TY  - JOUR
AB  - STUDY OBJECTIVES: To systemically describe the clinical features, polysomnography (PSG) finding, laboratory tests and single-nucleotide polymorphisms (SNPs) in a clinic based Chinese primary restless legs syndrome (RLS) population. METHODS: This observational study, conducted from January 2020 to October 2021 across 22 sleep labs in China, recruited 771 patients diagnosed with RLS following the 2014 RLSSG criteria. Clinical data, PSG testing, and laboratory examination and SNPs of patients with RLS were collected. A total of 32 SNPs in 24 loci were replicated using the Asian Screening Array chip, employing data from the Han Chinese Genomes Initiative as controls. RESULTS: In this study with 771 RLS patients, 645 had primary RLS, and 617 has DNA available for SNP study. Among the 645 primary RLS, 59.7% were women. 33% had a family history of RLS, with stronger familial influence in early-onset cases. Clinical evaluations showed 10.4% had discomfort in body parts other than legs. PSG showed that 57.1% of RLS patients had periodic leg movement index (PLMI) of >5/h and 39.1% had PLMI >15/h, respectively; 73.8% of RLS patients had an Apnea-Hypopnea Index (AHI) > 5/h, and 45.3% had an AHI >15/h. The laboratory examinations revealed serum ferritin levels <75 ng/ml in 31.6%, and transferrin saturation (TSAT) of <45% in 88.7% of RLS patients. Seven new SNPs in 5 genes showed a significant allelic association with Chinese primary RLS, with one previously reported (BTBD9) and four new findings (TOX3, PRMT6, DCDC2C, NOS1). CONCLUSIONS: Chinese RLS patients has specific characters in many aspects. A high family history with RLS not only indicates strong genetic influence, but also reminds us to consider the familial effect in the epidemiological study. Newly developed sequencing technique with large samples remains to be done.
AU  - Liang, R.*
AU  - Zhu, W.*
AU  - Gao, Y.*
AU  - Zhao, C.
AU  - Zhang, C.*
AU  - Xu, L.*
AU  - Zuo, Y.*
AU  - Lv, Y.*
AU  - Zhao, M.*
AU  - Li, C.*
AU  - Gao, J.*
AU  - Mei, J.*
AU  - Gong, X.*
AU  - Zhang, L.*
AU  - Shen, S.*
AU  - Yang, C.*
AU  - Ren, J.*
AU  - Liu, Y.*
AU  - Wang, Z.*
AU  - Wang, P.*
AU  - Zhou, J.*
AU  - Wang, F.*
AU  - Wu, J.*
AU  - Chen, J.*
AU  - Zhu, Y.*
AU  - Dong, X.*
AU  - Han, F.*
C1  - 70393
C2  - 55601
CY  - Radarweg 29, 1043 Nx Amsterdam, Netherlands
SP  - 123-130
TI  - Clinical features, polysomnography, and genetics association study of restless legs syndrome in clinic based Chinese patients: A multicenter observational study.
JO  - Sleep Med.
VL  - 117
PB  - Elsevier
PY  - 2024
SN  - 1389-9457
ER  - 

