Treatment Of Restless Legs Syndrome Research Articles

A randomized double-blind pilot study to evaluate the efficacy, safety, and tolerability of intravenous iron versus oral iron for the treatment of restless legs syndrome in patients with iron deficiency anemia.

Restless legs syndrome (RLS) is a neurological disorder that can have a profound effect on sleep and quality of life. Idiopathic RLS is associated with brain iron insufficiency despite normal peripheral iron stores. There is, however, a five- to six-fold increase in prevalence of RLS in patients with iron deficiency anemia (IDA). Several open-label trials have demonstrated symptomatic improvement in RLS following treatment of IDA using oral or intravenous iron supplementation. To date, there have been no randomized double-blind controlled trials of intravenous iron compared with oral iron for the treatment of RLS patients with IDA. In the current study, oral ferrous sulfate and ferumoxytol were compared for efficacy and speed of response for treatment of RLS occurring in patients with IDA. The planned recruitment for this study was 70 patients with RLS and IDA, to be randomly assigned 1:1 to oral or intravenous iron, using double-blind, double-dummy procedures. At Week 6, the primary outcomes of Clinical Global Impression-Improvement score and change from baseline in the International Restless Legs Syndrome Study Group rating scale score were assessed. Due to challenges, performing the clinical trial during the COVID-19 pandemic, final-week data were found missing for 30 patients. As a result, in order to maintain the prespecified statistical analysis, an additional 30 patients were recruited. Both IV and oral iron were associated with a marked improvement in RLS symptoms, with no statistically significant difference between treatment groups. No serious adverse events were observed in either treatment group.

Successful treatment of restless legs syndrome accompanied by headaches for 30 years with herbal prescriptions containing Paeoniae Radix: A case report

BackgroundRestless legs syndrome (RLS) is a neurological disorder that causes unpleasant symptoms in the legs when resting, which are relieved by movement. Pharmacotherapy is the standard treatment. However, current treatment provides only symptomatic relief and may result in adverse effects with long-term use. Treatment protocols using herbal medicines have emerged to compensate for this limitation. Case presentationA 70-year-old Asian woman visited our hospital with worsening headaches that had persisted for 30 years. Her headaches were aggravated by night-time lower-extremity discomfort. The patient was diagnosed with RLS based on the 2012 Revised International Restless Leg Syndrome Study Group Diagnostic Criteria (IRIS). The patient was prescribed herbal medicines, Shihogyeji-tang, Gyejibokryeong-hwan, and Jakyakgamcho-tang, all of which contain Paeoniae Radix. Fourteen days after starting herbal medicine treatment, the IRIS score decreased from 30 to 18. The patient experienced less leg discomfort. Moreover, her sleep time increased, and her headaches resolved. After 28 days of herbal treatment, the IRIS score decreased to 9. Importantly, the patient reported no sleep disturbance or headaches. Subsequently, conventional medications were discontinued. The patient remained stable (IRIS score: 9–10). Herbal treatment was discontinued on day 163. At the last follow-up, (day 364), the patient has not reported any symptom recurrence. ConclusionsWe described a female patient with a 30-year history of RLS symptoms and related sleep disturbances that induced chronic uncontrolled headaches, who experienced improvements shortly after using herbal medicines containing Paeoniae Radix. Conventional medications were discontinued and the patient had no recurrence of symptoms. Considering these, herbal medicines containing Paeoniae Radix may be a suitable alternative treatment for RLS and its related symptoms.

Dopamine Agonists in the Treatment of Restless Legs Syndrome: Too Much of a Good Thing?

Restless legs syndrome is a prevalent sensorimotor sleep disorder that worsens the quality of life. Dopamine agonists are widely used to relieve the symptoms of restless legs syndrome, even though these patients are in a “hyperdopaminergic” state. This treatment paradox inevitably leads to augmentation syndrome. Here, we review the pathophysiological basis of this deterioration in patients treated with dopamine agonists. Other treatment options are required with a focus on the neuromodulation of dopaminergic or non-dopaminergic pathways.

Clinical Efficacy and Safety of Intravenous Ferric Carboxymaltose for Treatment of Restless Legs Syndrome: A Multicenter, Randomized, Placebo-controlled Clinical Trial.

