International Restless Legs Syndrome Study Group Research Articles

Cost-effectiveness of TOMAC therapy for medication-refractory restless legs syndrome: an updated analysis based on Extension study data

Aims Patients with medication-refractory restless legs syndrome (RLS) have limited therapeutic options available for symptom relief. Tonic motor activation (TOMAC) presents a novel, non-invasive therapy for this patient population. The aim of this study was to conduct an updated cost-effectiveness analysis of TOMAC therapy based on recently available longer-term follow-up data. Materials and Methods A previously published decision-analytic Markov model was utilized to project strategy-specific costs and outcomes over three-years and lifetime for TOMAC compared to status quo treatment (control). Cohort characteristics were based on 24-week clinical data from the extension cohort of the RESTFUL study, which included longer-term follow-up of RESTFUL completers who were assigned to continue or discontinue TOMAC use (TOMAC and control, respectively). The primary analysis outcome was the incremental cost-effectiveness ratio (ICER) in $ per quality-adjusted life year (QALY) gained, calculated using change in International RLS Study Group Rating Scale (IRLS) score as the effect measure. Extensive sensitivity analyses were performed. Results TOMAC treatment improved IRLS by 5.9 versus control, resulting in estimated utility improvement of +0.05. Over three-years and lifetime, TOMAC added 0.14 and 0.73 QALYs, at incremental costs of $6,751 and $27,440, resulting in projected ICERs of $47,609 and $37,823 per QALY gained, respectively. TOMAC was found to be cost-effective across all tested sensitivity analyses. Limitations and Conclusion The inclusion of longer follow-up data in the current analysis confirms earlier exploratory cost-effectiveness findings and suggest TOMAC therapy may provide a high-value treatment option for patients with medication-refractory RLS.

A síndrome das pernas inquietas

Restless legs syndrome is a disorder of unknown cause that causes an irresistible urge to move the lower limbs, worsening at night, greatly disturbing sleep, with a consequent poor quality of life. It may begin in childhood, but diagnosis is usually late. It is also known as Willis-Ekbom Disease. It affects between 10% and 15% of the population. Iron deficiency is a frequently mentioned cause, which is why the study of iron metabolism is recommended. Clinical evaluation is normal, and it helps to identify possible secondary causes. The criteria for diagnosis were developed by the International Restless Legs Syndrome Study Group (IRLSG). In treatment, it is necessary to correct iron deficits and prescribe dopamine agonists. Many patients experience worsening of symptoms as they age.

Association between inflammatory cytokines and disease severity in restless legs syndrome.

This study aims to evaluate serum cytokine levels in individuals with primary Restless Legs Syndrome (RLS) and analyze their correlation with RLS symptom severity, sleep disturbances, anxiety, and depression. A case-control study was conducted involving 87 primary RLS patients and 100 healthy individuals undergoing health check-ups. Serum cytokine levels were assessed, and RLS severity was evaluated using the International Restless Legs Syndrome Study Group (IRLSSG) rating scale. Additionally, the Pittsburgh Sleep Quality Index (PSQI), 24-item Hamilton Depression Rating Scale (HAMD24), and 14-item Hamilton Anxiety Rating Scale (HAMA14) were utilized to assess symptom severity, sleep disturbances, and emotional states in RLS patients. Serum cytokine levels, including IL-6 and TNF-α, were significantly higher in RLS patients compared to controls (P < 0.05). Adjustment for disease duration, sex, age, BMI, SBP, and DBP revealed an independent association between serum IL-6 and RLS (OR = 1.46; 95% CI = 1.02-1.93; P = 0.003). Linear regression analysis demonstrated a significant correlation between IL-6 levels and IRLS scores (β = 0.123, P = 0.008). Elevated circulating levels of inflammatory cytokines in RLS patients suggest a potential role of inflammation in the pathogenesis of primary RLS. Additionally, serum cytokine levels correlate closely with disease severity.