TY  - JOUR
AB  - OBJECTIVE: This study aimed to assess the association of changes in sleep behaviors from adolescence to young adulthood with the risk of overweight/obesity, and the reverse relationship. METHODS: Data of 1978 participants was obtained from the 15- and 20-year follow-ups of the GINIplus and LISA birth cohorts. Insufficient sleep was defined as reported sleep duration <8 h for adolescents, <7 h for adults, and sleep difficulties as reported having sleeping difficulties. Logistic regression models were used to assess bidirectional associations of changes in insufficient sleep and sleep difficulties with overweight/obesity. The polygenic risk scores (PRS) for body mass index (BMI) was tested in a sub-sample (n = 918). RESULTS: Compared with sufficient sleep in both adolescence and young adulthood, insufficient sleep only in young adulthood was associated with an increased risk of overweight/obesity (odds ratio = 1.85, 95%confidence interval = [1.27-2.69]). Compared with no sleep difficulties at both time-points, only persistent sleep difficulties was associated with a higher risk of overweight/obesity (2.15 [1.22-3.77]). The PRS for BMI was associated with overweight/obesity (1.41 [1.17-1.70]), but no significant gene-sleep interaction effect was observed. Reversely, only persistent overweight/obesity was associated with increased risks of insufficient sleep (1.81 [1.21-2.70]), and sleep difficulties (1.77 [1.18-2.66]), respectively. CONCLUSIONS: Insufficient sleep only presented a cross-sectional association with overweight/obesity in young adulthood, while long-term sleep difficulties from adolescence to young adulthood was associated with young adult overweight/obesity. Reversely, long-term overweight/obesity from adolescence to young adulthood was associated with insufficient sleep and sleep difficulties in young adulthood.
AU  - Wang, M.
AU  - Flexeder, C.
AU  - Kilanowski, A.
AU  - Kress, S.*
AU  - Herberth, G.*
AU  - Schikowski, T.*
AU  - Peters, A.
AU  - Standl, M.
C1  - 66985
C2  - 53388
CY  - Radarweg 29, 1043 Nx Amsterdam, Netherlands
SP  - 401-410
TI  - Changes in sleep duration and sleep difficulties from adolescence to young adulthood and the risk of obesity: Bidirectional evidence in the GINIplus and LISA studies.
JO  - Sleep Med.
VL  - 101
PB  - Elsevier
PY  - 2023
SN  - 1389-9457
ER  - 

TY  - JOUR
AB  - Poor glycaemic control is found in diabetes, one of the most common, serious, non-communicable diseases worldwide. Trials suggest a relationship between glycaemic control and measures of sleep including duration and quality of sleep. Currently, the relationship between specific sleep stages (including slow-wave sleep (SWS), a sleep stage mainly found early in the night and linked to restorative functioning) and glycaemic control remains unclear. This systematic review aimed to synthesise the evidence of the effectiveness of specific sleep stage manipulation on measures of glycaemic control (insulin resistance, fasting and post-prandial glucose and insulin). Public databases (eg psychINFO, MEDLINE, Academic Search Complete, psychARTICLES, OpenDissertations, Scopus and Cochrane library) were searched for randomised controlled trials. Trials were included if they involved direct manipulation of SWS and/or rapid eye-movement sleep to explore the impact on measures of glycaemic control (insulin resistance, fasting and post-prandial glucose and insulin). Eight trials met the eligibility criteria, with four providing data for inclusion in one of the three meta-analyses. Insulin resistance was significantly higher in the SWS disruption when compared to the normal sleep condition, (p = 0.02). No significant differences were found for measures of fasting or post-prandial glucose or insulin. Risk of bias was considered low for performance bias, detection bias and incomplete outcome data, with unclear selection bias. This is an emerging area of research and this review provides preliminary findings and recommendations for future research around optimising sleep stage disruption (to further explore mechanisms) and sleep stage enhancement techniques (to explore potential interventions).
AU  - Johnson, J.M.*
AU  - Durrant, S.J.*
AU  - Law, G.R.*
AU  - Santiago, J.C.
AU  - Scott, E.M.*
AU  - Curtis, F.*
C1  - 64674
C2  - 52399
SP  - 50-58
TI  - The effect of slow-wave sleep and rapid eye-movement sleep interventions on glycaemic control: A systematic review and meta-analysis of randomised controlled trials.
JO  - Sleep Med.
VL  - 92
PY  - 2022
SN  - 1389-9457
ER  - 