Iron therapy is associated with improvements in restless legs syndrome (RLS). This multicenter, randomized, double-blind study evaluated the effect of intravenous ferric carboxymaltose (FCM) on RLS. A total of 209 adult patients with a baseline International Restless Legs Syndrome (IRLS) score ≥15 were randomized (1:1) to FCM (750mg/15mL) or placebo on study Days 0 and 5. Ongoing RLS medication was tapered starting on Day 5, with the goal of discontinuing treatment or achieving the lowest effective dose. Co-primary efficacy endpoints were change from baseline in IRLS total score and the proportion of patients rated as much/very much improved on the Clinical Global Impression-investigator (CGI-I) scale at Day 42 in the "As-Treated" population. The "As-Treated" population comprised 107 FCM and 101 placebo recipients; 88 (82.2%) and 68 (67.3%), respectively, completed the Day 42 assessment. The IRLS score reduction was significantly greater with FCM versus placebo: least-squares mean (95% confidence interval [CI]) -8.0 (-9.5, -6.4) versus -4.8 (-6.4, -3.1); P = 0.0036. No significant difference was observed in the proportion of FCM (35.5%) and placebo (28.7%) recipients with a CGI-I response (odds ratio 1.37 [95% CI: 0.76, 2.47]; P = 0.2987). Fewer patients treated with FCM (32.7%) than placebo (59.4%) received RLS interventions between Day 5 and study end (P = 0.0002). FCM was well tolerated. The IRLS score improved with intravenous FCM versus placebo, although the combination of both co-primary endpoints was not met. Potential methodological problems in the study design are discussed.

A survey-based approach on restless legs syndrome: practices and perspectives among Italian neurologists.

Restless Legs Syndrome (RLS) is a widely prevalent and complex neurological disorder. Despite notable advancements in managing RLS, the disorder continues to face challenges related to its recognition and management. This study seeks to gain comprehensive insights into the knowledge and clinical practices among Italian neurologists regarding RLS diagnosis, management, and treatment, comparing approaches among general neurologists, movement disorder specialists, and sleep experts. Members of the Italian Society of Neurology, the Italian Society of Parkinson and Movement Disorders, and the Italian Association of Sleep Medicine were invited to participate in a 19-question online survey. Among the 343 surveyed neurologists, 60% categorized RLS as a "sleep-related movement disorder." Forty% indicated managing 5-15 RLS patients annually, with sleep specialists handling the highest patient volume. Of note, only 34% adhered strictly to all five essential diagnostic criteria. The majority (69%) favored low-dosage dopamine agonists as their first-line treatment, with movement disorder specialists predominantly endorsing this approach, while sleep experts preferred iron supplementation. Regular screening for iron levels was widespread (91%), with supplementation typically guided by serum iron alterations. In cases of ineffective initial treatments, escalating dopamine agonist dosage was the preferred strategy (40%). These findings underscore a lack of a clear conceptualization of RLS, with a widespread misconception of the disorder as solely a movement disorder significantly influencing treatment approaches. Disparities in RLS understanding across neurology subspecialties underscore the necessity for improved diagnostic accuracy, targeted educational initiatives, and management guidelines to ensure consistent and effective RLS management.

Effect of Self-developed Ye’an Analgetic Decoction/Jiawei Shaoyao Gancao Decoction Combined with Tramadol on TCM Symptom Scores and RLS Severity of patients with Restless Legs Syndrome

