The association between sleep disturbances and blood pressure variability: a review of the literature.

Al Haddad, N., Costanian, C., Zibara, V., Bilen, Y., Kilani, H., Tohme, F., & Bahous, S. A. (2023)

Journal of clinical sleep medicine: JCSM official publication of the American Academy of Sleep Medicine, 10.5664/jcsm.10566. Advance online publication. https://doi.org/10.5664/jcsm.10566

Abstract

Study objectives: Sleep disturbances are an under-recognized public health issue that results in various adverse outcomes and disturbed quality of life. Blood pressure variability (BPV) is an emerging entity in assessing cardiovascular disease (CVD) risk and accumulating evidence sug-gests that BPV is closely associated with end-organ damage. This review aims to explore the as-sociation between sleep disturbances and blood pressure variability.

Methods: A comprehensive systematic literature search was conducted electronically using Web of Science, Ovid MEDLINE, PubMed and SCOPUS. The electronic search was restricted to relevant English language studies published between 1985 and August 2020. Most studies were prospec-tive cohorts in design. After applying eligibility criteria, 29 articles were included for synthesis.

Results: This review shows that sleep disturbances are linked with short-term, mid-term, and long-term BPV. Restless legs syndrome, shift work, insomnia, short sleep, long sleep, OSA and sleep deprivation were all positively associated with SBP or DBP fluctuations.

Conclusions: Given the prognostic implications of BPV and sleep disturbances on cardiovascular mortality, recognizing and treating both disorders is essential. More research is needed to exam-ine the impact of sleep disorders treatment on BPV and cardiovascular mortality.

Vitamin D and Restless Legs Syndrome: A Review of Current Literature.

Cederberg, K. L. J., Silvestri, R., & Walters, A. S. (2023).

Tremor and other hyperkinetic movements (New York, N.Y.), 13, 12. https://doi.org/10.5334/tohm.741

Abstract

This review presents a detailed summary of the current literature regarding RLS and vitamin D deficiency. To our knowledge it is the first review of its kind. We review the prevalence of vita-min D deficiency in RLS as well as the evidence for the use of vitamin D supplementation in RLS management. We further examine the literature for proteomic and genetic evidence of a role for vitamin D in the pathogenesis of RLS. An alteration in vitamin D binding protein in RLS is one of the most consistent findings in the proteomic studies. Furthermore, we examine the interac-tion of vitamin D with calcium, phosphorus, and parathyroid hormone and the possible role of these connections in RLS. We also explore the possible nexus between RLS and vitamin D in renal disease, cardiovascular and cerebrovascular disease as well as inflammation. In addition, we review the potential interaction between vitamin D and RLS with iron, dopamine and other neurotransmitter systems including the endogenous opiate, serotoninergic, glutamatergic and adenosinergic systems. We also explore the role of vitamin D in RLS Augmentation (i.e., the par-adoxical worsening of RLS symptoms when dopaminergic agents are used as a therapy for RLS). Although the literature is not entirely consistent in affirming vitamin D deficiency in RLS or the amelioration of RLS symptoms with vitamin D therapy, the collective studies overall indicate that vitamin D deficiency is common enough in RLS patients to suggest that RLS patients should have their vitamin D levels checked and any deficiency corrected as a standard of care.

Highlights: Patients with Restless Legs Syndrome (RLS) may be deficient in vitamin D and therapy with vitamin D may ameliorate RLS. We present the first review dedicated solely to evaluating the relationship between RLS and vitamin D and present a case for the role of vitamin D in RLS pathogenesis.

Free full text available: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10077981/

Restless Legs Syndrome in Chronic Kidney Disease- a Systematic Review.

Safarpour, Y., Vaziri, N. D., & Jabbari, B. (2023)

Tremor and other hyperkinetic movements (New York, N.Y.), 13, 10. https://doi.org/10.5334/tohm.752

Abstract

Objectives: The objective of this review is to provide updated information on the epidemiology, correlating factors and treatment of chronic kidney disease associated restless legs syndrome (CKD-A-RLS) in both adult and pediatric population.

Materials and methods: We have reviewed the Medline search and Google Scholar search up to May 2022, using key words restless legs syndrome, chronic kidney disease and hemodialysis and kidney transplant. The reviewed articles were studied for epidemiology, correlating factors, as well as pharmacologic and non-pharmacologic treatment options.

Results: Our search revealed 175 articles, 111 were clinical trials or cross- sectional studies and 64 were review articles. All 111 articles were retrieved and studied in detail. Of these, 105 fo-cused on adults and 6 on children. A majority of studies on dialysis patients reported a preva-lence between 15-30%, which is notably higher than prevalence of RLS in general population (5-10%). The correlation between presence of CKD-A-RLS with age, gender, abnormalities of hemo-gram, iron, ferritin, serum lipids, electrolytes and parathyroid hormones were also reviewed. The results were inconsistent and controversial. Limited studies have reported on the treat-ment of CKD-A-RLS. Non-pharmacological treatment focused on the effect(s) of exercise, acu-puncture, massage with different oils and infra-red light whereas, pharmacologic treatment op-tions include the effects of dopaminergic drugs, Alpha2-Delta ligands (gabapentin and pregaba-lin), vitamins E and C, and intravenous iron infusion.

Conclusion: This updated review showed that RLS is two to three times more common in pa-tients with CKD compared to the general population. More patients with CKD-A-RLS demon-strated increased mortality, increased incidence of cardiovascular accident, depression, insom-nia and impaired quality of life than those with CKD without RLS. Dopaminergic drugs such as levodopa, ropinirole, pramipexole and rotigotine as well as calcium channel blockers (gabapen-tin and pregabalin) are helpful for treatment of RLS. High quality studies with these agents are currently underway and hopefully confirm the efficacy and practicality of using these drugs in CKD-A-RLS. Some studies have shown that aerobic exercise and massage with lavender oil can improve symptoms of CKD-A- RLS suggesting that these measures can be useful as adjunct thera-py.

Free full text available: https://tremorjournal.org/articles/10.5334/tohm.752

Long-term Safety, Dose Stability, and Efficacy of Opioids for Patients With Restless Legs Syn-drome in the National RLS Opioid Registry.

Winkelman, J. W., Wipper, B., & Zackon, J. (2023)

Neurology, 100(14), e1520–e1528. https://doi.org/10.1212/WNL.0000000000206855

Abstract

Background and objectives: Restless legs syndrome (RLS) is a sensory-motor neurologic disorder. Low-dose opioids are prescribed for patients with refractory or augmented RLS. The long-term safety, dose stability, and efficacy of these medications for RLS treatment is still unclear. In this study, we report the 2-year longitudinal data in a sample of patients treated with opioids for RLS in the community.

Methods: The National RLS Opioid Registry is an observational longitudinal study consisting of individuals taking a prescribed opioid for diagnosed and confirmed RLS, most of whom experi-enced augmented symptoms from dopamine agonists. Information on opioid dosages, side ef-fects, past and current concomitant RLS treatments, RLS severity, psychiatric symptoms, and opioid abuse risk factors was collected at initial Registry entry and every 6 months thereafter by surveys on REDCap. No feedback or intervention was provided by the study staff to local provid-ers.

Results: Registry participants (n = 448) with 2-year longitudinal data available were mostly White, female, older than 60 years, and, at Registry entry, had been on opioids for a median of 1-3 years at a mean morphine milligram equivalent (MME) of 38.4 (SD = 43.5). No change in RLS severity in the overall cohort was observed over the 2-year follow-up period. The median change in daily opioid dose from baseline to 2 years was 0 MME (interquartile range = 0-10). While 41.1% of participants increased their dose during the follow-up period (median increase = 10 MME), 58.9% decreased their dose or saw no change. Only 8% and 4% saw increases of >25 MME and >50 MME, respectively. Ninety-five percent of those who increased opioid dose >25 or >50 MME had one of the following features: switching opioids, discontinuation of nonopioid RLS treatment medications, at least mild insomnia at baseline, a history of depression, male sex, younger than 45 years, and opioid use for comorbid pain.

Discussion: Low-dose opioid medications continue to adequately control symptoms of refractory RLS over 2 years of follow-up in most of the participants. A minority of patients did see larger dose increases, which were invariably associated with a limited number of factors, most notably changes in opioid and nonopioid RLS medications and opioid use for a non-RLS condition. Con-tinued longitudinal observations will provide insight into the long-term safety and efficacy of opioid treatment of severe, augmented RLS.

Free full text available: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10104616/

Pharmacological responsiveness of periodic limb movements in patients with restless legs syn-drome: a systematic review and meta-analysis.

Riccardi, S., Ferri, R., Garbazza, C., Miano, S., & Manconi, M. (2023).

Journal of clinical sleep medicine: JCSM: official publication of the American Academy of Sleep Medicine, 19(4), 811–822. https://doi.org/10.5664/jcsm.10440

Abstract

Study objectives: Periodic limb movements during sleep (PLMS) are a frequent finding in restless legs syndrome, but their impact on sleep is still debated, as well the indication for treatment. We systematically reviewed the available literature to describe which drug categories are effec-tive in suppressing PLMS, assessing their efficacy through a meta-analysis, when this was possi-ble.

Methods: The review protocol was preregistered on PROSPERO (CRD42021175848), and the systematic search was conducted on and EMBASE (last searched on March 2020). We included original human studies, which assessed PLMS modification on drug treatment with a full-night polysomnography, through surface electrodes on each tibialis anterior muscle. When at least 4 studies were available on the same drug or drug category, we performed a random-effect model meta-analysis.

Results: Dopamine agonists like pramipexole and ropinirole resulted the most effective, fol-lowed by l-dopa and other dopamine agonists. Alpha2delta ligands are moderately effective as well opioids, despite available data on these drugs are much more limited than those on dopa-minergic agents. Valproate and carbamazepine did not show a significant effect on PLMS. Clonazepam showed contradictory results. Perampanel and dypiridamole showed promising but still insufficient data. The same applies to iron supplementation.

Conclusions: Dopaminergic agents are the most powerful suppressors of PLMS. However, most therapeutic trials in restless legs syndrome do not report objective polysomnographic findings, there is a lack of uniformity in presenting results on PLMS. Longitudinal polysomnographic inter-ventional studies, using well-defined and unanimous scoring criteria and endpoints on PLMS are needed.

Emergence of restless legs syndrome during opioid discontinuation.

McCarter, S. J., Labott, J. R., Mazumder, M. K., Gebhard, J., Cunningham, J. L., Loukianova, L. L., Gilliam, W. P., & Lipford, M. C. (2023)

Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine, 19(4), 741–748. https://doi.org/10.5664/jcsm.10436

Abstract

Study objectives: The development of restless legs syndrome (RLS) has been rarely reported during and following opioid withdrawal. We aimed to determine the presence and severity of RLS symptoms during and after supervised opioid tapering.

Methods: Ninety-seven adults enrolled in the Mayo Clinic Pain Rehabilitation Center who un-derwent supervised prescription opioid tapering were prospectively recruited. RLS presence and severity was assessed with the Cambridge-Hopkins Questionnaire 13 and International Rest-less Legs Syndrome Study Group Rating Severity Scale at admission, midpoint, and dismissal from the program as well as 2 weeks, 4 weeks, and 3 months after completion. Frequency and severi-ty of RLS symptoms were compared between admission and each time point.

Results: Average age of the cohort was 52.6 ± 13.3 years with a morphine milligram equivalent dose for the cohort of 45.6 ± 48.3 mg. Frequency of RLS symptoms increased from 28% at ad-mission to peak frequency of 41% at 2 weeks following discharge from the Mayo Pain Rehabilita-tion Clinic (P = .01), returning to near baseline frequency 3 months after opioid discontinuation. International Restless Legs Syndrome Study Group Rating Severity Scale increased from baseline and then remained relatively stable at each time point following admission. Thirty-five (36.1%) participants developed de novo symptoms of RLS during their opioid taper, with those being exposed to higher morphine milligram equivalent doses having higher risk of developing RLS.

Conclusions: Moderately severe symptoms of RLS, as assessed by survey, occur commonly in in-dividuals undergoing opioid tapering, particularly if exposed to higher doses. In many cases, symptoms appear to be self-limited, although a minority develop persistent symptoms. Our re-sults may have implications for successful opioid tapering, but future confirmatory studies with structured clinician interview are needed to establish that these symptoms truly represent rest-less legs syndrome given the potential for RLS-mimicking symptoms in individuals with chronic pain syndromes.

The Effect of Cannabidiol for Restless Legs Syndrome/Willis-Ekbom Disease in Parkinson's Dis-ease Patients with REM Sleep Behavior Disorder: A Post Hoc Exploratory Analysis of Phase 2/3 Clinical Trial

de Almeida, C. M. O., Brito, M. M. C., Bosaipo, N. B., Pimentel, A. V., Sobreira-Neto, M. A., Tumas, V., Zuardi, A. W., Crippa, J. A. S., Hallak, J. E. C., & Eckeli, A. L. (2023)

Cannabis and cannabinoid research, 8(2), 374–378. https://doi.org/10.1089/can.2021.0158

Abstract

Background: Cannabidiol (CBD) is one of the main nonpsychoactive components of Cannabis sati-va and may represent an alternative treatment for Restless Legs Syndrome/Willis-Ekbom Disease (RLS/WED) in patients with Parkinson's disease (PD) and REM (Rapid Eye Movement) sleep behav-ior disorder (RBD). Objective: Our purpose was a post hoc exploratory analysis to evaluate the CBD's efficacy to improve the severity of RLS/WED symptoms in patients with PD and RBD.

Methods: A post hoc exploratory analysis of a phase II/III, a parallel, double-blind, placebo-controlled clinical trial was conducted in 18 patients with RLS/WED and PD plus RBD associated. Six patients were randomized to the CBD group in doses of 75-300 mg, and twelve received placebo capsules. They were followed up for 14 weeks. The primary outcome was the severity of RLS/WED by Restless Legs Syndrome Rating Scale of the International Restless Legs Syndrome Study Group (IRLSSG).

Results: CBD showed no difference in relationship to placebo for primary and secondary out-comes.

Conclusion: CBD showed no reduction in the severity of RLS/WED manifestation in patients with PD and RBD.

Attention deficit hyperactivity disorder and restless leg syndrome across the lifespan: A system-atic review and meta-analysis. Sleep medicine reviews, 69, 101770. Advance online publication.

Migueis, D. P., Lopes, M. C., Casella, E., Soares, P. V., Soster, L., & Spruyt, K. (2023).

https://doi.org/10.1016/j.smrv.2023

Abstract

This systematic review aims to assess the association between attention deficit hyperactivity disorder (ADHD) and restless legs syndrome (RLS) in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Databases were searched for original articles that reported prevalence data on ADHD and RLS until January 24th, 2023. Two independent reviewers evaluated the quality of the articles using the National Institutes of Health assessment tool. Among the 208 articles identified between 1996 and 2022, 29 were included. In large general population studies, 2.6-15.3% of participants met the RLS criteria, of which 3.2-17.4% presented with ADHD.

In the ADHD group, RLS symptoms ranged from 11 to 42.9% in children and 20-33.0% in adults. This suggests a strong co-occurrence between RLS and ADHD. A common characteristic of these conditions is sleep fragmentation, as discussed in the reviewed papers. Although large-scale studies with comparable diagnostic criteria across the lifespan are required, our findings may advocate a possible common physiological pathway, in-cluding sleep fragmentation and dopaminergic system impairment.

Circadian rhythm in restless legs syndrome.

Tang, M., Sun, Q., Zhang, Y., Li, H., Wang, D., Wang, Y., & Wang, Z. (2023)

Frontiers in neurology, 14, 1105463. https://doi.org/10.3389/fneur.2023.1105463

Abstract

Restless legs syndrome (RLS) is a sensorimotor disorder with a obvious circadian rhythm, as its symptoms often occur or worsen only in the evening or at night. The mechanisms behind the rhythms of RLS have not yet been fully elucidated. This review explores possible causes for the circadian fluctuations of the symptomatology, including the levels of iron, dopamine, melatonin, melanocortin, and thyroid-stimulating hormone in the brain, as well as conditions such as pe-ripheral hypoxia and microvascular function disorders.

The metabolic disturbances of the sub-stances above can create a pathological imbalance, which is further aggravated by physiological fluctuations of circadian rhythms, and results in the worsening of RLS symptoms at night. The review concludes with the suggestions for RLS treatment and research directions in the future.

Global prevalence of sleep disorders during menopause: a meta-analysis. Sleep & breathing = Schlaf & Atmung, 1–15

Salari, N., Hasheminezhad, R., Hosseinian-Far, A., Rasoulpoor, S., Assefi, M., Nankali, S., Nankali, A., & Mohammadi, M. (2023)

Advance online publication. https://doi.org/10.1007/s11325-023-02793-5

Abstract

Background: Sleep disorders are conditions that have long-term effects on health, quality of sexual function, productivity at work, and overall quality of life. Considering that reports on meno-pausal sleep disorders are heterogeneous, the aim of this research was to determine the global prevalence of sleep disorders during menopause by meta-analysis.

Methods: PubMed, Google Scholar, Scopus, WoS, ScienceDirect, and Embase databases were checked with suitable keywords. All screening stages of articles were reviewed based on PRISMA and their quality was determined based on STROBE. Data analysis, examination of heterogeneity, and publication bias of factors affecting heterogeneity were performed in CMA software.

Results: The overall prevalence of sleep disorders among postmenopausal women was 51.6% (95% CI: 44.6-58.5%). The upper prevalence of sleep disorders was among postmenopausal women at 54.7% (95% CI: 47.2-62.1%). The upper prevalence of sleep disorders in the same population category was related to restless legs syndrome with a prevalence of 63.8% (95% CI: 10.6-96.3%).

Conclusion: In this meta-analysis, sleep disorders during menopause were found to be common and significant. Therefore, it is recommended that health policymakers offer pertinent interven-tions in relation to the health and hygiene of sleep for women in menopause.

Free full text available: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9996569/pdf/11325_2023_Article_2793.pdf

Restless leg syndrome and risk of all-cause dementia: a nationwide retrospective cohort study

Kim, K. Y., Kim, E. H., Lee, M., Ha, J., Jung, I., & Kim, E. (2023)

Alzheimer's research & therapy, 15(1), 46.

https://doi.org/10.1186/s13195-023-01191-z

Abstract

Background: Restless leg syndrome (RLS) is associated with poor sleep quality, depression or anxiety, poor dietary patterns, microvasculopathy, and hypoxia, all of which are known risk fac-tors for dementia. However, the relationship between RLS and incident dementia remains un-clear. This retrospective cohort study aimed to explore the possibility that RLS could be deemed as a non-cognitive prodromal feature of dementia.

Methods: This was a retrospective cohort study using the Korean National Health Insurance Ser-vice-Elderly Cohort (aged ≥ 60). The subjects were observed for 12 years, from 2002 to 2013. Identifying patients with RLS and dementia was based on the 10th revised code of the Interna-tional Classification of Diseases (ICD-10). We compared the risk of all-cause dementia, Alzhei-mer's disease (AD), and vascular dementia (VaD) in 2501 subjects with newly diagnosed RLS and 9977 matched controls based on age, sex, and index date. The association between RLS and the risk of dementia was assessed using Cox regression hazard regression models. The effect of do-pamine agonists on the risk of dementia among RLS patients was also explored.

Results: The baseline mean age was 73.4, and the subjects were predominantly females (63.4%). The incidence of all-cause dementia was higher in the RLS group than that in the control group (10.4% vs 6.2%). A baseline diagnosis of RLS was associated with an increased risk of incident all-cause dementia (adjusted hazard ratio [aHR] 1.46, 95% confidence interval [CI] 1.24-1.72). The risk of developing VaD (aHR 1.81, 95% CI 1.30-2.53) was higher than that of AD (aHR 1.38, 95% CI 1.11-1.72). The use of dopamine agonists was not associated with the risk of subsequent demen-tia among patients with RLS (aHR 1.00, 95% CI 0.76-1.32).

Conclusions: This retrospective cohort study suggests that RLS is associated with an increased risk of incident all-cause dementia in older adults, providing some evidence that requires con-firmation through prospective studies in the future. Awareness of cognitive decline in patients with RLS may have clinical implications for the early detection of dementia.

Free full text available: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9987068/pdf/13195_2023_Article_1191.pdf

A Narrative Review of the Lesser Known Medications for Treatment of Restless Legs Syndrome and Pathogenetic Implications for Their Use

Yeh, P. G., Spruyt, K., DelRosso, L. M., & Walters, A. S. (2023)

Tremor and other hyperkinetic movements (New York, N.Y.), 13, 7. https://doi.org/10.5334/tohm.739

Abstract

Background: There are several well-known treatments for Restless Legs Syndrome (RLS), includ-ing dopamine agonists (pramipexole, ropinirole, rotigotine), anticonvulsants (gabapentin and its analogs, pregabalin), oral or intravenous iron, opioids and benzodiazepines. However, in clinical practice, treatment is sometimes limited due to incomplete response or side effects and it is necessary to be aware of other treatment options for RLS, which is the purpose of this review.

Methods: We performed a narrative review detailing all of the lesser known pharmacological treatment literature on RLS. The review purposefully excludes well-established, well-known treatments for RLS which are widely accepted as treatments for RLS in evidence-based reviews. We also have emphasized the pathogenetic implications for RLS of the successful use of these lesser known agents.

Results: Alternative pharmacological agents include clonidine which reduces adrenergic trans-mission, adenosinergic agents such as dipyridamole, glutamate AMPA receptor blocking agents such as perampanel, glutamate NMDA receptor blocking agents such as amantadine and keta-mine, various anticonvulsants (carbamazepine/oxcarbazepine, lamotrigine, topiramate, valproic acid, levetiracetam), anti-inflammatory agents such as steroids, as well as cannabis. Bupropion is also a good choice for the treatment of co-existent depression in RLS because of its pro-dopaminergic properties.

Discussion: Clinicians should first follow evidence-based review recommendations for the treat-ment of RLS but when the clinical response is either incomplete or side effects are intolerable other options can be considered. We neither recommend nor discourage the use of these op-tions, but leave it up to the clinician to make their own choices based upon the benefit and side effect profiles of each medication.

Free full text available: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9983500/pdf/tohm-13-1-739.pdf

Restless Legs Syndrome and Periodic Limb Movements of Sleep: From Neurophysiology to Clinical Practice

Kouri, I., Junna, M. R., & Lipford, M. C. (2023)

Journal of clinical neurophysiology : official publication of the American Electroencephalo-graphic Society, 40(3), 215–223. https://doi.org/10.1097/WNP.0000000000000934

Abstract

This article summarizes restless legs syndrome (RLS), periodic limb movements of sleep, and periodic limb movement disorder. RLS is a common sleep disorder with a prevalence of 5% to 15% in the general population. RLS can present in childhood, and incidence increases with age. RLS can be idiopathic or secondary to iron deficiency, chronic renal failure, peripheral neuropa-thy, and medications such as antidepressants (with higher rates for mirtazapine and venlafaxine, while bupropion may reduce symptoms at least in the short term), dopamine antagonists (neu-roleptic antipsychotic agents and antinausea medications), and possibly antihistamines. Man-agement includes pharmacologic agents (dopaminergic agents, alpha-2 delta calcium channel ligands, opioids, benzodiazepines) and nonpharmacologic therapies (iron supplementation, be-havioral management). Periodic limb movements of sleep are an electrophysiologic finding commonly accompanying RLS.

On the other hand, most individuals with periodic limb move-ments of sleep do not have RLS. The clinical significance of the movements has been argued. Periodic limb movement disorder is a distinct sleep disorder that arises in individuals without RLS and is a diagnosis of exclusion.

Effect of exergaming in people with restless legs syndrome with multiple sclerosis: A single-blind randomized controlled trial

Ozdogar, A. T., Ertekin, O., Kahraman, T., Dastan, S., & Ozakbas, S. (2023)

Multiple sclerosis and related disorders, 70, 104480. https://doi.org/10.1016/j.msard.2022.104480

Abstract

Background: Restless legs syndrome (RLS) is a sensory-motor disorder characterized by an uncom-fortable sensation in the lower extremity, triggered by sitting and lying positions and release with motion. There is strong evidence that RLS prevalence is higher in persons with multiple sclerosis (MS, pwMS) than in the general population. Current literature has shown that exergam-ing as non-pharmacological therapy may be an effective method for symptoms such as balance, walking, fatigue, cognitive functions in pwMS, but the effects on RLS are not known. Therefore, the study's main aim is to investigate the effects of exergaming in pwMS with RLS.

Methods: Thirty-one pwMS with RLS and 34 pwMS without RLS were randomly divided as exer-gaming group and control group. The outcome measures were International RLS Study Group Rating Scale, Modified Fatigue Impact Scale, MS Walking Scale, Timed 25-Foot Walk Test, Hospi-tal Anxiety and Depression Scale, Godin-Shephard Leisure-Time Physical Activity Questionnaire, Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, 6 min Walk Test, Timed and Up Go, MS International Quality of Life questionnaire, MS-Related Symptom Checklist.