TY  - JOUR
AB  - Restless legs syndrome (RLS) is a common sleep-related movement disorder in populations of European descent and disease risk is strongly influenced by genetic factors. Common variants have been assessed extensively in several genome-wide association studies, but the contribution of rarer genetic variation has not been investigated at this scale. We therefore genotyped a case–control set of 9246 individuals for mainly rare and low frequency exonic variants using the Illumina ExomeChip. However, standard single variant and gene-level association tests were negative. This does not preclude a role of rare variants in RLS, but is likely due to the small sample size and the limited selection of rare genetic variation captured on the array. Therefore, exome or whole genome sequencing should be performed rather than increasing the sample size of ExomeChip studies in order to identify rare risk variants for RLS.
AU  - Tilch, E.
AU  - Schormair, B.
AU  - Zhao, C.
AU  - Högl, B.*
AU  - Stefani, A.*
AU  - Berger, K.*
AU  - Trenkwalder, C.*
AU  - Bachmann, C.G.*
AU  - Hornyak, M.*
AU  - Fietze, I.*
AU  - Müller-Nurasyid, M.
AU  - Peters, A.
AU  - Herms, S.*
AU  - Nöthen, M.M.*
AU  - Müller-Myhsok, B.*
AU  - Oexle, K.
AU  - Winkelmann, J.
C1  - 64946
C2  - 52584
SP  - 26-30
TI  - ExomeChip-based rare variant association study in restless legs syndrome.
JO  - Sleep Med.
VL  - 94
PY  - 2022
SN  - 1389-9457
ER  - 

TY  - JOUR
AB  - Study objectives: Population-based studies on the association of objectively assessed physical activity (PA) with sleep among adolescents are rare. We examined this association by applying accelerometry and accounting for the day-by-day variability.Methods: Accelerometers (Actigraph GT3X) were worn for one week by 1223 participants during the 15-year follow-up of the German birth cohorts (German infant study on the Influence of Nutrition Intervention plus air pollution and genetics on allergy development, GINIplus) and (Influence of Lifestyle factors on the development of the Immune System and Allergies in East and West Germany, LISA) to measure PA and sleep. PA was categorised into sedentary, lifestyle and moderate-to-vigorous physical activity (MVPA) referring to Sasaki and Romanzini. Sleep was analysed according to the algorithm developed by Sadeh. Sleep quality was represented by sleep efficiency (SE), sleep onset latency (SOL) and time awake per hour after sleep onset (TAPH). Sleep and activity were additionally reported by diaries. Linear and generalized mixed-effects-models with logit-link with subject specific random intercepts were used stratified by sex and adjusted for confounding variables.Results: Physical activity appears to be associated only with sleep quality the following night. Among female participants, SE improved (beta = 0.12 [95% CI = (0.05; 0.18)]) per 10 minutes increase of MVPA. SOL decreased (OR = 0.83 [95% CI = (0.69; 0.99)]) among male participants with at least 60 min of MVPA per day. Engaging in leisure sport MVPA was associated with higher SE among female (b = 0.70 [95% CI = (0.22; 1.17)]) and male participants (b = 0.76 [95% CI = (0.18; 1.34)]). Also, TAPH among female (b = -0.37 [95% CI = (- 0.65; -0.09)]) and SOL among male subjects (OR = 0.70 [95% CI = (0.57; 0.85)]) decreased. Increasing lifestyle activity was related to longer SOL among female (OR = 1.36 [95% CI = (1.15; 1.62)]) and male subjects (OR = 1.32 [95% CI = ( 1.10; 1.58)]).Conclusions: In this large population-based sample of German adolescents MVPA and leisure sport improved short term sleep quality, supporting regular PA in adolescents for their health benefit.
AU  - Negele, L.E.
AU  - Flexeder, C.
AU  - Koletzko, S.*
AU  - Bauer, C.P.*
AU  - von Berg, A.*
AU  - Berdel, D.*
AU  - Schikowski, T.*
AU  - Standl, M.
AU  - Peters, A.
AU  - Schulz, H.
C1  - 59507
C2  - 48886
CY  - Radarweg 29, 1043 Nx Amsterdam, Netherlands
SP  - 65-74
TI  - Association between objectively assessed physical activity and sleep quality in adolescence. Results from the GINIplus and LISA studies.
JO  - Sleep Med.
VL  - 72
PB  - Elsevier
PY  - 2020
SN  - 1389-9457
ER  - 