Efficacy and safety of TOMAC for treatment of medication-naïve and medication-refractory restless legs syndrome: A randomized clinical trial and meta-analysis

Objective/backgroundThere is a significant unmet need for safe and effective nonpharmacological therapies for restless legs syndrome (RLS). The objective was to evaluate the efficacy and safety of tonic motor activation (TOMAC) in patients with RLS. Patients/methodsA multicenter, randomized, participant-blinded, sham-controlled trial enrolled 45 adults with primary moderate-to-severe RLS who were either medication-naïve (n = 20) or medication-refractory (n = 25). Participants were 1:1 randomized to TOMAC (n = 22) or sham (n = 23) for two weeks and instructed to self-administer 30-min TOMAC sessions when they experienced RLS symptoms. The primary outcome was mean change in International RLS Study Group Rating Scale (IRLS) total score. A subsequent meta-analysis included the present trial and a previous randomized clinical trial that enrolled medication-naïve RLS patients. ResultsIRLS reduction was significantly greater for TOMAC than sham (TOMAC -6.59 vs. sham −2.17; mean difference (MD) = −4.42; 95 % confidence interval [CI] −1.57 to −7.26; p = 0.0040). Subgroup analysis showed similar IRLS mean difference for medication-refractory (MD = −4.50; p = 0.02) and medication-naïve (MD = −4.40; p = 0.08) cohorts, which was significantly different from sham only for the medication-refractory cohort. Meta-analysis of combined data from 33 medication-naïve RLS patients showed a significant reduction in mean IRLS score after two weeks for TOMAC compared to sham (MD = −4.30; 95 % CI -1.36 to −7.24; p = 0.004). ConclusionsThe present trial confirmed previous reports documenting efficacy and safety of TOMAC in refractory RLS and indicated similar effect sizes in refractory versus naïve subgroups. The meta-analysis demonstrated that TOMAC significantly improves RLS symptoms in naïve participants.

Effect of Restless leg syndrome on the sleep quality of medical students of university in rural Sindh

Background: Restless legs syndrome a neurological condition its symptoms appear with gnawing sensation, cramps and feels like unpleasant sensations during period of rest and mid of sleep. A set of criteria for a more consistent diagnosis of this condition, which frequently causes severe sleep problems, it was devised and published by the recently established International RLS Study Group (IRLSSG) fifty years later the research has shown that, although its symptoms are preventable and manageable, but RLS is still under diagnosed since the IRLSSG criteria were published. Materials and methods: All medical students were considered as the population of the study. Convenient specific young adults selected a sample of 200 students. Besides that, students with a history of trauma and infection had exaggerated routines and recent viral infections also having pain with cramps in calf muscles, which increased during inactivity and rest at night. The questionnaires were administered from the students, with the permission of the ethical review committee of Bhitai dental &amp; medical College Mirpurkhas. Informed consent-form taken. Data collection procedures were applied standard questionnaire used International Restless Legs Syndrome Study Group (IRLLSG). The data were analyzed by SPSS-25. Percentage, mean, standard deviation, and chi-square were applied to measure the severity and overall score of RlS. Result: The medical students 119 were male and 81 female. Participants had demographic data mean of age 1.26, (SD=.544). 57.5% male, 42.5% female in the age group of 18–28. Sleep problem were found in male had moderate 25 (21.0%) and severe in 15 (12.6%) students, in very severe of RLS symptoms were less in count 13 (10.9%), A female participant was affected with RLS moderate 54 (27.0%), mild in 43 (21.5%), moderate RLS in 26 (32.1%) some participants in severe had low 30 (15.0%) RLS found, moreover participants had none 20 (24.5%) RLS symptoms. The significant valued (p=.296). Conclusion: It was concluded that RLS is a sleep disorder it mostly in male than female students. Severity of RLS symptoms mild to moderate among participants.

Restless Legs Syndrome Affects Sleep in de novo Parkinson's Disease Patients.

