758 PMCID: PMC11280425 DOI: 10.3390/nu16142315] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2024] [Revised: 07/14/2024] [Accepted: 07/16/2024] [Indexed: 07/28/2024] Open
Abstract
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.
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Affiliation(s)
| | | | - Irene Cabrera-Martos
- Department of Physical Therapy, Faculty of Health Sciences, University of Granada, 18016 Granada, Spain; (P.G.-P.); (J.M.-N.); (M.C.V.)
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Perger E, Silvestri R, Bonanni E, Di Perri MC, Fernandes M, Provini F, Zoccoli G, Lombardi C. Gender medicine and sleep disorders: from basic science to clinical research. Front Neurol 2024; 15:1392489. [PMID: 39050129 PMCID: PMC11267506 DOI: 10.3389/fneur.2024.1392489] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2024] [Accepted: 06/24/2024] [Indexed: 07/27/2024] Open
Abstract
Several pivotal differences in sleep and sleep disorders are recognized between women and men. This is not only due to changes in hormonal balance during women's reproductive life, such as in pregnancy and menopause. Women are more likely to report insomnia and non-specific symptoms of apneas, such as fatigue or mood disturbance, compared to men. Thus, it is important for clinicians and researchers to take sex and gender differences into account when addressing sleep disorders in order to acknowledge the biology unique to women. We present a narrative review that delves into the primary sleep disorders, starting from basic science, to explore the impact of gender differences on sleep and the current status of research on women's sleep health.
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Affiliation(s)
- Elisa Perger
- Istituto Auxologico Italiano, IRCCS, Sleep Disorders Center and Department of Cardiovascular, Neural and Metabolic Sciences, San Luca Hospital, Milan, Italy
| | - Rosalia Silvestri
- Sleep Medicine Center, Neurophysiopathology and Movement Disorders Unit, Department of Clinical and Experimental Medicine, University of Messina, AOU “G. Martino”, Messina, Italy
| | - Enrica Bonanni
- Sleep Disorder Center, Neurology Unit, Azienda Ospedaliero-Universitaria Pisana and Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Maria Caterina Di Perri
- Sleep Medicine Center, Neurophysiopathology and Movement Disorders Unit, Department of Clinical and Experimental Medicine, University of Messina, AOU “G. Martino”, Messina, Italy
| | - Mariana Fernandes
- Epilepsy Centre, Department of Systems Medicine, University of Rome “Tor Vergata”, Rome, Italy
- Neurology Unit, University Hospital of Rome “Tor Vergata”, Rome, Italy
| | - Federica Provini
- IRCCS, Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy
- Department of Biomedical and Neuromotor Sciences, Università di Bologna, Bologna, Italy
| | - Giovanna Zoccoli
- Department of Biomedical and Neuromotor Sciences, Università di Bologna, Bologna, Italy
| | - Carolina Lombardi
- Istituto Auxologico Italiano, IRCCS, Sleep Disorders Center and Department of Cardiovascular, Neural and Metabolic Sciences, San Luca Hospital, Milan, Italy
- Department of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy
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Lomas K, Morgan K, Haines V, Hartescu I, Beizaee A, Barnes J, Zambelli Z, Ravikumar M, Rossi V. Homes Heat Health protocol: an observational cohort study measuring the effect of summer temperatures on sleep quality. BMJ Open 2024; 14:e086797. [PMID: 38964790 PMCID: PMC11227782 DOI: 10.1136/bmjopen-2024-086797] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2024] [Accepted: 06/11/2024] [Indexed: 07/06/2024] Open
Abstract
INTRODUCTION Quality sleep is essential to our health and well-being. Summertime temperatures in the bedrooms of homes in temperate climates are increasing, especially in city apartments. There is very little empirical evidence of the effect of temperature on sleep when people are sleeping in their own bedroom. The Homes Heat Health project seeks to develop a measurable definition of temperature-related sleep disturbance and the effects on health, and so produce a credible criterion for identifying overheating in new and existing homes. METHODS AND ANALYSIS A cohort of at least 95 people that live in London apartments and who are free of significant personal and health factors that could affect sleep are being recruited for an ongoing observational cohort study. A baseline questionnaire determines their customary sleep patterns and health. The geometrical form and thermal characteristics of their apartments is being recorded along with temperature, relative humidity and in some apartments CO2 levels, throughout one summer. Actigraphy records nightly sleep disturbance and every morning an app-based diary captures perceived sleep quality. Questionnaires following spells of hot weather capture changes in sleep pattern, sleep quality, and consequential health and well-being. ETHICS AND DISSEMINATION The study protocol was approved by the Loughborough University ethics committee. The participants will receive both verbal and written information explaining the purpose of the study, what is expected of them, the incentives for participating and the feedback that will be provided. The results will be reported bi-annually to a project advisory board. Presentations will be made at conferences and the methods, intermediary and final results, in academic journals. Informing government bodies, professional organisations, construction industry representatives and housing providers is of particular importance.
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Affiliation(s)
| | | | | | | | | | - Jo Barnes
- Loughborough University, Loughborough, UK
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Boyer TM, Vaught AJ, Gemmill A. Variation and correlates of psychosocial wellbeing among nulliparous women with preeclampsia. Pregnancy Hypertens 2024; 36:101121. [PMID: 38552368 PMCID: PMC11162915 DOI: 10.1016/j.preghy.2024.101121] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2023] [Revised: 02/28/2024] [Accepted: 03/24/2024] [Indexed: 04/04/2024]
Abstract
OBJECTIVES To identify classes of psychosocial stressors among women who developed preeclampsia and to evaluate the associations between these classes and correlates of psychosocial wellbeing. STUDY DESIGN We performed a secondary analysis of women who developed preeclampsia (n = 727) from the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-be (nuMoM2b) cohort (2010-2013). Latent class analysis was used to identify classes of social stressors based on seven psychological and sociocultural indicators. Associations between latent classes and correlates (demographics, health behavior, and health-systems level) were estimated using multinomial logistic regression. MAIN OUTCOME MEASURES Classes of psychosocial wellbeing. RESULTS Among women who developed preeclampsia, three classes reflective of psychosocial wellbeing were identified: Class 1: Intermediate Psychosocial Wellbeing (53 %), Class 2: Positive Psychosocial Wellbeing (31 %), Class 3: Negative Psychosocial Wellbeing (16 %). Women in the Negative Psychosocial Wellbeing Class were more likely to have poor sleep and a sedentary lifestyle compared with the Positive and Intermediate Psychosocial Wellbeing Classes. Both the Negative and Intermediate Psychosocial Wellbeing Classes reported concern about their quality of medical care compared with the Positive Psychosocial Wellbeing Class (adjusted odds ratio [aOR]: 6.19, 95 % confidence interval [CI]: 3.37, 11.36 and aOR: 2.19, 95 % CI: 1.31, 3.65, respectively). CONCLUSIONS Women who develop preeclampsia are heterogenous and experience different intensities of internal and external stressors. Understanding the linkages between psychosocial wellbeing during pregnancy and modifiable behavioral and structural factors may inform future tailored management strategies for preeclampsia and the optimization of maternal postpartum health.