Results: 26 pwMS with RLS (11 exergaming group, 15 control group) and 27 pwMS without RLS (12 exergaming group, 15 control group) were included in 8-week post-treatment analyses. After an 8-week long-term follow-up, 16 pwMS with and without RLS completed the protocol. The RLS severity (p = 0.004), anxiety level (p = 0.024), sleep quality (0.005), walking (0.004), and balance functions (0.041) were improved in pwMS with RLS exergaming group, while RLS severity in-creased in control group (p = 0.004). At 8-week follow-up, the effect of exergaming on RLS se-verity, quality of life, sleep quality, and walking capacity was preserved. There was significant improvement in gait and balance functions in pwMS without RLS exergaming group, there was no significant differences control group. In 8-week follow-up, improvement obtained in pwMS without RLS exergaming group was not preserved.

Conclusions: This study suggests that exergaming training could be an effective method for man-aging RLS severity, anxiety, sleep quality, gait, balance, and quality of life in pwMS with RLS.

Restless legs syndrome in patients with psoriasis: association with inflammation and sleep quality

Solak, B., Aydın, B., Yüksekal, G., & Yaldız, M. (2023)

International journal of dermatology, 62(4), 501–507. https://doi.org/10.1111/ijd.16532

Abstract

Background: We aimed to evaluate if psoriasis associated with restless legs syndrome (RLS) due to its close relationship with metabolic disorders.

Methods: This was a cross-sectional study in which the relationship between RLS and psoriasis was evaluated. Seventy consecutive psoriasis patients and 70 controls without any skin disorder were included in this study. Data including age, gender, body weight, height, and Psoriasis Area Severity Index (PASI) scores were recorded. Diagnosis of RLS was established using International RLS Study Group (IRLSSG) diagnostic criteria. International RLS Rating Scale (IRLSRS) was used to evaluate the severity of symptoms. Each participant completed forms of the Pittsburgh Sleep Quality Index (PSQI), the Epworth Sleepiness Scale (ESS), and the Dermatology Life Quality Index (DLQI).

Results: The RLS frequency in patients with psoriasis was 18.6% vs. 5.7% in the control group (P = 0.018). In psoriasis patients, BMI, DLQI, IRLSRS, hemoglobin, ferritin, CRP, and uric acid levels were significantly higher than those of the controls. In psoriasis patients with RLS, PASI, DLQI, PSQI, IRLSRS scores, CRP level, and BMI were significantly higher, and hemoglobin level was sig-nificantly lower relative to the psoriasis patients without RLS. PASI score was the sole inde-pendent associate of RLS presence in psoriasis patients.

Conclusion: Restless legs syndrome was significantly more common in psoriasis patients, and the presence of RLS was associated with significantly more severe psoriasis, more severe systemic inflammation, lower serum hemoglobin values, worse quality of life, and sleep quality.

Neuroprotective Effect of Melatonin on Sleep Disorders Associated with Parkinson's Disease.

Hu, X., Li, J., Wang, X., Liu, H., Wang, T., Lin, Z., & Xiong, N. (2023).

Antioxidants (Basel, Switzerland), 12(2), 396. https://doi.org/10.3390/antiox12020396

Abstract

Parkinson's disease (PD) is a complex, multisystem disorder with both neurologic and systemic manifestations, which is usually associated with non-motor symptoms, including sleep disorders. Such associated sleep disorders are commonly observed as REM sleep behavior disorder, insom-nia, sleep-related breathing disorders, excessive daytime sleepiness, restless legs syndrome and periodic limb movements. Melatonin has a wide range of regulatory effects, such as synchroniz-ing circadian rhythm, and is expected to be a potential new circadian treatment of sleep disor-ders in PD patients. In fact, ongoing clinical trials with melatonin in PD highlight melatonin's therapeutic effects in this disease. Mechanistically, melatonin plays its antioxidant, anti-inflammatory, anti-excitotoxity, anti-synaptic dysfunction and anti-apoptotic activities. In addi-tion, melatonin attenuates the effects of genetic variation in the clock genes of Baml1 and Per1 to restore the circadian rhythm. Together, melatonin exerts various therapeutic effects in PD but their specific mechanisms require further investigations.

Restless legs syndrome in patients with chronic low back pain

Baykal Şahin, H., Karacaoğlu, S., Çapkın, E., & Kara, F. (2023)

British journal of pain, 17(1), 23–27. https://doi.org/10.1177/20494637221119582

Abstract

Background: Based on studies showing that both chronic low back pain (LBP) and restless legs syndrome (RLS) have similar pathophysiological mechanisms, we aimed to investigate the preva-lence of RLS in patients with chronic LBP and to define which demographic and clinical features are prominent in those with LBP accompanied by RLS.

Methods: One hundred and two eligible, volunteer participants with chronic LBP were enrolled in this study. Visual analog scale (VAS), the Oswestry Disability Index (ODI), Pittsburgh Sleep Qual-ity Index, Beck Depression Inventory, and Short Form-36 scales were applied to the patients. All patients were evaluated face-to-face for RLS using the International RLS study group diagnostic criteria.

Results: Most of our patients were women (52%). The mean age was 40.96±13.34 years and the mean disease duration was 46.16±41.98 months. RLS was detected in 36 (35.3%) of the patients with LBP. It was found that the female gender was more dominant in patients with RLS and the difference was statistically significant (p < 0.001). The amount of coffee intake was significantly higher in patients with RLS compared to those without RLS (p = 0.001). The disease duration for LBP was significantly higher in the patients with RLS (p = 0.003). VAS score, ODI score, PUKI score, and Beck depression score were significantly higher in the RLS group (p value were 0.048, 0.040, 0.007, and 0.043, respectively). In the evaluation of quality of life, all parameters except role emotional limitations and mental health were found to be significantly worse in the RLS group.

Dopamine agonists and risk of lung cancer in patients with restless legs syndrome.

Hernandez-Con, P., Shults, J., Willis, A. W., & Yang, Y. X. (2023)

Pharmacoepidemiology and drug safety, 10.1002/pds.5596. Advance online publication. https://doi.org/10.1002/pds.5596

Abstract

Purpose: To examine the association between long-term use of dopamine agonists (DAs) and the risk of lung cancer in patients with restless legs syndrome (RLS).

Methods: We conducted a retrospective cohort study using Optum Clinformatics® database. We included adults ≥40 years diagnosed with RLS during the study period (1/2006-12/2016). Follow-up started with the first RLS diagnosis and ended on the earliest of: incident diagnosis of lung cancer, end of enrollment in the database or end of the study period. The exposure of interest was cumulative duration of DAs use, measured in a time-varying manner. We constructed a mul-tivariable Cox regression model to estimate HRs and 95% CIs for the association between lung cancer and cumulative durations of DA use, adjusting for potential confounding variables.

Results: We identified 295 042 patients with a diagnosis of RLS. The mean age of the cohort was 62.9; 66.6% were women and 82.3% were white. The prevalence of any DA exposure was 40.3%. Compared to the reference group (no use and ≤1 year), the crude HRs for lung cancer were 1.16 (95% CI 0.99-1.36) and 1.14 (95% CI 0.86-1.51) for 1-3 years and >3 years of cumula-tive DA use, respectively. The adjusted HR for lung cancer was 1.05 (95% CI 0.88-1.25) for 1-3 years and 1.02 (95% CI 0.76-1.37) for >3 years of cumulative DA use, respectively.

Conclusions: At typical doses for the clinical management of RLS, long-term DA use was not asso-ciated with risk of lung cancer.

Free full text available https://onlinelibrary.wiley.com/doi/10.1002/pds.5596

Evaluation of Serum Selenium Level, Quality of Sleep, and Life in Pregnant Women With Restless Legs Syndrome.

Laleli Koc, B., Elmas, B., Tugrul Ersak, D., Erol, S. A., Kara, O., & Sahin, D. (2023).

Biological trace element research, 201(3), 1143–1150. https://doi.org/10.1007/s12011-022-03447-5

Abstract

Restless legs syndrome (RLS) is a multifactorial disease that patients describe as restlessness in their legs, which creates a desire to move their legs, especially in the evening and at rest. This study aims to investigate serum selenium levels in RLS and document the quality of sleep and life in pregnant women with RLS according to International Restless Legs Syndrome Study Group (IRLSSG) diagnostic criteria. Thirty-eight moderate to severe RLS patients with pregnancy at 38-41 weeks of gestation were determined as the case group, and 38 women with healthy gesta-tional age-matched pregnancies were determined as the control group. Maternal serum seleni-um levels were compared between the RLS case group and the group of healthy pregnant wom-en at the time of hospitalization for delivery.

The Pittsburgh Sleep Quality Index (PSQI) and The Quality of Life Scale (SF-36) were applied to the patients. The mean selenium level (µg/L) was statistically significantly lower in the RLS group (53.24 ± 10.28), compared to the healthy preg-nant population (58.95 ± 11.29) (P = 0.024). The PSQI score was significantly higher in the RLS case group (P = 0.033). Especially sleep efficiency (P = 0.018) and daytime dysfunction (P = 0.032) sub-parameters were affected. The SF-36 questionnaire was examined and a significant difference was detected between the two groups in role emotional (P = 0.026), social function-ing (P = 0.023), and body pain (P = 0.044) sub-parameters.

Serum selenium level was significantly lower, the sleep quality of the RLS group was impaired and their quality of life was affected in pregnant women with RLS. Further studies are needed to determine whether selenium re-placement in pregnant women with RLS is feasible or not.

Long-term Safety, Dose Stability, and Efficacy of Opioids for Patients With Restless Legs Syn-drome in the National RLS Opioid Registry.

Winkelman, J. W., Wipper, B., & Zackon, J. (2023)

Neurology, 10.1212/WNL.0000000000206855. Advance online publication. https://doi.org/10.1212/WNL.0000000000206855

Abstract

Background and objectives: Restless legs syndrome (RLS) is a sensory-motor neurological disor-der. Low-dose opioids are prescribed for patients with refractory or augmented Restless Legs Syndrome (RLS). The long-term safety, dose stability and efficacy of these medications for RLS treatment is still unclear. We report here the 2-year longitudinal data in a sample of patients treated with opioids for RLS in the community.

Methods: The National RLS Opioid Registry is an observational longitudinal study consisting of individuals taking a prescribed opioid for diagnosed and confirmed RLS, the vast majority of whom had augmented symptoms from dopamine agonists. Information on opioid dosages, side effects, past and current concomitant RLS treatments, RLS severity, psychiatric symptoms, and opioid abuse risk factors were collected at initial Registry entry and every 6 months thereafter by surveys on REDCap. No feedback or intervention is provided by the study staff to local pro-viders.

Results: Registry participants (n=448) with 2-year longitudinal data available were mostly white, female, over 60 years old, and, at Registry entry, had been on opioids for a median of 1-3 years at a mean morphine milligram equivalent (MME) of 38.4 (SD=43.5). No change in RLS severity in the overall cohort was observed over the 2-year follow-up period. The median change in daily opioid dose from baseline to 2-years was 0 MME [IQR=0-10]. While 41.1% of participants in-creased their dose during the follow-up period (median increase=10 MME), 58.9% decreased their dose or saw no change. Only 8% and 4% saw increases of >25 MME and >50 MME respec-tively. Ninety-five percent of those who increased opioid dose >25 or >50 MME had one of the following features: switching opioids, discontinuation of non-opioid RLS treatment medications, at least mild insomnia, history of depression, male sex, age <45, and opioid use for comorbid pain.

Discussion: Low-dose opioid medications continue to adequately control symptoms of refractory RLS over 2 year follow-up in the majority of participants. A minority of patients did see larger dose increases, which were invariably associated with a limited number of factors, most notably changes in opioid and non-opioid RLS medications and opioid use for a non-RLS condition. Con-tinued longitudinal observations will provide insight on the long-term safety and efficacy of opi-oid treatment of severe, augmented RLS.

Classification of evidence: This study provides Class IV evidence that opioid doses increase in roughly 40% of patients, in the majority by small amounts, over a two-year period when pre-scribed for adult refractory restless leg syndrome.

Pharmacological responsiveness of periodic limb movements in patients with restless legs syndrome: a systematic review and meta-analysis.

Riccardi, S., Ferri, R., Garbazza, C., Miano, S., & Manconi, M. (2023)

Journal of clinical sleep medicine: JCSM: official publication of the American Academy of Sleep Medicine.

Abstract

Study objectives: Periodic limb movements during sleep (PLMS) are a frequent finding in restless legs syndrome (RLS), but their impact on sleep is still debated, as well the indication for treat-ment.

We systematically reviewed the available literature to describe which drug categories are effec-tive in suppressing PLMS, assessing their efficacy through a meta-analysis, when this was possi-ble.

Methods: The review protocol was preregistered on PROSPERO (CRD42021175848) and the sys-tematic search was conducted on PubMed and EMBASE (last searched on March 2020). We in-cluded original human studies, which assessed PLMS modification on drug treatment with a full night polysomnography (PSG), through surface electrodes on each tibialis anterior muscle. When at least 4 studies were available on the same drug or drug category, we performed a random effect model meta-analysis.

Results: Dopamine agonists like pramipexole and ropinirole resulted the most effective, fol-lowed by L-Dopa and other dopamine agonists. Alpha2delta ligands are moderately effective as well opioids, despite available data on these drugs are much more limited than those on dopa-minergic agents. Valproate and carbamazepine did not show a significant effect on PLMS. Clonazepam showed contradictory results. Perampanel and dypiridamole showed promising but still insufficient data. The same applies to iron supplementation.

Conclusions: Dopaminergic agents are the most powerful suppressors of PLMS. However, most therapeutic trials in RLS do not report objective polysomnographic findings, there's a lack of uniformity in presenting results on PLMS. Longitudinal polysomnographic interventional studies, using well-defined and unanimous scoring criteria and endpoints on PLMS are needed.

Emergence of restless legs syndrome during opioid discontinuation.

McCarter, S. J., Labott, J. R., Mazumder, M. K., Gebhard, J., Cunningham, J. L., Loukianova, L. L., Gilliam, W. P., & Lipford, M. C. (2023).

Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine, 10.5664/jcsm.10436. Advance online publication. https://doi.org/10.5664/jcsm.10436

Abstract

Study objectives: The development of restless legs syndrome (RLS) has been rarely reported during and following opioid withdrawal. We aimed to determine the presence and severity of RLS symptoms during and after supervised opioid tapering.

Methods: Ninety-seven adults enrolled in the Mayo Pain Rehabilitation Clinic (PRC) who under-went supervised prescription opioid tapering were prospectively recruited. RLS presence and severity was assessed with the Cambridge-Hopkins Questionnaire 13 and International Restless Legs Syndrome Study Group Rating Severity Scale (IRLSS) at admission, midpoint, and dismissal from the program as well as 2 weeks, 4 weeks, and 3 months after completion. Frequency and severity of RLS symptoms were compared between admission and each time point.

Results: Average age of the cohort was 52.6 ± 13.3 years with a morphine milligram equivalent (MME) dose for the cohort of 45.6 ± 48.3 mg. Frequency of RLS symptoms increased from 28% at admission to peak frequency of 41% at two weeks following discharge from the PRC (p=0.01), returning to near baseline frequency 3 months after opioid discontinuation. IRLSS increased from baseline and then remained relatively stable at each time point following admission. Thir-ty-five (36.1%) participants developed de novo symptoms of RLS during their opioid taper, with those being exposed to higher MME doses having higher risk of developing RLS.

Conclusions: Moderately severe symptoms of RLS, as assessed by survey, occur commonly in in-dividuals undergoing opioid tapering, particularly if exposed to higher doses. In many cases, symptoms appear to be self-limited, although a minority develop persistent symptoms. Our re-sults may have implications for successful opioid tapering, but future confirmatory studies with structured clinician interview are needed to establish that these symptoms truly represent rest-less legs syndrome given the potential for RLS-mimicking symptoms in individuals with chronic pain syndromes.

The prevalence of and risk factors for restless legs syndrome: A nationwide study.

AlShareef S. M. (2023).

Frontiers in psychiatry, 13, 987689. https://doi.org/10.3389/fpsyt.2022.987689

Abstract

Objectives: Restless legs syndrome (RLS) is a neglected diagnosis, and most individuals with RLS do not access effective therapies. There has yet to be a nationwide study of the prevalence of and associated risk factors for RLS in Saudi Arabia.

Materials and methods: A population-wide survey was administered to Saudi Arabian adults to assess RLS prevalence and its association with other clinical and demographic variables. RLS was defined according to 2012 IRLSSG Diagnostic Criteria. Persistent RLS was defined as symptoms occurring more than a few nights each week, and RLS causing significant daytime impairment was defined as symptoms causing "severe" excessive daytime sleepiness measured by the Ep-worth Sleepiness Scale. Associations were evaluated using univariate analyses and binary logistic regression.

Results: 10,106 individuals completed the survey. Persistent RLS was reported in 11.9% of par-ticipants, which caused significant daytime impairment in 1.2% of participants. In multivariable analysis, younger age (OR 0.96, 95% CI 0.95-0.97; p < 0.001), tobacco smoking (OR 1.28, 95% CI 1.07-1.53; p = 0.008), anxiety (OR 1.34-1.42; p < 0.05), and moderate to severe depressive symptoms (OR 1.52-2.40; p < 0.01) were associated with persistent RLS. Younger age (OR 0.96, 95% CI 0.93-0.99; p = 0.015), female gender (OR 2.28, 95% CI 1.32-3.94; p = 0.003), and moder-ately severe to severe depressive symptoms (OR 13.59 and 26.7, respectively; p < 0.001) were independently associated with RLS causing significant daytime impairment.

Conclusion: RLS is common in adults in Saudi Arabia and is often co-morbid with moderate to severe depressive symptoms. Both RLS and depression represent a silent epidemic in Saudi Ara-bia requiring active inquiry by all healthcare workers to reduce their burden and impact.

Free full text available https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9842666/

A Narrative Review of the Lesser Known Medications for Treatment of Restless Legs Syndrome and Pathogenetic Implications for Their Use

Yeh, P. G., Spruyt, K., DelRosso, L. M., & Walters, A. S. (2023)

Tremor and other hyperkinetic movements (New York, N.Y.), 13, 7. https://doi.org/10.5334/tohm.739

Abstract

Background: There are several well-known treatments for Restless Legs Syndrome (RLS), includ-ing dopamine agonists (pramipexole, ropinirole, rotigotine), anticonvulsants (gabapentin and its analogs, pregabalin), oral or intravenous iron, opioids and benzodiazepines. However, in clinical practice, treatment is sometimes limited due to incomplete response or side effects and it is necessary to be aware of other treatment options for RLS, which is the purpose of this review.

Methods: We performed a narrative review detailing all of the lesser known pharmacological treatment literature on RLS. The review purposefully excludes well-established, well-known treatments for RLS which are widely accepted as treatments for RLS in evidence-based reviews. We also have emphasized the pathogenetic implications for RLS of the successful use of these lesser known agents.

Results: Alternative pharmacological agents include clonidine which reduces adrenergic trans-mission, adenosinergic agents such as dipyridamole, glutamate AMPA receptor blocking agents such as perampanel, glutamate NMDA receptor blocking agents such as amantadine and keta-mine, various anticonvulsants (carbamazepine/oxcarbazepine, lamotrigine, topiramate, valproic acid, levetiracetam), anti-inflammatory agents such as steroids, as well as cannabis. Bupropion is also a good choice for the treatment of co-existent depression in RLS because of its pro-dopaminergic properties.

Discussion: Clinicians should first follow evidence-based review recommendations for the treat-ment of RLS but when the clinical response is either incomplete or side effects are intolerable other options can be considered. We neither recommend nor discourage the use of these op-tions, but leave it up to the clinician to make their own choices based upon the benefit and side effect profiles of each medication.

Free full text available: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9983500/pdf/tohm-13-1-739.pdf

Inflammatory factors and restless legs syndrome: A systematic review and meta-analysis.

Jiménez-Jiménez, F. J., Alonso-Navarro, H., García-Martín, E., & Agúndez, J. A. G. (2022)

Journal of clinical neurophysiology : official publication of the American Electroencephalo-graphic Society, 40(3), 215–223. https://doi.org/10.1097/WNP.0000000000000934

Abstract

The possible role of inflammatory factors in the pathogenesis of restless legs syndrome (RLS) is not well understood. Because several inflammatory diseases have shown an association with the risk for RLS, the measurement of serum/plasma levels of inflammatory factors has been a matter of a scarce number of studies. We performed a systematic review and a meta-analysis to assess the possible association of serum/plasma levels of inflammatory markers with the risk for RLS. Our results showed a significant trend towards higher serum/plasma C reactive protein (CRP) levels and higher neutrophil-to-lymphocyte (NLR) ratio in patients diagnosed with RLS than in controls, although statistical significance disappeared after applying the random-effects model. Further studies are needed to confirm the suggested possible role of inflammatory factors in the pathogenesis of RLS.

Worldwide estimation of restless legs syndrome: a systematic review and meta-analysis of prevalence in the general adult population.

Broström, A., Alimoradi, Z., Lind, J., Ulander, M., Lundin, F., & Pakpour, A. (2023)

Journal of sleep research, e13783. Advance online publication. https://doi.org/10.1111/jsr.13783

Abstract

This systematic review, meta-analysis and meta-regression assessed the prevalence of restless legs syndrome (RLS) in the general adult population. Studies identified in Scopus, PubMed, Web of Science, and PsycInfo between January 2000 and February 2022 were included if they used a case-control or cross-sectional design and reported data regarding the prevalence of RLS. The protocol was pre-registered in the International Prospective Register of Systematic Reviews (PROSPERO; CRD42022300709). A total of 97 studies including 483,079 participants from 33 different countries met the eligibility criteria. The Newcastle Ottawa Scale was used to evaluate the methodological quality, and the fill-and-trim method was used to correct probable publica-tion bias, while the jack-knife method was performed to assess small study effect. The corrected overall pooled prevalence of RLS was 3% (95% confidence interval [CI] 1.4%-3.8%). The pooled prevalence of RLS syndrome was affected by methodological quality (no data from non-respondents in the included studies), gender (higher among women), study design (lower preva-lence in case-control versus cohort and cross-sectional studies). The figures for corrected pooled prevalence among men, women, alcohol consumers and smokers were 2.8% (95% CI 2%-3.7%); 4.7% (95% CI 3.2%-6.3%); 1.4% (95% CI 0%-4.2%); and 2.7% (95% CI 0%-5.3%), respectively. The prevalence among male and female participants was lower in community-based versus non-community-based studies. Moreover, the prevalence was higher in developed versus developing countries and among elders versus adults. In conclusion, RLS is a common disorder in the gen-eral adult population, with a higher prevalence in women; however, prevalence data are affect-ed by study design and quality.

Free full text available https://onlinelibrary.wiley.com/doi/epdf/10.1111/jsr.13783

Effects of acupuncture on sensory symptoms and motor signs in patients with restless legs syndrome: A crossover randomized controlled trial.

Fukutome, T., & Murashima, K. (2022)

Medicine, 101(51), e32317. https://doi.org/10.1097/MD.0000000000032317

Abstract

Background: Rapid effects of acupoint injection (acuinjection) at 4 acupoints (4P) (ST36, GB41, SP6, and BL60) on legs presenting sensory symptoms and motor signs in restless legs syndrome (RLS) were first described in a case report. This study aimed to confirm the beneficial effects of acuinjection.

Methods: A randomized, controlled, single-blinded, prospective crossover study was conducted during 2018 to 2021. Adult volunteers (age ≥ 20 years) with RLS symptoms for > 2 weeks were included. Eight adults were enrolled and randomized to receive acuinjection (Verum group) or sham injection (Sham group). The effects of acuinjection on discomfort and periodic leg move-ment (PLM) were evaluated using the suggested immobilization test in a crossover design. The acupoint used was 4P, and normal saline solution (0.1-0.25 mL) was injected in both groups. Leg discomfort was measured using the visual analog scale (VAS), and PLM was measured using an electromyogram. To compare the VAS scores between the groups, repeated measures analysis of variance was used, and the Student t test was used to assess the mean discomfort score (MLDS: average of the 6 VAS scores) and PLM index (PLMI) (defined as the degree of PLM/hour).

Results: A significant difference in the VAS score was observed; however, no significant differ-ence was noted in the PLMI between the groups. The MLDS was significantly lower in the Verum group than in the Sham group.

Conclusion: Acuinjection at 4P remarkably inhibited leg discomfort in patients with RLS. Despite the drastic PLM suppression in 1 patient by acuinjection, a statistically significant inhibition of PLM was not confirmed. The results of our study can be applied easily and safely in clinical situa-tions where it is necessary to temporarily reduce or eliminate RLS symptoms.

Free full text available https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9794214/

Therapeutic effects of magnesium and vitamin B6 in alleviating the symptoms of restless legs syndrome: a randomized controlled clinical trial.

Jadidi, A., Rezaei Ashtiani, A., Khanmohamadi Hezaveh, A., & Aghaepour, S. M. (2022).

BMC complementary medicine and therapies, 23(1), 1. https://doi.org/10.1186/s12906-022-03814-8

Abstract

Background and objective: Restless legs syndrome/Willis-Ekbom Disease (RLS/WED) is one of the most prevalent sleep disorders. There are contradicting data about the effectiveness of magne-sium and vitamin B6 in alleviating the symptoms of this condition. Therefore, this study aimed to assess the efficacy of magnesium and vitamin B6 in alleviating the symptoms of RLS/WED.