Restless legs syndrome (RLS) is common in Parkinson's disease (PD) patients and can affect the motor symptoms and non-motor symptoms (NMSs) of PD patients. This study aimed to identify the clinical factors affected by RLS in patients with PD. We included 369 de novo PD patients. RLS was assessed by face-to-face interviews and the motor symptoms and NMSs of the patients were assessed using relevant scales. RLS frequency in the patients was 12.2% (45/369). PD patients with RLS (PD-RLS) exhibited a greater global Pittsburgh Sleep Quality Index (PSQI) score than those without RLS (PD-No RLS). PD-RLS exhibited significantly greater scores in the daytime dysfunction and sleep disturbances components of the PSQI than PD-No RLS. PD-RLS exhibited a significantly greater score in the sleep/fatigue domain of the Non-Motor Symptoms Scale than PD-No RLS. The International RLS Study Group rating scale score was significantly related to PSQI components scores in the sleep disturbances, sleep latency, habitual sleep efficiency, and subjective sleep quality. RLS frequency in de novo PD patients is higher than that in the general population, and the main NMS affected by RLS in these patients is sleep disturbances. Therefore, it is necessary to manage RLS in PD patients with sleep disturbances.

Restless leg syndrome in systemic lupus erythematosus: Associations with disease activity, quality of life and depression

ObjectivesThe aim of this study was to determine the prevalence of restless leg syndrome (RLS) among patients with SLE, describe their clinical characteristics, examine its impact on health-related quality of life (HRQoL), and evaluate its association with depression. MethodsA total of 124 SLE patients were recruited, with data on demographics, and clinical features collected. RLS diagnosis was based on the international RLS study group criteria, while depression was assessed by the patient health questionnaire. HRQoL was assessed by a disease-specific validated questionnaire, the LupusQoL, pain intensity was examined through the pain visual analogue scale, and disease activity was evaluated via the patient global assessment. These variables were compared between SLE patients with RLS and without RLS using t-tests or Wilcoxon and the chi-square test of independence for categorical variables. A p-value ≤0.05 was considered statistically significant. ResultsAmong the SLE patients (mean age 48, 87.1 % women), 32 % had RLS. The SLE patients with RLS were found to have a longer delay in diagnosis (1 vs 0.5 years; p = 0.019) and were less likely to be employed (65 % vs 45 %, p = 0.040) compared to non-RLS patients. In addition, RLS patients were more likely to have coexisting Major Depressive Disorder (MDD) (p = 0.019), higher levels of pain (p = 0.006) and disease activity based on patient global assessment (p = 0.014). Further, most of the domains of LupusQoL were significantly lower in the RLS patients group suggesting a worse HRQoL. ConclusionRLS was present in one-third of the SLE cohort, significantly impairing HRQoL and correlating with depression, higher pain, and increased disease activity. These findings underscore the importance of early RLS detection and management in SLE patients.

The Frequency and Associated Factors of Restless Leg Syndrome among Pregnant Women in 3rd Trimester

Background: Restless leg syndrome (RLS), also known as Willis-Ekbom disease, is characterized by an uncomfortable sensation in the legs, often occurring at the onset of sleep, which triggers an irrepressible urge to move the legs. This condition is particularly prevalent among pregnant women, with symptoms typically worsening during the third trimester. Despite its impact, many pregnant women are unaware of RLS, attributing their discomfort to normal pregnancy symptoms. Objective: To assess the frequency and associated factors of RLS in pregnant females during the third trimester and to evaluate its impact on their quality of life. Methods: A cross-sectional study was conducted involving 250 pregnant females in their third trimester, recruited from Shalimar Hospital, Nawaz Sharif Hospital, Zahida Welfare Trust, Alshad Clinic, Ali Hospital, Ahsan Hospital, Nargis Clinic, Manawa Government Hospital, and Sultan Medical Center. Participants aged 15-45 years were included, while those with rheumatoid arthritis, diabetes mellitus, neurological disorders, preeclampsia, and gestational diabetes mellitus were excluded. Data were collected using structured questionnaires incorporating the International Restless Legs Syndrome Study Group (IRLSSG) criteria and the Pittsburgh Sleep Quality Index (PSQI). Ethical approval was obtained, and the study adhered to the Declaration of Helsinki principles. Statistical analysis was performed using SPSS version 25, with descriptive statistics, frequencies, and graphical representations employed to summarize and analyze the data. Results: The mean age of participants was 26.32 years (SD = 5.08). The prevalence of RLS in the third trimester was found to be 89.2%. The age group most affected was 18-23 years. Factors associated with RLS included inadequate calcium intake (40.4%), insufficient daily water intake (40.4%), poor food intake (48%), mood disturbances (89.2%), lack of movement or light exercise (78%), caffeine consumption (16%), disturbances in sexual activities (48%), and disruption in daily activities (45.2%). Conclusion: RLS is highly prevalent among pregnant women, particularly in the third trimester, significantly impacting their quality of life. Despite its prevalence, many women remain unaware of RLS, mistaking it for typical pregnancy discomfort. Raising awareness and implementing screening and management strategies during prenatal care could improve the quality of life for affected women.