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Affiliation(s)
| | - Arthur J Vaught
- Division of Maternal Fetal Medicine, Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Alison Gemmill
- Department of Population, Family and Reproductive Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
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Maharjan S, Dua R, Saini LK, Kumar N, Gupta R. Prevalence and predictors of restless legs syndrome among patients having stable chronic obstructive pulmonary disease. Sleep Med 2024; 118:32-38. [PMID: 38588638 DOI: 10.1016/j.sleep.2024.03.041] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/15/2023] [Revised: 02/13/2024] [Accepted: 03/27/2024] [Indexed: 04/10/2024]
Abstract
BACKGROUND Patients having COPD share some factors, e.g., chronic hypoxemia, anemia of chronic disease and nicotine use, which are also the risk factors for RLS hence predispose them to experience RLS in higher then general population. There are limited studies with methodological constraints evaluating the prevalence and/or correlates of RLS among patients with COPD. METHODS Consecutive adult patients of either gender, having stable COPD as per GOLD guidelines 2021, were assessed for RLS using IRLSSG (2014) criteria (excluding RLS mimics) and the severity of RLS was determined in participants having RLS. Phenomenology of RLS, past medical history and laboratory parameters were gathered. Insomnia and depression were assessed using the insomnia severity index and PHQ-9, respectively. RESULTS Participants' (N = 210) mean age was 63.02 ± 8.19 years, and 83.8% of subjects were men. 12.9% of participants were found to have RLS. Among those having RLS, nearly half (51.9%) had moderate symptoms, and 18.5% experienced severe symptoms. RLS was more prevalent among younger, females, those having severe COPD, participants having exacerbation of COPD in the previous year, lower post-bronchodilator FEV1, higher dyspnea and COPD assessment test score. Multivariate analysis showed that younger age, female gender, lower post-bronchodilator FEV1, lower FEV1/FVC ratio and higher serum creatinine increased the odds of having RLS. Depressive symptoms were more frequent in participants having RLS. CONCLUSIONS The present study found that the prevalence of RLS among patients with stable COPD was higher than the general population. Female gender, younger age, higher airflow limitation and higher serum creatinine (though in the physiological range) increase the odds of having RLS. Stable patients with COPD having these characteristics must be screened for RLS.
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Affiliation(s)
- Sabbu Maharjan
- Departments of Psychiatry, All India Institute of Medical Sciences, Veerbhadra Marg, Rishikesh, 249203, India
| | - Ruchi Dua
- Departments of Pulmonary Medicine, All India Institute of Medical Sciences, Veerbhadra Marg, Rishikesh, 249203, India
| | - Lokesh Kumar Saini
- Departments of Pulmonary Medicine, All India Institute of Medical Sciences, Veerbhadra Marg, Rishikesh, 249203, India.
| | - Niraj Kumar
- Departments of Neurology, All India Institute of Medical Sciences, Veerbhadra Marg, Rishikesh, 249203, India
| | - Ravi Gupta
- Departments of Psychiatry, All India Institute of Medical Sciences, Veerbhadra Marg, Rishikesh, 249203, India
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Schormair B, Zhao C, Bell S, Didriksen M, Nawaz MS, Schandra N, Stefani A, Högl B, Dauvilliers Y, Bachmann CG, Kemlink D, Sonka K, Paulus W, Trenkwalder C, Oertel WH, Hornyak M, Teder-Laving M, Metspalu A, Hadjigeorgiou GM, Polo O, Fietze I, Ross OA, Wszolek ZK, Ibrahim A, Bergmann M, Kittke V, Harrer P, Dowsett J, Chenini S, Ostrowski SR, Sørensen E, Erikstrup C, Pedersen OB, Topholm Bruun M, Nielsen KR, Butterworth AS, Soranzo N, Ouwehand WH, Roberts DJ, Danesh J, Burchell B, Furlotte NA, Nandakumar P, Earley CJ, Ondo WG, Xiong L, Desautels A, Perola M, Vodicka P, Dina C, Stoll M, Franke A, Lieb W, Stewart AFR, Shah SH, Gieger C, Peters A, Rye DB, Rouleau GA, Berger K, Stefansson H, Ullum H, Stefansson K, Hinds DA, Di Angelantonio E, Oexle K, Winkelmann J. Genome-wide meta-analyses of restless legs syndrome yield insights into genetic architecture, disease biology and risk prediction. Nat Genet 2024; 56:1090-1099. [PMID: 38839884 PMCID: PMC11176086 DOI: 10.1038/s41588-024-01763-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2023] [Accepted: 04/19/2024] [Indexed: 06/07/2024]
Abstract
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 (rg = 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.