Methods: A single-blind study was conducted on individuals with this illness for at least three months. Randomly, 75 patients were assigned into three groups: magnesium, vitamin B6, and placebo. The experimental group received daily doses of 40 mg vitamin B6 or 250 mg magnesi-um oxide. While others in the control group merely received a placebo. Patients' disease sever-ity and sleep quality were evaluated three times using standard questionnaires (at the beginning of the study, one and two months after therapy). Utilizing SPSS22 software and the ANOVA, t-test, and repeated measure tests, statistical analysis was conducted.

Results: The mean and standard deviation of sleep quality and disease severity at the beginning of the trial and throughout the first month following the intervention did not differ statistically between the three groups. In the second month following the intervention, the mean and standard deviation of sleep quality and disease severity were significantly different (P = 0.001).

Conclusion: Taking magnesium and vitamin B6 supplements can reduce the severity of symptoms of RLS/WED patients and improve their sleep quality.

Free full text available https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9804944/

Olanzapine-induced restless leg syndrome (Willis-Ekbom disease): A case report

Das, S., Prasad, S., Anand, A., Das, A., Obinna Anugwom, G., & Oladunjoye, F. (2022)

SAGE open medical case reports, 10, 2050313X221145583. https://doi.org/10.1177/2050313X221145583

Abstract

Restless leg syndrome, also known as Willis-Ekbom disease, is a neurological sensorimotor disor-der accompanied by an irresistible urge to move the legs with a fluctuating course of symptoms. It is a common disorder affecting all ages, with existing comorbidities and positive family history being associated with increased prevalence. Herein, we present a case of a 51-year-old female diagnosed with the bipolar affective disorder who developed restless leg syndrome following the use of olanzapine. Olanzapine is a second-generation antipsychotic which can cause restless leg syndrome due to its anti-dopaminergic action on the nervous system, particularly the spinal cord. Existing literature on olanzapine-induced restless leg syndrome has suggested managing this disorder by reducing the dose or replacing olanzapine with other drugs such as clonazepam, quetiapine, and aripiprazole. In our case, olanzapine was not replaced with other medications as the patient showed a significant improvement in bipolar affective disorder symptoms using olanzapine. Instead, clonazepam was added to the treatment regimen which was scheduled to be taken before olanzapine

Free full text available https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9772929/

Exploration of restless legs syndrome under the new concept: A review.

Liu, Z., Guan, R., & Pan, L. (2022)

Medicine, 101(50), e32324. https://doi.org/10.1097/MD.0000000000032324

Abstract

Restless leg syndrome (Restless legs syndrome, RLS) is a common neurological disorder. The pathogenesis of RLS remains unknown, and recent pathophysiological developments have shown the contribution of various genetic markers, neurotransmitter dysfunction, and iron deficiency to the disease, as well as other unidentified contributing mechanisms, particularly chronic renal dysfunction. RLS enhancement syndrome is frequently observed in patients with RLS who have received long-term dopamine agonist therapy, manifesting as a worsening of RLS symptoms, usu-ally associated with an increase in the dose of dopamine agonist. Some patients with RLS can adequately control their symptoms with non-pharmacological measures such as massage and warm baths. First-line treatment options include iron supplementation for those with evidence of reduced iron stores, or gabapentin or pregabalin, as well as dopamine agonists, such as pramipexole. Second-line therapies include opioids such as tramadol. RLS seriously affects the quality of life of patients, and because its pathogenesis is unclear, more biological evidence and treatment methods need to be explored.

Free full text available https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9771278/

Restless Legs Syndrome After Aripiprazole Discontinuation: A Case Report and Review of Literature

Dokuz, G., Ergün, S., & Topçuoğlu, V. (2022)

Psychiatria Danubina, 34(4), 738–740. https://doi.org/10.24869/psyd.2022.738

No abstract available.

Free full text available https://www.psychiatria-danubina.com/UserDocsImages/pdf/dnb_vol34_no4/dnb_vol34_no4_738.pdf

Lateral Subdermic Venous Plexus Insufficiency: The Association of Varicose Veins with Restless Legs Syndrome and Nocturnal Leg Cramps.

Pyne, R., Shah, S., Stevens, L., & Bress, J. (2022)

Journal of vascular and interventional radiology: JVIR, S1051-0443(22)01416-6. Advance online publication. https://doi.org/10.1016/j.jvir.2022.12.019

Abstract

Purpose: To identify whether nocturnal symptoms of restless legs syndrome (RLS) and muscle cramps in the legs are associated specifically with lateral subdermic venous plexus (LSVP) insuffi-ciency and whether treatment can provide symptomatic relief.

Materials and methods: A retrospective cross-sectional observational study of 506 patients at a single site analysed whether RLS/nighttime leg cramping symptoms were associated with venous reflux in the LSVP on comprehensive venous ultrasound (CVU). Treatment outcomes of ultra-sound-guided foam sclerotherapy (USGFS) were followed out to one year.

Results: Of 209 patients who reported restless legs symptoms, 179 (85%) demonstrated an ab-normal LSVP. 214 patients reported night time muscle cramping, of which 197 (92%) demon-strated an abnormal LSVP. Among 124 patients presenting with both symptoms, 113 (91%) demonstrated an abnormal LSVP. Conversely, of the 83 patients who presented with neither RLS nor nocturnal cramping, 2 (2%) had an abnormal LSVP. Of 242 symptomatic patients with ab-normal LSVP who underwent treatment, technical success rate was 100%. At 90-day follow-up, 224 (93%) reported continued relief, which was maintained at follow-up out to one year at 93% (224 of 242). When substratified, 90 patients presented primarily with RLS/cramping and showed only LSVP reflux, and when treated all 90 (100%) had significant or complete relief of symptoms.

Conclusion: Lateral subdermic venous plexus insufficiency demonstrates an association with symptoms of RLS and nocturnal leg cramps. LSVP treatment using USGFS demonstrated high technical and clinical success rates with symptomatic relief out to one year, most pronounced when LSVP was the only treated vein.

Free full text available https://www.jvir.org/article/S1051-0443(22)01416-6/pdf

Restless legs syndrome and cognitive function among adults: a systematic review and meta-analysis.

Wang, S., Zheng, X., Huang, J., Lin, J., Yang, T., Xiao, Y., Jiang, Q., Li, C., & Shang, H. (2022)

Journal of neurology, http://doi.org/10.1007/s00415-022-11484-2 Advance online publication. https://doi.org/10.1007/s00415-022-11484-2

Abstract

Background: Changes in the cognitive function of patients with restless legs syndrome is a grow-ing area of research. Although several studies have been performed to investigate the associa-tion between restless legs syndrome (RLS) and cognitive function, the outcomes are still contro-versial. The meta-analysis aimed to elucidate the relationship between RLS and cognition, in-cluding global cognition and various cognitive domains including memory, attention, executive function, and spatial cognition.

Methods: We searched the MEDLINE, EMBASE, and Web of Science databases from inception to November 2022 to screen eligible records. The means and standard deviations of cognitive test scores were obtained to calculate the standard mean difference and 95% confidence intervals.

Results: A total of 1437 records were collected from the initial search and 16 records involving 4635 individuals were ultimately included in the systematic review and meta-analysis. Our data suggest negative associations between RLS and global cognition (SMD, - 0.42; 95% CI - 0.72 to - 0.11; I2 = 76.6%) and attention (SMD, - 0.43; 95% CI - 0.73 to - 0.12; I2 = 85.3%). No significant differences in memory (SMD, - 0.01; 95% CI - 0.31 to 0.28; I2 = 68.0%), executive function (SMD, - 0.10; 95% CI, - 0.30 to 0.11; I2 = 52.1%), or spatial cognition (SMD, - 0.17; 95% CI - 0.38 to 0.03; I2 = 58.5%) were observed between the RLS and control groups. Moreover, the strength of the results was modified by age but not by sex or region.

Conclusions: Our findings suggest that RLS is negatively correlated with cognitive function, par-ticularly global cognition, and attention. However, the causal relationship, considering more confounders, is worthy of further exploration.

Restless legs syndrome in patients with psoriasis: association with inflammation and sleep quality

Solak, B., Aydın, B., Yüksekal, G., & Yaldız, M. (2022)

International journal of dermatology, 10.1111/ijd.16532. Advance online publication. https://doi.org/10.1111/ijd.16532

Abstract

Background: We aimed to evaluate if psoriasis associated with restless legs syndrome (RLS) due to its close relationship with metabolic disorders.

Methods: This was a cross-sectional study in which the relationship between RLS and psoriasis was evaluated. Seventy consecutive psoriasis patients and 70 controls without any skin disorder were included in this study. Data including age, gender, body weight, height, and Psoriasis Area Severity Index (PASI) scores were recorded. Diagnosis of RLS was established using International RLS Study Group (IRLSSG) diagnostic criteria. International RLS Rating Scale (IRLSRS) was used to evaluate the severity of symptoms. Each participant completed forms of the Pittsburgh Sleep Quality Index (PSQI), the Epworth Sleepiness Scale (ESS), and the Dermatology Life Quality Index (DLQI).

Results: The RLS frequency in patients with psoriasis was 18.6% vs. 5.7% in the control group (P = 0.018). In psoriasis patients, BMI, DLQI, IRLSRS, hemoglobin, ferritin, CRP, and uric acid levels were significantly higher than those of the controls. In psoriasis patients with RLS, PASI, DLQI, PSQI, IRLSRS scores, CRP level, and BMI were significantly higher, and hemoglobin level was sig-nificantly lower relative to the psoriasis patients without RLS. PASI score was the sole inde-pendent associate of RLS presence in psoriasis patients.

Conclusion: Restless legs syndrome was significantly more common in psoriasis patients, and the presence of RLS was associated with significantly more severe psoriasis, more severe systemic inflammation, lower serum hemoglobin values, worse quality of life, and sleep quality.

Cognitive strategies to improve symptoms of restless legs syndrome.

Chenini, S., Barateau, L., Guiraud, L., Rollin, M. L., Lopez, R., Jaussent, I., Beziat, S., & Dauvilliers, Y. (2022).

Journal of sleep research, e13794. Advance online publication. https://doi.org/10.1111/jsr.13794

Abstract

Symptoms of restless legs syndrome are relieved by movement. Whether a cognitive task de-creases sensory discomfort remains understudied. We aimed to assess the frequency of patients with restless legs syndrome who report decreased sensory discomfort during cognitive activities, and quantify this decrease during a cognitive task. Three-hundred and fifty-eight consecutive adults with restless legs syndrome (age 55.17 ± 14.62 years; 55.87% women; 27.65% treated) answered the question: "Does the intensity of your restless legs syndrome symptoms decrease when you perform activities other than moving your legs?" rated on a nine-point Likert scale (from fully-agree to totally-disagree). A subgroup of 65 consecutive drug-free patients underwent an 80-min suggested immobilisation test at 20:00 hours to quantify legs discomfort on a visual analogue scale before polysomnography, including 40 patients performing a cognitive task (bal-loon analogue risk task) from the 60 to 80 min.

A total of 130 (36.3%) patients reported a decrease, 158 (44.1%) no decrease, and 70 (19.5%) uncertain changes in severity of restless legs syndrome symptoms during cognitive activities, with a similar proportion whether treated or not. Patients experiencing a decrease had less severe restless legs syndrome symptoms. In the suggested immobilisation test, mixed-effect regression models showed that legs discomfort decreased in patients performing the cognitive task while it continued to increase in those without task, with a larger difference in patients reporting a self-reported decrease in restless legs syndrome during cognitive activities. In con-clusion, one-third of patients reported a self-reported decrease of restless legs syndrome symp-toms during cognitive activities, this improvement in restless legs syndrome was confirmed dur-ing a sustained cognitive task. Cognitive strategies could be implemented for the management of restless legs syndrome.

Possible etiologies of restless legs syndrome in pregnancy: a narrative review

Mendes, A., & Silva, V. (2022).

Sleep science (Sao Paulo, Brazil), 15(4), 471–479. https://doi.org/10.5935/1984-0063.20220080

Abstract

Restless legs syndrome (RLS) is a sensorimotor disorder characterized by an urgent need to move the legs, due to the presence of a discomfort sensation in the lower limbs, especially at rest. Generally, it relieves with movement. There are several studies that argue the existence of an association between this syndrome and pregnancy. However, the pathophysiological mecha-nisms of this disorder in pregnancy are misunderstood. The objective of this narrative review is to identify and discuss some possible etiologies of RLS in pregnancy. A literature search was per-formed in the PubMed and ResearchGate databases by using the following search strategies: "restless legs syndrome", "restless legs syndrome in pregnancy", "pregnancy and vitamin D defi-ciency" and "pregnancy and zinc".

The publications were initially sorted through their title. After the initial process, inclusion and exclusion criteria were applied. The included articles were sorted by authors, year, journal of publication, type of study, and organized by chronological order of publication. Among the main findings, hormonal changes, iron metabolism, vitamin D deficiency, genetic factors, zinc and magnesium fluctuations have been some of the hypotheses supporting the development or worsening of this disorder in pregnancy.

Dopamine also appears to be correlated with hormonal changes, iron metabolism, ferritin, folic acid and vitamin D deficiency. In conclusion, there are several hypotheses trying to link restless legs syndrome with pregnancy. The most covered were hormonal fluctuations and iron metabolism. However, this thematic is still highly discussed, cre-ating the need for additional and thorough research.

Free full text available https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9670777/

Possible association between vitamin B12 deficiency and restless legs syndrome

Geng, C., Yang, Z., Xu, P., & Zhang, H. (2022)

Clinical neurology and neurosurgery, 223, 107477. https://doi.org/10.1016/j.clineuro.2022.107477

Abstract

Background: Restless Legs Syndrome (RLS) can be defined as a sleep disorder. However, whether changes in the serum vitamin B12 levels are involved in the pathophysiological mechanism of RLS remains unclear. Our study aimed to determine whether vitamin B12 levels are inde-pendently related to the occurrence of RLS.

Methods: The serum vitamin B12 levels of 80 patients with RLS and 80 age- and gender-matched healthy controls (HC) were retrospectively analyzed.

Results: Serum vitamin B12 levels in the RLS group were significantly reduced, while the levels of creatinine, and homocysteine were higher (P < 0.05). In addition, multivariate logistic regres-sion revealed serum vitamin B12 to be independently associated with RLS (p < 0.05; odds ra-tio=0.97; 95 % confidence interval: 0.96-0.98). Pearson correlation analysis indicated that serum vitamin B12 level was negatively correlated with the International Restless Legs Scales (IRLS) score, and the 24-item Hamilton Depression Rating Scale (HAMD24) score (r = -0.025, P = 0.023, r = -0.295, P = 0.001).

Conclusion: Patients with RLS had significant vitamin B12 deficiency compared to HC. Such defi-ciency significantly affects severity of symptoms and depression symptoms. In addition, de-creased serum vitamin B12 levels are independently associated with the development of RLS, which illustrates the complex relationship between vitamin B12 and RLS. Prospective vitamin B12 treatment studies are needed to confirm this relationship and to evaluate the efficacy of vitamin B12 as a treatment for RLS patients.

Uncovering the mechanism of Radix Paeoniae Alba in the treatment of restless legs syndrome based on network pharmacology and molecular docking

Liu, J., Liu, S., Hao, L., Liu, F., Mu, S., & Wang, T. (2022)

Medicine, 101(46), e31791. https://doi.org/10.1097/MD.0000000000031791

Abstract

Restless legs syndrome (RLS) is a neurological motor disorder with a high prevalence. The treat-ment efficacy of RLS is unsatisfactory. Radix Paeoniae Alba (RPA) can effectively treat RLS symp-toms such as the discomfort of the legs. RPA has great potential for the development of new medications for RLS. Hence, we explored the mechanism of RPA in the treatment of RLS using network pharmacology and molecular docking. The active components and targets of RPA were obtained from the Traditional Chinese Medicine System Pharmacology database and analysis platform and PharmMapper platform. The RLS-related targets were found in GeneCards, OMIM, DrugBank, and DisGeNET databases. The overlapping targets of RPA and RLS were then collected. The "active components-overlapping targets" network was built, and network topology analysis was performed. Furthermore, Cytoscape 3.9.1 software was used to screen the key components of RPA in the treatment of RLS.

Protein-protein interaction was performed using the Search Tool for the Retrieval of Interacting Genes. The gene ontology functions and Kyoto Encyclopedia of Genes and Genomes signaling pathways were analyzed using ClusterProfiler, PathView, and other R packages to reveal the main mechanism of RPA in treating RLS. Component and protein structures were downloaded from the Traditional Chinese Medicine System Pharmacology and Protein Data Bank databases, respectively. The AutoDock 4.2.6 software was used for molecular docking. A total of 12 active components and 109 targets of RPA, as well as 2387 RLS-related targets, were collected. Follow-ing that, 47 overlapping targets were obtained. Furthermore, 5 key components and 12 core targets were screened.

The results of gene ontology functions were as follows: 2368 biological processes, 264 molecular functions, and 164 cellular components. A total of 207 Kyoto Encyclopedia of Genes and Ge-nomes signaling pathways were obtained, including the lipid and atherosclerosis pathway, the endocrine resistance pathway, the prolactin signaling pathway, and the IL-17 signaling pathway. The components and the core targets completed molecular docking stably. RPA has multi-component, multi-target, and multi-pathway characteristics in treating RLS, which could provide a basis for future research and improve clinical efficacy.

Free full text available https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9678500/

Noninvasive Vagus Nerve Stimulation: A New Therapeutic Approach for Pharmacoresistant Rest-less Legs Syndrome

Hartley, S., Bao, G., Zagdoun, M., Chevallier, S., Lofaso, F., Leotard, A., & Azabou, E. (2022)

Neuromodulation : journal of the International Neuromodulation Society, S1094-7159(22)01335-6. Advance online publication. https://doi.org/10.1016/j.neurom.2022.10.046

Abstract

Aims: This work aimed to study the effect of noninvasive vagus nerve stimulation on severe rest-less legs syndrome (RLS) resistant to pharmacotherapy.

Materials and methods: Patients with severe pharmacoresistant RLS were recruited from a ter-tiary care sleep center. Intervention was one-hour weekly sessions of transauricular vagus nerve stimulation (tVNS) in the left cymba concha, for eight weeks. The primary outcome measure was the score on the International Restless Legs Rating Scale (IRLS); secondary outcome measures were quality of life (Restless Legs Syndrome Quality of Life scale [RLSQOL]), mood disorders using the Hospital Anxiety and Depression scale subscale for depression (HADD) and Hospital Anxiety and Depression scale subscale for anxiety (HADA), and objective sleep latency, sleep duration, efficiency, and leg movement time measured by actigraphy.

Results: Fifteen patients, 53% male, aged mean 62.7 ± 12.3 years with severe RLS, reduced qual-ity of life, and symptoms of anxiety and depression, were included. The IRLS improved from baseline to session eight: IRLS 31.9 ± 2.9 vs 24.6 ± 5.9 p = 0.0003. Of these participants, 27% (4/15) had a total response with a decrease below an IRLS score of 20; 40% (6/15) a partial re-sponse with an improvement in the IRLS > 5 but an IRLS above 20; and 33% (5/15) were nonre-sponders. After tVNS, quality of life improved (RLSQOL 49.3 ± 18.1 vs 80.0 ± 19.6 p = 0.0005), as did anxiety (HADA 8.9 ± 5.4 vs 6.2 ± 5.0 p = 0.001) and depression (HADD 5.2 ± 4.5 vs 4.0 ± 4.0 p = 0.01). No significant change was found in actigraphic outcome measures.

Conclusions: In this pilot study, tVNS improved the symptoms of RLS in 66% of participants (10/15) with severe pharmacoresistant RLS, with concomitant improvements in quality of life and mood. Randomized controlled trials evaluating therapeutic efficacy of tVNS in RLS are need-ed to confirm these promising findings

Does physical activity timing differentially correlate with symptoms of restless legs syndrome in adults with multiple sclerosis?

Cederberg, K. L. J., Jeng, B., Sasaki, J. E., Schuetz, M. L., Mathison, B. G., & Motl, R. W. (2022)

Sleep medicine, 100, 120–127. https://doi.org/10.1016/j.sleep.2022.08.001

Abstract

Objective/background: The present study examined the associations among physical activity dur-ing different times of the day (i.e., morning, midday,evening) and days of the week(i.e., week-days, weekend days) with restless legs syndrome(RLS) severity and sleep quality in adults with multiple sclerosis(MS).

Patients/methods: Participants (N = 39) completed the International Restless Legs Syndrome Study Group Scale and the Pittsburgh Sleep Quality Index as measures of RLS severity and global sleep quality, respectively, and wore an ActiGraph GT3X + on the non-dominant hip for seven days for measuring physical activity (i.e., light physical activity [LPA], moderate-to-vigorous physi-cal activity [MVPA], and steps).

Results: There was a significant effect of time of day wherein participants had more midday ac-tivity compared with morning or evening for LPA, MVPA, and steps; there was no effect of day of the week. Spearman's rho correlations across the week indicated higher evening LPA, evening steps, and overall daily steps (ρ = -0.42, ρ = -0.51, ρ = -0.40, respectively) were associated with lower RLS severity. Similar associations were demonstrated for weekdays (ρ = -0.39, ρ = -0.50, ρ = -0.41, respectively) and weekend days (ρ = -0.44, ρ = -0.51, ρ = -0.39, respectively). Higher evening MVPA on weekend days (ρ = -0.42) was associated with lower RLS severity. Higher morn-ing and overall daily LPA (ρ = 0.34, ρ = 0.33, respecitvely) were associated with worse sleep quality. Similar associations were demonstrated on weekdays (ρ = 0.33, ρ = 0.37, respectively) and more evening MVPA (ρ = 0.32) was associated with worse sleep quality. On weekend days, more morning MVPA (ρ = 0.42) was associated with worse sleep quality.

Conclusions: Our results suggest that undertaking physical activity, particularly LPA and steps, in evenings may be important for managing symptoms of RLS without worsening sleep quality.

A longitudinal study of restless legs symptoms among patients with depression.

Auvinen, P., Koponen, H., Kautiainen, H., Korniloff, K., Ahonen, T., Vanhala, M., & Mäntyselkä, P. (2022).

Nordic journal of psychiatry, 76(8), 584–590. https://doi.org/10.1080/08039488.2022.2038265

Abstract

Background: The aim of this study was to analyse the relationship between depressive symptoms and clinical depression and restless legs symptoms in a longitudinal primary care setting.

Methods: The prevalence of restless legs symptoms at baseline and after a six-year follow-up was studied in 474 patients with depressive symptoms and 333 population-based control subjects without depressive symptoms. Depressive symptoms at the baseline and after the six-year fol-low-up were evaluated with the Beck Depression Inventory (BDI) Second Edition. A psychiatric diagnosis was confirmed with a diagnostic interview (M.I.N.I.). Statistical comparisons between groups were made using analysis of variance (ANOVA) for continuous variables and a chi-square test or logistic models for categorical variables. Repeated measures were analysed using general-izing estimating equations (GEE) models.

Results: At baseline the prevalence of restless legs symptoms was 24.3% in control subjects, 43.8% in the patients with depressive symptoms without a depression diagnosis, and 49.3% in clinically depressed patients. During the follow-up up the prevalence of restless legs symptoms declined significantly (p = 0.003). In addition to baseline restless legs symptoms, the prognostic factors for restless legs symptoms among patients with clinical depression were age and BDI score. In the control subjects, moderate and high leisure time physical activity was inversely associated with restless legs symptoms at the follow-up.

Conclusions: A higher level of baseline depressive symptoms was a risk factor for restless legs symptoms in patients with clinical depression. In the prevention and treatment of restless legs symptoms among the patients with depression, the priority is the effective treatment of depres-sion.

Free full text available https://www.tandfonline.com/doi/full/10.1080/08039488.2022.2038265

Effects of aromatherapy massage on the severity of restless legs syndrome in hemodialysis pa-tients: A randomized clinical trial.

Amrollahi, A., Rafiei, A., Bahri, A., & Nasiriani, K. (2022)

Therapeutic apheresis and dialysis: official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy, 26(6), 1131–1136. https://doi.org/10.1111/1744-9987.13802

Abstract

Background: Restless legs syndrome (RLS) is one of the most common problems among hemodi-alysis (HD) patients. This study determined the effect of aromatherapy massage with lavender oil on the severity of RLS in HD patients.

Methods: This randomized clinical trial was performed on 42 HD patient that were randomly assigned to intervention and control groups. Patients in the intervention group underwent 4 weeks of effleurage massage with lavender oil. The information was collected using RLS Ques-tionnaire. Data analysis were done performed using SPSS16.

Results: Based on the findings, the mean score of the severity of RLS showed a significant differ-ence between the groups after the intervention (p = 0.0001). In addition, there was a significant difference between the scores of RLS in the intervention group before and after intervention (p = 0.0001).

Conclusion: The use of lavender oil during massage therapy can serve as a complementary treatment along with other care to alleviate the symptoms of RLS.

Free full text available https://onlinelibrary.wiley.com/doi/10.1111/1744-9987.13802

Usefulness of electronic stimulation in restless legs syndrome: a pilot study.