A comprehensive look at inflammation in RLS: assessing NLR, MLR, PLR, SII, SIRI, and microR

Aims: Restless legs syndrome (RLS) has been linked to systemic inflammation. The number of studies investigating inflammation in RLS patients is extremely limited. The purpose of this study is to examine the possible role of proinflammatory parameters in RLS, specifically neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), systemic inflammatory response index (SIRI), and microR.&#x0D; Methods: The study included 100 patients admitted to the neurology outpatient clinic diagnosed with RLS using the International Restless Legs Syndrome Study Group ((IRLSSG) scale and 100 healthy controls. Hemogram results were obtained from both RLS patients and healthy controls, while ferritin, folate, vitamin D and B12, and C-reactive protein (CRP) levels were obtained only from RLS patients.&#x0D; Results: The median age of the patient group was 52.50 (43-60.75), while the median age of the healthy group was 51.00 (50-53). The patient group is 37% male, while the healthy group is 34% male. It doesn't vary by age or gender (p=0.658). The two groups showed significant differences in PLR (

Restless legs syndrome in patients with obstructive sleep apnea: Association between apnea severity and symptoms of depression, insomnia, and daytime sleepiness

ObjectiveTo determine if the prevalence and severity of restless legs syndrome (RLS) varies with apnea severity and analyze differences between the sexes in terms of comorbid RLS with symptoms of depression, insomnia, and daytime sleepiness in patients with obstructive sleep apnea (OSA). MethodsSymptoms of depression, insomnia, and daytime sleepiness were defined as Patient Health Questionnaire–9 score ≥10, Insomnia Severity Index score ≥15, and Epworth Sleepiness Scale score ≥11. Multivariate logistic and linear regression analyses were conducted. ResultsIn 707 adults with OSA (85.1% males), 16.1% (n = 114) had comorbid RLS. The prevalence of RLS was markedly lower in those with moderate and severe OSA than in those with mild OSA. Similarly, the odds of RLS significantly decreased with increasing apnea-hypopnea index. After controlling for age and sex, in patients with comorbid RLS, the International RLS Study Group Rating Scale scores were negatively correlated with apnea-hypopnea index and a nadir peripheral oxygen saturation during sleep. The presence of RLS was more likely to be associated with symptoms of depression, insomnia, and daytime sleepiness after controlling for confounding variables, but only in men. ConclusionsRLS is frequently noted in combination with OSA, with a female preponderance. The severities of OSA and RLS may be negatively associated. In patients with OSA, sex-related differences in terms of comorbid RLS with symptoms of depression, insomnia, and daytime sleepiness warrant further investigations.

Correlates of Restless Legs Syndrome in Older People.

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

The Melanocortin and Endorphin Neuropeptides in Patients with Restless Legs Syndrome.