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Affiliation(s)
- Barbara Schormair
- Institute of Neurogenomics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
- Institute of Human Genetics, TUM School of Medicine and Health, Technical University of Munich, Munich, Germany.
| | - Chen Zhao
- Institute of Neurogenomics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
- Institute of Human Genetics, TUM School of Medicine and Health, Technical University of Munich, Munich, Germany
| | - Steven Bell
- Department of Oncology, University of Cambridge, Cambridge, UK
- Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK
- Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Cambridge, UK
| | - Maria Didriksen
- Department of Clinical Immunology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
- Department of Neuroscience, University of Copenhagen, Copenhagen, Denmark
| | | | - Nathalie Schandra
- Institute of Neurogenomics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
- Institute of Human Genetics, TUM School of Medicine and Health, Technical University of Munich, Munich, Germany
| | - Ambra Stefani
- Sleep Disorders Clinic, Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria
| | - Birgit Högl
- Sleep Disorders Clinic, Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria
| | - Yves Dauvilliers
- Sleep-Wake Disorders Center, Department of Neurology, Hôpital Gui-de-Chauliac, CHU Montpellier, Institut des Neurosciences de Montpellier, INSERM, Université de Montpellier, Montpellier, France
| | - Cornelius G Bachmann
- SomnoDiagnostics, Osnabrück, Germany
- Department of Neurology, University Medical Center Göttingen, Göttingen, Germany
| | - David Kemlink
- Department of Neurology and Centre of Clinical Neuroscience, Charles University, First Faculty of Medicine and General University Hospital, Prague, Czech Republic
| | - Karel Sonka
- Department of Neurology and Centre of Clinical Neuroscience, Charles University, First Faculty of Medicine and General University Hospital, Prague, Czech Republic
| | - Walter Paulus
- Department of Neurology, Ludwig Maximilians University Munich, Munich, Germany
| | - Claudia Trenkwalder
- Paracelsus-Elena-Klinik, Kassel, Germany
- Department of Neurosurgery, University Medical Center Göttingen, Göttingen, Germany
| | - Wolfgang H Oertel
- Institute of Neurogenomics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
- Department of Neurology, Philipps-University Marburg, Marburg, Germany
| | | | - Maris Teder-Laving
- Estonian Genome Center, Institute of Genomics, University of Tartu, Tartu, Estonia
| | - Andres Metspalu
- Estonian Genome Center, Institute of Genomics, University of Tartu, Tartu, Estonia
| | - Georgios M Hadjigeorgiou
- Department of Neurology, Nicosia General Hospital Medical School, University of Cyprus, Nicosia, Cyprus
| | - Olli Polo
- Bragée ME/CFS Center, Stockholm, Sweden
| | - Ingo Fietze
- Department of Pulmonology, Center of Sleep Medicine, Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - Owen A Ross
- Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, FL, USA
| | | | - Abubaker Ibrahim
- Sleep Disorders Clinic, Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria
| | - Melanie Bergmann
- Sleep Disorders Clinic, Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria
| | - Volker Kittke
- Institute of Neurogenomics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
- Institute of Human Genetics, TUM School of Medicine and Health, Technical University of Munich, Munich, Germany
| | - Philip Harrer
- Institute of Neurogenomics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
- Institute of Human Genetics, TUM School of Medicine and Health, Technical University of Munich, Munich, Germany
| | - Joseph Dowsett
- Department of Clinical Immunology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - Sofiene Chenini
- Sleep-Wake Disorders Center, Department of Neurology, Hôpital Gui-de-Chauliac, CHU Montpellier, Institut des Neurosciences de Montpellier, INSERM, Université de Montpellier, Montpellier, France
| | - Sisse Rye Ostrowski
- Department of Clinical Immunology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
- Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
| | - Erik Sørensen
- Department of Clinical Immunology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - Christian Erikstrup
- Department of Clinical Immunology, Aarhus University Hospital, Aarhus, Denmark
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Ole B Pedersen
- Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
- Department of Clinical Immunology, Zealand University Hospital, Køge, Denmark
| | - Mie Topholm Bruun
- Department of Clinical Immunology, Odense University Hospital, Odense, Denmark
| | - Kaspar R Nielsen
- Department of Clinical Immunology, Aalborg University Hospital, Aalborg, Denmark
| | - Adam S Butterworth
- British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
- British Heart Foundation Centre of Research Excellence, University of Cambridge, Cambridge, UK
- National Institute for Health and Care Research Blood and Transplant Research Unit in Donor Health and Behaviour, University of Cambridge, Cambridge, UK
- Health Data Research UK Cambridge, Wellcome Genome Campus and University of Cambridge, Cambridge, UK
- Victor Phillip Dahdaleh Heart and Lung Research Institute, University of Cambridge, Cambridge, UK
| | - Nicole Soranzo
- National Institute for Health and Care Research Blood and Transplant Research Unit in Donor Health and Behaviour, University of Cambridge, Cambridge, UK
- Department of Haematology, University of Cambridge, Cambridge, UK
- Department of Human Genetics, the Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK
| | - Willem H Ouwehand
- Department of Haematology, University of Cambridge, Cambridge, UK
- NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, UK
- Department of Haematology, University College London Hospitals, London, UK
| | - David J Roberts
- National Institute for Health and Care Research Blood and Transplant Research Unit in Donor Health and Behaviour, University of Cambridge, Cambridge, UK
- Radcliffe Department of Medicine and National Health Service Blood and Transplant, Oxford, UK
- Department of Haematology and BRC Haematology Theme, Churchill Hospital, Headington, Oxford, UK
| | - John Danesh
- British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
- British Heart Foundation Centre of Research Excellence, University of Cambridge, Cambridge, UK
- National Institute for Health and Care Research Blood and Transplant Research Unit in Donor Health and Behaviour, University of Cambridge, Cambridge, UK