TY  - JOUR
AB  - Restless legs syndrome (RLS) is a complex disorder that involves sensory and motor systems. The major pathophysiology of RLS is low iron concentration in the substantia nigra containing the cell bodies of dopamine neurons that project to the striatum, an area that is crucial for modulating movement. People who have RLS often present with normal iron values outside the brain; recent studies implicate several genes are involved in the syndrome. Like most complex diseases, animal models usually do not faithfully capture the full phenotypic spectrum of disease, which is a uniquely human construct. Nonetheless, animal models have proven useful in helping to unravel the complex pathophysiology of diseases such as RLS and suggesting novel treatment paradigms. For example, hypothesis-independent genome-wide association studies (GWAS) have identified several genes as increasing the risk for RLS, including . BTBD9. Independently, the murine homolog . Btbd9 was identified as a candidate gene for iron regulation in the midbrain in mice. The relevance of the phenotype of another of the GWAS identified genes, . MEIS1, has also been explored. The role of . Btbd9 in iron regulation and RLS-like behaviors has been further evaluated in mice carrying a null mutation of the gene and in fruit flies when the BTBD9 protein is degraded. The . BTBD9 and . MEIS1 stories originate from human GWAS research, supported by work in a genetic reference population of mice (forward genetics) and further verified in mice, fish flies, and worms. Finally, the role of genetics is further supported by an inbred mouse strain that displays many of the phenotypic characteristics of RLS. The role of animal models of RLS phenotypes is also extended to include periodic limb movements.
AU  - Allen, R.P.*
AU  - Donelson, N.C.*
AU  - Jones, B.C.*
AU  - Li, Y.*
AU  - Manconi, M.*
AU  - Rye, D.B.*
AU  - Sanyal, S.*
AU  - Winkelmann, J.
C1  - 50217
C2  - 42237
SP  - 23-28
TI  - Animal models of RLS phenotypes.
JO  - Sleep Med.
VL  - 31
PY  - 2017
SN  - 1389-9457
ER  - 

TY  - JOUR
AB  - This issue of Sleep Medicine includes the reports from the IRLSSG (International Restless Legs Syndrome Study Group) science conference held in Monterey, California from October 23rd to the 26th. Over the past decade, major research advances have been made that strongly impact and alter our understanding of both the biological basis for RLS and also its health consequences. The purpose of the IRLSSG Science Meeting was to review these advances and frame a discussion on the next steps to be taken in each area of research.
AU  - Garcia Borreguero, D.*
AU  - Winkelmann, J.
AU  - Allen, R.P.*
C1  - 52813
C2  - 44175
SP  - 1-2
TI  - Introduction: Towards a better understanding of the science of RLS/WED.
JO  - Sleep Med.
VL  - 31
PY  - 2017
SN  - 1389-9457
ER  - 

TY  - JOUR
AB  - Background/Objective Although the association of disturbed sleep with specific chronic conditions is well known, the relationship between sleep disturbances and multiple diseases is less clear. Therefore, the objectives of this study were to examine the independent relationships of various sleep disturbances with 1) multimorbidity (≥2 chronic conditions) and 2) commonly co-occurring pairs of chronic conditions. Methods Analyses were based on data from 4127 individuals aged ≥65 years participating in the population-based cross-sectional Cooperative Health Research in the Region of Augsburg (KORA) Age Study conducted from 2008 to 2009 in Germany. Sex-specific odds ratios (OR) and 95% confidence intervals (CI) were calculated from sequential logistic regression models. Results Neither short nor long daily sleep duration was significantly associated with multimorbidity among men; a significant positive relationship was identified regarding short sleep duration among women (OR 2.16, 95% CI: 1.42–3.30). While insomnia and all unique symptoms of insomnia were connected to multimorbidity among women in the multivariable models, the relationship concerning trouble falling asleep no longer remained significant after adjustment for all covariables among men. Regarding commonly co-occurring pairs of conditions, the clearest associations were observed between insomnia and daytime tiredness with joint diseases/eye diseases in men and joint diseases/heart diseases in women. Conclusions There seems to be sex-specific particularities in the relationship between sleep disturbances and sleep duration with multimorbidity and commonly co-occurring pairs of chronic conditions in older adults from the general population.
AU  - Helbig, A.K.
AU  - Stöckl, D.
AU  - Heier, M.
AU  - Thorand, B.
AU  - Schulz, H.
AU  - Peters, A.
AU  - Ladwig, K.-H.
AU  - Meisinger, C.
C1  - 50850
C2  - 42572
SP  - 151-159
TI  - Relationship between sleep disturbances and multimorbidity among community-dwelling men and women aged 65–93 years: Results from the KORA Age Study.
JO  - Sleep Med.
VL  - 33
PY  - 2017
SN  - 1389-9457
ER  - 