Objective: To investigate the effect of self-developed Ye’an Analgetic Decoction/Jiawei Shaoyao Gancao Decoction on Traditional Chinese Medicine (TCM) symptom scores and RLS Severity of patients with restless legs syndrome (RLS).
 Methods: This was a clinical comparative study. Eighty patients with RLS admitted to Baoding No.1 Central Hospital from January 2022 to December 2022 were randomly divided into observation group and control group(n=40). Patients in the control group were given basic and oral tramadol treatment, while those in the observation group were given self-developed Ye’an Analgetic Decoction/Jiawei Shaoyao Gancao Decoction based on the treatment in the control group. The differences of TCM symptom scores, RLS severity (IRLS), quality of life (QOL-RLS), sleep quality (PSQI) and clinical efficacy between the two groups were compared.
 Results: Before treatment, no statistically significant differences were observed in the TCM symptom scores, IRLS scores, QOL-RLS scores and PSQI scores between the two groups (p>0.05). After treatment, the above scores decreased significantly in both groups, with a higher degree of decrease in the observation group than in the control group, indicating statistically significant differences (p<0.05). The QOL-RLS scores were significantly higher in the observation group than in the control group, with a statistically significant difference (p<0.05). The overall response rate in the observation group was 95.00%, which was higher than that in the control group (80.00%), with a statistically significant difference (p<0.05).
 Conclusion: Self-developed Ye’an Analgetic Decoction/Jiawei Shaoyao Gancao Decoction leads to numerous benefits in the treatment of RLS, such as obviously ameliorating patients’ clinical symptoms, reducing RLS severity, and improving their quality of life and sleep quality.
 doi: https://doi.org/10.12669/pjms.40.5.8400
 How to cite this: Zhou B, Li W, Li Y, Sun D, Du X. Effect of Self-developed Ye’an Analgetic Decoction/Jiawei Shaoyao Gancao Decoction Combined with Tramadol on TCM Symptom Scores and RLS Severity of patients with Restless Legs Syndrome. Pak J Med Sci. 2024;40(5):---------. doi: https://doi.org/10.12669/pjms.40.5.8400
 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Transcutaneous electrical nerve stimulation in the management of restless legs syndrome symptoms: A single-blind, parallel-group clinical study.

The aim of this study was to investigate the additional effect of transcutaneous electrical nerve stimulation (TENS) on the control of the symptoms of restless legs syndrome (RLS). A total of 46 randomly selected patients diagnosed with RLS were divided into two groups in a single-blind study to either receive pramipexole (0.25 mg daily) plus 10 sessions of TENS or only pramipexole (0.25 mg daily) for 4 weeks. The severity of the symptoms was determined according to the International Restless Legs Syndrome Rating Scale (IRLSRS) and the Pittsburgh sleep quality index (PSQI) at the beginning of the treatment, post-treatment, and at an 8 week follow-up. A significant time interaction was observed between the groups for all measurement outcomes, revealing differences in favour of the experimental group's IRLSRS and PSQI scores. A notable improvement was also observed in the IRLSRS and PSQI scores in both groups at the end of treatment and during the 8 week follow-up period. In comparison with pramipexole monotherapy, the results of this study showed that the use of TENS therapy combined with a low dose of pramipexole (0.25 mg daily) is therapeutically beneficial in the treatment of RLS over an 8 week follow-up period.

Drugs and exercise as treatment of restless legs syndrome in an animal model with iron deficiency

Drugs and exercise as treatment of restless legs syndrome in an animal model with iron deficiency

Application of Repetitive Transcranial Magnetic Stimulation for the Treatment of Restless Legs Syndrome: A Pilot Study

ObjectiveTo explore effects of high frequency repetitive transcranial magnetic stimulation (rTMS) on restless legs syndrome (RLS) patients. Methods18 primary RLS patients were divided into rTMS group and sham stimulation group. rTMS treatment group received 15 Hz high-frequency rTMS to stimulate the leg motor representative area of the frontal cortex for 14 days and the sham stimulation group received 15 Hz high-frequency rTMS sham stimulation in primary motor cortex for 14 days. ResultsAfter rTMS, RLS severity scale score, Pittsburgh sleep quality index (PSQI), Hamilton anxiety scale (HAMA) as well as Hamilton depression scale (HAMD24) in rTMS treatment group are significantly lower than before treatment; 1 month and 2 months after treatment, the score remained at low level. Meanwhile, no significant changes have been observed in the above index before rTMS stimulation for the sham stimulation group after 14 days, after 1 month and 2 months. In addition, the results of correlation analysis suggested for all the 18 RLS patients, there was a positive correlation between PSQI score and HAMA as well as HAMD24 scores before and after rTMS stimulation. In addition, the RLS severity score was also positively correlated with PSQI, HAMA and HAMD24 scores. ConclusionsHigh frequency rTMS stimulation reduces the frequency and severity of RLS, improves the quality of sleep, anxiety as well as depression of the patients, and the curative effect can sustain for 2 months. High-frequency rTMS may be used as an alternative treatment option for improving the RLS patients’ quality of life.