- Health Data Research UK Cambridge, Wellcome Genome Campus and University of Cambridge, Cambridge, UK
- Victor Phillip Dahdaleh Heart and Lung Research Institute, University of Cambridge, Cambridge, UK
- Department of Human Genetics, the Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK
| | | | | | | | - Christopher J Earley
- Center for Restless Legs Syndrome, Department of Neurology, Johns Hopkins University, Baltimore, MD, USA
| | - William G Ondo
- Department of Neurology, Methodist Neurological Institute, Weill Cornell Medical School, Houston, TX, USA
| | - Lan Xiong
- The Neuro (Montreal Neurological Institute-Hospital), McGill University, Montreal, Quebec, Canada
- Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada
| | - Alex Desautels
- Centre d'Études Avancées en Médecine du Sommeil, Hôpital du Sacré-Cœur de Montréal, Montreal, Quebec, Canada
- Department of Neurosciences, Université de Montréal, Montreal, Quebec, Canada
| | - Markus Perola
- Clinical and Molecular Metabolism Research Program (CAMM), Faculty of Medicine, University of Helsinki, Helsinki, Finland
- Department of Public Health and Welfare, National Institute for Health and Welfare, Helsinki, Finland
| | - Pavel Vodicka
- Department of Molecular Biology of Cancer, Institute of Experimental Medicine, Academy of Science of Czech Republic, Prague, Czech Republic
- First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic
- Biomedical Centre, Faculty of Medicine in Pilsen, Charles University in Prague, Pilsen, Czech Republic
| | - Christian Dina
- L'institut du thorax, CNRS, INSERM, Nantes Université, Nantes, France
| | - Monika Stoll
- Department of Genetic Epidemiology, Institute for Human Genetics, University of Münster, Münster, Germany
| | - Andre Franke
- Institute of Clinical Molecular Biology, Kiel University, Kiel, Germany
| | - Wolfgang Lieb
- PopGen Biobank and Institute of Epidemiology, Christian Albrechts University Kiel, Kiel, Germany
| | - Alexandre F R Stewart
- John and Jennifer Ruddy Canadian Cardiovascular Genetics Centre, University of Ottawa Heart Institute, Ottawa, Ontario, Canada
| | - Svati H Shah
- Department of Medicine, Duke University School of Medicine, Durham, NC, USA
- Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC, USA
| | - Christian Gieger
- Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
- Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
| | - Annette Peters
- Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
- German Research Center for Cardiovascular Disease (DZHK), partner site Munich Heart Alliance, Hannover, Germany
- Chair of Epidemiology, Institute for Medical Information Processing, Biometry and Epidemiology, Medical Faculty, Ludwig-Maximilians-Universität München, Munich, Germany
| | - David B Rye
- Department of Neurology, Emory University, Atlanta, GA, USA
| | - Guy A Rouleau
- The Neuro (Montreal Neurological Institute-Hospital), McGill University, Montreal, Quebec, Canada
- Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada
- Department of Human Genetics, McGill University, Montreal, Quebec, Canada
| | - Klaus Berger
- Institute of Epidemiology and Social Medicine, University of Münster, Münster, Germany
| | | | | | | | | | - Emanuele Di Angelantonio
- British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
- British Heart Foundation Centre of Research Excellence, University of Cambridge, Cambridge, UK
- National Institute for Health and Care Research Blood and Transplant Research Unit in Donor Health and Behaviour, University of Cambridge, Cambridge, UK
- Health Data Research UK Cambridge, Wellcome Genome Campus and University of Cambridge, Cambridge, UK
- Victor Phillip Dahdaleh Heart and Lung Research Institute, University of Cambridge, Cambridge, UK
- Health Data Science Research Centre, Fondazione Human Technopole, Milan, Italy
| | - Konrad Oexle
- Institute of Neurogenomics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
- Institute of Human Genetics, TUM School of Medicine and Health, Technical University of Munich, Munich, Germany
- Neurogenetic Systems Analysis Group, Institute of Neurogenomics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
| | - Juliane Winkelmann
- Institute of Neurogenomics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
- Institute of Human Genetics, TUM School of Medicine and Health, Technical University of Munich, Munich, Germany
- Munich Cluster for Systems Neurology (SyNergy), Munich, Germany
- German Center for Mental Health (DZPG), partner site Munich-Augsburg, Munich-Augsburg, Germany
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Mayer-Suess L, Ibrahim A, Moelgg K, Cesari M, Knoflach M, Högl B, Stefani A, Kiechl S, Heidbreder A. Sleep disorders as both risk factors for, and a consequence of, stroke: A narrative review. Int J Stroke 2024; 19:490-498. [PMID: 37885093 PMCID: PMC11134986 DOI: 10.1177/17474930231212349] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2023] [Accepted: 10/18/2023] [Indexed: 10/28/2023]
Abstract
BACKGROUND AND PURPOSE Sleep disorders are increasingly implicated as risk factors for stroke, as well as a determinant of stroke outcome. They can also occur secondary to the stroke itself. In this review, we describe the variety of different sleep disorders associated with stroke and analyze their effect on stroke risk and outcome. METHODS A search term-based literature review ("sleep," "insomnia," "narcolepsy," "restless legs syndrome," "periodic limb movements during sleep," "excessive daytime sleepiness" AND "stroke" OR "cerebrovascular" in PubMed; "stroke" and "sleep" in ClinicalTrials.gov) was performed. English articles from 1990 to March 2023 were considered. RESULTS Increasing evidence suggests that sleep disorders are risk factors for stroke. In addition, sleep disturbance has been reported in half of all stroke sufferers; specifically, an increase is not only sleep-related breathing disorders but also periodic limb movements during sleep, narcolepsy, rapid eye movement (REM) sleep behavior disorder, insomnia, sleep duration, and circadian rhythm sleep-wake disorders. Poststroke sleep disturbance has been associated with worse outcome. CONCLUSION Sleep disorders are risk factors for stroke and associated with worse stroke outcome. They are also a common consequence of stroke. Recent guidelines suggest screening for sleep disorders after stroke. It is possible that treatment of sleep disorders could both reduce stroke risk and improve stroke outcome, although further data from clinical trials are required.