Based upon similarities between the urge to move and sensory discomfort of restless legs syndrome (RLS) and properties of melanocortin hormones, including their incitement of movement and hyperalgesia, we assessed plasma and cerebrospinal fluid (CSF) α-melanocyte-stimulating hormone (α-MSH) and β-endorphin in RLS patients and controls. Forty-two untreated moderate-to-severe RLS patients and 44 matched controls underwent venipuncture at 19:00, 20:30, and 22:00; 37 RLS and 36 controls had lumbar puncture at 21:30. CSF and plasma were analyzed for pro-opiomelanocortin (POMC), adrenocorticotropin hormone (ACTH), α-MSH, β-MSH, and β-endorphin by immunoassay. RLS severity was assessed by International RLS Study Group Severity Scale. RLS participants were 52.7 ± 12.0 years old, 61.9% were women, 21.4% had painful RLS, and RLS severity was 24.8 ± 9.0. Controls had similar age and sex. Plasma ACTH, α-MSH, and β-endorphin were similar between groups. Plasma POMC was significantly greater in RLS than controls (17.0 ± 11.5 vs 12.7 ± 6.1fmol/ml, p = 0.048). CSF ACTH was similar between groups. CSF β-MSH was significantly higher in painful than nonpainful RLS or controls (48.2 ± 24.8 vs 32.1 ± 14.8 vs 32.6 ± 15.2pg/ml, analysis of variance [ANOVA] p = 0.03). CSF α-MSH was higher in RLS than controls (34.2 ± 40.9 vs 20.3 ± 11.0pg/ml, p = 0.062). CSF β-EDP was lowest in painful RLS, intermediate in nonpainful RLS, and highest in controls (8.0 ± 3.4 vs 10.8 ± 3.1 vs 12.3 ± 5.0pg/ml, ANOVA p = 0.049). The ratio of the sum of CSF α- and β-MSH to CSF β-endorphin was highest, intermediate, and lowest in painful RLS, nonpainful RLS, and controls (p = 0.007). CSF β-MSH is increased and CSF β-endorphin decreased in RLS patients with painful symptoms. ANN NEUROL 2024;95:688-699.

Evaluation of Restless Leg Syndrome in Patients with Non-Dialysis Dependent Chronic Kidney Disease at Fatima Memorial Hospital Lahore: A Cross-sectional Study

Objective: To determine the occurrence of restless leg syndrome in individuals with non-dialysis-dependent chronic kidney disease.Study Design: A descriptive cross-sectional study.Place and Duration of Study: The study was carried out at the Outpatient Department (OPD) of Fatima Memorial Hospital, Lahore, Pakistan, from March 2020 to August 2020.Methods: A total of 280 CKD patients not dependent on dialysis were included in the study. The data were collected through interviews containing questions from international restless leg syndrome study group (IRLSSG). Patients were stratified into different stages according to the estimated glomerular filtration rate (eGFR). Restless leg syndrome was diagnosed by analyzing the responses of the interview marked by the examiner. Results: Among 280 patients, 15.7% (n=44) of chronic kidney disease patients were noted to have restless leg syndrome. The syndrome was significantly more frequent in females and was associated with higher CKD stages (Stage V &gt; Stage III and IV). There was no association with either age or BMI.Conclusion: Restless leg syndrome is more common in chronic kidney disease stage V as compared to lower chronic kidney disease stages (III &amp; IV). If untreated, it can affect patients' quality of life and increase the risk of cardiovascular activities.&#x0D; How to cite this: Basit MB, Sabir O, Shahid AH, Kanwal A, Qadri GA, Rizvi N. Evaluation of Restless Leg Syndrome in Patients with NonDialysis Dependent Chronic Kidney Disease at Fatima Memorial Hospital Lahore: A Cross-sectional study. Life and Science. 2024; 5(1): 95-100.doi: http://doi.org/10.37185/LnS.1.1.516

Prevalence and clinical correlates of restless legs syndrome in psychiatric patients: A cross-sectional study from North India.