RESTLESS LEG SYNDROME (RLS) AND ASSOCIATED

Background: Restless leg syndrome has been a problem for a large percentage of the population as it affects many aspects of life. The aim of this research was to outline the effect of restless leg syndrome on the human body and related diseases that can affect human wellbeing. Methods: The research methodology was done through the cross-sectional process and therefore, the research design that can be included in the descriptive research design. The selected research design would be justified for the present research methodology as a survey would be done with a proper questionnaire. Hence, the selected research design would help in describing and interpreting the collected data. The population that the present research involved in the research methodology belonged to the patients who are suffering from restless legs syndrome disease. The people who go to the national government hospitals for the medication process would be the target population for the survey method. Results: Study included 803 participants in which all of them responded to study survey questions. Study participants believe that restless leg syndrome is not a genetic disorder (n= 359, 44.7%). More than half of study participants reported that taking medicines will help with RLS (n= 436, 54.3%). There were 607 participants reported that daily exercise would help in diminishing the RLS (75.6%). Furthermore, 492 participants considered exercise is essential for RLS (61.2%). Participants were asked about the pain degree with regard to leading a life with restless leg disorder. More than half of participants reported that it is moderate painful (n= 456, 56.8%) Regarding the duration of treatment of restless leg syndrome, than half of participants reported the duration to be moderate span of time (n= 408, 50.8%). Conclusion: In conclusion, this research was a population-based study with a large sample size, and its findings indicate that RLS is widespread among study population. This indicated that RLS could be more prevalent, manifest differently in patients, and have distinct risk factors. Study participants believe that restless leg syndrome is not a genetic disorder. More than half of study participants reported that taking medicines will help with RLS. Participants also reported that daily exercise would help in diminishing the RLS and considered exercise is essential for RLS.

Acupuncture Treatment for Restless Legs Syndrome: A Review of Randomized Controlled Trials

Acupuncture Treatment for Restless Legs Syndrome: A Review of Randomized Controlled Trials

Adjunctive tonic motor activation enables opioid reduction for refractory restless legs syndrome: a prospective, open-label, single-arm clinical trial

BackgroundThere is a large population of restless legs syndrome (RLS) patients who are refractory to medication. Whereas experts recommend off-label opioids as an effective long-term treatment for refractory RLS, reducing opioid dose could substantially reduce side effects and risks. Tonic motor activation (TOMAC) is a nonpharmacological therapeutic device indicated for refractory RLS. Here, we investigated if TOMAC could enable opioid dose reduction for refractory RLS.MethodsThis prospective, open-label, single-arm clinical trial [NCT04698343] enrolled 20 adults taking ≤ 60 morphine milligram equivalents (MMEs) per day for refractory RLS. Participants self-administered 30-min TOMAC sessions bilaterally over the peroneal nerve when RLS symptoms presented. During TOMAC treatment, opioid dose was reduced iteratively every 2–3 weeks until Clinician Global Impression of Improvement (CGI-I) score relative to baseline exceeded 5. Primary endpoint was percent of participants who successfully reduced opioid dose ≥ 20% with CGI-I ≤ 5. Secondary endpoints included mean successful percent opioid dose reduction with CGI-I ≤ 5.ResultsOn average, participants were refractory to 3.2 medications (SD 1.6) and were taking a stable dose of opioids for 5.3 years (SD 3.9). Seventy percent of participants (70%, 14 of 20) successfully reduced opioid dose ≥ 20% with CGI-I ≤ 5. Mean percent opioid dose reduction with CGI-I ≤ 5 was 29.9% (SD 23.7%, n = 20) from 39.0 to 26.8 MME per day. Mean CGI-I score at the reduced dose was 4.0 (SD 1.4), indicating no change to RLS severity.ConclusionsFor refractory RLS, TOMAC enabled substantial opioid dose reduction without increased RLS symptoms. These results suggest that TOMAC has the potential to reduce the risk profile associated with opioid therapy for refractory RLS.Trial registrationClinicalTrials.gov trial number NCT04698343 registered on January 6, 2021.

Ar yra ryšys tarp migrenos ir neramių kojų sindromo?