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Affiliation(s)
- Lukas Mayer-Suess
- Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria
| | - Abubaker Ibrahim
- Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria
| | - Kurt Moelgg
- Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria
| | - Matteo Cesari
- Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria
| | - Michael Knoflach
- Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria
- VASCage—Research Centre on Clinical Stroke Research, Innsbruck, Austria
| | - Birgit Högl
- Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria
| | - Ambra Stefani
- Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria
- Neurological Clinical Research Institute, Massachusetts General Hospital, Boston, MA, USA
| | - Stefan Kiechl
- Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria
- VASCage—Research Centre on Clinical Stroke Research, Innsbruck, Austria
| | - Anna Heidbreder
- Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria
- Department of Neurology, Johannes Kepler University Linz, Linz, Austria
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Butt NI, Ghoauri MSA, Waris U, Sabeh D, Qaisar F. Frequency of Restless Legs Syndrome in Pakistani Patients With Type 2 Diabetes Mellitus. Cureus 2024; 16:e62624. [PMID: 39027768 PMCID: PMC11257648 DOI: 10.7759/cureus.62624] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/18/2024] [Indexed: 07/20/2024] Open
Abstract
Objective To determine the frequency of restless legs syndrome (RLS) among Pakistani patients with type 2 diabetes mellitus. Methods This observational cross-sectional study was carried out in the Department of Medicine at Bahawal Victoria Hospital, Quaid-e-Azam Medical College, Bahawalpur, Pakistan, from January 2024 to May 2024. The National Institute of Health (NIH) diagnostic criteria were used to diagnose RLS. Type 2 diabetes mellitus was defined as patients with an HbA1c greater than 7.0%, two random blood glucose readings of ≥200 mg/dL, a previous history of diabetes diagnosis, or those taking anti-hyperglycemic medicines. Patients with a history of leg surgery or amputation, iron deficiency anemia, alcoholism, end-stage kidney disease, chronic liver disease, those on hemodialysis, and pregnant women were excluded from the study. After ethical approval and informed consent were obtained, 255 patients with type 2 diabetes mellitus were included in the study using a non-probability consecutive sampling technique. Demographic information including age, gender, and duration of diabetes was noted, and patients were assessed for diabetes control, peripheral neuropathy, retinopathy, and RLS Patient records were assessed for HbA1c levels and urine examination to diagnose nephropathy. All data were entered into SPSS version 23. A Chi-Square test was applied post-stratification using a p-value of less than 0.05 as significant. Results The mean age was 53.5 ± 12.8 years with 140 (54.9%) females. The mean duration of the disease and mean HbA1c were 6.8 ± 5.4 years and 9.8 ± 2.5%, respectively, with 191 (74.9%) patients having poor control of diabetes. Peripheral neuropathy was seen in 131 (51.4%) patients, retinopathy in 58 (22.7%), and nephropathy in 23 (9.0%). RLS was present in 34 (13.3%) patients with type 2 diabetes mellitus, showing a significant association with diabetes control (p-value = 0.001), peripheral neuropathy (p-value = 0.016), retinopathy (p-value = 0.006), and nephropathy (p-value = 0.011), but not with age (p-value = 0.122), gender (p-value = 0.217), or duration of diabetes (p-value = 0.922). Conclusion RLS was not an uncommon finding in patients with type 2 diabetes mellitus, being more common among those with poor diabetes control and the presence of other complications such as neuropathy, nephropathy, and retinopathy.
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Affiliation(s)
- Nauman Ismat Butt
- Internal Medicine/Rheumatology, Azra Naheed Medical College, Superior University, Lahore, PAK
| | | | - Umaima Waris
- Medicine, Azra Naheed Medical College, Superior University, Lahore, PAK
| | - Dure Sabeh
- Medicine, Bahawal Victoria Hospital, Quaid-e-Azam Medical College, Bahawalpur, PAK
| | - Fahad Qaisar
- Medicine, Bahawal Victoria Hospital, Quaid-e-Azam Medical College, Bahawalpur, PAK
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Guerroumi M, Aquil A, El Kherchi O, Ait Bouighoulidne S, Belhaj Haddou M, Elgot A. Evaluation of the relationship between restless legs syndrome, mental status, and sleep disorders among Moroccan women during their third trimester of pregnancy. Ann Med Surg (Lond) 2024; 86:2626-2632. [PMID: 38694400 PMCID: PMC11060302 DOI: 10.1097/ms9.0000000000001987] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2023] [Accepted: 03/08/2024] [Indexed: 05/04/2024] Open
Abstract
Background Restless legs syndrome (RLS) is a motor disorder encountered during pregnancy and leads to psychological and sleep impairments. The latter seems to be non-restorative and its occurrence alters the quality of life of pregnant women. The objective of this study was to evaluate the prevalence of RLS and its relationship with both anxio-depressive symptoms and sleep disorders among a population of Moroccan pregnant women during their third trimester of pregnancy. Methods A cross-sectional study was conducted in a population of pregnant women in their third trimester (n=178) admitted to two health facilities in the city of Marrakech: Youssef Ibn Tachafine and Oasis. The face-to-face questionnaire was used to collect data including demographic and clinical characteristics, the four diagnostic criteria of RLS, the Pittsburgh Sleep Quality Index (PSQI), and the Hospital Anxiety and Depression Scale (HADS). Patients were divided into two groups RLS+ (women with RLS) and RLS- (women without RLS). Results The prevalence of RLS was 59.5%; this syndrome was more common in the ninth month (74.15%) compared with the seventh and eighth months. Sleep impairment, including sleep efficiency, was significantly higher in RLS+ than RLS- (P-value 0.05). Anxiety but not depression is significantly increased in RLS+ compared to RLS- (48.11% versus 38.8%, P = 0.000). There were no significant differences between RLS+ and RLS- in terms of socio-demographic and other clinical characteristics. Conclusion RLS is encountered during the prenatal period, with a higher prevalence in the last trimester. During this stage of pregnancy, women suffering from RLS were vulnerable to anxiety and sleep disorders. Prevention and early diagnosis of RLS could be a proactive healthcare management leading to better health outcomes and better conditions of pregnancy, which precedes childbirth.