Restless legs syndrome (RLS) is a neuro-sensorimotor disorder which is scarcely researched and is commonly missed in routine psychiatry practice. To evaluate the prevalence of RLS and its correlates in patients with anxiety, depression, and somatoform disorders. A cross-sectional single-center study was undertaken in patients aged 18-65 years suffering from ICD-10 (International Statistical Classification of Diseases-10th edition) diagnosis of anxiety, depressive, and somatoform disorders. RLS was evaluated by using diagnostic criteria of International Restless Legs Syndrome Study Group (IRLSSG) and severity measured on IRLSSG scale. Depression and anxiety were rated on Hamilton Depression and Anxiety Rating Scales respectively, insomnia severity measured by Insomnia Severity Index (ISI), and quality of life measured by WHO Quality of Life-Brief version (WHO-QOL BREF) scale. Serum ferritin levels were measured for evaluating iron deficiency. The rate of RLS was 66.7%, 50%, and 48% in patients with depressive, anxiety, and somatoform disorders, respectively, with no significant inter-group difference. Nearly one-third of patients suffered from severe to very severe symptoms of RLS, and quality of life was poorest in those with depressive disorders. RLS was significantly higher in females (P = 0.019), who were married (P = 0.040), diagnosed with severe depression (P = 0.029), and abused benzodiazepines (P = 0.045). On binary logistic regression, female gender and presence of clinical insomnia predicted occurrence of RLS. The prevalence of RLS is very high in patients with common psychiatric disorders which is often missed. Clinical enquiry and examination for reversible causes such as iron deficiency may assist in its diagnosis and improve clinical outcome.

Global prevalence of restless legs syndrome among hemodialysis patients: A systematic review and meta-analysis.

Restless legs syndrome (RLS) is a common complaint in patients undergoing hemodialysis (HD). Despite the fact that the estimated prevalence of RLS among HD patients is widely reported, these results varied significantly in the relevant literature. Due to this limitation, the aim of this study was to determine the global prevalence of RLS among HD patients. This systematic review was conducted and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses 2020 statement. We searched the electronic databases: Cochrane Library, PubMed, Embase, Web of Science, Scopus, Cumulative Index to Nursing and Allied Health Literature, China Knowledge Resource Integrated Database, Wanfang Database, Chinese Biomedical Database, and Weipu Database. A random effects model was employed to calculate pooled prevalence rates. The global pooled prevalence of RLS in HD patients was 27.2% (95% CI: 24.8-29.7). Stratified analyses demonstrated that included studies with sample size <100 had the highest pooled prevalence of RLS. The prevalence of RLS using clinical interviews and questionnaires was 28.7% (95% CI: 25.2-32.2) and 25.9% (95% CI: 22.8-29.1), respectively. RLS prevalence is higher in females (29.7%, 95% CI: 26.2-33.2) HD patients than in males (23.5%, 95% CI: 20.9-26.0), and the African region has the highest prevalence in the world when the diagnostic criteria were restricted to the 2003 version of International RLS Study Group criteria, the prevalence of RLS was highest (28.9%, 95% CI: 25.9-31.9). Our results revealed a high RLS prevalence in HD patients worldwide. However, the prevalence of RLS among HD patients varied significantly based on sample size, data collection method, gender, diagnostic criteria, and geographical region.

Spinal cord stimulation in severe pharmacoresistant restless legs syndrome—two case reports

Restless legs syndrome is a prevalent, sleep-related sensorimotor disorder with relevant impact on the patients’ quality of life. For patients suffering from severe, pharmacoresistant restless legs syndrome, few therapeutic options remain to alleviate symptoms. In this case series, two patients with severe, pharmacoresistant restless legs syndrome were treated with epidural spinal cord stimulation and repeatedly assessed with polysomnography, including sleep structure and periodic limb movements as objective biomarkers not subject to placebo effects, during a 6-month follow-up period. One of the patients experienced excellent short- and long-term efficacy on subjective symptom severity (International RLS Study group rating scale 1 vs. 34 points at 3 months) and objective sleep parameters such as sleep architecture and periodic limb movements during sleep, while the second patient only reported short-term benefits from spinal cord stimulation. Ultimately, both patients opted for removal of the device for inefficacy. Based on the complex pathophysiology of restless legs syndrome and presumed mechanism of action of spinal cord stimulation in chronic pain disorders, we provide a detailed hypothesis on the possible modulating effect of spinal cord stimulation on the key symptoms of restless legs syndrome. Apart from describing a new therapeutic option for pharmacoresistant restless legs syndrome, our findings might also provide further insights into the pathophysiology of the syndrome.