TY  - JOUR
AU  - Salminen, A.V.*
AU  - Garrett, L.
AU  - Rozman, J.
AU  - Schormair, B.*
AU  - Fuchs, H.
AU  - Gailus-Durner, V.
AU  - Hrabě de Angelis, M.
AU  - Hölter, S.M.
AU  - Winkelmann, J.*
C1  - 54498
C2  - 45578
CY  - Po Box 211, 1000 Ae Amsterdam, Netherlands
SP  - E290-E291
TI  - Circadian locomotor activity in meis1 knock-out mice.
JO  - Sleep Med.
VL  - 40
PB  - Elsevier Science Bv
PY  - 2017
SN  - 1389-9457
ER  - 

TY  - JOUR
AB  - At the outset of genetic studies in restless legs syndrome (RLS), the disorder was assumed to be a classical monogenic disorder that runs in families. However, years of family studies did not reveal any causally-related genes or genetic variants. The advent of high-throughput genotyping technology led to a change; genome-wide association studies in large case-control samples became feasible, which led to the identification of first genetic risk variants for RLS. Variants detected by this approach are common ones, which that individually confer only a minor increase in risk of disease. Overall, the currently known risk variants in six genomic loci account for only a small proportion of the genetically determined susceptibility to RLS. Additional risk loci and individual variants remain to be discovered. First studies indicate that rare genetic variants are also important contributors in RLS. These are expected to have a larger impact on the phenotype and may thus prove to be excellent candidates for functional studies and, in the long-term, targets for developing therapeutics or preventive measures. To enable their discovery, large-scale studies including tens of thousands of affected individuals may be needed. Next-generation sequencing technologies such as whole exome or whole genome sequencing will be essential for this endeavor. Even though the number of known risk variants is still limited, they have been indispensable in terms of deciphering the underlying pathophysiology of RLS, providing the molecular starting points for animal models and in vitro studies to understand disease mechanisms. In addition, genetic risk variants can be valuable tools for disentangling the phenotypic complexity observed in RLS. Testing RLS risk variants for associations with periodic limb movements (PLMs) identified a significant role of some of the variants and suggested PLMs as an endophenotype in RLS. Further advances in genetics research in RLS will be driven by large-scale sequencing projects and the identification of additional common, but also rarer risk variants with larger effects on disease risk. Another uncharted territory in RLS research epigenetic effect on gene activity. Overall, genetic studies continue to hold great potential for understanding biology of the disease.
AU  - Winkelmann, J.
AU  - Schormair, B.
AU  - Xiong, L.*
AU  - Dion, P.A.*
AU  - Rye, D.B.*
AU  - Rouleau, G.A.*
C1  - 50295
C2  - 42169
SP  - 18-22
TI  - Genetics of restless legs syndrome.
JO  - Sleep Med.
VL  - 31
PY  - 2017
SN  - 1389-9457
ER  - 

TY  - JOUR
AB  - In this article, we review the original findings from MRI and autopsy studies that demonstrated brain iron status is insufficient in individuals with restless legs syndrome (RLS). The concept of deficient brain iron status is supported by proteomic studies from cerebrospinal fluid (CSF) and from the clinical findings where intervention with iron, either dietary or intravenous, can improve RLS symptoms. Therefore, we include a section on peripheral iron status and how peripheral status may influence both the RLS symptoms and treatment strategy. Given the impact of iron in RLS, we have evaluated genetic data to determine if genes are directly involved in iron regulatory pathways. The result was negative. In fact, even the HFE mutation C282Y could not be shown to have a protective effect. Lastly, a consistent finding in conditions of low iron is increased expression of proteins in the hypoxia pathway. Although there is lack of clinical data that RLS patients are hypoxic, there are intriguing observations that environmental hypoxic conditions worsen RLS symptoms; in this chapter we review very compelling data for activation of hypoxic pathways in the brain in RLS patients. In general, the data in RLS point to a pathophysiology that involves decreased acquisition of iron by cells in the brain. Whether the decreased ability is genetically driven, activation of pathways (eg, hypoxia) that are designed to limit cellular uptake is unknown at this time; however, the data strongly support a functional rather than structural defect in RLS, suggesting that an effective treatment is possible.
AU  - Connor, J.R.*
AU  - Patton, S.M.*
AU  - Oexle, K.
AU  - Allen, R.P.*
C1  - 50297
C2  - 42301
TI  - Iron and restless legs syndrome: Treatment, genetics and pathophysiology.
JO  - Sleep Med.
PY  - 2016
SN  - 1389-9457
ER  - 