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Affiliation(s)
- Maroua Guerroumi
- Hassan First University of Settat, Higher Institute of Health Sciences, Laboratory of Sciences and Health Technologies, Epidemiology and Biomedical Unit
| | - Amina Aquil
- Hassan First University of Settat, Higher Institute of Health Sciences, Laboratory of Sciences and Health Technologies, Epidemiology and Biomedical Unit
| | - Ouassil El Kherchi
- Hassan First University of Settat, Higher Institute of Health Sciences, Laboratory of Sciences and Health Technologies, Epidemiology and Biomedical Unit
| | - Salma Ait Bouighoulidne
- Hassan First University of Settat, Higher Institute of Health Sciences, Laboratory of Sciences and Health Technologies, Epidemiology and Biomedical Unit
| | - Meryam Belhaj Haddou
- Hassan First University of Settat, Higher Institute of Health Sciences, Laboratory of Sciences and Health Technologies, Epidemiology and Biomedical Unit
- University Teaching Hospital Mohammed VI, Marrakech, Morocco
| | - Abdeljalil Elgot
- Hassan First University of Settat, Higher Institute of Health Sciences, Laboratory of Sciences and Health Technologies, Epidemiology and Biomedical Unit
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Park BS, Heo CM, Lee YJ, Park S, Kim YW, Son S, Kwon H, Park Y, Kim Y, Lee DA, Park KM. Difference in functional connectivity between end-stage renal disease patients with and without restless legs syndrome: A prospective study. Sleep Breath 2024; 28:673-681. [PMID: 37889458 DOI: 10.1007/s11325-023-02943-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2023] [Revised: 10/11/2023] [Accepted: 10/18/2023] [Indexed: 10/28/2023]
Abstract
PURPOSE The purpose of this study was to examine differences in functional connectivity between patients with end-stage renal disease (ESRD) with and without restless legs syndrome (RLS). In addition, the study aimed to identify any potential associations between RLS severity and functional connectivity. METHODS We enrolled patients with ESRD who had been undergoing hemodialysis. Patients with and without RLS were separated into two groups. Using functional near-infrared spectroscopy (fNIRS) and a graph theory approach, we determined the functional connectivity of patients with ESRD. The data were collected during a 300-s resting state evaluation performed in the dialysis room prior to dialysis. RESULTS Eighteen of 48 patients with ESRD were diagnosed with RLS, whereas 30 patients did not exhibit RLS symptoms. Notably, functional connectivity metrics differed significantly between patients with and without RLS. Specifically, patients with ESRD and RLS displayed higher values for mean clustering coefficient (0.474 vs. 0.352, p = 0.001), global efficiency (0.520 vs. 0.414, p = 0.001), strength (6.538 vs. 4.783, p = 0.001), and transitivity (0.714 vs. 0.521, p = 0.001), while values for diameter (5.451 vs. 7.338, p = 0.002), eccentricity (4.598 vs. 5.985, p = 0.004), and characteristic path length (2.520 vs. 3.271, p = 0.002) were lower in patients with ESRD and RLS compared to those without RLS. In addition, there were correlations between the RLS severity score and the assortative coefficient (r = 0.479, p = 0.044), the small-worldness index (r = -0.475, p = 0.046), and transitivity (r = 0.500, p = 0.034). CONCLUSIONS We demonstrated differences in functional connectivity between patients with ESRD with and without RLS, which may shed light on the pathophysiology of RLS. Notably, a number of functional connectivity metrics demonstrated strong associations with RLS severity. Our study also confirmed the applicability of fNIRS as a tool for investigating functional connectivity in patients with RLS.
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Affiliation(s)
- Bong Soo Park
- Department of Internal Medicine, Haeundae Paik Hospital, Inje University College of Medicine, Busan, Korea
| | - Chang Min Heo
- Department of Internal Medicine, Haeundae Paik Hospital, Inje University College of Medicine, Busan, Korea
| | - Yoo Jin Lee
- Department of Internal Medicine, Haeundae Paik Hospital, Inje University College of Medicine, Busan, Korea
| | - Sihyung Park
- Department of Internal Medicine, Haeundae Paik Hospital, Inje University College of Medicine, Busan, Korea
| | - Yang Wook Kim
- Department of Internal Medicine, Haeundae Paik Hospital, Inje University College of Medicine, Busan, Korea
| | - SungHyun Son
- Department of Internal Medicine, BMS Hanseo Hospital, Busan, Korea
| | - Hyukyong Kwon
- Department of Internal Medicine, BMS Hanseo Hospital, Busan, Korea
| | - Youngchan Park
- Department of Internal Medicine, BMS Hanseo Hospital, Busan, Korea
| | - Yunmi Kim
- Department of Internal Medicine, Busan Paik Hospital, Inje University College of Medicine, Busan, Korea
| | - Dong Ah Lee
- Department of Neurology, Haeundae Paik Hospital, Inje University College of Medicine, Busan, Korea
| | - Kang Min Park
- Department of Neurology, Haeundae Paik Hospital, Inje University College of Medicine, Busan, Korea.
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Kim B, Kim TY, Choi EJ, Lee M, Kim W, Lee SA. Restless legs syndrome in patients with obstructive sleep apnea: Association between apnea severity and symptoms of depression, insomnia, and daytime sleepiness. Sleep Med 2024; 117:40-45. [PMID: 38507975 DOI: 10.1016/j.sleep.2024.03.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2023] [Revised: 01/26/2024] [Accepted: 03/09/2024] [Indexed: 03/22/2024]
Abstract
OBJECTIVE To determine if the prevalence and severity of restless legs syndrome (RLS) varies with apnea severity and analyze differences between the sexes in terms of comorbid RLS with symptoms of depression, insomnia, and daytime sleepiness in patients with obstructive sleep apnea (OSA). METHODS Symptoms of depression, insomnia, and daytime sleepiness were defined as Patient Health Questionnaire-9 score ≥10, Insomnia Severity Index score ≥15, and Epworth Sleepiness Scale score ≥11. Multivariate logistic and linear regression analyses were conducted. RESULTS In 707 adults with OSA (85.1% males), 16.1% (n = 114) had comorbid RLS. The prevalence of RLS was markedly lower in those with moderate and severe OSA than in those with mild OSA. Similarly, the odds of RLS significantly decreased with increasing apnea-hypopnea index. After controlling for age and sex, in patients with comorbid RLS, the International RLS Study Group Rating Scale scores were negatively correlated with apnea-hypopnea index and a nadir peripheral oxygen saturation during sleep. The presence of RLS was more likely to be associated with symptoms of depression, insomnia, and daytime sleepiness after controlling for confounding variables, but only in men. CONCLUSIONS RLS is frequently noted in combination with OSA, with a female preponderance. The severities of OSA and RLS may be negatively associated. In patients with OSA, sex-related differences in terms of comorbid RLS with symptoms of depression, insomnia, and daytime sleepiness warrant further investigations.
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Affiliation(s)
- Boyoung Kim
- Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, South Korea
| | - Tae-Young Kim
- Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, South Korea
| | - Eun-Ju Choi
- Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, South Korea
| | - Myeongwoo Lee
- Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, South Korea
| | - Wontae Kim
- Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, South Korea
| | - Sang-Ahm Lee
- Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, South Korea.