Migraine and restless legs syndrome are diseases that disturb the normal quality of human life. Moreover, comorbidity of these disorders determines even more difficult condition of the patients. Migraine is a headache that can cause severe throbbing pain, usually on one side of the head, and it is often accompanied by nausea, vomiting, and extreme sensitivity to light and sound. Migraine is one of the reasons that can cause unhealthy sleep, and if sleep is disturbed, this leads to the provocation of migraine attacks. Sleep disorders have various clinical manifestations, one of which is restless legs syndrome. It is a neurosensory impairment which is characterized by an unrelenting urge to move the legs that occurs or worsens at rest. For this reason, patients may complain of impaired sleep. Although the relationship between migraine and restless legs syndrome and their pathogenesis is not fully understood, current research suggests that these diseases may be related. People with restless legs syndrome are 1.23 to 2.65 times more likely to develop migraine attacks. It is believed that the occurrence of both diseases is determined by several pathophysiological factors, such as the activity of the dopamin- ergic system, iron deficiency, genetic predisposition, and changes in the gray matter of the brain. Although the association between restless legs syndrome and migraine is being investigated, the predominant pathophysiological link has not yet been established. Separate treatment of these diseases has been known for a long time. The principle of migraine treatment is to suppress pain and reduce the frequency of attacks. Treatment for restless legs syndrome is based on the relief of symptoms. Unfortunately, a common treatment for both diseases in relation to each other has not yet been approved. Because of the similar pathophysiology of these disorders, drugs that affect the dopaminergic system (e.g., pramipexole) are currently being investigated in order to relieve the symptoms of restless legs syndrome and migraine attacks.

Exploring the causes of augmentation in restless legs syndrome.

Long-term drug treatment for Restless Legs Syndrome (RLS) patients can frequently result in augmentation, which is the deterioration of symptoms with an increased drug dose. The cause of augmentation, especially derived from dopamine therapy, remains elusive. Here, we review recent research and clinical progress on the possible mechanism underlying RLS augmentation. Dysfunction of the dopamine system highly possibly plays a role in the development of RLS augmentation, as dopamine agonists improve desensitization of dopamine receptors, disturb receptor interactions within or outside the dopamine receptor family, and interfere with the natural regulation of dopamine synthesis and release in the neural system. Iron deficiency is also indicated to contribute to RLS augmentation, as low iron levels can affect the function of the dopamine system. Furthermore, genetic risk factors, such as variations in the BTBD9 and MEIS1 genes, have been linked to an increased risk of RLS initiation and augmentation. Additionally, circadian rhythm, which controls the sleep-wake cycle, may also contribute to the worsening of RLS symptoms and the development of augmentation. Recently, Vitamin D deficiency has been suggested to be involved in RLS augmentation. Based on these findings, we propose that the progressive reduction of selective receptors, influenced by various pathological factors, reverses the overcompensation of the dopamine intensity promoted by short-term, low-dose dopaminergic therapy in the development of augmentation. More research is needed to uncover a deeper understanding of the mechanisms underlying the RLS symptom and to develop effective RLS augmentation treatments.

Incident mental health episodes after initiation of gabapentinoids vs. dopamine agonists for early-onset idiopathic restless legs syndrome

Limited long-term safety information exists for gabapentinoid treatment of idiopathic restless legs syndrome (RLS). We estimated incident mental health-related emergency department visits and hospitalizations with a primary mental health diagnosis (primary outcome) among early-onset idiopathic RLS patients following first-line treatment initiation and examined outcome risk with gabapentinoids compared with dopamine agonists (DAs). A retrospective cohort study was conducted using administrative claims data from 2012 to 2019. Adults with early-onset (18–44 years) idiopathic RLS initiating either gabapentinoids or DAs within 60 days of new diagnosis were followed up to two years. Incidence rates were calculated and a log-binomial regression model with propensity score weighting estimated relative risk of the outcome and of substance use disorders (SUDs) as a secondary analysis with gabapentinoids. Among a cohort of 6,672 patients, 4,986 (74.7%) initiated DAs and 1,686 (25.3%) gabapentinoids. Incidence of the primary outcome (49.8 [95% CI 40.8–69.3] per 1,000 person-years) and SUDs (49.5 [95% CI 40.6–59.9] per 1,000 person-years) were higher in the gabapentinoid group compared with the DA group. A statistically significant risk of mental health diagnoses with gabapentinoids was not detected, but SUD risk was significant after covariate adjustment. High-risk mental health comorbidities (i.e., SUDs) should be considered when initiating RLS treatments.