Cho, Y. W., Lee, Y. S., Ku, J., & Kim, K. T. (2022)

The International journal of neuroscience, 132(12), 1225–1228. https://doi.org/10.1080/00207454.2021.1879065

Abstract

Purpose: This study aims to investigate the effect of electronic stimulation (ES) as a non-pharmacological treatment in restless legs syndrome (RLS).

Methods: This is a randomized, single-blind study. A total of 46 patients were included, consist-ing of an active group and a sham group with 22 and 24 members, respectively. The stimulation was administered to bilateral lower legs using the tapping mode (3 Hz) on a handheld ES device, and symptom changes were measured in both groups. The effects of the stimuli were analyzed with repeated measures ANOVA.

Results: The symptom severity was significantly reduced in the active group, and showed signifi-cant interaction effects in the time * group (F = 4.441, p = 0.031). Although both the active and sham groups reported improved symptoms upon receiving longer periods of treatment, the ef-fect of the ES was greater in the active group.

Conclusions: ES treatment resulted in symptom improvement when using ideal levels of stimula-tion intensity. ES can be considered as a non-pharmacological treatment option for RLS

Can calcitonin gene-related peptide monoclonal antibody improve migraine and restless legs syndrome?

Suzuki, S., Suzuki, K., Shiina, T., Kobayashi, S., & Hirata, K. (2022).

Journal of the neurological sciences, 443, 120462. https://doi.org/10.1016/j.jns.2022.120462

Abstract

Background: A significant association between migraine and restless legs syndrome (RLS) has been reported, and their coexistence is not uncommon. We report a patient with concomitant migraine and RLS who showed improvement of both migraine and RLS symptoms after treat-ment with galcanezumab, a calcitonin gene-related peptide (CGRP) monoclonal antibody.

Case presentation: A 47-year-old woman had been treated in our outpatient headache clinic for migraine without aura. She had RLS since childhood and had been treated with dopamine ago-nists and α2δ ligands. Over the past 2 months, the patient suffered from frequent migraine headaches and worsening RLS symptoms, despite ongoing treatment. Therefore, galcanezumab was started. After 1 month, the number of headache days decreased from 20 to 4, and her score on the International RLS Study Group Rating Scale improved from 38 to 10. Her pho-to/phono/osmo-phobia were also markedly improved. The efficacy of galcanezumab for both headache and RLS was sustained over 5 months.

Conclusion: We report a case of improvement of both migraine and RLS after treatment with CGRP monoclonal antibody. Additional studies are needed to clarify how CGRP antagonism af-fects RLS symptoms in patients with migraine and RLS comorbidity

Explainable Machine-Learning-Based Characterization of Abnormal Cortical Activities for Work-ing Memory of Restless Legs Syndrome Patients.

Kim, M., Kim, H., Seo, P., Jung, K. Y., & Kim, K. H. (2022).

Sensors (Basel, Switzerland), 22(20), 7792. https://doi.org/10.3390/s22207792

Abstract

Restless legs syndrome (RLS) is a sensorimotor disorder accompanied by a strong urge to move the legs and an unpleasant sensation in the legs and is known to accompany prefrontal dysfunc-tion. Here, we aimed to clarify the neural mechanism of working memory deficits associated with RLS using machine-learning-based analysis of single-trial neural activities. A convolutional neural network classifier was developed to discriminate the cortical activities between RLS pa-tients and normal controls. A layer-wise relevance propagation was applied to the trained classi-fier in order to determine the critical nodes in the input layer for the output decision, i.e., the time/location of cortical activities discriminating RLS patients and normal controls during work-ing memory tasks. Our method provided high classification accuracy (~94%) from single-trial event-related potentials, which are known to suffer from high inter-trial/inter-subject variation and low signal-to-noise ratio, after strict separation of training/test/validation data according to leave-one-subject-out cross-validation. The determined critical areas overlapped with the corti-cal substrates of working memory, and the neural activities in these areas were correlated with some significant clinical scores of RLS.

Free full text available https://www.mdpi.com/1424-8220/22/20/7792

Is Restless Legs Syndrome De Facto Thyroid Disease?

Suwała, S., Rzeszuto, J., Glonek, R., Krintus, M., & Junik, R. (2022)

Biomedicines, 10(10), 2502. https://doi.org/10.3390/biomedicines10102502

Abstract

While a primary role in the pathogenesis of restless legs syndrome (RLS) has been attributed to dysfunction of the dopaminergic system and impaired iron metabolism (particularly in the cen-tral nervous system), it has been hypothesized that an imbalance between thyroid hormones and dopaminergic activity may be the starting point for all aspects of RLS.

Although this hypoth-esis was proposed more than a decade ago, it has not yet been verified beyond doubt. The main aim of this study is to compare the prevalence of RLS in a population of patients with the most common thyroid gland diseases with a population of individuals with a healthy thyroid gland. The study included 237 participants divided into smaller groups according to the thyroid disease concerning them. Each participant had a laboratory diagnosis, an ultrasound scan and an assess-ment of the fulfilment of RLS criteria according to the International Restless Legs Syndrome Study Group (IRLSSG) criteria. The results obtained were subjected to statistical analysis.

RLS is significantly more common in patients with known thyroid disease; Hashimoto's disease, among others, manifests a 2.56× higher risk of a positive diagnosis for RLS than the general population. The association of RLS with thyroid disease is notable, although it is difficult to conclude une-quivocally that there is a cause-and-effect relationship between the two. Further investigation into a potentially autoimmune cause of restless legs syndrome should be considered.

Free full text available https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9599059/

Sleep disturbances and restless legs syndrome in postmenopausal women with early breast can-cer given adjuvant aromatase inhibitor therapy.

Pedersini, R., di Mauro, P., Amoroso, V., Castronovo, V., Zamparini, M., Monteverdi, S., Laini, L., Schivardi, G., Cosentini, D., Grisanti, S., Marelli, S., Ferini Strambi, L., & Berruti, A. (2022)

Breast (Edinburgh, Scotland), 66, 162–168. https://doi.org/10.1016/j.breast.2022.10.006

Abstract

Introduction: Whether adjuvant therapy with aromatase inhibitors (AIs) causes sleep disturb-ances or not in postmenopausal women with early breast cancer (EBC) is still a controversial issue.

Methods: Between March 2014 and November 2017, validated questionnaires for assessing in-somnia, anxiety, depression, quality of life (QoL) and restless legs syndrome (RLS) were adminis-tered to 160 EBC patients at baseline and after 3, 6, 12, and 24 months of AI therapy.

Results: AI therapy significantly decreased the patients' QoL, but did not influence insomnia, anxiety, or depression. However, it significantly increased the frequency and severity of RLS. Patients with RLS at baseline (19%) or who developed RLS during AI therapy (26.3%) reported statistically lower quality of sleep, higher anxiety and depression, and worse QoL compared to patients who never reported RLS (54.7%).

Conclusion: Although AI therapy does not affect sleep quality, it may increase RLS frequency. The presence of RLS could identify a group of EBC patients who may benefit from psychological support.

Free full text available https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9593725/

Restless legs syndrome in multiple sclerosis is related to retinal thinning.

Akmaz, O., Koskderelioglu, A., Eskut, N., Sahan, B., & Kusbeci, T. (2022)

Photodiagnosis and photodynamic therapy, 40, 103169. https://doi.org/10.1016/j.pdpdt.2022.103169

Abstract

Background: Restless legs syndrome (RLS) is one of the most frequent comorbidities accompany-ing multiple sclerosis. Patients with multiple sclerosis (MS) show thinning in the retinal layers throughout the disease. The thinning is related to acute attacks and progression and atrophy of the brain. Optical coherence tomography (OCT) provides relevant information on the pathophys-iology of MS. We aimed to evaluate OCT parameters in patients with MS to investigate any changes related to the coexistence of RLS.

Methods: We consecutively enrolled 75 adults with relapsing remitting MS. Participants were assessed by using demographic and clinical parameters along with the excessive sleepiness in the daytime (ESS), fatigue severity scale (FSS), and RLS severity scale (IRLSSG). The thickness of the peripapillary retinal nerve fiber layer (pRNFL), macular thickness (MT), and macular ganglion cell - inner plexiform layer (MGCIPL) complex was measured with spectral-domain OCT.

Results: Of the 75 participants, 20 were found to have RLS, and 55 did not. Scores of ESS, FSS, and MS disability (EDSS) were worse in patients with RLS. There was no significant difference in retinal nerve fiber layer thickness except for the inferior quadrant (p = 0.029). The mean inferi-or pRNFL thickness was 104.5 ± 22.6 μm in the RLS (+) group and 114.2 ± 21.6 μm in the RLS (-) group.

Conclusion: Patients with RLS had excessive daytime sleepiness, were more fatigued, had higher EDSS scores, and had a thinner retinal layer in the inferior quadrant. Overall, data from the study suggest a possible relationship between retinal volume changes in MS patients with RLS.

Peripheral Iron Metabolism is Associated with Leg Movements on Polysomnography but Not with the Severity of Restless Legs Syndrome or Its Impact on Patients.

Wang, T., Xu, J., Xu, Q., Zhao, R., Pan, L., Zhu, D., Pan, Y., Chen, L., Lou, G., Xu, X., Wang, J., & Zhang, L. (2022).

Nature and science of sleep, 14, 1829–1842. https://doi.org/10.2147/NSS.S378970

Abstract

Purpose: This study investigated the associations of peripheral iron status with different manifes-tations of restless legs syndrome (RLS), including leg movements (LMs) on polysomnography (PSG), disease severity, and impact on patients.

Patients and methods: In this cross-sectional study, 108 patients with RLS were enrolled at Sir Run Run Shaw Hospital's Center for Sleep Medicine. Demographic information, disease charac-teristics, RLS severity, and impact on patients were assessed through a semi-structured ques-tionnaire. Peripheral iron indicators [serum ferritin, iron, and transferrin concentrations; unsatu-rated iron-binding capacity (UIBC) and total iron-binding capacity (TIBC); transferrin saturation (TSAT)] were measured following PSG to assess sleep stages, respiratory events, microarousals and LM parameters. Data from patients with and without ferritin concentration < 50 µg/L were compared in crude analyses, and Spearman correlations of other iron indicators with RLS data were examined. An ordinal logistic regression model was used to adjust for age, sex, body mass index, years of education, age at the time of RLS onset, prior treatment (yes/no), C-reactive pro-tein (CRP)/hemoglobin level, total sleep time and apnea-hypopnea index.

Results: Multivariate analysis showed that periodic LMs during sleep (PLMS) and other LM pa-rameters were significantly associated with a ferritin concentration < 50 µg/L, UIBC, TIBC, and serum transferrin concentration, but not serum iron or TSAT. By contrast, the severity and im-pact of RLS were not associated with a ferritin concentration < 50 µg/L or other peripheral iron indicators in the multivariate model.

Conclusion: In this study, peripheral iron status was associated mainly with motor components (LMs on PSG) rather than sensory components (severity and impact of RLS) after adequately con-trolling for potential confounders, such as CRP and hemoglobin levels. Commonly used periph-eral iron metabolism indicators may therefore not be ideal biomarkers of RLS severity or impact on patients.

Free full text available https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9575586/

Evaluation of Serum Selenium Level, Quality of Sleep, and Life in Pregnant Women With Rest-less Legs Syndrome.

Laleli Koc, B., Elmas, B., Tugrul Ersak, D., Erol, S. A., Kara, O., & Sahin, D. (2022).

Biological trace element research, https://doi.org/10.1007/s12011-022-03447-5 Advance online publication. https://doi.org/10.1007/s12011-022-03447-5

Abstract

Restless legs syndrome (RLS) is a multifactorial disease that patients describe as restlessness in their legs, which creates a desire to move their legs, especially in the evening and at rest. This study aims to investigate serum selenium levels in RLS and document the quality of sleep and life in pregnant women with RLS according to International Restless Legs Syndrome Study Group (IRLSSG) diagnostic criteria.

Thirty-eight moderate to severe RLS patients with pregnancy at 38-41 weeks of gestation were determined as the case group, and 38 women with healthy gesta-tional age-matched pregnancies were determined as the control group. Maternal serum seleni-um levels were compared between the RLS case group and the group of healthy pregnant wom-en at the time of hospitalization for delivery.

The Pittsburgh Sleep Quality Index (PSQI) and The Quality of Life Scale (SF-36) were applied to the patients. The mean selenium level (µg/L) was statistically significantly lower in the RLS group (53.24 ± 10.28), compared to the healthy preg-nant population (58.95 ± 11.29) (P = 0.024). The PSQI score was significantly higher in the RLS case group (P = 0.033). Especially sleep efficiency (P = 0.018) and daytime dysfunction (P = 0.032) sub-parameters were affected. The SF-36 questionnaire was examined and a significant difference was detected between the two groups in role emotional (P = 0.026), social function-ing (P = 0.023), and body pain (P = 0.044) sub-parameters. Serum selenium level was significant-ly lower, the sleep quality of the RLS group was impaired and their quality of life was affected in pregnant women with RLS.

Further studies are needed to determine whether selenium re-placement in pregnant women with RLS is feasible or not.

Correlation between vitamin D and poor sleep status in restless legs syndrome.

Geng, C., Yang, Z., Kong, X., Xu, P., & Zhang, H. (2022)

Frontiers in endocrinology, 13, 994545. https://doi.org/10.3389/fendo.2022.994545

Abstract

Background: Restless Legs Syndrome (RLS) is closely related to poorer sleep quality. Vitamin D can regulate sleep regulation, cell proliferation, and differentiation. To measure whether vita-min D has predictive value for poor sleep quality in RLS was our aim in this study.

Methods: To analyze the serum levels of 25-hydroxyvitamin D [25(OH)D] in 95 RLS patients. We used the Pittsburgh Sleep Quality Index (PSQI) to measure sleep quality. Subjects had been di-vided into a normal and poor-sleeper groups according to the PSQI score. Using correlation and regression analysis to explore underlying etiologies that affect sleep disorder in RLS patients.

Results: Patients in the poor-sleeper group had significantly lower vitamin D levels in compari-son to the normal group. The serum vitamin D levels were negative correlate with PSQI scores after adjusting for confounding factors. In addition, regression analysis showed that vitamin D could act as a predictor for sleep disorders in RLS patients (odds ratio [OR] = 0.008, p = 0.004). The area under the curve (AUC), cut-off value, sensitivity, and specificity of serum vitamin D was 0.967 (95% CI 0.935-0.998), 16.84 ng/ml, 87.5%, and 93.7% by receiver operating characteristic (ROC) analysis.

Conclusion: Our study confirmed the relationship between poorer sleep quality and vitamin D in RLS. However, the causal relationship between vitamin D deficiency and RLS is currently incon-clusive. The effect of vitamin D supplementation is needed to confirm as the therapeutic strate-gies for sleep disorders in RLS patients in future work.

Free full text available https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9519848/

Restless legs syndrome due to brainstem stroke: A systematic review

Kalampokini, S., Poyiadjis, S., Vavougios, G. D., Artemiadis, A., Zis, P., Hadjigeorgiou, G. M., & Bargiotas, P. (2022)

Acta neurologica Scandinavica, 146(5), 440–447. https://doi.org/10.1111/ane.13702

Abstract

Restless Legs Syndrome (RLS) is a sleep-related movement disorder, which can also result from brainstem pathology. A systematic review of articles published in the electronic databases Pub-Med and Web of Science was conducted to summarize the existent literature on RLS associated with a brainstem stroke. We identified eight articles including 19 subjects with RLS due to brainstem ischemic lesion. The symptoms occurred simultaneously with the infarction (66.7%) or few days after (33.3%). The most common location of infarction was pons and less commonly medulla. In most cases (68.4%), symptoms were unilateral. In the majority of those cases (92.3%), the contralateral limb was affected due to a lateral pons infarction. RLS symptoms after infarction improved or resolved in almost 90% of cases within a few days up to 3 months. In almost all patients who received dopaminergic treatment (11 out of 13, 91.7%), the symptoms improved significantly or resolved completely. Screening for RLS has to be considered in pa-tients suffering a brainstem stroke, particularly anteromedial pontine infarction. The appearance of acute unilateral RLS symptoms, usually in association with other sensorimotor deficits, should prompt the clinician to consider a vascular event in the brainstem. RLS in these cases seem to have a favorable outcome and respond well to dopaminergic treatment.

Free full text available https://onlinelibrary.wiley.com/doi/10.1111/ane.13702

Polysomnographic features of idiopathic restless legs syndrome: a systematic review and meta-analysis of 13 sleep parameters and 23 leg movement parameters.

Zhang, H., Zhang, Y., Ren, R., Yang, L., Shi, Y., Vitiello, M. V., Sanford, L. D., & Tang, X. (2022)

Journal of clinical sleep medicine: JCSM : official publication of the American Academy of Sleep Medicine, 18(11), 2561–2575. https://doi.org/10.5664/jcsm.10160

Abstract

Study objectives: This study aims to explore the polysomnographically measured sleep and leg movement differences between idiopathic restless legs syndrome (RLS) patients and healthy controls.

Methods: An electronic literature search was conducted in EMBASE, MEDLINE, all EBM databases, CINAHL, and PsycINFO. Only observational case-control studies were included in the meta-analysis. The differences in 13 sleep parameters and 23 leg movement parameters between RLS patients and healthy controls were explored.

Results: Thirty-eight studies were identified for systematic review, 31 of which were used for meta-analysis. Meta-analyses revealed significant reductions in total sleep time, sleep efficiency, stage N2 and rapid eye movement (REM) sleep percentages, and increases in wake time after sleep onset, stage shifts per hour, stage N1 percentage, REM latency, arousal index, and apnea-hypopnea index. Some leg movement parameters, such as periodic limb movement during sleep (PLMS) index, PLMS sequence duration, number of PLMS sequence, and periodicity index, were higher in RLS patients compared with healthy controls. Further, our meta-analysis revealed a higher PLMS index during non-REM sleep compared with that during REM sleep.

Conclusions: RLS patients manifest a lightening of sleep, increased sleep fragmentation, and greater sleep-related breathing disruption and limb movements during sleep relative to healthy normal individuals. The distributions of PLMS during a night's sleep may provide more infor-mation to clarify the specific characteristics of leg movements in RLS. PLMS in RLS are concen-trated in non-REM sleep. The periodicity index may be a more sensitive and specific marker of RLS than the PLMS index.

Pharmacologic and Nonpharmacologic Treatment of Restless Legs Syndrome

Anguelova, G. V., Vlak, M., Kurvers, A., & Rijsman, R. M. (2022).

Sleep medicine clinics, 17(3), 407–419. https://doi.org/10.1016/j.jsmc.2022.06

Abstract

Restless legs syndrome (RLS) is a sleep-related disorder defined by an urgency to move the legs, usually combined with uncomfortable or unpleasant sensations, which occurs or worsens during rest, usually in the evening or at night, and disappears with the movement of the legs. RLS can be classified as idiopathic or primary, and secondary to comorbid conditions (eg, renal disease, polyneuropathy). The pathophysiology of RLS is still unclear. This article provides an updated practical guide for the treatment of primary RLS in adults.

Restless Legs Syndrome and the Use of Antipsychotic Medication: An Updated Literature Review.

Saber, W. K., Almuallim, A. R., & Algahtani, R. (2022).

Cureus, 14(8), e27821. https://doi.org/10.7759/cureus.27821

Abstract

Restless legs syndrome or Willis-Ekbom disease (RLS/WED) is a sleep-related movement disorder characterized by an urge to move the legs. This impulse is usually accompanied by an uncomfortable and unpleasant sensation in the legs, which worsens at night and during periods of inactivity and is relieved by movement. Several studies in the literature reported the association between RLS and different antipsychotic medications. with Olanzapine, Quetiapine, and Clozapine identified as the most common causes. The literature suggests that the development of RLS in antipsychotic users may be attributed to the inhibition of dopaminergic neurotransmission or the impact of antipsychotics on iron metabolism. Diagnosing antipsychotic-induced RLS remains a substantial challenge in clinical practice, with challenges in the management of this condition also being widely reported in the current literature. In this article, we will review the evidence suggesting the association between RLS and the use of antipsychotic medications, differentiate between RLS and other movement disorders, and give a brief review of the pathophysiology, diagnosis, and management of RLS and its challenges among psychotic patients.

Free full text available: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9481228/

Clonazepam for the management of sleep disorders.

Raggi, A., Mogavero, M. P., DelRosso, L. M., & Ferri, R. (2022)

Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology, 10.1007/s10072-022-06397-x. Advance online publication. https://doi.org/10.1007/s10072-022-06397-x

Abstract

Background: The objectives of this review and meta-analysis of polysomnographic data are those to focus on the clinical use of clonazepam for the management of sleep disorders by re-analyzing clinical trials and randomized clinical trials which have been published in peer-reviewed journals.

Methods: A review of the literature including clinical trials and randomized controlled trials was performed in PubMed®, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement protocol. A random effects model meta-analysis was then carried out for the four more frequently reported polysomnographic measures: total sleep time, sleep latency, sleep efficiency, and periodic leg movement during sleep (PLMS) index.

Results: A total of 33 articles were retrieved and screened in full text, of which 18 met the criteria for review; among the latter, nine met the criteria for meta-analysis. The studies included in the review involved patients with insomnia, REM sleep behavior disorder, sleep bruxism, and restless leg syndrome or PLMS which reported, most often, an increase in total sleep time with clonazepam. A clear sleep-promoting effect of clonazepam was found also by meta-analysis.

Discussion and conclusions: Our results indicate that the pharmacological treatment of sleep disorders with clonazepam must always be personalized according to the type of patient, the risk of addiction and the concomitant presence of respiratory disorders are key factors to take into account. However, in light of the clinical evidence of the few studies in the literature on the different types of disorders, more studies on the use of clonazepam (also in association with first choice treatments) are definitely needed.

Polysomnographic nighttime features of Restless Legs Syndrome: A systematic review and meta-analysis

Geng, C., Yang, Z., Zhang, T., Xu, P., & Zhang, H. (2022)

Frontiers in neurology, 13, 961136. https://doi.org/10.3389/fneur.2022.961136

Abstract

Background: Restless Legs Syndrome (RLS) is a common sleep disorder. Polysomnographic (PSG) studies have been used to explore the night sleep characteristics of RLS, but their relationship with RLS has not been fully analyzed and researched.

Methods: We searched the Cochrane Library electronic literature, PubMed, and EMBASE databases to identify research literature comparing the differences in polysomnography between patients with RLS and healthy controls (HCs).

Results: This review identified 26 studies for meta-analysis. Our research found that the rapid eye movement sleep (REM)%, sleep efficiency (SE)%, total sleep time (TST) min, and N2 were significantly decreased in patients with RLS compared with HCs, while sleep latency (SL) min, stage shifts (SS), awakenings number (AWN), wake time after sleep onset (WASO) min, N1%, rapid eye movement sleep latency (REML), and arousal index (AI) were significantly increased. Additionally, there was no significant difference among N3%, slow wave sleep (SWS)%, and apnea-hypopnea index (AHI).

Conclusion: Our findings demonstrated that architecture and sleep continuity had been disturbed in patients with RLS, which further illustrates the changes in sleep structure in patients with RLS. In addition, further attention to the underlying pathophysiological mechanisms of RLS and its association with neurodegenerative diseases is needed in future studies.

Free full text available: https://www.frontiersin.org/articles/10.3389/fneur.2022.961136/full

Pharmacological and non-pharmacological treatments for restless legs syndrome in end-stage kidney disease: a systematic review and component network meta-analysis.

Chen, J. J., Lee, T. H., Tu, Y. K., Kuo, G., Yang, H. Y., Yen, C. L., Fan, P. C., & Chang, C. H. (2022).

Nephrology, dialysis, transplantation: official publication of the European Dialysis and Transplant Association - European Renal Association, 37(10), 1982–1992. https://doi.org/10.1093/ndt/gfab290

Abstract

Background: Restless legs syndrome (RLS) is common among patients with end-stage kidney disease (ESKD) and is associated with poor outcomes. Several recently published studies had focused on pharmacological and non-pharmacological treatments of RLS, but an updated meta-analysis has not been conducted.

Methods: The study population was adult ESKD patients on dialysis with RLS. Randomized controlled trials (RCTs) were selected. The primary outcome was reduction in RLS severity. The secondary outcomes were improvement in sleep quality and treatment-related adverse events. Frequentist standard network meta-analysis (NMA) and additive component NMA were performed. The evidence certainty was assessed using the Confidence in NMA (CINeMA) framework.

Results: A total of 24 RCTs with 1252 participants were enrolled and 14 interventions were compared. Cool dialysate produced the largest RLS severity score reduction {mean difference [MD] 16.82 [95% confidence interval (CI) 10.635-23.02]} and a high level of confidence. Other potential non-pharmacological interventions include intradialytic stretching exercise [MD 12.00 (95% CI 7.04-16.97)] and aromatherapy massage [MD 10.91 (95% CI 6.96-14.85)], but all with limited confidence of evidence. Among the pharmacological interventions, gabapentin was the most effective [MD 8.95 (95% CI 1.95-15.85)], which also improved sleep quality [standardized MD 2.00 (95% CI 0.47-3.53)]. No statically significant adverse events were detected.

Conclusions: The NMA supports that cool dialysate is appropriate to treat patients with ESKD and RLS. Gabapentin is the most effective pharmacological intervention and also might improve sleep quality. Further parallel RCTs with sufficient sample sizes are required to evaluate these potential interventions and long-term effects.