TY  - JOUR
AB  -  A Task Force was established by the International Restless Legs Syndrome Study Group (IRLSSG) in conjunction with the European Restless Legs Syndrome Study Group (EURLSSG) and the RLS Foundation (RLS-F) to develop evidence-based and consensus-based recommendations for the prevention and treatment of long-term pharmacologic treatment of dopaminergic-induced augmentation in restless legs syndrome/Willis-Ekbom disease (RLS/WED).The Task Force made the following prevention and treatment recommendations:. As a means to prevent augmentation, medications such as α2δ ligands may be considered for initial RLS/WED treatment; these drugs are effective and have little risk of augmentation. Alternatively, if dopaminergic drugs are elected as initial treatment, then the daily dose should be as low as possible and not exceed that recommended for RLS/WED treatment. However, the physician should be aware that even low dose dopaminergics can cause augmentation. Patients with low iron stores should be given appropriate iron supplementation. Daily treatment by either medication should start only when symptoms have a significant impact on quality of life in terms of frequency and severity; intermittent treatment might be considered in intermediate cases.Treatment of existing augmentation should be initiated, where possible, with the elimination/correction of extrinsic exacerbating factors (iron levels, antidepressants, antihistamines, etc.). In cases of mild augmentation, dopamine agonist therapy can be continued by dividing or advancing the dose, or increasing the dose if there are breakthrough night-time symptoms. Alternatively, the patient can be switched to an α2δ ligand or rotigotine. For severe augmentation the patient can be switched either to an α2δ ligand or rotigotine, noting that rotigotine may also produce augmentation at higher doses with long-term use. In more severe cases of augmentation an opioid may be considered, bypassing α2δ ligands and rotigotine.
AU  - García-Borreguero, D.*
AU  - Silber, M.H.*
AU  - Winkelman, J.W.*
AU  - Högl, B.*
AU  - Bainbridge, J.*
AU  - Buchfuhrer, M.*
AU  - Hadjigeorgiou, G.M.*
AU  - Inoue, Y.*
AU  - Manconi, M.*
AU  - Oertel, W.*
AU  - Ondo, W.G.*
AU  - Winkelmann, J.
AU  - Allen, R.P.*
C1  - 48485
C2  - 41153
CY  - Amsterdam
SP  - 1-11
TI  - Guidelines for the first-line treatment of restless legs syndrome/Willis-Ekbom disease, prevention and treatment of dopaminergic augmentation: A combined task force of the IRLSSG, EURLSSG, and the RLS-foundation.
JO  - Sleep Med.
VL  - 21
PB  - Elsevier Science Bv
PY  - 2016
SN  - 1389-9457
ER  - 

TY  - JOUR
AU  - Schulte, E.C.*
AU  - Gross, N.*
AU  - Slawik, H.*
AU  - Winkelmann, J.
C1  - 28743
C2  - 33538
CY  - Amsterdam
SP  - 155–156
TI  - "Malignant restless legs syndrome" - a curse or a blessing?
JO  - Sleep Med.
VL  - 15
IS  - 1
PB  - Elsevier Science
PY  - 2014
SN  - 1389-9457
ER  - 