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Al-Kassmy J, Alsalmi M, Kang W, Huot P. Anticonvulsant Agents for Treatment of Restless Legs Syndrome: A Case Report With Lamotrigine and a Review of the Literature. Neurologist 2024; 29:173-178. [PMID: 38250816 DOI: 10.1097/nrl.0000000000000552] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2024]
Abstract
INTRODUCTION Restless Legs Syndrome (RLS) is a neurological disorder primarily treated with pregabalin and gabapentin, followed by dopamine agonists later in the process due to the risk of augmenting RLS symptoms. In addition, clinical reports have disclosed varying degrees of success employing other agents in patients unresponsive to traditional agents. Here, we present a patient who had success in the reduction of RLS symptoms with lamotrigine, a broad-spectrum anticonvulsant. Previously, lamotrigine had been used in 2 trials with successful treatment of RLS. CASE REPORT We present a 58-year-old right-handed lady with long-standing history of smoking, hypertension, dyslipidaemia, prediabetes, gastro-esophageal reflux disease, asthma, strabismus, uterine cancer, severe and debilitating course of RLS accompanied by unexplained deterioration. The patient initially demonstrated abnormal sensation in all her limbs, which worsened with radiotherapy treatment, and was eventually diagnosed with RLS based on the diagnostic criteria. Subsequent examinations were unremarkable and revealed no further explanation for the deterioration of the RLS symptoms. While the complexity of the patient's medical history had exposed her to a variety of medications, she reported that only lamotrigine, in addition to her original regimen of methadone and pramipexole, offered significant symptomatic relief. It must be noted that no adverse side effects, including impulse-control disorder, were reported by the patient. CONCLUSIONS We present a case of a woman whose deteriorating symptoms of RLS were successfully alleviated by the administration of lamotrigine. This is only the third case in the literature to have successfully utilized lamotrigine as a treatment option for RLS.
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Affiliation(s)
- Jawad Al-Kassmy
- Royal College of Surgeons in Ireland, School of Medicine, Dublin, Ireland
| | - Mohammed Alsalmi
- Department of Neurosciences, Division of Neurology, Movement Disorder Clinic, McGill University Health Centre
| | - Woojin Kang
- Neurodegenerative Disease Group, Montreal Neurological Institute-Hospital (The Neuro)
| | - Philippe Huot
- Department of Neurosciences, Division of Neurology, Movement Disorder Clinic, McGill University Health Centre
- Neurodegenerative Disease Group, Montreal Neurological Institute-Hospital (The Neuro)
- Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada
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Makharia A, Agarwal A, Srivastava AK, Garg D. Current updates in Restless Legs Syndrome: A pragmatic review. ANNALS OF MOVEMENT DISORDERS 2024; 7:55-77. [DOI: 10.4103/aomd.aomd_48_24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2024] [Accepted: 08/01/2024] [Indexed: 01/03/2025] Open
Abstract
AbstractRestless legs syndrome (RLS), also called Willis–Ekbom disease (WED), affects approximately 3% of the global population, with higher incidence in Caucasians and women. This review explores the latest advancements in the diagnosis, pathophysiology, and management of RLS, and it highlights the recent changes in diagnostic criteria that improve specificity. The diagnostic spectrum now includes atypical presentations involving the upper limbs and other body parts. The new diagnostic specifiers categorize RLS more effectively into chronic-persistent or intermittent types, and a clinical significance specifier has been introduced to better address the disorder’s effects on daily life. RLS management has shifted toward a balanced approach with non-pharmacological strategies and lifestyle changes, supported by updated pharmacological treatment protocols including iron therapy designed to mitigate risks such as augmentation. Notably, gabapentinoids have emerged as a superior treatment option over dopamine agonists owing to their lower risk of augmentation and superior safety profile. Innovative treatments, such as the FDA-approved tonic motor activation device and new pharmacological agents, serve as alternatives for treating medication-refractory RLS, thereby expanding the therapeutic landscape. Additionally, this review addresses the specific considerations for managing RLS in special groups, including pregnant women, individuals with chronic kidney disease, and patients with comorbid conditions such as Parkinson’s disease and multiple sclerosis. We emphasizes the dynamic nature of RLS research and highlight the critical need for ongoing studies to further elucidate the complex mechanisms underlying RLS, as well as to refine the treatment modalities to enhance patient outcomes.
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Affiliation(s)
- Archita Makharia
- Department of Neurology, All India Institute of Medical Sciences, New Delhi, India
| | - Ayush Agarwal
- Department of Neurology, All India Institute of Medical Sciences, New Delhi, India
| | | | - Divyani Garg
- Department of Neurology, All India Institute of Medical Sciences, New Delhi, India
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Okuno K, Wang L, Almeida FR. Focus of dental sleep medicine on obstructive sleep apnea in older adults: A narrative review. J Prosthodont Res 2024; 68:227-236. [PMID: 37648523 DOI: 10.2186/jpr.jpr_d_23_00047] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/01/2023]
Abstract
PURPOSE To review dental sleep medicine in older adults based on the literature. STUDY SELECTION This narrative review focuses on sleep physiology, common sleep disorders, and obstructive sleep apnea (OSA) in older adults and their management. RESULTS Sleep physiology differs between older and younger adults, with sleep disturbances occurring more frequently in older adults. The prevalence of insomnia increases in older adults due to age-related changes in sleep physiology. Insomnia, sleep-disordered breathing, periodic limb movement disorder, restless legs syndrome, and rapid eye movement (REM) sleep behavior disorder are common sleep disorders in older adults. OSA is more prevalent in older adults, and its effects on them are considered more substantial than those on younger adults. The treatment of older patients with mandibular advancement devices may be less effective and more complex owing to potential impairments in oral and dental health. Furthermore, the prevalence of edentulism in older adults is decreasing while life expectancy is increasing. CONCLUSIONS As older adults have comorbidities that affect sleep quality, dentists should consider the effects of sleep physiology and sleep disorders in these patients. OSA may decrease the quality of life and increase the risk of developing other diseases. Therefore, dentists proposing treatment with mandibular advancement devices need to inform patients of their potential lack of efficacy and the requirement for careful follow-up owing to known and unknown side effects.