Free full text available: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9494057/

Restless legs syndrome severity associated with reduced physical function in adults with multiple sclerosis

Cederberg, K., Schuetz, M. L., Mathison, B., & Motl, R. W. (2022).

Gait & posture, 97, 56–61. https://doi.org/10.1016/j.gaitpost.2022.06.012

Abstract

Background: Restless legs syndrome (RLS) is a sleep disorder that occurs in approximately 26 % of adults with multiple sclerosis (MS) and may be associated with reduced physical function.

Research question: The present study examined the relationship between RLS symptomology (i.e., overall severity, frequency, and occurrence) and physical function outcomes in adults with MS who had RLS.

Methods: Participants (N = 22) with MS who had RLS came into the laboratory for a single session wherein a rater performed a brief neurological examination for scoring the Expanded Disability Status Scale (EDSS) and completed a demographics questionnaire, the International Restless Legs Syndrome Study Group Scale (IRLS), and the Restless Legs Syndrome Scale-6 (RLS-6) followed by the Short Physical Performance Battery (SPPB) and the Six-minute Walk Test (6 MW).

Results: Bivariate Spearman's rho correlation analyses indicated total IRLS had a strong, negative association with total distance traveled during the 6 MW (ρ = -0.50) and a moderate association with SPPB scores (ρ = -0.43), but not EDSS scores (ρ = 0.28). RLS severity during the day while active had strong, negative associations with total distance traveled during the 6 MW (ρ = -0.61) and SPPB scores (ρ = -0.52), but not EDSS scores (ρ = 0.13).

Significance: We observed associations between worse overall RLS severity and RLS severity during the day while active with reduced performance during the 6 MW and lower SPPB scores. The management of RLS may offer an opportunity for mitigating reductions in physical function in adults with MS who have RLS.

Restless Legs Syndrome Severity and Cognitive Function in Adults With Multiple Sclerosis: An Exploratory Pilot Study.

Cederberg, K., Mathison, B., Schuetz, M. L., & Motl, R. W. (2022).

International journal of MS care, 24(4), 154–161. https://doi.org/10.7224/1537-2073.2020-120

Abstract

Background: Restless legs syndrome (RLS) is a sleep disorder present in as many as 26% of persons with multiple sclerosis (MS) and can be associated with cognitive function. The present study examined the relationships between RLS symptoms (severity, frequency, occurrence) and cognitive function in adults with MS who have RLS.

Methods: Twenty-two participants attended 1 laboratory session and completed the International Restless Legs Syndrome Study Group Rating Scale (IRLS), the Restless Legs Syndrome-6 Scale, and then the Brief International Cognitive Assessment for Multiple Sclerosis battery consisting of the Symbol Digit Modalities Test; California Verbal Learning Test, Second Edition; and Brief Visuospatial Memory Test-Revised.

Results: Nonparametric bivariate correlations indicated that worse IRLS total severity was associated with slower processing speed (ρ = -0.42), worse verbal memory (ρ = -0.63), and worse visual memory (ρ = -0.61); worse RLS severity at falling asleep was associated with worse verbal memory (ρ = -0.45) and worse visual memory (ρ = -0.55); and worse RLS severity during the day while active was associated with slower processing speed (ρ = -0.58), worse verbal memory (ρ = -0.52), and worse visual memory (ρ = -0.60).

Conclusions: These results suggest that those with more severe RLS, including worse symptoms at falling asleep and during the day while active, might experience worse cognitive function, particularly processing speed and memory. Future research should evaluate whether treatment of RLS symptoms can offer new opportunities for managing cognitive dysfunction in adults with MS.

Free full text available: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9296052/

Association between clinical outcomes and restless legs syndrome in Japanese patients with ulcerative colitis.

Kitakata, S., Furukawa, S., Miyake, T., Shiraishi, K., Tange, K., Hashimoto, Y., Yagi, S., Ninomiya, T., Suzuki, S., Shibata, N., Murakami, H., Ohashi, K., Tomida, H., Yamamoto, Y., Takeshita, E., Ikeda, Y., & Hiasa, Y. (2022).

Journal of sleep research, e13691. Advance online publication. https://doi.org/10.1111/jsr.13691

Abstract

Restless legs syndrome (RLS) is a common sleep disorder in the Western population. The prevalence of restless legs syndrome in the Japanese population is 4.6%. Inflammatory and/or immune alteration might be associated with the development of restless legs syndrome. Ulcerative colitis is a chronic inflammatory bowel disease. Evidence regarding the association between ulcerative colitis and the prevalence of restless legs syndrome is limited. Herein, we investigated the association between clinical outcomes and the prevalence of restless legs syndrome in Japanese patients with ulcerative colitis. This was a cross-sectional study using baseline data from a prospective cohort study. Subjects in this study were 273 patients with ulcerative colitis. The definition of restless legs syndrome was achieved using a self-administered questionnaire based on the diagnostic criteria for restless legs syndrome in an epidemiological study approved by the Executive Committee of the International Restless Leg Syndrome Study Group in 2002.

Clinical outcomes were clinical remission and mucosal healing. The association between clinical remission and mucosal healing and the prevalence of restless legs syndrome was assessed by multivariate logistic regression analyses. The percentage of clinical remission and mucosal healing was 58.4% and 63.1%, respectively. The prevalence of restless legs syndrome in this cohort was 4.7%. Clinical remission (adjusted odds ratio 0.23, 95% confidence interval 0.05-0.93) and mucosal healing (adjusted odds ratio 0.23, 95% confidence interval 0.05-0.90) were independently inversely associated with restless legs syndrome. No association between serum haemoglobin and restless legs syndrome was found.

In conclusion, clinical remission and mucosal healing were independently and inversely associated with the prevalence of restless legs syndrome in Japanese patients with ulcerative colitis.

Prevalence of insomnia and restless legs syndrome in patients with upper airway stimulation therapy and effects on treatment outcomes.

Jomha, M., Dabboussi, T., Parker, N. P., Manchanda, S., Chernyak, Y., & Stahl, S. M. (2022)

Sleep medicine, 98, 121–126. https://doi.org/10.1016/j.sleep.2022.06.016

Abstract

Objective: This study aims to explore the prevalence of insomnia and restless legs syndrome (RLS) and the possible effects of these conditions on treatment adherence and outcomes in patients with upper airway stimulation (UAS) therapy for the treatment of obstructive sleep apnea.

Methods: Consecutive patients who underwent UAS system implantation were retrospectively studied. Patients without insomnia or RLS, insomnia, RLS, and both insomnia and RLS were compared. The apnea-hypopnea index (AHI), in-lab UAS titration data, Epworth Sleepiness Scale (ESS), and adherence to UAS therapy were compared.

Results: Sixty-four patients who had UAS implantation and completed post-implant in-lab UAS titration were identified. Insomnia was present in 47%, RLS in 28%, and both insomnia and RLS in 14%. During in-lab titration, the AHI improved for all groups and did not differ across groups. The arousal index on in-lab titration was higher in patients with both RLS and insomnia compared to those without these conditions. At the time of the in-lab titration, the hours of UAS therapy usage were reduced for patients with RLS (4.7 ± 1.9 h/night, p = 0.027) compared to those without RLS (6.0 ± 2.0 h/night). The ESS was higher in patients with RLS compared to those without RLS at in-lab titration.

Conclusion: Insomnia and RLS are common in patients using UAS therapy. A decrease in UAS usage and higher ESS were present in patients with RLS. Further research evaluating the long-term effects of insomnia and RLS in UAS therapy usage and benefit is needed.

Restless legs syndrome: prevention with Pycnogenol® and improvement of the venoarteriolar response.

Belcaro, G., Rohdewald, P., Cesarone, M. R., Scipione, C., Scipione, V., Cornelli, U., Luzzi, R., Cotellese, R., Dugall, M., Hosoi, M., Corsi, M., & Feragalli, B. (2022).

Panminerva medica, 64(2), 253–258. https://doi.org/10.23736/S0031-0808.20.04046-X

Abstract

Background: The aim of this registry study was to evaluate the preventive efficacy of Pycnogenol® (French maritime pine bark, standardized extract), an anti-inflammatory and antioxidant supplement, previously used for muscular pain and cramps, in otherwise healthy subjects with restless legs syndrome (RLS).

Methods: Two management groups were formed: one using the standard management (SM) and one using SM and Pycnogenol® 150 mg/day for 4 weeks.

Results: Forty-five subjects were included in the study, 21 took Pycnogenol® and 24 were in the SM group. After 4 weeks no side effects or tolerability problems were observed. Compliance was optimal. The two groups were comparable at baseline. Limb sensations were assessed with a Visual Analogue Scale Line (0 to 4). There was a statistically non-significant improvement with SM in all subjects. Improvement with Pycnogenol® supplementation was significant (P<0.05) for all assessed parameters with important clinical meanings as 19 out of 21 supplemented subjects reported a clear benefit from supplementation. Resting flux - slightly elevated at inclusion - was normalized in the supplemented group (P<0.05) as seen by a decrease in flux. The venoarteriolar response - affected at inclusion in all subjects with RLS - was improved with the supplement, indicating a better axon-axon reflex response and a lower level of subclinical neural alteration. The need for pain managements was significantly reduced (P<0.05) with supplementation after 4 weeks, as only 4/21 supplemented subjects vs. 16/24 in the SM-only group had to use analgesics. Thermography of the leg did not reveal any significant asymmetry of perfusion. Oxidative stress as plasma free radicals (PFR) was significantly improved (reduced) (P<0.05) in subjects using Pycnogenol®. Likewise, minimal edema, measured with the edema tester, was significantly decreased with Pycnogenol®.

Conclusions: Pycnogenol® prevents or relieves symptoms associated with restless leg syndrome and positively affects the venoarteriolar response. Future studies in this condition, including more complex subjects may indicate the role of Pycnogenol® in this common and still obscure syndrome and in subclinical muscular and neurological alterations.

Restless legs syndrome: Over 50 years of European contribution

Khachatryan, S. G., Ferri, R., Fulda, S., Garcia-Borreguero, D., Manconi, M., Muntean, M. L., & Stefani, A. (2022)

Journal of sleep research, 31(4), e13632. https://doi.org/10.1111/jsr.13632

Abstract

Restless legs syndrome (RLS) is a sensorimotor neurological disorder characterised by an urge to move the limbs with a circadian pattern (occurring in the evening/at night), more prominent at rest, and relieved with movements. RLS is one of the most prevalent sleep disorders, occurring in 5%-10% of the European population. Thomas Willis first described RLS clinical cases already in the 17th century, and Karl-Axel Ekbom described the disease as a modern clinical entity in the 20th century. Despite variable severity, RLS can markedly affect sleep (partly through the presence of periodic leg movements) and quality of life, with a relevant socio-economic impact. Thus, its recognition and treatment are essential. However, screening methods present limitations and should be improved. Moreover, available RLS treatment options albeit providing sustained relief to many patients are limited in number. Additionally, the development of augmentation with dopamine agonists represents a major treatment problem. A better understanding of RLS pathomechanisms can bring to light novel treatment possibilities. With emerging new avenues of research in pharmacology, imaging, genetics, and animal models of RLS, this is an interesting and constantly growing field of research. This review will update the reader on the current state of RLS clinical practice and research, with a special focus on the contribution of European researchers.

Free full text available: https://onlinelibrary.wiley.com/doi/10.1111/jsr.13632

Relationship of restless legs syndrome with number of pregnancies, duration of pregnancy and positive family history.

Jurjević, L. Č., & Telarović, S. (2022)

Women's health (London, England), 18, 17455057221109371. https://doi.org/10.1177/17455057221109371

Abstract

Objectives: The aim of this cross-sectional study was to examine the correlation between gestational age and number of previous pregnancies in group of pregnant women with restless legs syndrome and the connection of restless legs syndrome with family history positive versus family history negative group of pregnant and non-pregnant women.

Methods: Four hundred and sixty-two women were involved in this study: 231 pregnant women and the same number of non-pregnant women of compatible age as a control group. We defined restless legs syndrome as presence of International Restless Legs Syndrome Study Group criteria. During the face-to-face interview with the researcher, respondents answered questions about duration of pregnancy, number of previous pregnancies and family history of restless legs syndrome.

Results: Before the 16th week of pregnancy, restless legs syndrome appeared in 7.1% of pregnant women and after 16 weeks of pregnancy in 22.6% of them (t = 2.07, p = 0.039). Restless legs syndrome appeared in 11.4% of pregnant women without restless legs syndrome in the family and in 74.2% of pregnant women who did have restless legs syndrome in the family (t = 7.67, p < 0.001). It was also found that among non-pregnant women with a family history of restless legs syndrome, 42.9% had restless legs syndrome, and among those without a family history of restless legs syndrome, only 4.9% had restless legs syndrome (t = 3.49, p = 0.001). No statistically significant correlation between restless legs syndrome and number of previous pregnancies in pregnant women has been found.

Conclusion: Our study confirmed a higher frequency of restless legs syndrome in women pregnant for 17 or more weeks and in both pregnant and non-pregnant women with a positive family history of this syndrome. We have not proven a connection between restless legs syndrome and multiparity.

Free full text available: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9272156/

Striatal mechanism of the restless legs syndrome

Lai, Y. Y., Hsieh, K. C., Chew, K. T., Nguyen, D., & Siegel, J. M. (2022)

Sleep, 45(7), zsac110. https://doi.org/10.1093/sleep/zsac110

Abstract

Study objectives: Brain iron deficiency has been reported to be associated with the restless legs syndrome (RLS). However, 30%-50% of RLS patients do not respond to iron therapy, indicating that mechanisms other than brain iron deficiency may also participate in this disease. The striatum is known to be involved in the modulation of motor activity. We speculated that dysfunction of the striatum may induce RLS.

Methods: Two groups, wild-type (WT) and iron-deficient (ID) rats were used. Each group was divided into two subgroups, control and N-methyl-d-aspartate striatal-lesioned. After baseline recording, striatal-lesioned wild-type (WT-STL) and striatal-lesioned iron-deficient (ID-STL) rats were given pramipexole and thioperamide injections. Iron-deficient and ID-STL rats were then given a standard rodent diet for 4 weeks, and their sleep and motor activity were recorded.

Results: WT-STL rats showed periodic leg movements (PLM) in wake, an increase in PLM in slow wave sleep (SWS), a decrease in rapid-eye-movement sleep, and a decrease in the daily average duration of episodes in SWS. The sleep-wake pattern and motor activity did not differ between ID and ID-STL rats. Thioperamide or pramipexole injection decreased PLM in sleep and in wake in WT-STL rats and ID-STL rats. Unlike ID rats, whose motor hyperactivity can be reversed by iron replacement, PLM in wake and in sleep in ID-STL rats were not fully corrected by iron treatment.

Conclusions: Lesions of the striatum generate RLS-like activity in rats. Dysfunction of the striatum may be responsible for failure to respond to iron treatment in some human RLS patients.

How effective are treatment guidelines for augmented RLS?

Yeung Laiwah, J., & Winkelman, J. W. (2022)

Sleep, 45(7), zsac108. https://doi.org/10.1093/sleep/zsac108

Abstract

Study objectives: The objective of this study was to assess the effectiveness of current treatment guidelines for restless legs syndrome (RLS) augmentation in patients on dopamine agonists (DAs) which recommend a cross-titration strategy to an alpha-2-delta ligand (A2D) and/or opioid.

Methods: Consecutive new consultations for RLS with both augmentation and active treatment with DAs at the time of initial assessment were included if followed >5 months. Clinical information from the semi-structured initial consultation, and subsequent visits until their most recent/final visit was extracted. Clinical Global Impression-Severity (CGI-S) and Clinical Global Impression-Improvement (CGI-I) scores were retrospectively determined by two independent evaluators.

Results: In the 63 patients with augmented RLS on DAs, followed for 5-59 months (mean = 28, SD = 14), the average age was 67.6 (SD = 9.8) and 63% were female. Mean duration of prior dopaminergic therapy was 11.6 years (SD = 6.7) and average pramipexole equivalent dose was 1.23 mg (SD = 1.22 mg). At baseline, RLS was "moderate-markedly" severe (CGI-S = 4.9). At the final/most recent visit, 78% (49/63) were classified as Responders (CGI-I ≤ 2, "Much" or "Very Much Improved") with an average CGI-S of 2.4 ("borderline-mildly ill"). Responders (59%) were more likely to have discontinued DAs than Non-Responders (40%), and mean opioid doses were higher in Responders (39 vs 20 MME). No differences in baseline DA dose, final A2D dose, or iron therapy were observed between groups. Responders did have significantly more severe RLS, more sleep maintenance insomnia, and greater subjective daytime sleepiness at baseline (p < 0.05).

Conclusions: Guideline-based management is effective in most patients with augmented RLS.

Restless Leg Syndrome in Hemodialysis Patients: A Narrative Review.

Matar, S. G., El-Nahas, Z. S., Aladwan, H., Hasanin, M., Elsayed, S. M., Nourelden, A. Z., Benmelouka, A. Y., & Ragab, K. M. (2022).

The neurologist, 27(4), 194–202. https://doi.org/10.1097/NRL.0000000000000436

Abstract

Background: Restless legs syndrome (RLS) is a clinical entity characterized by sensory-motor manifestations commonly observed in end-stage renal illness. Evidence suggests that RLS is a multifactorial phenomenon that can be influenced by many critical factors, including genetic predisposition, dietary patterns, and deficiency in some vitamins. Iron metabolism disorders and metabolic derangements have been generally accepted as predisposing elements in RLS. Furthermore, both pharmacological and neuroimaging studies demonstrated dopamine deficiency and dopamine receptors decrease in basal ganglia during RLS.

Review summary: A literature search was done in three databases (PubMed, Google Scholar, and Cochrane) to identify the pertinent articles discussing the epidemiology, pathogenesis, and management of RLS in hemodialysis patients. RLS can affect the morbidity and mortality of patients treated with dialysis. It also has significant impacts on the quality of life since it can lead to insomnia, increased fatigue, mental health troubles, and other movement problems. Appropriate measures should be considered in this particular population so to prevent and treat RLS. Many drugs and other nonpharmacological methods have been investigated to attenuate the disease's severity. No treatment, however, could offer long-term effects.

Conclusion: Further efforts are still required to improve the understanding of RLS pathogenic trends to find more specific and efficient therapies. A wide range of treatment options is available. However, it can be individualized according to the patients' several factors.

F wave in restless legs syndrome, as an electrophysiological response of clinical relief.

Kenar, S. G., Dirik, E. B., Tutal Gursoy, G., Kayali, N., & Bilen, S. (2022).

Neurological research, 44(8), 719–725. https://doi.org/10.1080/01616412.2022.2042123

Abstract

Objective: The study aimed to evaluate the impact of postural changes on the F wave-related parameters and whether those changes were associated with clinical relaxation, which was achieved in restless legs syndrome patients with standing up.

Methods: F wave duration (FWD), compound muscle action potential duration (CMAPD), and FWD/CMAPD ratio were evaluated in supine and upward positions in 18 restless legs syndrome patients and compared with 18 age and gender-matched healthy volunteers.

Results: FWD/CMAPD was significantly higher for the tibial nerve at supine position (p = 0.043) but not at upright position (p = 0.206) and for ulnar nerve, both at supine (p = 0.007) and upright positions (p = 0.023) in RLS patients compared to controls. Ulnar FWD decreased significantly at the upright position in both control and RLS patients (p = 0.035, p = 0.028, respectively). CMAPD decreased only in the control group with standing up for both ulnar and tibial nerves (p = 0.048, p = 0.017, respectively).

Discussion: Ulnar and tibial FWD/CMAPD ratios increased in RLS patients compared to controls. However, FWD/CMAPD was not affected by the posture within the groups. Postural change seems to be a factor that decreased ulnar FWD both in RLS patients and the control group. Ulnar and tibial CMAPD reduced only in healthy controls with an upright position. Tibial and ulnar FWD/CMAPD ratios are favorable electrophysiological parameters diagnosing RLS. The tibial FWD/CMAPD ratio loses its significance only when the patient stands up, reflecting the clinical relief achieved with the postural change.

A network meta-analysis of the effectiveness and safety of drugs for restless legs syndrome in dialysis patients.

Tang, M., Ge, J., Sun, K. X., Cui, B., Guan, Y., & Wang, J. W. (2022).

Seminars in dialysis, 35(4), 293–306. https://doi.org/10.1111/sdi.13021

Abstract

Objective: To evaluate the efficacy and safety of nine pharmacological interventions for restless legs syndrome (RLS) in dialysis patients.

Methods: An electronic database was used to retrieve eligible trials from PubMed, Cochrane, Embase, and Web of Science. Stata 14.2 software was used to perform network meta-analysis. The primary measure was the RLS score, and the secondary measure was used to evaluate the side effects of the drug. The surface under the cumulative ranking curve method was used to rank the merits of intervention measures. A comparison of the two interventions is shown on a league table.

Results: Finally, nine randomized controlled trials (RCTs) with a total of 377 participants were included. From the results of the network meta-analysis, all treatments ranked higher than placebo in terms of improving clinical symptoms, but only vitamin C (standardized mean difference [SMD] = -1.47 95% confidence interval [CI] -2.89, -0.05) showed significant differences compared with placebo. In terms of safety, there were no serious adverse reactions to any of the treatments compared to placebo.

Conclusion: Currently, existing evidence suggests that vitamin C may be the most ideal drug to improve the symptoms of RLS in dialysis patients.

Restless sleep disorder, restless legs syndrome, and periodic limb movement disorder-Sleep in motion

DelRosso, L. M., Mogavero, M. P., & Ferri, R. (2022).

Pediatric pulmonology, 57(8), 1879–1886. https://doi.org/10.1002/ppul.25305

Abstract

Sleep-related movement disorders (SRMDs) represent an important part of pediatric sleep disorders. The most common complaint in SRMD is restless sleep at night. Restless sleep is reported in up to 80% of children with restless legs syndrome (RLS) and children with periodic limb movements of sleep (PLMS) disorder (PLMD). However, restless sleep causing daytime behavioral consequences can be seen in children without another apparent condition and has recently been identified as a new independent primary pediatric sleep disorder, called restless sleep disorder (RSD).

This study describes these three main SRMDs (RSD, RLS, and PLMD), explains the new consensus criteria for RSD, emphasizes the rapidly evolving areas of research in this field, and proposes recommendations for future research. In particular, the published data constitute convincing evidence that sleep-related movements are disruptors of sleep quality and continuity.

However, while important advancements have recently been reported in adults, a detailed analysis of the phenomenology and consequences of sleep-related movements has just started in children.

New approaches, standardized diagnostic methods, and specific guidelines are needed in the field of pediatric SRMD.

The Effect of Cannabidiol for Restless Legs Syndrome/Willis-Ekbom Disease in Parkinson's Disease Patients with REM Sleep Behavior Disorder: A Post Hoc Exploratory Analysis of Phase 2/3 Clinical Trial. Cannabis and cannabinoid research.

de Almeida, C., Brito, M., Bosaipo, N. B., Pimentel, A. V., Sobreira-Neto, M. A., Tumas, V., Zuardi, A. W., Crippa, J., Hallak, J., & Eckeli, A. L. (2022).

https://doi.org/10.1089/can.2021.0158bstract

Abstract

Background: Cannabidiol (CBD) is one of the main non psychoactive components of Cannabis sativa and may represent an alternative treatment for Restless Legs Syndrome/Willis-Ekbom Disease (RLS/WED) in patients with Parkinson's disease (PD) and REM (Rapid Eye Movement) sleep behaviour disorder (RBD). Objective: Our purpose was a post hoc exploratory analysis to evaluate the CBD's efficacy to improve the severity of RLS/WED symptoms in patients with PD and RBD.

Methods: A post hoc exploratory analysis of a phase II/III, a parallel, double-blind, placebo-controlled clinical trial was conducted in 18 patients with RLS/WED and PD plus RBD associated. Six patients were randomized to the CBD group in doses of 75-300 mg, and twelve received placebo capsules. They were followed up for 14 weeks. The primary outcome was the severity of RLS/WED by Restless Legs Syndrome Rating Scale of the International Restless Legs Syndrome Study Group (IRLSSG).

Results: CBD showed no difference in relationship to placebo for primary and secondary outcomes. Conclusion: CBD showed no reduction in the severity of RLS/WED manifestation in patients with PD and RBD.

Restless Sleep Disorder (RSD): a New Sleep Disorder in Children. A Rapid Review. Current neurology and neuroscience reports, 22(7), 395–404.

DelRosso, L. M., Mogavero, M. P., Ferri, R., & Bruni, O. (2022).

https://doi.org/10.1007/s11910-022-01200-y

Abstract

Purpose of review: Restless sleep disorder (RSD) is a recently identified pediatric sleep disorder characterized by frequent movements during sleep associated with daytime symptoms. In this review we summarize the expanding evidence of the clinical presentation of RSD, potential pathophysiology, associated comorbidities, and current treatment options that will help the pediatrician identify children with RSD in a timely manner.