TY  - JOUR
AB  - OBJECTIVE: We aimed to examine the association between various sleep disturbances and falls among older individuals from the general population while considering the influence of age and dizziness. METHODS: Data were derived from the population-based cross-sectional KORA (Cooperative Health Research in the Region of Augsburg)-Age study, whereby information was conducted in standardized telephone interviews with 4127 men and women aged ⩾65years in 2008 and 2009. Unstratified and stratified (by age and dizziness) multivariable logistic regression model analyses were performed. RESULTS: The multivariable analysis showed a marginally significant association between trouble staying asleep and ⩾1 fall in the previous year (odds ratio [OR], 1.23 [95% confidence interval (CI), 1.01-1.50]). This association was more pronounced in participants older than the age of 75years (OR, 1.58 [95% CI, 1.16-2.16]) and in individuals without dizziness (OR, 1.35 [95% CI, 1.04-1.76]). There was no association between daytime sleepiness and falls in the fully-adjusted models, but the odds of falls in the previous year in individuals older than the age of 75years were significantly higher for individuals with difficulty falling asleep. Although sleep duration was not associated with falls in multivariable analyses when stratified by dizziness, sleep duration of 9h daily was significantly associated with higher odds of experiencing at least one fall in the previous year. CONCLUSIONS: Our study suggested that the positive relationship between a trend towards longer sleep duration, trouble falling and staying asleep, and falls is strongest in older individuals and in individuals who did not experience dizziness in the previous year.
AU  - Helbig, A.K.
AU  - Döring, A.
AU  - Heier, M.
AU  - Emeny, R.T.
AU  - Zimmermann, A.-K.
AU  - Autenrieth, C.S.
AU  - Ladwig, K.-H.
AU  - Grill, E.*
AU  - Meisinger, C.
C1  - 28033
C2  - 32912
SP  - 1356-1363
TI  - Association between sleep disturbances and falls among the elderly: Results from the German Cooperative Health Research in the Region of Augsburg-age study.
JO  - Sleep Med.
VL  - 14
IS  - 12
PB  - Elsevier Science
PY  - 2013
SN  - 1389-9457
ER  - 

TY  - JOUR
AB  - Usually symptoms of restless legs syndrome (RLS) respond well to treatment with dopaminergic drugs, opiates, or anticonvulsant medications. Yet sometimes symptoms can be severe and become refractory, even to high-dose combination therapy. Here we present two cases of familial RLS with rigorous and unusual motor and sensory symptoms in the form of episodes of myoclonic hyperkinesias and painful sensations in addition to more characteristic features of RLS. Stepwise reduction of all RLS-and antidepressant medication down to opiate monotherapy-and subsequent opiate rotation led to an improvement of symptoms. Yet in both cases, reintroduction of low-dose dopaminergic drugs was necessary to achieve satisfactory treatment effect. We have termed this form of RLS refractory to multiple combinations of all classes of commonly used drugs malignant RLS. Therapeutically simplification and reduction of the drug scheme and opiate rotation should be considered in malignant RLS.
AU  - Schulte, E.C.
AU  - Gross, N.*
AU  - Slawik, H.*
AU  - Winkelmann, J.
C1  - 25133
C2  - 31825
SP  - 575-577
TI  - When restless legs syndrome turns malignant.
JO  - Sleep Med.
VL  - 14
IS  - 6
PB  - Elsevier Science
PY  - 2013
SN  - 1389-9457
ER  - 