Restless legs syndrome is prevalent in adults with cystic fibrosis and impacts sleep quality

BackgroundRestless legs syndrome (RLS) is a sensorimotor disorder that is prevalent in chronic inflammatory conditions. RLS prevalence, risk factors, and impact on sleep in CF have not been extensively characterized to date. MethodsAn initial cohort was examined, including 75 persons with CF (PwCF) and 75 control subjects, to look at the prevalence and severity of RLS. A second validation cohort of 191 PwCF was then enrolled from two CF centers to examine risk factors for RLS. A diagnosis of RLS was made according to the International RLS Study Group (IRLSSG) criteria. Sleep quality was identified using the Pittsburgh sleep quality index (PSQI). Epworth sleepiness scale (ESS) was used to measure daytime sleepiness. We then analyzed laboratory and clinical risk factors and sleep symptoms for potential risk factors for RLS. ResultsIn the initial cohort, 36 % of PwCF had RLS, and 9 % of these had significant RLS. In contrast, only 15 % of controls had RLS, and none had significant RLS. In the second larger validation cohort with 191 subjects, a comparable prevalence of RLS was identified. Higher hemoglobin A1c, use of SSRI/SNRI medications, worse PSQI and ESS sleep quality scores, lower lung function, and higher antibiotic usage were significantly associated with a diagnosis of RLS. By multivariate multinominal logistic regression analysis, higher HbA1c and worse PSQI global sleep quality scores were independent predictors of significant RLS. ConclusionsRLS is highly prevalent in CF. Higher HbA1c and poor sleep quality, signified by higher PSQI, were each independent predictors of RLS.

Restless legs syndrome affects sleep in de novo Parkinson's disease patients.

Restless legs syndrome (RLS) is common in Parkinson's disease (PD) patients and can affect the motor symptoms and non-motor symptoms (NMSs) of PD patients. The aim of this study was to identify the clinical factors affected by RLS in patients with PD. We included 369 de novo PD patients. RLS was assessed via face-to-face interviews and the motor symptoms and NMSs of the patients were assessed using relevant scales. RLS frequency in the patients was 12.2% (45/369). PD patients with RLS (PD-RLS) exhibited a greater global Pittsburgh Sleep Quality Index (PSQI) score than those without RLS (PD-No RLS). PD-RLS exhibited significantly greater scores in the daytime dysfunction and sleep disturbances components of the PSQI than PD-No RLS. PD-RLS exhibited a significantly greater score in the cardiovascular, sleep/fatigue, and attention/memory subdomain of the Non-Motor Symptoms Scale than PD-No RLS. The International RLS Study Group rating scale score was significantly related to PSQI components scores in the sleep disturbances, sleep latency, habitual sleep efficiency, and subjective sleep quality. RLS frequency in de novo PD patients is higher than that in the general population, and the main NMS affected by RLS in these patients is sleep disturbances. Therefore, it is necessary to manage RLS in PD patients with sleep disturbances.

Cost-Effectiveness of Tonic Motor Activation (TOMAC) Therapy for Patients with Restless Legs Syndrome: An Exploratory Analysis.