Recent findings: RSD is diagnosed in 7.7% of children referred evaluated in a pediatric sleep center. Children with RSD present with frequent nightly movements during sleep for at least 3 months, and have daytime symptoms related to poor sleep quality including excessive sleepiness, hyperactivity, irritability among other symptoms. Current evidence shows an increased sympathetic predominance, increased NREM sleep instability, and iron deficiency, as well as increased prevalence in parasomnias and attention deficit hyperactivity disorder. Consensus diagnostic criteria were recently published to diagnose RSD and emergent evidence suggests that iron supplementation improves its nighttime and daytime symptoms.

Validation and Diagnostic Accuracy of Hindi Restless Legs Syndrome (RLS-H) Screening Tool. Journal of neurosciences in rural practice, 13(2), 307–314.

Sharma, A., Singh, R., & Rai, N. K. (2022)

https://doi.org/10.1055/s-0042-1744230

Abstract

Background: Restless legs syndrome (RLS), a prevalent and treatable entity, has high impact on quality of life, requiring a better screening tool for its early detection. Thus, present study aimed to derive a Hindi RLS (RLS-H) screening tool for its use in Indian population.

Materials and Methods: RLS-H screening tool, derived by translating first four criteria of 2012 revised International Restless Legs Syndrome Study Group (IRLSSG) diagnostic criteria in Hindi and was validated in 50 RLS and 50 non-RLS patients. This validated RLS-H tool was used to screen 1,066 patients attending neurology clinic for assessing its diagnostic accuracy. Internal consistency, discriminatory validity, and various diagnostic yields were calculated. IRLSSG was used as gold standard for final diagnosis of RLS.

Results: RLS-H screening tool had an internal consistency of 0.910. No correlation was found between RLS-H screening tool and Epworth sleepiness scale, Pittsburgh sleep quality index, or International Restless Legs Syndrome Study Group rating scale indicating satisfactory discriminant validity. Prevalence of RLS was 13.6%. The question (Q)1 had highest sensitivity (97.9%) and Q4 had highest specificity (92.66%). Thus, its combinations (Q1 + Q4) along with addition of Q2 or Q3 were compared for best combination of diagnostic accuracy. A minimum cutoff value of RLS-H screening tool was 2.5 for considering patients requiring detailed RLS evaluation.

Conclusion: RLS-H screening tool can be used as a screening tool for early detection of RLS among susceptible patients. Patients answering "yes" to more than two questions (cutoff = 2.5) or "yes" to Q1 and Q4 should be interviewed and assessed for RLS.

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Comparison of the Effect of Reflexology and Swedish Massage on Restless Legs Syndrome and Sleep Quality in Patients Undergoing Hemodialysis: a Randomized Clinical Trial. International journal of therapeutic massage & bodywork, 15(2), 1–13.

Ghanbari, A., Shahrbabaki, P. M., Dehghan, M., Mardanparvar, H., Abadi, E., Emami, A., & Sarikhani-Khorrami, E. (2022).

https://doi.org/10.3822/ijtmb.v15i2.705

Abstract

Background: Patients undergoing hemodialysis experience painful complications such as restless leg syndrome and poor sleep quality, which negatively affect their quality of life.

Purpose: This study aimed to compare the effect of reflexology and Swedish massage on restless leg syndrome and sleep quality in patients undergoing hemodialysis.

Method: This is a randomized clinical trial conducted on 90 patients undergoing hemodialysis. The two intervention groups received either foot reflexology (n = 30) or Swedish massage (n = 30) for four weeks. In the sham group (n = 30), a simple touch of the knee down was performed with the same conditions as the intervention groups. Each sample completed the International Restless Leg Syndrome and Pittsburgh Sleep Quality Index Questionnaires before, immediately after, and one month after the intervention.

Result: The results showed that immediately after the intervention, restless leg syndrome and sleep quality were significantly better in the foot reflexology massage group than the Swedish massage and sham groups (PRLS < 0.001, PPSQI < 0.001); also, changes in restless leg syndrome and sleep quality, respectively, before and one-month follow-up after the intervention were not significant in all three groups (PRLS = 0.47, PPSQI = 0.95), (PRLS = 0.91, PPSQI = 0.87).

Conclusion: Reflexology and Swedish massage, as complementary methods, can improve the restless leg syndrome and sleep quality of patients undergoing hemodialysis. However, foot reflexology massage had been more effective.

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Treatment of Depression with Vortioxetine in a Patient with Comorbid Major Depressive Disorder and Restless Legs Syndrome: A Case Report. Noro psikiyatri arsivi, 59(2), 164–166.

Yilbaş B. (2022)

https://doi.org/10.29399/npa.27827

Abstract

Many case reports have shown that the use of antidepressants can lead to restless legs syndrome (RLS). Vortioxetine is a new generation antidepressant with a multimodal mechanism of action on serotonin receptors. In this case report, partial improvement in RLS symptoms after treatment with vortioxetine in a patient with a co-diagnosis of major depressive disorder and restless legs syndrome will be discussed. A 59-year-old female patient was admitted to the psychiatry outpatient clinic due to depressive complaints for three months. In the control examination, it was learned that the patient had complaints of RLS that had been going on for about 20 years. RLS symptoms were increased with selective serotonin reuptake inhibitors (SSRI) used by the patient. In the follow-up examination in the first month after vortioxetine treatment, clinically significant improvement was observed in the patient's depressive complaints, while a partial reduction in RLS symptoms was observed.

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Advanced network neuroimaging as an approach to unravel the pathophysiology of restless legs syndrome. Sleep, 45(7), zsac125.

Costales, B., Vouri, S. M., Brown, J. D., Setlow, B., & Goodin, A. J. (2022)

https://doi.org/10.1093/sleep/zsac125

No abstract available

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Treatment initiation and utilization patterns of pharmacotherapies for early-onset idiopathic restless legs syndrome. Sleep medicine, 96, 70–78.

Costales, B., Vouri, S. M., Brown, J. D., Setlow, B., & Goodin, A. J. (2022)

https://doi.org/10.1016/j.sleep.2022.05.003

Abstract

Objective/background: Restless legs syndrome (RLS) is a complex condition associated with circadian rhythm that disrupts sleep and can cause multisystemic consequences. This study assesses pharmacotherapy treatment initiation, estimates annual treatment prevalence, and assesses treatment patterns for early-onset idiopathic RLS.

Methods: We used the MarketScan Commercial Claims Database from 2012 to 2019 to conduct a new user retrospective cohort study. Annual treatment prevalence was calculated from a cross-sectional sample. Newly diagnosed adults with early-onset (18-44 years) idiopathic RLS who initiated on and off-label gabapentinoids, dopamine agonists, or levodopa/carbidopa were included. Among monotherapy users who had one year of insurance enrollment, treatment patterns (single fill, continuous use of initiated therapy, switching, and add-on therapy) were examined and mean time on the initial treatment (as a measure of persistence) was calculated.

Results: In total, 6, 828 patients were initiated on monotherapy treatment for early-onset idiopathic RLS in which 4,638 met all inclusion criteria. In 2019, annual prevalence of monotherapy treatment of diagnosed patients for ropinirole was 171.3/1,000 patients; 85.0/1,000 patients for pramipexole; and 132.1/1,000 patients for gabapentin. Overall, 22.3% (n = 1,033) of patients maintained their initiated pharmacotherapy for the entire year. Rotigotine had the longest persistence (mean 185.4 [161.4 SD] days) but this user group was the smallest (n = 29). Gabapentin enacarbil, pregabalin, and rotigotine use was low (2.8% total).

Conclusion: Ropinirole, pramipexole, and gabapentin were initiated most often for early-onset idiopathic RLS. FDA-approved agents for RLS, including gabapentin enacarbil and rotigotine, were used less frequently. In general, persistence was low for all RLS study drugs examined.

The association between restless leg syndrome and anxiety in Parkinson's disease: a case-control study. Neurological research, 44(6), 475–482.

Zhang, L., Wan, Z., He, X., Cheng, L., Wang, P., Li, J., & Du, J. (2022)

https://doi.org/10.1080/01616412.2021

Abstract

Objective: To shed light on the association between restless leg syndrome (RLS) and anxiety in Parkinson's disease (PD) population.

Methods: This was a case-control study including 129 PD participants with and without anxiety who presented to the Aerospace Center Hospital in Beijing, China. Anxiety was evaluated by using the Beck Anxiety Index score. RLS was assessed using the minimal diagnostic criteria of the International Restless Legs Study Group and RLS symptom frequency and treatment. We then examined the relationship between RLS and anxiety by logistic regression models and subgroup as well as interaction analyses.

Results: The proportion of RLS in PD with anxiety was significantly higher in the PD without anxiety (p < 0.001). The multivariate logistic regression models indicated that PD participants with RLS had a 5.98-fold higher risk of anxiety in PD than those without RLS (OR, 6.98; 95% CI, 2.77-17.59). Subgroup analyses indicated that PD with RLS tended to be associated with a greater risk of anxiety in all stratified subgroups (adjusted ORs >1). Furthermore, the interaction analyses revealed no interactive role in the association between RLS and anxiety.

Conclusions: The present case-control study suggests that RLS is an independent risk factor for anxiety in PD patients. Early attention and targeted treatment for RLS may be necessary for mood management in PD. Larger prospective cohort studies are wanted to validate these findings.

Cross-Sectional Design: Link Between Parkinson's Pain and Restless Leg Syndrome. Journal of geriatric psychiatry and neurology, 35(4), 622–626

Paul, D. A., Qureshi, A. R., Jamal, M. K., & Rana, A. Q. (2022)

https://doi.org/10.1177/08919887211036188

Abstract

Objective: Prior research suggests that restless leg syndrome (RLS) is prevalent in Parkinson's disease (PD) with insufficient evidence to support the relationship between RLS, PD, and pain. This study explored the relationship between pain in PD patients and its association with the prevalence and severity of RLS.

Method: 127 PD patients were assessed for PD and RLS using the U.K. Brain bank Criteria and the Restless Leg Syndrome diagnostic criteria, respectively. These patients were also assessed for pain perception and interference using the Brief Pain Inventory.

Results: The results demonstrated Parkinson's disease patients who reported pain scored 23 more Restless Leg Syndrome prevalence points (p < 0.05), and 8.5 counts higher for Restless Leg Syndrome severity (p < 0.05) compared to the group of Parkinson's disease patients denying pain.

Discussion: The presence of pain in PD patients indicated a higher RLS prevalence and an increased RLS severity. This finding suggests patients suffering from pain interference may experience more severe RLS symptoms. This demonstrates an inextricable link and association between pain in PD patients and RLS. Further robust investigations are required to elucidate any potential causative links, which can inform more holistic treatment principles.

The Prevalence and Predictors of Restless Legs Syndrome in Patients with Liver Cirrhosis. Healthcare (Basel, Switzerland), 10(5), 822

Plotogea, O. M., Diaconu, C. C., Gheorghe, G., Stan-Ilie, M., Oprita, R., Sandru, V., Bacalbasa, N., & Constantinescu, G. (2022).

https://doi.org/10.3390/healthcare10050822

Abstract

Introduction and aim: Sleep disorders are highly prevalent in patients with liver cirrhosis. The aim of this study was to investigate the prevalence of restless legs syndrome (RLS), as well as its risk factors and possible predictors, in a cohort of patients with liver cirrhosis.

Material and methods: We performed a cross-sectional prospective study over a period of 14 months and enrolled 69 patients with liver cirrhosis, after applying the inclusion and exclusion criteria. The cases of RLS were assessed according to the International Restless Legs Syndrome Study Group (IRLSSG) criteria and severity scale.

Results: Out of the total number of patients, 55% fulfilled the criteria for RLS. Age, diabetes, severity of cirrhosis, serum creatinine, glomerular filtration rate (GFR), and mean hemoglobin were associated with the presence of RLS. Moreover, there was a significantly higher prevalence of RLS among patients with decompensated cirrhosis. From all the risk factors introduced into the multivariate analysis, only the GFR could predict the presence of RLS.

Conclusions: This research shows that patients with liver cirrhosis have a high risk of RLS. Even though there are multiple risk factors associated with RLS, only the GFR could predict its occurrence in our cohort.

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Is There a Place for Medicinal Cannabis in Treating Patients with Sleep Disorders? What We Know so Far. Nature and science of sleep, 14, 957–968

Maddison, K. J., Kosky, C., & Walsh, J. H. (2022)

https://doi.org/10.2147/NSS.S340949

Abstract

The legalization of cannabis for medicinal, and in some countries, recreational, purposes in addition to growth in the cannabis industry has meant that cannabis use and interest in the area has increased rapidly over the past 20 years. Treatment of poor sleep and sleep disorders are two of the most common reasons for the current use of medicinal cannabis.

However, evidence for the role of medical cannabis in the treatment of sleep disorders has not been clearly established, thus making it challenging for clinicians to make evidence-based decisions regarding efficacy and safety. This narrative review summarizes the highest quality clinical evidence currently available in relation to the use of medicinal cannabis for the treatment of sleep disorders including insomnia, obstructive sleep apnea, restless legs syndrome, rapid eye movement sleep behavior disorder, nightmare disorder and narcolepsy.

A summary of the effect of cannabis on sleep quality and architecture is also presented. Currently, there is insufficient evidence to support the routine use of medicinal cannabis as an effective and safe treatment option for any sleep disorder. Nevertheless, emerging evidence is promising and warrants further investigation using standardized cannabinoid products and validated quantitative measurement techniques.

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Treatment initiation and utilization patterns of pharmacotherapies for early-onset idiopathic restless legs syndrome. Sleep medicine, 96, 70–78. Advance online publication

Costales, B., Vouri, S. M., Brown, J. D., Setlow, B., & Goodin, A. J. (2022).

https://doi.org/10.1016/j.sleep.2022.05.003

Abstract

Objective/background: Restless legs syndrome (RLS) is a complex condition associated with circadian rhythm that disrupts sleep and can cause multisystemic consequences. This study assesses pharmacotherapy treatment initiation, estimates annual treatment prevalence, and assesses treatment patterns for early-onset idiopathic RLS.

Methods: We used the MarketScan Commercial Claims Database from 2012 to 2019 to conduct a new user retrospective cohort study. Annual treatment prevalence was calculated from a cross-sectional sample. Newly diagnosed adults with early-onset (18-44 years) idiopathic RLS who initiated on and off-label gabapentinoids, dopamine agonists, or levodopa/carbidopa were included. Among monotherapy users who had one year of insurance enrollment, treatment patterns (single fill, continuous use of initiated therapy, switching, and add-on therapy) were examined and mean time on the initial treatment (as a measure of persistence) was calculated.

Results: In total, 6, 828 patients were initiated on monotherapy treatment for early-onset idiopathic RLS in which 4,638 met all inclusion criteria. In 2019, annual prevalence of monotherapy treatment of diagnosed patients for ropinirole was 171.3/1,000 patients; 85.0/1,000 patients for pramipexole; and 132.1/1,000 patients for gabapentin. Overall, 22.3% (n = 1,033) of patients maintained their initiated pharmacotherapy for the entire year. Rotigotine had the longest persistence (mean 185.4 [161.4 SD] days) but this user group was the smallest (n = 29). Gabapentin enacarbil, pregabalin, and rotigotine use was low (2.8% total).

Conclusion: Ropinirole, pramipexole, and gabapentin were initiated most often for early-onset idiopathic RLS. FDA-approved agents for RLS, including gabapentin enacarbil and rotigotine, were used less frequently. In general, persistence was low for all RLS study drugs examined.

A case of restless legs syndrome after BNT162b2 mRNA COVID-19 vaccination. Neurology and clinical neuroscience, 10(3), 178–180

Ito, H., Kuroki, T., Horiuchi, S., & Shinya, Y. (2022)

https://doi.org/10.1111/ncn3.12594

Abstract

Restless legs syndrome (RLS) can be secondary to several disorders. We present an 87-year-old woman who developed RLS 2 days after the first injection of BNT162b2 mRNA coronavirus disease 2019 vaccine. The symptoms of RLS tended to improve and eventually resolved with the administration of gabapentin.

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Alterations of Functional Connectivity in Patients With Restless Legs Syndrome. Journal of clinical neurology (Seoul, Korea), 18(3), 290–297

Park, K. M., Kim, K. T., Kang, K. W., Park, J. A., Seo, J. G., Kim, J., Chang, H., Kim, E. Y., Cho, Y. W., & RLS Subcommittee of the Korean Sleep Research Society (2022)

https://doi.org/10.3988/jcn.2022.18.3.290

Abstract

Restless legs syndrome (RLS) is a common neurological illness marked by a strong desire to move one's legs, usually in association with uncomfortable sensations. Recent studies have investigated brain networks and connectivity in RLS. The advent of network analysis has greatly improved our understanding of the brain and various neurological disorders. A few studies have investigated alterations in functional connectivity in patients with RLS. This article reviews functional connectivity studies of patients with RLS, which have identified significant alterations relative to healthy controls in several brain networks including thalamic, salience, default-mode, and small-world networks. In addition, network changes related to RLS treatment have been found, including to repetitive transcranial magnetic stimulation, transcutaneous spinal cord direct-current stimulation, and dopaminergic drugs. These findings suggest that the underlying pathogenesis of RLS includes alterations in the functional connectivity in the brain and that RLS is a network disorder.

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The conundrum of the origin of restless legs syndrome. Sleep, 45(5), zsac018

Lin W. S. (2022).

https://doi.org/10.1093/sleep/zsac018

Abstract

No abstract available

Striatal mechanism of the restless legs syndrome. Sleep, zsac110. Advance online publication

Lai, Y. Y., Hsieh, K. C., Chew, K. T., Nguyen, D., & Siegel, J. M. (2022)

https://doi.org/10.1093/sleep/zsac110

Abstract

Study objectives: Brain iron deficiency has been reported to be associated with the restless legs syndrome (RLS). However, 30%-50% of RLS patients do not respond to iron therapy, indicating that mechanisms other than brain iron deficiency may also participate in this disease. The striatum is known to be involved in the modulation of motor activity. We speculated that dysfunction of the striatum may induce RLS.

Methods: Two groups, wild-type (WT) and iron-deficient (ID) rats were used. Each group was divided into 2 subgroups, control and N-methyl-D-aspartate striatal-lesioned. After baseline recording, striatal-lesioned wild-type (WT-STL) and striatal-lesioned iron-deficient (ID-STL) rats were given pramipexole and thioperamide injections. Iron-deficient and ID-STL rats were then given a standard rodent diet for 4 weeks, and their sleep and motor activity were recorded.

Results: WT-STL rats showed periodic leg movements (PLM) in wake, an increase in PLM in slow wave sleep (SWS), a decrease in rapid-eye-movement sleep, and a decrease in the daily average duration of episodes in SWS. The sleep-wake pattern and motor activity did not differ between ID and ID-STL rats. Thioperamide or pramipexole injection decreased PLM in sleep and in wake in WT-STL rats and ID-STL rats. Unlike ID rats, whose motor hyperactivity can be reversed by iron replacement, PLM in wake and in sleep in ID-STL rats were not fully corrected by iron treatment.

Conclusions: Lesions of the striatum generate RLS-like activity in rats. Dysfunction of the striatum may be responsible for failure to respond to iron treatment in some human RLS patients.

How Effective Are Treatment Guidelines for Augmented RLS?. Sleep, zsac108. Advance online publication

Yeung Laiwah, J., & Winkelman, J. W. (2022)

https://doi.org/10.1093/sleep/zsac108

Abstract

Study objectives: The objective of this study was to assess the effectiveness of current treatment guidelines for RLS augmentation in patients on dopamine agonists (DA) which recommend a cross-titration strategy to an alpha-2-delta ligand (A2D) and/or opioid.

Methods: Consecutive new consultations for RLS with both augmentation and active treatment with a dopamine agonist at the time of initial assessment were included if followed >5 months. Clinical information from the semi-structured initial consultation, and subsequent visits until their most recent/final visit was extracted. Clinical Global Impression-Severity (CGI-S) and Improvement (CGI-I) scores were retrospectively determined by two independent evaluators.

Results: In the 63 augmented RLS patients on a dopamine agonist, followed for 5-59 months (mean=28, SD=14), the average age was 67.6 (SD=9.8) and 63% were female. Mean duration of prior dopaminergic therapy was 11.6 years (SD=6.7) and average pramipexole equivalent dose was 1.23 mg (SD=1.22mg). At baseline, RLS was "moderate-markedly" severe (CGI-S=4.9).At the final/most recent visit, 78% (49/63) were classified as Responders (CGI-I≤2, "Much" or "Very Much Improved") with an average CGI-S of 2.4 ("borderline-mildly ill"). Responders (59%) were more likely to have discontinued DAs than Non-responders (40%), and mean opioid doses were higher in Responders (39 vs 20 MME). No differences in baseline DA dose, final A2D dose, or iron therapy were observed between groups. Responders did have significantly more severe RLS, more sleep maintenance insomnia, and greater subjective daytime sleepiness at baseline (p<0.05).

Conclusions: Guideline-based management is effective in most patients with augmented RLS on dopamine agonists.

Revisiting brain iron deficiency in restless legs syndrome using magnetic resonance imaging. NeuroImage. Clinical, 34, 103024

Beliveau, V., Stefani, A., Birkl, C., Kremser, C., Gizewski, E. R., Högl, B., & Scherfler, C. (2022).

https://doi.org/10.1016/j.nicl.2022.103024

Abstract

Study objectives: Studies on brain iron content in restless legs syndrome (RLS) using magnetic resonance imaging (MRI) are heterogeneous. In this study, we sought to leverage the availability of a large dataset including a range of iron-sensitive MRI techniques to reassess the association between brain iron content and RLS with added statistical power and to compare these results to previous studies.

Methods: The relaxation rates R2, R2', and R2* and quantitative susceptibility are MRI parameters strongly correlated to iron content. In general, these parameters are sensitive to magnetic field variations caused by iron particles. These parameters were quantified within iron-rich brain regions using a fully automatized approach in a cohort of 72 RLS patients and individually age and gender-matched healthy controls identified from an existing dataset acquired at the Sleep Laboratory of the Department of Neurology, Medical University of Innsbruck. 3 T-MRI measures were corrected for age and volume of the segmented brain nuclei and results were compared with previous findings in a meta-analysis.

Results: In our cohort, RLS patients had increased R2* signal in the caudate and increased quantitative susceptibility signal in the putamen and the red nucleus compared to controls, suggesting increased iron content in these areas. The meta-analysis revealed no significant pooled effect across all brain regions. Furthermore, potential publication bias was identified for the substantia nigra.

Conclusions: Normal and increased iron content of subcortical brain areas detected in this study is not in line with the hypothesis of reduced brain iron storage, but favors CSF investigations and post mortem studies indicating alteration of brain iron mobilization and homeostasis in RLS.

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ExomeChip-based rare variant association study in restless legs syndrome. Sleep medicine, 94, 26–30.

Tilch, E., Schormair, B., Zhao, C., Högl, B., Stefani, A., Berger, K., Trenkwalder, C., Bachmann, C. G., Hornyak, M., Fietze, I., Müller-Nurasyid, M., Peters, A., Herms, S., Nöthen, M. M., Müller-Myhsok, B., Oexle, K., & Winkelmann, J. (2022)

https://doi.org/10.1016/j.sleep.2022.04.001

Abstract

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.

Iron Deficiency in Women's Health: New Insights into Diagnosis and Treatment. Advances in therapy, 39(6), 2438–2451

Moisidis-Tesch, C. M., & Shulman, L. P. (2022)

https://doi.org/10.1007/s12325-022-02157-7

Abstract

Iron deficiency (ID), with or without anemia, is commonly found worldwide and affects the health and wellbeing of pregnant and nonpregnant women. Symptoms of ID- which include fatigue, pica (ice craving), restless legs syndrome, poor concentration and work function, increased susceptibility to infection, and cardiovascular stress- can cause significant morbidity and reduced quality of life. The etiologies of iron deficiency in women are usually specific to each community. In the developing world, iron deficiency is usually associated with poor iron intake and parasitic infections, whereas in higher income regions, iron deficiency is typically the result of heavy, abnormal uterine bleeding, and pregnancy. Iron-poor diets and poor iron absorption resulting from gut disorders can also play a role.

Diagnosis of iron deficiency is usually straightforward and characterized by a low ferritin level; however, the diagnosis can be challenging in women with concomitant inflammatory disorders, in which case a low percent transferrin saturation, performed after an overnight fast, can inform on the need for iron. Therapy is frequently initiated with oral iron salts; however, use of these oral regimens is commonly associated with adverse events, mostly gastrointestinal in nature, that have been shown to adversely impact compliance, continuation, and the achievement of therapeutic goals.

A further impediment to the effectiveness of oral iron is its poor absorption because of comorbidity (i.e., celiac disease, gastritis, etc.), surgery (bariatric), or physiologic inhibitory mechanisms. As such, intravenous (IV) iron regimens are increasingly being used to treat ID, as such regimens have been shown to avoid the gastrointestinal adverse events commonly associated with oral regimens. Indeed, IV iron has been shown to provide adequate iron replacement in women with functional iron deficiencies as well as those with ID resulting from inflammatory disorders- patients often resistant to oral iron therapy.

More recent IV iron regimens have been shown to provide iron replacement in a safe and effective manner, being associated with more salutary adverse event profiles than earlier IV iron regimens. In fact, these iron regimens can provide a complete replacement dose in a single 15-60-min visit.