Effectiveness of exercise and pramipexole in the treatment of restless leg syndrome: Implications on the dopaminergic system and PTPRD

ObjectiveDopaminergic dysfunction, iron reduction and variations in the PTPRD gene (protein tyrosine phosphatase receptor type delta) may be associated with restless leg syndrome (RLS). Here, we evaluate the effect of pramipexole (PPX) and exercise on genes and proteins associated with RLS and on sleep patterns in spontaneously hypertensive rats (SHR). MethodsAnimals were distributed into 4 groups: 1) Control (CTRL); 2) Exercise (EX); 3) Exercise and pramipexole (EX + PPX); and 4) Pramipexole (PPX). PPX treatment was performed daily (0.125 mg/kg), while exercise was conducted over 5 sessions per week, both for 4 weeks. ResultsEX + PPX increased the protein levels of PTPRD, reduced the protein levels of the enzyme tyrosine hydroxylase (TH) and improved sleep parameters in both cycles; on the other hand, the use of PPX reduced mRNA and protein levels of PTPRD and TH but improved the sleep pattern in the light cycle. However, in the dark cycle, pramipexole caused the worsening of symptoms. ConclusionsWe suggest that the improvement in sleep pattern by EX + PPX may be associated with the increased protein levels of PTPRD and that EX + PPX can reverse the negative effects of PPX.

Medicinal Mushroom, Ganoderma Lucidum, Improves Painful Symptoms in Patients with Restless Legs Syndrome

Restless legs syndrome (RLS) is a prevalent sensorimotor sleep disorder that worsens quality of life. All the currently available drug treatments for RLS have limitations. Extracts of the mushroom Ganoderma lucidum (GL) have shown several beneficial biological effects in neurodegenerative diseases. The objective of the present study was to evaluate the effect of a 2-month course of GL extract on the intensity of painful RLS symptoms.

Dopamine agonists pramipexole, ropinirole and rotigotine for the treatment of restless legs syndrome in pregnancy

Dopamine agonists pramipexole, ropinirole and rotigotine for the treatment of restless legs syndrome in pregnancy

Restless Legs Syndrome and Restless Sleep Disorder in Children.

Restless legs syndrome (RLS) affects 2% of children presenting with symptoms of insomnia, restless sleep, decreased quality of life, and effects on cognition and behavior. The International RLS Study Group and the American Academy of Sleep Medicine have published guidelines for the diagnosis and treatment of RLS in children. Restless sleep disorder has been recently identified in children and presents with frequent movements during sleep and daytime symptoms with polysomnography findings of at least 5 large muscle movements at night. Treatment options for both disorders include iron supplementation, either oral or intravenous with improvement in nighttime and daytime symptoms.

0713 Long-term response to tonic motor activation (TOMAC) therapy for refractory restless legs syndrome

Abstract Introduction There is a large population of patients who have become refractory to first-line treatments for Restless Legs Syndrome, partially due to augmentation to dopamine agonist medications. For patients with refractory RLS, tonic motor activation (TOMAC) is a noninvasive medical device therapy with promising short-term safety and efficacy. Here, we evaluated the response to TOMAC over a longer duration of >24 weeks. Methods In the RESTFUL study, 133 patients with primary moderate-severe refractory RLS were 1:1 randomized to TOMAC or sham control for weeks 1 to 4 followed by open-label TOMAC for weeks 5 to 8. The final 50 participants to complete the RESTFUL study were invited to continue TOMAC treatment for an additional 24 weeks (weeks 9 to 32) in an extension study. Participants were instructed to self-administer one 30-minute TOMAC session bilaterally over the peroneal nerve whenever RLS symptoms presented. Efficacy was assessed by comparing responses from baseline (RESTFUL study entry, week 0) to week 32 on Clinician Global Impressions-Improvement (CGI-I) responder rate, Patient Global Impressions-Improvement (PGI-I) responder rate, and International RLS Study Group Rating Scale (IRLS) total score. Additional analyses compared responses from week 8 (RESTFUL study completion) to week 32. Results Of the 50 eligible participants, 44 consented to the extension study and 42 completed. CGI-I responder rate relative to baseline increased from 64% at week 8 to 76% at week 32. PGI-I responder rate relative to baseline increased from 68% at week 8 to 77% at week 32. IRLS total score reduced from 24.5 at baseline to 17.1 at week 8 to 12.9 at week 32, a reduction of 11.6 points from baseline to week 32. There were no moderate or severe device-related AEs. Conclusion TOMAC resulted in substantial and clinically significant reduction in RLS symptom severity that was maintained through >24 weeks of treatment. Furthermore, there was a trend towards increased efficacy with continued use of TOMAC. These data suggest that TOMAC could represent a potential long-term treatment for the chronic condition of refractory RLS. Support (if any) Funding was provided by Noctrix Health, Inc.