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Affiliation(s)
- Kentaro Okuno
- Department of Geriatric Dentistry, Osaka Dental University, Hirakata, Japan
- Center for Dental Sleep Medicine, Osaka Dental University Hospital, Osaka, Japan
| | - Liqin Wang
- Department of Geriatric Dentistry, Osaka Dental University, Hirakata, Japan
| | - Fernanda R Almeida
- Department of Oral Health Sciences, Faculty of Dentistry, The University of British Columbia, Vancouver, Canada
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Broström A, Alimoradi Z, Odzakovic E, Kaldo V, Jernelöv S, Lind J, Ulander M, Pakpour A. Quality of life among patients with restless legs syndrome: A systematic review and meta-analysis. J Clin Neurosci 2024; 122:80-91. [PMID: 38489955 DOI: 10.1016/j.jocn.2024.02.027] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2023] [Revised: 02/02/2024] [Accepted: 02/27/2024] [Indexed: 03/17/2024]
Abstract
OBJECTIVE The primary aim was to estimate the pooled mean score of quality of life (QoL) (total, mental and physical health components) among patients with Restless Legs Syndrome (RLS). Secondary aims were to assess: (I) QoL differences for RLS vs. control groups, (II) heterogeneity and possible sources; and (III) moderating variables. METHODS Studies identified in PubMed, Scopus, Web of Science, and ProQuest between January 2000 and December 2022 were included. Methodological quality was assessed with Newcastle Ottawa Scale. The protocol was pre-registered (PROSPERO, CRD42023387318). RESULTS Twenty-seven studies (20121 participants, 12 countries) were included. The corrected pooled estimated mean score of QoL was 47.92 (27 studies, CI 95 %: 43.11 to 52.72, range 0-100, i.e., low-high QoL) and was marginally affected by publication year (increased 0.89 by each year, p = 0.12). The corrected pooled estimated mean score of the mental health component was 47.32 (17 studies, 95 % CI: 43.12 to 51.51, range 0-100) and influenced by RLS instrument (decreased with recent versions, p = 0.05). The corrected pooled estimated mean score of the physical health component was 39.08 (17 studies, 95 % CI: 33.05 to 45.10, range 0-100), with no statistically significant moderator. The pooled estimated QoL scores were statistically significantly lower in RLS patients compared to control groups with standardized mean difference (SMD) of -0.78, -0.57 and -0.50 respectively for overall QoL (24 studies), physical and mental health components (14 studies). Total QoL SMD was affected by proportion of women. CONCLUSION Low QoL was revealed among RLS patients, which was statistically significantly reduced compared to control groups.
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Affiliation(s)
- Anders Broström
- School of Health and Welfare, Jönköping University, Jönköping, Sweden; Department of Clinical Neurophysiology, Linköping University Hospital, Linköping, Sweden; Department of Health and Caring Sciences, Western Norway University of Applied Sciences, Bergen, Vestlandet, Norway.
| | - Zainab Alimoradi
- Social Determinants of Health Research Centre, Research Institute for Prevention of Non-Communicable Diseases, Qazvin University of Medical Sciences, Qazvin, Iran
| | - Elzana Odzakovic
- School of Health and Welfare, Jönköping University, Jönköping, Sweden
| | - Viktor Kaldo
- Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, & Stockholm Health Care Services, Region Stockholm, Sweden; Department of Psychology, Faculty of Health and Life Sciences, Linnaeus University, Växjö, Sweden
| | - Susanna Jernelöv
- Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, & Stockholm Health Care Services, Region Stockholm, Sweden; Division of Psychology, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden
| | - Jonas Lind
- Department of Biomedical and Clinical Sciences, Division of Neurobiology. Linköping University, Linköping Sweden; Section of Neurology, Department of Internal Medicine, County Hospital Ryhov, Jönköping, Sweden
| | - Martin Ulander
- Department of Clinical Neurophysiology, Linköping University Hospital, Linköping, Sweden; Department of Biomedical and Clinical Sciences, Division of Neurobiology. Linköping University, Linköping Sweden
| | - Amir Pakpour
- School of Health and Welfare, Jönköping University, Jönköping, Sweden
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Liampas I, Siokas V, Kyrozis A, Sakoutis G, Yannakoulia M, Kosmidis MH, Sakka P, Scarmeas N, Hadjigeorgiou GM, Dardiotis E. Longitudinal Cognitive Trajectories in Older Adults with Restless Legs Syndrome or Willis-Ekbom Disease. Life (Basel) 2024; 14:430. [PMID: 38672702 PMCID: PMC11051192 DOI: 10.3390/life14040430] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2024] [Revised: 02/21/2024] [Accepted: 03/22/2024] [Indexed: 04/28/2024] Open
Abstract
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.
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Affiliation(s)
- Ioannis Liampas
- Department of Neurology, University Hospital of Larissa, School of Medicine, University of Thessaly, 41100 Larissa, Greece; (V.S.); (G.S.); (G.M.H.); (E.D.)
| | - Vasileios Siokas
- Department of Neurology, University Hospital of Larissa, School of Medicine, University of Thessaly, 41100 Larissa, Greece; (V.S.); (G.S.); (G.M.H.); (E.D.)
| | - Andreas Kyrozis
- 1st Department of Neurology, Aiginition Hospital, National and Kapodistrian University of Athens Medical School, 11528 Athens, Greece; (A.K.); (N.S.)
| | - George Sakoutis
- Department of Neurology, University Hospital of Larissa, School of Medicine, University of Thessaly, 41100 Larissa, Greece; (V.S.); (G.S.); (G.M.H.); (E.D.)
| | - Mary Yannakoulia
- Department of Nutrition and Dietetics, Harokopio University, 17671 Athens, Greece
| | - Mary H. Kosmidis
- Laboratory of Cognitive Neuroscience, School of Psychology, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece;
| | - Paraskevi Sakka
- Athens Association of Alzheimer’s Disease and Related Disorders, 11636 Marousi, Greece;
| | - Nikolaos Scarmeas
- 1st Department of Neurology, Aiginition Hospital, National and Kapodistrian University of Athens Medical School, 11528 Athens, Greece; (A.K.); (N.S.)
- Taub Institute for Research in Alzheimer’s Disease and the Aging Brain, The Gertrude H. Sergievsky Center, Department of Neurology, Columbia University, New York, NY 10032, USA
| | - Georgios M. Hadjigeorgiou
- Department of Neurology, University Hospital of Larissa, School of Medicine, University of Thessaly, 41100 Larissa, Greece; (V.S.); (G.S.); (G.M.H.); (E.D.)
- Department of Neurology, Medical School, University of Cyprus, 2408 Nicosia, Cyprus
| | - Efthimios Dardiotis
- Department of Neurology, University Hospital of Larissa, School of Medicine, University of Thessaly, 41100 Larissa, Greece; (V.S.); (G.S.); (G.M.H.); (E.D.)
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