TY  - JOUR
AB  - Background: Restless legs syndrome (RLS) is a frequent neurological disorder which is presented in idiopathic and secondary form. Idiopathic RLS is associated with common genetic variants in four chromosomal regions. Recently, multiple sclerosis (MS) was identified as a common cause for secondary RLS. The aim of our study was to evaluate the prevalence of RLS among Czech patients with MS and to further analyze the impact of known genetic risk factors for RLS in patients with MS. Methods: Each patient underwent a semi-structured interview. A patient was considered to be affected by RLS if all four standard criteria had ever been met in their lifetime. The sample was genotyped using 12 single nucleotide polymorphisms within the four genomic regions, which were selected according to the results of previous genome-wide association studies. Results: A total of 765 subjects with MS were included in the study and the diagnosis of RLS was confirmed in 245 subjects (32.1%, 95% CI 28.7-35.4%). The genetic association study included 642 subjects; 203 MS patients with RLS were compared to 438 MS patients without RLS. No significant association with MEIS 1, BTBD9, and PTPRD gene variants was found despite sufficient statistical power for the first two loci. There was a trend for association with the MAP2K5/SCOR1 gene - the best model for the risk allele was the recessive one (p nominal = 0.0029. p corrected for four loci and two models = 0.023, odds ratio = 1.60). Conclusion: We confirmed that RLS prevalence was high in patients with multiple sclerosis, but this form did not share all genetic risk variants with idiopathic RLS.
AU  - Vávrová, J.
AU  - Kemlink, D.*
AU  - Sonka, K.*
AU  - Havrdova, E.*
AU  - Horakova, D.*
AU  - Pardini, B.*
AU  - Müller-Myhsok, B.*
AU  - Winkelmann, J.
C1  - 8572
C2  - 29949
SP  - 848-851
TI  - Restless legs syndrome in Czech patients with multiple sclerosis: An epidemiological and genetic study.
JO  - Sleep Med.
VL  - 13
IS  - 7
PB  - Elsevier
PY  - 2012
SN  - 1389-9457
ER  - 

TY  - JOUR
AB  - Augmentation of symptom severity is the main complication of dopaminergic treatment of restless legs syndrome (RLS). The current article reports on the considerations of augmentation that were made during a European Restless Legs Syndrome Study Group (EURLSSG)-sponsored Consensus Conference in April 2006 at the Max Planck Institute (MPI) in Munich, Germany, the conclusions of which were endorsed by the International RLS Study Group (IRLSSG) and the World Association of Sleep Medicine (WASM). The Consensus Conference sought to develop a better understanding of augmentation and generate a better operational definition for its clinical identification. DESIGN AND METHODS: Current concepts of the pathophysiology, clinical features, and therapy of RLS augmentation were evaluated by subgroups who presented a summary of their findings for general consideration and discussion. Recent data indicating sensitivity and specificity of augmentation features for identification of augmentation were also evaluated. The diagnostic criteria of augmentation developed at the National Institutes of Health (NIH) conference in 2002 were reviewed in light of current data and theoretical understanding of augmentation. The diagnostic value and criteria for each of the accepted features of augmentation were considered by the group. A consensus was then developed for a revised statement of the diagnostic criteria for augmentation. RESULTS: Five major diagnostic features of augmentation were identified: usual time of RLS symptom onset each day, number of body parts with RLS symptoms, latency to symptoms at rest, severity of the symptoms when they occur, and effects of dopaminergic medication on symptoms. The quantitative data available relating the time of RLS onset and the presence of other features indicated optimal augmentation criteria of either a 4-h advance in usual starting time for RLS symptoms or a combination of the occurrence of other features. A paradoxical response to changes in medication dose also indicates augmentation. Clinical significance of augmentation is defined. CONCLUSION: The Consensus Conference agreed upon new operational criteria for the clinical diagnosis of RLS augmentation: the MPI diagnostic criteria for augmentation. Areas needing further consideration for validating these criteria and for understanding the underlying biology of RLS augmentation are indicated.
AU  - García-Borreguero, D.*
AU  - Allen, R.P.*
AU  - Kohnen, R.*
AU  - Högl, B.*
AU  - Trenkwalder, C.*
AU  - Oertel, W.*
AU  - Hening, W.A.*
AU  - Paulus, W.*
AU  - Rye, D.*
AU  - Walters, A.*
AU  - Winkelmann, J.
AU  - Earley, C.J.*
AU  - International Restless Legs Syndrome Study Group (*)
C1  - 3175
C2  - 24787
SP  - 520-530
TI  - Diagnostic standards for dopaminergic augmentation of restless legs syndrome: Report from a World Association of Sleep Medicine-International Restless Legs Syndrome Study Group consensus conference at the Max Planck Institute.
JO  - Sleep Med.
VL  - 8
IS  - 5
PB  - Elsevier
PY  - 2007
SN  - 1389-9457
ER  -