Restless legs syndrome is associated with long-COVID in women. Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine, 18(5), 1413–1418

Weinstock, L. B., Brook, J. B., Walters, A. S., Goris, A., Afrin, L. B., & Molderings, G. J. (2022).

https://doi.org/10.5664/jcsm.9898

Abstract

Study objectives: Sleep disturbance is common in long-COVID (LC). Restless legs syndrome (RLS) is characterized by sleep disturbance and has been reported after viral infections. Therefore, we evaluated RLS symptoms cross-sectionally in individuals with LC at both current and pre-coronavirus disease 2019 (pre-COVID-19) time points.

Methods: Adults on LC-focused Facebook pages were recruited for an online assessment of symptoms before COVID-19 infection and during their present LC state in a cross-sectional manner. The LC group documented baseline symptoms retrospectively. Questions were included about the presence/severity of RLS symptoms and assessments of fatigue, quality of life, and sleep apnea. A control group was recruited and included individuals ≥ 18 years of age who never had overt symptoms of COVID-19. Pregnancy was an exclusion criterion for both groups.

Results: There were 136 participants with LC (89.7% females, age 46.9 ± 12.9 years) and 136 controls (65.4% females, age 49.2 ± 15.5). RLS prevalence in females with LC was 5.7% pre-COVID-19 and 14.8% post-COVID-19 (P < .01) vs 6.7% in control females. Severity of RLS was moderate in both groups. Logistic regression predicting post-COVID-19 RLS among females with LC failed to find significant effects of hospitalization, sleep apnea, neuropathic pain severity, or use of antihistamines and antidepressants.

Conclusions: The baseline prevalence of RLS in females with LC was similar to the general population group as well as to patients in epidemiological studies. The prevalence significantly increased in the LC state. Postinfectious immunological mechanisms may be at play in the production for RLS symptoms.

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Clinical Efficacy and Safety of Massage for the Treatment of Restless Leg Syndrome in Hemodialysis Patients: A Meta-Analysis of 5 Randomized Controlled Trials. Frontiers in psychiatry, 13, 843263

Xia, M., He, Q., Ying, G., Fei, X., Zhou, W., & He, X. (2022).

https://doi.org/10.3389/fpsyt.2022.843263

Abstract

Aim: We conducted this meta-analysis to evaluate the clinical efficacy and safety of massage for the treatment of hemodialysis patients with restless leg syndrome (RLS).

Methods: A comprehensive literature search was performed using the PubMed database, EMBASE database (via OVID), and the Cochrane Library in order to identify eligible randomized controlled trials (RCTs) published before August 31, 2021. After extracted essential data and assessed risk of bias of each eligible study, we calculated the pooled estimate of RLS score and safety after treatment. Statistical analysis was performed by using Review Manager 5.3.

Results: Five studies involving 369 hemodialysis patients with RLS were analyzed. The RLS score after treatment [mean difference (MD), -12.01; 95% confidence interval (CI), -14.91 to -9.11] and mean difference of RLS score at the beginning and end of treatment [mean difference (MD), -11.94; 95% confidence interval (CI), -15.45 to -8.43] in a massage group was significantly better than that in route care group. Subgroup analysis suggested that massage with lavender oil also significantly reduced the RLS score after treatment (MD, -14.22; 95% CI, -17.81 to -10.63) and mean difference of RLS score at the beginning and end of treatment (MD, -14.87; 95% CI, -18.29 to -11.45) compared with route care. Meanwhile, massage regime significantly relieved RLS severity compared with route care but did not increase adverse events.

Conclusion: Massage may be a preferred treatment modality for hemodialysis patients with RLS because it effectively reduces RLS symptoms, relieves RLS severity, and does not increase the risk of adverse events. However, future study with a larger sample size is warranted due to the fact that only limited number of eligible studies with small sample size are enrolled.

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The Effects of Cannabinoids on Sleep. Journal of primary care & community health, 13, 21501319221081277

Kolla, B. P., Hayes, L., Cox, C., Eatwell, L., Deyo-Svendsen, M., & Mansukhani, M. P. (2022)

https://doi.org/10.3390/healthcare10050822

Abstract

he use of cannabis products to help with sleep and various other medical conditions by the public has increased significantly in recent years. Withdrawal from cannabinoids can lead to sleep disturbance. Here, we describe a patient who developed significant insomnia leading to worsening anxiety, mood, and suicidal ideation in the setting of medical cannabis withdrawal, prompting presentation to the Emergency Department and inpatient admission. There is a limited evidence base for the use of cannabis products for sleep. We provide a comprehensive review evaluating the literature on the use of cannabis products on sleep, including an overview of cannabis and related psychoactive compounds, the current state of the law as it pertains to the prescribing and use of these substances, and potential side effects and drug interactions. We specifically discuss the impact of cannabis products on normal sleep and circadian sleep-wake rhythms, insomnia, excessive daytime sleepiness, sleep apnea, parasomnias, and restless legs syndrome. We also describe the effects of cannabis withdrawal on sleep and how this increases relapse to cannabis use. Most of the studies are observational but the few published randomized controlled trials are reviewed. Our comprehensive review of the effects of cannabis products on normal sleep and sleep disorders, relevant to primary care providers and other clinicians evaluating and treating patients who use these types of products, shows that cannabis products have minimal to no effects on sleep disorders and may have deleterious effects in some individuals. Further research examining the differential impact of the various types of cannabinoids that are currently available on each of these sleep disorders is required.

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Prevalence of sleep disorders in children with chronic kidney disease: a meta-analysis. Pediatric nephrology (Berlin, Germany), 10.1007/s00467-022-05536-y [Titel anhand dieser DOI in Citavi-Projekt übernehmen]

Kang, K. T., Lin, M. T., Chen, Y. C., Lee, C. H., Hsu, W. C., & Chang, R. E. (2022)

https://doi.org/10.1007/s00467-022-05536-y

Abstract

Background: The reported prevalence of sleep disorders in children with chronic kidney disease (CKD) varies greatly. A quantitative meta-analysis to estimate the prevalence of sleep disorders among pediatric CKD patients may provide further information.

Objectives: The objective of this study is to estimate the prevalence of sleep disorders in children with CKD. The study protocol was registered on PROSPERO (registration number CRD42021268378).

Data sources: Two authors independently searched the PubMed, MEDLINE, EMBASE, and Cochrane review databases up to June 2021.

Study eligibility criteria: Eligible studies include data of prevalence of sleep disorders in children with CKD.

Study appraisal and synthesis methods: The prevalence of restless legs syndrome, sleep-disordered breathing, pediatric obstructive sleep apnea (i.e., apnea-hypopnea index > 1 event/h in polysomnography), excessive daytime sleepiness, and insomnia/insufficient sleep was estimated using a random-effects model. Subgroup analyses were conducted to compare the prevalence of sleep disorders between children on dialysis and not on dialysis. This meta-analysis included 12 studies with 595 children (mean age: 12.9 years; gender ratio: 55.6% boys; mean sample size: 49.6 patients).

Results: The prevalence of restless legs syndrome in children with CKD was 21% (95% confidence interval [CI], 14-30%). The prevalence of sleep-disordered breathing, pediatric obstructive sleep apnea, excessive daytime sleepiness, and insomnia/insufficient sleep was 22% (95% CI, 12-36%), 34% (95% CI, 19-53%), 27% (95% CI, 17-41%), and 14% (95% CI, 7-27%), respectively. Subgroup analysis revealed the pooled prevalence of excessive daytime sleepiness was significantly higher in children on dialysis than in children not on dialysis (43.3% vs. 11.2%; P = 0.018). Children on dialysis also had a high prevalence of other sleeping disorders, although the differences did not reach statistical significance. Children with CKD exhibited a 3.9-fold (95% CI, 1.37 to 10.93) increased risk of restless legs syndrome and a 9.6-fold (95% CI, 3.57 to 25.76) increased risk of excessive daytime sleepiness compared with controls.

Limitations: The selected papers are of small sample size, lack of a control group, and exhibit substantial heterogeneity.

Conclusions: Sleep disorders are common in children with CKD. Our results indicate that while the prevalence rates of various sleep disorders were higher in children on dialysis than in children not on dialysis, the prevalence of excessive daytime sleepiness was statistically significant in children on dialysis. A higher resolution version of the Graphical abstract is available as Supplementary information.

Restless Leg Syndrome in Hemodialysis Patients: A Narrative Review. The neurologist, 10.1097/NRL.0000000000000436 [Titel anhand dieser DOI in Citavi-Projekt übernehmen]

Matar, S. G., El-Nahas, Z. S., Aladwan, H., Hasanin, M., Elsayed, S. M., Nourelden, A. Z., Benmelouka, A. Y., & Ragab, K. M. (2022)

https://doi.org/10.1097/NRL.0000000000000436

Abstract

Background: Restless legs syndrome (RLS) is a clinical entity characterized by sensory-motor manifestations commonly observed in end-stage renal illness. Evidence suggests that RLS is a multifactorial phenomenon that can be influenced by many critical factors, including genetic predisposition, dietary patterns, and deficiency in some vitamins. Iron metabolism disorders and metabolic derangements have been generally accepted as predisposing elements in RLS. Furthermore, both pharmacological and neuroimaging studies demonstrated dopamine deficiency and dopamine receptors decrease in basal ganglia during RLS.

Review summary: A literature search was done in three databases (PubMed, Google Scholar, and Cochrane) to identify the pertinent articles discussing the epidemiology, pathogenesis, and management of RLS in hemodialysis patients. RLS can affect the morbidity and mortality of patients treated with dialysis. It also has significant impacts on the quality of life since it can lead to insomnia, increased fatigue, mental health troubles, and other movement problems. Appropriate measures should be considered in this particular population so to prevent and treat RLS. Many drugs and other nonpharmacological methods have been investigated to attenuate the disease's severity. No treatment, however, could offer long-term effects.

Conclusion: Further efforts are still required to improve the understanding of RLS pathogenic trends to find more specific and efficient therapies. A wide range of treatment options is available. However, it can be individualized according to the patients' several factors.

D3 Receptors and Restless Legs Syndrome. Current topics in behavioral neurosciences, 10.1007/7854_2022_351 [Titel anhand dieser DOI in Citavi-Projekt übernehmen]

Clemens S. (2022

https://doi.org/10.1007/7854_2022_351

Abstract

Restless Legs Syndrome (RLS) is a sensorimotor disorder that severely affects sleep. It is characterized by an urge to move the legs that is often accompanied by periodic limb movements during sleep (PLMS). RLS has a high prevalence in the population and is usually a life-long condition.

While its origins remain unclear, RLS is initially highly responsive to treatment with dopaminergics that target the D3 receptor. However, over time patients often develop a gradual tolerance that can lead to the emergence of adverse effects and the augmentation of the symptoms. While the basal ganglia and the striatum control leg movements, the lumbar spinal cord is the gateway for the sensory processing of the symptoms and critical for the associated leg movements. D3 receptors are highly expressed in nucleus accumbens (NAc) of the striatum and the sensory-processing areas of the spinal dorsal horn. In contrast, D1 receptors are strongly expressed throughout the entire striatum and in the ventral horn of the spinal cord.

Long-term treatment with D3 receptor full agonists is associated with an upregulation of the D1 receptor subtype, and D3 and D1 receptors can form functional heteromers, in which the D3R controls the D1R function. It is conceivable that the switch from beneficial treatment to augmentation observed in RLS patients after prolonged D3R agonist exposure may be the result of unmasked D1-like receptor actions.

An Exploratory Randomized Controlled Trial of a 12-Week Yoga Versus Educational Film Program for the Management of Restless Legs Syndrome: Feasibility and Acceptability. Journal of integrative and complementary medicine, 28(4), 309–319

Selfe, T. K., Montgomery, C., Klatt, M., Wen, S., Sherman, K. J., & Innes, K. E. (2022)

https://doi.org/10.1089/jicm.2021.0182

Abstract

Objectives: The primary objectives of this pilot trial were to assess the study feasibility and acceptability of the 12-week yoga and educational film programs for the management of restless legs syndrome (RLS) in preparation for a future randomized controlled trial (RCT).

Materials and Methods: This pilot, parallel-arm, randomized feasibility trial was conducted at two sites, Morgantown, WV and Columbus, OH. Yoga group participants attended 75-min Iyengar yoga classes, twice weekly for 4 weeks, then once a week for 8 weeks (16 total classes) and completed a 30-min homework routine on nonclass days. Educational film group participants attended once weekly, 75-min classes (12 total classes), which included information on RLS and other sleep disorders, RLS management including sleep hygiene practices, and complementary therapies. Feasibility and acceptability outcomes included program satisfaction and recruitment, retention, and adherence rates. In addition, participants were asked their preferences regarding three yoga class schedule scenarios for a future study. Attendance, yoga, and treatment logs were collected weekly. Program evaluation and yoga scheduling questionnaires were collected at week 12.

Results: Forty-one adults with moderate to severe RLS were randomized to a 12-week yoga (n = 19) or educational film (n = 22) program. Thirty participants (73%) completed the program. Yoga and education group participants attended an average of 13.0 ± 0.84 (81%) and 10.3 ± 0.3 classes (85%), respectively. Participants from both groups indicated satisfaction with the study. All yoga group respondents to the program evaluation reported they would likely (n = 6) or very likely (n = 7) continue yoga practice; 86.7% of education group respondents (13 of 15) indicated that they were likely (n = 7) or very likely (n = 6) to make lasting changes based on what they had learned. The preferred schedule for a future study was a 16-week study with once-weekly yoga classes.

Conclusions: The findings of this study suggest that a larger RCT comparing yoga with an educational film group for the management of RLS is feasible.

Trial registration: Clinicaltrials.gov: NCT03570515; 02/01/2017.

Common Sleep Disorders in Adults: Diagnosis and Management. American family physician, 105(4), 397–405

Holder, S., & Narula, N. S. (2022)

https://doi.org/10.1093/sleep/zsac018

Abstract

Sleep disorders are common in the general adult population and are associated with adverse effects such as motor vehicle collisions, decreased quality of life, and increased mortality. Patients with sleep disorders can be categorized into three groups: people with problems falling asleep, people with behavior and movement disturbances during sleep, and people with excessive daytime sleepiness.

Insomnia, the most common sleep disorder, is defined by difficulty initiating sleep, maintaining sleep, or both, resulting in daytime consequences. Insomnia is diagnosed by history and is treated with cognitive behavior therapy, with or without medications. Rapid eye movement sleep behavior disorder is characterized by increased muscle tone during rapid eye movement sleep, resulting in patients acting out their dreams with potentially harmful effects. Rapid eye movement sleep behavior disorder is diagnosed by polysomnography and treated with melatonin or clonazepam. Restless legs syndrome is defined by an urge to move the legs that worsens when at rest. Restless legs syndrome is treated with gabapentin or dopamine agonists, depending on the severity.

Narcolepsy is characterized by excessive daytime sleepiness, cataplexy, sleep paralysis, and sleep hallucinations. Diagnosis is suggested by the history and can be confirmed with polysomnography and a multiple sleep latency test the following day. Narcolepsy is treated with behavior modifications and medications such as stimulants, selective serotonin reuptake inhibitors, sodium oxybate, and pitolisant. Obstructive sleep apnea may be diagnosed in patients with excessive snoring and witnessed apneas and can be diagnosed using overnight polysomnography.

Treatment consists of positive airway pressure therapy while sleeping in conjunction with weight loss.

Attention-deficit/hyperactivity and obsessive-compulsive symptoms in adult patients with primary restless legs syndrome. Applied neuropsychology. Adult, 1–8.

Mazurie, Z., Mayo, W., & Ghorayeb, I. (2022)

https://doi.org/10.1080/23279095.2022.2057857

Abstract

Comorbidity between Restless Legs Syndrome and Attention-Deficit/Hyperactivity Disorder remains a matter of debate. This putative association, possibly reflecting a shared brain iron homeostasis and dopaminergic dysfunction, supports the hypothesis of a neurodevelopmental component in Restless Legs Syndrome pathogenesis.

The aim of this study was to investigate Attention-Deficit/Hyperactivity Disorder and Obsessive-Compulsive Disorder symptoms prevalence in adult patients with primary Restless Legs Syndrome compared to another ill group of patients with obstructive sleep apnea syndrome to control for the disease specific effects on psychiatric symptoms and a healthy individuals control group.

Clinical data were obtained through standardized and validated self-administrated questionnaires evaluating Attention-Deficit/Hyperactivity Disorder and Obsessive-Compulsive Disorder symptoms frequencies in 139 outpatients with idiopathic Restless Legs Syndrome, 111 patients with treated obstructive sleep apnea syndrome and 136 healthy subjects. Our findings demonstrate a higher prevalence of Attention-Deficit/Hyperactivity Disorder symptoms among both male and female patients with Restless Legs Syndrome, compared to obstructive sleep apnea syndrome patients and healthy subjects (33.3 and 43.5%, respectively, p < 0.001). Only women presented a strong relationship between Attention-Deficit/Hyperactivity Disorder and Restless Legs Syndrome severity (p < 0.001). Male and female in the three groups showed similar Obsessive-Compulsive Disorder symptom prevalence.

These findings indicate that Attention-Deficit/Hyperactivity Disorder symptoms among adult patients with Restless Legs Syndrome populations are a robust phenomenon. These data provide arguments in favor of an enlargement of the clinical neuropsychological presentation of Restless Legs Syndrome and question the role of decreased brain iron of these psychiatric symptoms.

Depressive Symptoms and Suicidal Thoughts in Restless Legs Syndrome. Movement disorders : official journal of the Movement Disorder Society, 37(4), 812–825

Chenini, S., Barateau, L., Guiraud, L., Denis, C., Rassu, A. L., Lopez, R., Jaussent, I., & Dauvilliers, Y. (2022)

https://doi.org/10.1002/mds.28903

Abstract

Background: Whether depression and suicide thoughts relate to restless legs syndrome (RLS) or comorbidities associated with RLS remain unclear.

Objectives: To determine frequency of depressive symptoms and suicidal thoughts in patients with RLS and their change after RLS treatment, associated clinical and polysomnographic factors, and current major depressive episode (MDE) frequency and suicide risk in RLS.

Methods: Overall, 549 untreated patients with RLS and 549 age-, sex-, and education level-matched controls completed a standardized evaluation, including the Beck Depression Inventory-II that has one item on suicide thoughts. Patients underwent a polysomnographic recording and completed the Urgency, Premeditation, Perseverance, Sensation Seeking Impulsive Behavior scale. In a subgroup of 153 patients, current MDE and suicide risk were assessed with the face-to-face Mini-International Neuropsychiatric Interview (MINI). A subgroup of 152 patients were evaluated in untreated and treated conditions.

Results: The frequency of depressive symptoms (32.5%) and suicidal thoughts (28%) was 10-fold and 3-fold higher, respectively, in patients with RLS than controls. Current MDE (10.5%) and suicidal risk (19.9%) (MINI) were also high. Moderate-to-severe depressive symptoms were associated with young age, female sex, insomnia symptoms, and urgency dimension. The suicide risk was associated with depression, impulsiveness, and RLS severity. RLS treatment improved depressive symptoms but not suicidal thoughts.

Conclusion: The rate of depressive symptoms, depression, and suicidal thoughts/risk was higher in patients with RLS, with key associations with insomnia symptoms, urgency dimension, and RLS severity. These results emphasize the importance of detecting these symptoms in current practice and of evaluating their change after treatment, especially in young women, to improve RLS management.

Factors associated with augmentation in patients with restless legs syndrome. European journal of neurology, 29(4), 1227–1231

Heim, B., Ellmerer, P., Stefani, A., Bergmann, M., Brandauer, E., Seppi, K., Högl, B., & Djamshidian, A. (2022)

https://doi.org/10.1111/ene.15221

Abstract

Background and purpose: Augmentation is a paradoxical reaction mainly to dopaminergic medication in patients with restless legs syndrome (RLS), but the exact pathomechanism remains unclear. The aim of this study was to identify factors associated with augmentation in RLS patients.

Methods: RLS patients with and without current or previous augmentation were recruited. Demographic characteristics, history of smoking, questionnaires for depression, alexithymia, and impulsivity, and RLS severity were obtained.

Results: We included 122 patients, of whom half had a history of augmentation. Patients with augmentation had a longer disease duration (p = 0.001), had higher RLS severity scores (p = 0.013), had higher levodopa equivalent doses (p < 0.001), had higher scores for alexithymia (p = 0.028), had higher prevalence of impulse control disorders (p < 0.001), more often had a history of smoking (p = 0.039), were more often currently smoking (p = 0.015), and had more average pack-years (p = 0.016).

Conclusions: Here, we describe several factors commonly associated with augmentation in RLS. These may help clinicians to screen and treat patients carefully to avoid the challenging side effect of augmentation.

Does Repeated Dosing of Intravenous Ferric Carboxymaltose Alleviate Symptoms of Restless Legs Syndrome?.

Park, H. R., Choi, S. J., & Joo, E. Y. (2022). Journal of clinical medicine, 11(6), 1673. https://doi.org/10.3390/jcm11061673

Abstract

Background: Several studies have reported the efficacy of intravenous (IV) iron for patients with restless legs syndrome (RLS), but little is known about the efficacy or safety of repeated IV iron treatment. The aim of this study was to evaluate the effectiveness of repeated doses of IV ferric carboxymaltose (FCM) in treating RLS symptoms.

Methods: Patients who received FCM more than twice for RLS from April 2016 to January 2020 were retrospectively reviewed. Patients who had shown positive response to initial IV FCM re-visited the clinic when their symptoms returned, and received repeated IV FCM (1000 mg). Blood iron panels were measured before initial and repeated IV FCM. We defined 'responders' as patients with a greater than 40% decrease in International Restless Legs Study Group Severity Scale (IRLS) compared with pre-treatment levels.

Results: A total of 42 patients, including 26 with primary RLS, 5 with gastrectomy, and 11 with anemia, completed the evaluation. Patients received IV FCM infusion 2-4 times. A total of 21 of 26 (80.8%) primary cases of RLS, 4 of 5 (80.0%) patients with a history of gastrectomy, and 9 of 11 (81.8%) patients with anemia responded to repeated FCM treatment. Serum ferritin levels of patients with primary RLS were higher before the second treatment than the baseline levels. There were no serious adverse events observed in the study.

Conclusions: Repeated IV FCM for recurring symptoms is an effective treatment for primary RLS and RLS associated with iron deficiency. Serum ferritin might not be a reliable factor to monitor the sustained effects of IV iron for RLS.

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Restless Legs Symptoms and Periodic Leg Movements in Sleep Among Patients with Parkinson's Disease.

Bliwise, D. L., Karroum, E. G., Greer, S. A., Factor, S. A., & Trotti, L. M. (2022). Journal of Parkinson's disease, 10.3233/JPD-213100

Advance online publication: https://doi.org/10.3233/JPD-213100

Abstract

Background: The association between restless legs syndrome (RLS) and Parkinson's disease (PD) remains controversial, with epidemiologic and descriptive evidence suggesting some potential overlap while mechanistic/genetic studies suggesting relative independence of the conditions.

Objective: To examine a known, objectively measured endophenotype for RLS, periodic leg movements (PLMS) in sleep, in patients with PD and relate that objective finding to restless legs symptoms.

Methods: We performed polysomnography for one (n = 8) or two (n = 67) consecutive nights in 75 PD patients and examined the association of PLMS with restless legs symptoms.

Results: We found no association between restless legs symptoms and PLMS in PD. Prevalence of both was similar to data reported previously in other PD samples.

Conclusion: We interpret these results as suggesting that restless legs symptoms in PD patients may represent a different phenomenon and pathophysiology than RLS in the non-PD population.

The prevalence and potential aetiological factors associated with restless legs syndrome in patients with chronic kidney disease: a cross-sectional study. International urology and nephrology

Brzuszek, A., Hazara, A. M., & Bhandari, S. (2022). , 10.1007/s11255-022-03166-9 [Titel anhand dieser DOI in Citavi-Projekt übernehmen] .

Advance online publication

Abstract

Background: There is limited understanding of aetiological factors of and treatment options for restless leg syndrome (RLS) in patients with chronic kidney disease (CKD). This study aimed to estimate the prevalence of RLS in CKD patients and identify factors that may contribute to RLS.

Methods: A questionnaire-based cross-sectional study of patients with CKD stage 4 (CKD 4), pre-dialysis stage 5 (CKD-5ND) and haemodialysis-dependent stage 5 (CKD-5D) was conducted. Eligible patients were enrolled from the local dialysis units and renal clinics. The International RLS Study Group rating scale was used to establish the diagnosis of RLS and quantify its severity.

Results: 212 patients with CKD 4 (n = 92), CKD-5ND (n = 14) and CKD-5D (n = 106) were included. The overall prevalence of RLS was 32.1%. Women had a significantly higher odds of having RLS despite adjustment for age, diabetes, cardiovascular disease and whether patients were on dialysis (odds ratio 2.8 [95% confidence intervals 1.5-5.2]). In pre-dialysis groups, patients with RLS had significantly higher serum ferritin (323.9 [SD 338.1] vs 177.5 [SD 178.5] µg/L, p = 0.020) compared to non-RLS patients. In dialysis patients (CKD-5D), those with RLS had significantly higher total white cell (8.0 [SD 3.5] vs 6.8 [SD 1.9] × 109/L, p = 0.026) and neutrophil (6.4 [SD 3.9] vs 4.6 [SD1.7] × 109/L, p = 0.002) counts compared to patients without RLS.