Tonic motor activation (TOMAC) therapy is a novel non-pharmacologic treatment approach for patients suffering from medication-refractory restless legs syndrome (RLS). The objective of this study was to explore the potential cost-effectiveness of TOMAC in the US healthcare system. A decision-analytic Markov model was constructed to project strategy-specific treatment costs and benefits over 3years and lifetime. Cohort characteristics (mean age 57.4years, 39.8% male) and treatment effects were derived from the sham-controlled RESTFUL study. Study-observed International RLS Study Group (IRLS) scores were used to estimate changes in healthcare resource utilization and quality of life based on mapping algorithms informed by published data. The incremental cost-effectiveness ratio (ICER) was evaluated against establishedwillingness-to-pay thresholds of $50,000/$150,000 per QALY to determine cost-effectiveness. Extensive scenario analyses were performed, including longer-term extension study data. TOMAC and sham reduced IRLS scores from baseline 25.3 to 18.10 and 21.60, respectively, at 4weeks (treatment effect - 3.4 vs. sham), with an increase in utility from 0.80 to 0.84 (0.75-0.84 vs. baseline). Over 3years and lifetime, the TOMAC vs. sham effect size corresponded to an added 0.10 and 0.49 QALYs (2.36 vs. 2.26; 12.59 vs. 12.10) at incremental costs of $8061 and $36,373 ($36,707 vs. $28,646; $224,040 vs.$187,667), resulting in ICER estimates of$83,822 and $73,600, respectively. Compared to baseline, TOMAC resulted in ICER estimates of$29,569 and $23,690 over 3years and lifetime, respectively. TOMAC remained cost-effective or dominant across all scenarios, with ICERs ranging from $10,530-$83,822 and - $8061 to $29,569 vs. sham and baseline, respectively. Larger TOMAC effect sizes, achieved per extension study data, further increased cost-effectiveness. Based on this exploratory analysis of published trial data, TOMAC therapy appears to offer meaningful improvements in patient health-related quality at net costs that render it a cost-effective intervention. Further analyses are warranted.

Restless legs syndrome in multiple sclerosis patients: Prevalence, impact, and association with disease-modifying therapies in a Saudi Arabian pilot study

BackgroundRestless legs syndrome (RLS) emerges as a notable sleep disorder characterized by distressing sensations within the lower extremities. Its prevalence appears to be higher among patients afflicted with multiple sclerosis (MS) compared to the general population. Despite this observation, the understanding of the intricacies of RLS and its repercussions within the context of MS patients in Saudi Arabia remains limited. MethodsEmploying a cross-sectional design, a comprehensive investigation was undertaken at King Fahad Armed Forces Hospital in Jeddah, Saudi Arabia, spanning from November 2021 to March 2022. A cohort of 66 individuals diagnosed with MS was recruited and subjected to an assessment for RLS employing the revised diagnostic criteria outlined by the International Restless Legs Syndrome Study Group (IRLSSG). Furthermore, the Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, and Sleepiness Scale were employed to gage the extent of RLS's impact on sleep quality and daily functioning. ResultsThe prevalence of RLS amidst the MS cohort was determined to be 30.4%. An observable association was discerned between RLS presence and higher scores on the Expanded Disability Status Scale (p < 0.001), along with diminished sleep quality scores (p < 0.001) and elevated fatigue scores based on IRLSSG criteria (p < 0.001). Within the studied MS cases, 98.5 % exhibited the relapsing-remitting subtype. Further investigation demonstrated that patients treated with Fingolimod or Ocrevus presented normal IRLSSG scores, whereas those undergoing Rituximab treatment manifested an even distribution between normal and moderate scores. Correspondingly, patients receiving interferons showcased 72.2 % with normal scores and 27.8 % with mild scores. Notably, a statistically significant variance in IRLSSG scores was observed when contrasting Fingolimod and Aubagio treatments (P < 0.001). ConclusionThe presence of RLS as a comorbidity in MS patients within the Saudi Arabian context emerges as a significant finding, exerting a discernible detrimental influence on both disability status and sleep quality. This study underscores the need for further investigations aimed at unraveling the intricate pathophysiological underpinnings, identification of risk factors, and exploration of therapeutic modalities for RLS in this population. Furthermore, additional research endeavors are warranted to elucidate the diverse impact of various disease-modifying therapies on clinical outcomes.