Conclusion: RLS remains a significant problem in patients with CKD and may be related to underlying inflammation. Targeting this pathway may be useful. Prevalence of RLS, diagnosed using validated measures, is higher than previous reports.

Impulskontrollstörning kan vara biverkan av dopaminagonister [Exposure to dopamine agonists for treatment of restless legs syndrome led to suffering of ICD].

Sklivanioti, M., & Greenfield, A. (2022). Lakartidningen, 119, 21192.

Abstract

Impulse control disorders (ICD) may occur with the use of dopamine agonists (DAA), a class of medication usually prescribed for Parkinson's disease but also restless legs syndrome (RLS) and prolactinoma. We describe a case that illustrates, in consistence with international literature, how exposure to DAA for treatment of RLS can lead to suffering of ICD with devastating consequences. Discontinuation of the dopaminergic agent (and potentially switching to another medication of a different class) can be an effective management strategy, and we suggest that it is very important to improve the knowledge of this phenomenon among clinicians and prompt active screening for ICD in this population.

Restless legs syndrome in patients with multiple sclerosis: evaluation of risk factors and clinical impact.

Lebrato Hernández, L., Prieto León, M., Cerdá Fuentes, N. A., Uclés Sánchez, A. J., Casado Chocán, J. L., & Díaz Sánchez, M. (2022). Neurologia (Barcelona, Spain), 37(2), 83–90.

https://doi.org/10.1016/j.nrleng.2018.12.018

Abstract

Introduction: Restless legs syndrome (RLS) is a disorder characterised by an irresistible urge to move the legs, usually accompanied by unpleasant sensations. It is more frequent in patients with multiple sclerosis (MS) than in the general population.

Objectives: To evaluate the prevalence of RLS, defined according to the 4 essential requirements included in the diagnostic criteria proposed by the International Restless Leg Syndrome Study Group, in a cohort of patients with MS; and to identify potential risk factors and the clinical impact of RLS.

Results: The sample included 120 patients with MS, with a mean age of symptom onset of 40 years and an average disease duration of 46 months. The prevalence rate of RLS was 23.3%. MS progression time was significantly shorter in patients with RLS (P=.001). A recent relapse, and symptoms of anxiety, depression, and neuropathic pain were significantly associated with risk of RLS (P=.001, P<.001, P<.001, and P=.001, respectively). In addition, patients with RLS had a greater risk of poor sleep quality, fatigue, daytime sleepiness, and poor quality of life than those without RLS (P=.002, P=.017, P=.013, and P=.009, respectively).

Conclusions: RLS should be considered in the neurological evaluation of patients with MS; early diagnosis and treatment would improve the quality of life of patients with MS presenting RLS.

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Brain Iron Deficiency Changes the Stoichiometry of Adenosine Receptor Subtypes in Cortico-Striatal Terminals: Implications for Restless Legs Syndrome.

Rodrigues, M. S., Ferreira, S. G., Quiroz, C., Earley, C. J., García-Borreguero, D., Cunha, R. A., Ciruela, F., Köfalvi, A., & Ferré, S. (2022). (Basel, Switzerland), 27(5), 1489.

https://doi.org/10.3390/molecules27051489

Abstract

Brain iron deficiency (BID) constitutes a primary pathophysiological mechanism in restless legs syndrome (RLS). BID in rodents has been widely used as an animal model of RLS, since it recapitulates key neurochemical changes reported in RLS patients and shows an RLS-like behavioral phenotype. Previous studies with the BID-rodent model of RLS demonstrated increased sensitivity of cortical pyramidal cells to release glutamate from their striatal nerve terminals driving striatal circuits, a correlative finding of the cortical motor hyperexcitability of RLS patients. It was also found that BID in rodents leads to changes in the adenosinergic system, a downregulation of the inhibitory adenosine A1 receptors (A1Rs) and upregulation of the excitatory adenosine A2A receptors (A2ARs). It was then hypothesized, but not proven, that the BID-induced increased sensitivity of cortico-striatal glutamatergic terminals could be induced by a change in A1R/A2AR stoichiometry in favor of A2ARs. Here, we used a newly developed FACS-based synaptometric analysis to compare the relative abundance on A1Rs and A2ARs in cortico-striatal and thalamo-striatal glutamatergic terminals (labeled with vesicular glutamate transporters VGLUT1 and VGLUT2, respectively) of control and BID rats. It could be demonstrated that BID (determined by measuring transferrin receptor density in the brain) is associated with a selective decrease in the A1R/A2AR ratio in VGLUT1 positive-striatal terminals.

Free full text available: https://www.mdpi.com/1420-3049/27/5/1489

Vitamin D Supplementation and Sleep: A Systematic Review and Meta-Analysis of Intervention Studies.

Abboud M. (2022). Nutrients, 14(5), 1076.

https://doi.org/10.3390/nu14051076

Abstract

Background: Vitamin D deficiency is associated with sleep disorders and poor sleep quality. Whether vitamin D supplementation (VDS) helps resolve these problems remains unclear.

Objective: To systematically review the effect of VDS on sleep quantity, quality, and disorders, and perform a meta-analysis of available data.

Methods: The reporting of this review followed the PRISMA statement. VDS human interventions studies that reported on sleep quality, quantity, or disorders were included. Medline, CINAHL, EMBASE, PsycInfo, the Cochrane Library, Clinicaltrials.gov, and the ICTRP were searched, in addition to the references of the included articles and previous relevant reviews, without language or time restrictions. Included studies were critically appraised, findings were narratively synthesized, and a meta-analysis was conducted. Furthermore, the overall certainty of the evidence was assessed.

Results: A total of 19 studies were included (13 randomized controlled trials (RCTs), 1 opportunistic addition to an RCT, 4 pre-post studies, and 1 pre-post study analyzed as a case series); 3 RCTs were meta-analyses. The risk of bias was generally low. Pre-post studies showed a significant improvement in sleep quality with VDS. Similarly, the results of the meta-analysis revealed a statistically significant decrease in the Pittsburgh Sleep Quality Index with VDS compared with placebo (mean difference, -2.33 (95% CI, -3.09, -1.57); p &lt; 0.001; I2 = 0%), with a moderate certainty of evidence. The results regarding the effect of VDS on sleep-related impairment, difficulty, and disorders, as well as sleepiness and restless legs syndrome, were not unanimous.

Conclusions: VDS is promising in improving sleep quality; however, its effect on sleep quantity and disorders needs to be further investigated.

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Restless legs syndrome severity in the National RLS Opioid Registry during the COVID-19 pandemic.

Wipper, B., Romero-Gutierrez, C., & Winkelman, J. W. (2022). Sleep medicine, 90, 96–101.

https://doi.org/10.1016/j.sleep.2022.01.011

Abstract

Objective/background: No research has yet assessed the impact of the coronavirus disease 2019 (COVID-19) pandemic on restless legs syndrome (RLS). We hypothesized that RLS symptom severity would be increased during the COVID-19 pandemic in a sample of patients with diagnosed RLS.

Patients/methods: The National RLS Opioid Registry is a longitudinal observational study of patients using opioid medications for treatment of RLS. Questionnaires assessing RLS symptom severity, medication dosages, sleep disturbance, depression, and anxiety are administered at baseline and at recurring 6-month surveys. Survey responses from the outset of the pandemic in April/May 2020 were compared to responses completed by other participants in January/February 2020 (between-subjects analysis), as well as responses by the same participants at baseline, approximately six months later in September 2020 through February 2021, and approximately one year later in March through June 2021 (within-subjects analyses).

Results: These analyses provide evidence for higher RLS symptom severity scores at the outset of the COVID-19 pandemic in the US. Symptom severity scores were still elevated on subsequent questionnaires completed over six months into the pandemic but had returned towards baseline by the spring of 2021. Participants with increases in RLS severity were significantly more likely than others to see increases in sleep disturbance, depression, and anxiety.

Conclusions: This is the first study demonstrating increased RLS symptom severity during the earliest stage of the COVID-19 pandemic. These findings warrant similar investigations in other patient populations and suggest that clinicians should attend to RLS symptoms during times of socioeconomic and/or political uncertainty.

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Restless legs syndrome affecting the head region: "restless head syndrome"

Balgetir, F., Gönen, M., Berilgen, A., Aytaç, E., Demir, C. F., & Müngen, B. (2022). Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology, 43(4), 2565–2570.

https://doi.org/10.1007/s10072-021-05667-4

Abstract

Objective: Restless legs syndrome (RLS) is a well-established disease that has recently been shown to have variants affecting the arms, face, abdomen, and genital area. To our knowledge, there has been no study reporting on the RLS variant affecting the head region.

Methods: The retrospective study reviewed a total of 460 patients who presented to Fırat University Medical School and were diagnosed as having RLS based on the International Restless Legs Syndrome Study Group (IRLSSG) criteria between June 2017 and January 2020. Of these, 18 patients that presented with head-related RLS symptoms (in addition to legs or arms) and four cases that presented with isolated head involvement were included in the study.

Results: In 15 out of 18 (81.8%) patients, the restless head syndrome was accompanied by restless arm syndrome (RAS). In the remaining four (18.2%) patients, the disease involved the head region alone. The disease initially emerged in a single region in the body and gradually spread to one or multiple other regions in most patients and the symptoms were relieved by head rubbing. Serum iron level was low in 8 (36.4%) patients and normal in 14 (63.6%) patients. All the patients had normal cranial imaging and the symptoms were eliminated after dopaminergic therapy.

Conclusions: Although RLS typically involves the legs alone, it may also affect other body parts such as upper extremities, abdomen, face, and genital area. We propose that the novel RLS variant described in the present study could be termed "restless head syndrome."

Restless Legs Syndrome among patients receiving antipsychotic and antidepressant drugs.

Elrassas, H. H., Elsayed, Y., Abdeen, M. S., Shady, M. M., Shalash, A., & Morsy, M. (2022). Human psychopharmacology, 37(2), e2817.

https://doi.org/10.1002/hup.2817

Abstract

Background: Patients with Restless Legs Syndrome (RLS) experience psychological distress and diminished quality of life. Antipsychotics and antidepressants are known to be linked to RLS.

Aims: This study aims to investigate the presence of RLS in psychiatric patients who receive antipsychotic and antidepressant drugs and to determine potential risk factors for its occurrence.

Methods: Two hundred patients who received antipsychotic and antidepressant drugs for more than 1 month were recruited from two tertiary psychiatric centers in Cairo, Egypt. One hundred apparently healthy volunteers were also included. All patients and controls were screened using the four-items questionnaire (Arabic version) for RLS. RLS severity was scored according to the validated Arabic version of International Restless Legs Syndrome Study Group rating scale (IRLS). Mimicking conditions were carefully investigated and excluded.

Results: Forty-one percent of the patients who receive antipsychotic and antidepressant drugs were found to have RLS. Family history, past history and smoking are potential risk factors. Trazodone and haloperidol were less associated with RLS.

Conclusions: Although limited by its cross-sectional design, these findings suggest that patients who receive antipsychotic and antidepressant are susceptible to RLS. However, these results need to be replicated on a wider scale.

Stroke-related restless legs syndrome: epidemiology, clinical characteristics, and pathophysiology.

Wang, X. X., Feng, Y., Tan, E. K., Ondo, W. G., & Wu, Y. C. (2022). Sleep medicine, 90, 238–248.

https://doi.org/10.1016/j.sleep.2022.02.001

Abstract

Stroke-related restless legs syndrome (RLS) is one of stroke-related sleep disorders, which may be due to de novo RLS after stroke onset or an exacerbation of RLS symptoms after incident stroke. To date, the diagnostic rate of stroke-related RLS is low but it has a significant effect on patients' daily life and functional outcome. This review provides an overview of the epidemiology, clinical characteristics, pathophysiology, and impact on functional outcome of stroke-related RLS.

Recognition of emotional face expressions in patients with restless legs syndrome.

Mail Gurkan, Z., Tantik Pak, A., Parlakkaya, F. B., Kilicarslan, T., Yilmaz, O., & Sengul, Y. (2022). Applied neuropsychology. Adult, 1–6. Advance online publication.

https://doi.org/10.1080/23279095.2022.2043326

Abstract

Objective: Restless legs syndrome (RLS) is one of the commonest neurologic diseases. Along with sensory and motor symptoms, cognitive impairment and psychiatric features can be seen with RLS. The present study, was planned to look for evidence of cognitive impairment by evaluating facial emotion recognition (FER) in patients with RLS.

Methods: In this study, 80 patients with RLS and 50 healthy controls (HCs) were included. Demographic data were recorded. All patients with RLS and HCs were tested with Beck anxiety inventory (BAI), Beck depression inventory (BDI) and with Ekman's test for recognition of facial emotions.

Results: Sixty-three of the patients with RLS and 37 of the HCs were female. The mean age of the patients was 45.41 ± 8.24, and the mean age of HCs was 43.12 ± 10.35. The patients and HCs were similar regarding sex, age, educational status, and marital status. Patients with RLS had FER difficulties comparing HCs. There was a negative correlation between Ekman's test scores and BDI (r = -0.311, p < 0.001) and BAI scores (r = -0.379, p < 0.001).

Conclusion: FER is an invaluable research topic regarding cognitive function in RLS, which may help us develop different perspectives in terms of revealing the pathophysiology and is very important for the well-being of the patients' social interactions.

Serum Trace Elements Concentrations in Patients with Restless Legs Syndrome.

Jiménez-Jiménez, F. J., Ayuso, P., Alonso-Navarro, H., Calleja, M., Díez-Fairén, M., Álvarez, I., Pastor, P., Plaza-Nieto, J. F., Navarro-Muñoz, S., Turpín-Fenoll, L., Millán-Pascual, J., Recio-Bermejo, M., García-Ruiz, R., García-Albea, E., Agúndez, J., & García-Martín, E. (2022). Antioxidants (Basel, Switzerland), 11(2), 272.

https://doi.org/10.3390/antiox11020272

Abstract

Increased brain and serum zinc levels in patients with idiopathic restless legs syndrome (idiopathic RLS or iRLS) were described when compared with controls, suggesting a possible role of zinc in the pathogenesis of this disease. However, serum magnesium, calcium, manganese, iron, and copper levels of RLS patients were similar to controls, suggesting a specific impairment of zinc-dependent metabolism in RLS. The aim of this study is to assess the serum concentrations of trace elements involved in oxidative stress or causing peripheral nerve toxicity in a large series of patients with iRLS and controls. We determined serum levels of iron, copper, manganese, zinc, magnesium, selenium, calcium, aluminium, lead, cadmium, arsenic and mercury in 100 patients diagnosed with iRLS and in 110 age- and sex-matched controls using Inductively Coupled Plasma Mass Spectrometry. Serum copper, magnesium, selenium, and calcium concentrations were significantly higher in RLS patients than in controls. These differences were observed both in men and women. There were no major correlations between serum trace metal concentrations and age at onset of RLS or RLS severity, nor was there any association with a family history of RLS or drug response. This study shows an association between increased serum concentrations of copper, magnesium, selenium, and calcium with RLS in a Spanish Caucasian population and does not confirm the previously reported increase in serum zinc concentrations in patients suffering from this disease, suggesting that the different accuracy of the analytical methods used could have influenced the inconsistent results found in the literature.

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Coexistence of restless legs syndrome and multiple sclerosis aggravates anxiety and depression.

Sevim, S., Demirkiran, M., Terzi, M., Yüceyar, N., Taşdelen, B., Idiman, E., Kürtüncü, M., Boz, C., Tuncel, D., Karabudak, R., Siva, A., Özcan, A., Neyal, M., Göksel, B. K., Gazaloğlu, G. B., Balal, M., Şen, S., Baklan, M. A., Gündüz, T., Tuncer, A., … Uygunoğlu, U. (2022). Arquivos de neuro-psiquiatria, 80(2), 168–172.

https://doi.org/10.1590/0004-282X-ANP-2020-0400

Abstract

Background: Among the comorbidities that accompany multiple sclerosis (MS), restless legs syndrome (RLS) is one of the most common. Anxiety and depression are common psychological comorbidities that impact the quality of life of patients with MS (PwMS), as well as patients with RLS.

Objective: To investigate the psychiatric burden of MS and RLS coexistence, we conducted a nationwide, multicenter and cross-sectional survey.

Methods: Participants were assessed by using demographic and clinical parameters along with the Hamilton Anxiety and Hamilton Depression Scales (HAM-A and HAM-D).

Results: Out of the 1,068 participants, 173 (16.2%) were found to have RLS [RLS(+)] and 895 (83.8%) did not [RLS(-)]. The mean scores for HAM-A and HAM-D were significantly higher among RLS(+) subjects than among RLS(-) subjects (p<0.001 for all variables).

Conclusions: According to our data, the presence of RLS in PwMS may increase the occurrence of both anxiety and depression symptoms. Awareness and treatment of RLS in PwMS could possibly reduce the symptoms of psychiatric comorbidities originating from RLS.

A longitudinal study of restless legs symptoms among patients with depression.

Auvinen, P., Koponen, H., Kautiainen, H., Korniloff, K., Ahonen, T., Vanhala, M., & Mäntyselkä, P. (2022). Nordic journal of psychiatry, 1–7. Advance online publication.

https://doi.org/10.1080/08039488.2022.2038265

Abstract

Background: The aim of this study was to analyse the relationship between depressive symptoms and clinical depression and restless legs symptoms in a longitudinal primary care setting.

Methods: The prevalence of restless legs symptoms at baseline and after a six-year follow-up was studied in 474 patients with depressive symptoms and 333 population-based control subjects without depressive symptoms. Depressive symptoms at the baseline and after the six-year follow-up were evaluated with the Beck Depression Inventory (BDI) Second Edition. A psychiatric diagnosis was confirmed with a diagnostic interview (M.I.N.I.). Statistical comparisons between groups were made using analysis of variance (ANOVA) for continuous variables and a chi-square test or logistic models for categorical variables. Repeated measures were analysed using generalizing estimating equations (GEE) models.

Results: At baseline the prevalence of restless legs symptoms was 24.3% in control subjects, 43.8% in the patients with depressive symptoms without a depression diagnosis, and 49.3% in clinically depressed patients. During the follow-up up the prevalence of restless legs symptoms declined significantly (p = 0.003). In addition to baseline restless legs symptoms, the prognostic factors for restless legs symptoms among patients with clinical depression were age and BDI score. In the control subjects, moderate and high leisure time physical activity was inversely associated with restless legs symptoms at the follow-up.

Conclusions: A higher level of baseline depressive symptoms was a risk factor for restless legs symptoms in patients with clinical depression. In the prevention and treatment of restless legs symptoms among the patients with depression, the priority is the effective treatment of depression.

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F wave in restless legs syndrome, as an electrophysiological response of clinical relief.

Kenar, S. G., Dirik, E. B., Tutal Gursoy, G., Kayali, N., & Bilen, S. (2022). Neurological research, 1–7. Advance online publication.

https://doi.org/10.1080/01616412.2022.2042123

Abstract

Objective: The study aimed to evaluate the impact of postural changes on the F wave-related parameters and whether those changes were associated with clinical relaxation, which was achieved in restless legs syndrome patients with standing up.

Methods: F wave duration (FWD), compound muscle action potential duration (CMAPD), and FWD/CMAPD ratio were evaluated in supine and upward positions in 18 restless legs syndrome patients and compared with 18 age and gender-matched healthy volunteers.

Results: FWD/CMAPD was significantly higher for the tibial nerve at supine position (p = 0.043) but not at upright position (p = 0.206) and for ulnar nerve, both at supine (p = 0.007) and upright positions (p = 0.023) in RLS patients compared to controls. Ulnar FWD decreased significantly at the upright position in both control and RLS patients (p = 0.035, p = 0.028, respectively). CMAPD decreased only in the control group with standing up for both ulnar and tibial nerves (p = 0.048, p = 0.017, respectively).

Discussion: Ulnar and tibial FWD/CMAPD ratios increased in RLS patients compared to controls. However, FWD/CMAPD was not affected by the posture within the groups. Postural change seems to be a factor that decreased ulnar FWD both in RLS patients and the control group. Ulnar and tibial CMAPD reduced only in healthy controls with an upright position. Tibial and ulnar FWD/CMAPD ratios are favorable electrophysiological parameters diagnosing RLS. The tibial FWD/CMAPD ratio loses its significance only when the patient stands up, reflecting the clinical relief achieved with the postural change.

Prevalence of restless legs syndrome in pregnant women: a systematic review and meta-analysis.

Abdi, A., Hussein Shareef, O., Dalvand, S., Ghanei Gheshlagh, R., & Hasanpour Dehkordi, A. (2021). Przeglad epidemiologiczny, 75(3), 402–412.

https://doi.org/10.32394/pe.75.37

Abstract

Background: Restless legs syndrome (RLS) is a neurological disorder characterized by sleep disorders, which leads to adverse health consequences in the mother and fetus. Studies have reported different prevalence rates for RLS in pregnant women. This systematic review and meta-analysis aimed to estimate the prevalence of RLS in pregnant women.

Methods: A literature search was performed via national and international databases, including Scientific Information Database (SID), MagIran, IranMedex, Google Scholar, Science Direct, PubMed, ProQuest, and Scopus. In total, 31 articles were selected without a time limit. The random effects model was used to analyze the data, and the heterogeneity between the studies was examined using the I2 index. The analyses were performed in the Stata software, version 12 and R, version 4.

Results: The reviewed studies (n=31) were conducted on a total sample size of 59,151, and the prevalence of RLS in pregnant women was estimated at 21.4% [95% confidence interval CI: 17.7-25.1]. Asia with a prevalence rate of 18.5%, [95% CI: 13.8-23.1] and Europe with a prevalence rate of 25.5%, [95% CI: 19.5-31.6] had the lowest and highest RLS prevalence, respectively. No significant correlations were observed between the prevalence of RLS, publication year of the articles (P=0.972), and participants' age (P=0.202).

Conclusion: According to the results, RLS is highly common in pregnant women, and it is essential to identify women with RLS to control and eliminate the adverse consequences of the disorder.

The Role of Vitamin D in Sleep Disorders of Children and Adolescents: A Systematic Review.

Prono, F., Bernardi, K., Ferri, R., & Bruni, O. (2022). International journal of molecular sciences, 23(3), 1430.

https://doi.org/10.3390/ijms23031430

Abstract

This review investigates the association between vitamin D and sleep disorders. Vitamin D is an essential nutrient known to play an important role in the growth and bone health of the human body, but it also appears to play a role in sleep. The goal of our review is to examine the association between vitamin D and sleep disorders in children and adolescents. We summarize the evidence about the role and the mechanism of action of vitamin D in children and adolescents with sleep disorders such as insomnia, obstructive sleep apnea (OSA), restless legs syndrome (RLS), and other sleep disorders. Systematic electronic database searches were conducted using Pubmed and Cochrane Library. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was followed. The studies that met the established inclusion criteria were analyzed and compared. Results suggest a strict relationship between vitamin D deficiency in children and sleep disorders. There is evidence that vitamin D is implicated in the different neurochemical mechanisms involved in sleep regulation and mainly in the serotonergic and dopaminergic pathways. This might be responsible for the association of vitamin D deficiency and restless sleep, sleep hyperhidrosis, OSA, and RLS.

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Leg movement activity during sleep in multiple sclerosis with and without restless legs syndrome.

Ferri, R., Sparasci, D., Castelnovo, A., Miano, S., Tanioka, K., Tachibana, N., Carelli, C., Riccitelli, G. C., Disanto, G., Zecca, C., Gobbi, C., & Manconi, M. (2022). Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine, 18(1), 11–20.

https://doi.org/10.5664/jcsm.9466

Abstract

Study objectives: To carry out an analysis of leg movement activity during sleep in a polysomnography dataset of patients with multiple sclerosis (MS) in comparison to idiopathic restless legs syndrome (iRLS) and healthy controls.

Methods: In this cross-sectional, observational, instrumental study, 57 patients (males/females: 11/46; mean age 46.2 ± 10.2 years) with a diagnosis of MS underwent a telephone interview assessing the 5 standard diagnostic criteria for RLS and polysomnography. Sleep architecture and leg movement activity during sleep were subsequently compared: 1) 40 patients with MS without RLS (MS-RLS) vs 28 healthy controls; 2) 17 patients with MS with RLS (MS+RLS) vs 35 patients with iRLS; 3) MS+RLS vs MS-RLS.

Results: MS-RLS and MS+RLS presented increased sleep latency, percentage of sleep stage N1, and reduced total sleep time compared to healthy controls and iRLS, respectively. The periodic limb movements during sleep (PLMS) index was higher in MS-RLS than in healthy controls (P = .035) and lower in MS+RLS compared to iRLS (P = .024). PLMS in MS+RLS were less periodic, less often bilateral, and with shorter single movements compared to the typical PLMS in iRLS.

Conclusions: MS is a risk factor for RLS, PLMS, and for a lower sleep quality in comparison to healthy patients. PLMS in MS+RLS are fewer and shorter if compared to iRLS. Our results suggest a dissociation between motor (PLMS) and sensory symptoms (RLS sensory component) in RLS secondary to MS, with possible treatment implications.

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