International RLS Study Group Rating Scale Research Articles

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.

Bilateral high-frequency noninvasive peroneal nerve stimulation evokes tonic leg muscle activation for sleep-compatible reduction of restless legs syndrome symptoms.

Restless legs syndrome (RLS) is a prevalent sleep disorder with limited treatment options. Bilateral high-frequency noninvasive peroneal nerve stimulation (NPNS) reduces RLS symptoms. Here, we sought to characterize the mechanism of action for NPNS and identify predictors of treatment response. We hypothesized that, similar to voluntary leg movements, NPNS reduces RLS symptoms by activating leg muscles. For 20 adults with moderate-severe RLS, we tested this hypothesis by recording surface electromyography (EMG) from the tibialis anterior leg muscle while administering NPNS at varying amplitudes to determine the minimum NPNS amplitude that evoked EMG activity (motor threshold) and maximal NPNS amplitude that was not distracting (therapeutic intensity level). Afterwards, participants self-administered NPNS (at the therapeutic intensity level) and sham control for 14 days, each in randomized order. Efficacy was defined as International RLS Study Group Rating Scale (IRLS) score difference for NPNS compared with sham. NPNS consistently activated leg muscles; NPNS evoked EMG activity at the therapeutic intensity level for 19 of 20 participants (mean TIL: 26.6 mA, mean MT: 18.3 mA). Evoked EMG activity was tonic (not phasic) and sustained over time. Evoked EMG activity predicted efficacy; participants with lower motor thresholds had greater IRLS improvement (r = .45, P = .046). NPNS treatment did not interfere with self-reported sleep onset (NPNS: 16% of nights; sham: 11%; P = .629) and frequently improved self-reported sleep onset (NPNS: 52% of nights; sham: 15%; P = .002). These results demonstrate that NPNS reduces RLS symptoms by activating afferent pathways, thereby generating tonic and sustained leg muscle activity without interfering with sleep. Registry: ClinicalTrials.gov; Name: Noninvasive Peripheral Nerve Stimulation for Restless Legs Syndrome; URL: https://clinicaltrials.gov/ct2/show/NCT04700683; Identifier: NCT04700683. Charlesworth JD, Adlou B, Singh H, Buchfuhrer MJ. Bilateral high-frequency noninvasive peroneal nerve stimulation evokes tonic leg muscle activation for sleep-compatible reduction of restless legs syndrome symptoms. J Clin Sleep Med. 2023;19(7):1199-1209.

Long-Term Effects of Positive Airway Pressure Treatment on Restless Legs Syndrome Severity in Obstructive Sleep Apnea Syndrome

To research how long-term positive airway pressure (PAP) therapy affects the severity of restless legs syndrome in patients with obstructive sleep apnea syndrome (OSASThe study included 320 individuals that were diagnosed with moderate and severe OSAS using polysomnography (PSG) and under PAP treatment. Among these patients, the demographic data of 72 patients who met the diagnostic criteria of restless legs syndrome (RLS) were analyzed. The patients were evaluated with the International RLS Study Group rating scale (IRLS) before and at the 12th month after PAP in the treatment of OSAS. The mean body mass index of the 72 patients with OSAS and RLS was 31.2 (±5.8), and their mean apnea-hypopnea index was 44.9±27.7. The prevalence of RLS in moderate and severe OSAS was 24%. There was a negative correlation between the IRLS score and mean oxygen saturation all night (r: -0.075), minimum oxygen saturation all night (r: -0.125), time spent below <90% saturation (r: -0.172), and sleep efficiency (r: 0.087) on PSG performed before PAP treatment, as well as a negative correlation between the IRLS score and weekly PAP use hours at the 12th month after PAP treatment (r: -0.316; p<0.001). The data obtained from this study suggest that the coexistence of OSAS and RLS is common and should not be overlooked in the diagnosis of comorbid diseases. Long-term PAP treatment is effective in reducing RLS symptoms. Further studies are needed on this subject.

The relationship between the frequency and severity of restless legs syndrome and anaemia in patients with ankylosing spondylitis

Background Background The study aims to determine the frequency of restless legs syndrome (RLS) in patients with ankylosing spondylitis (AS) and the relationship between the International Restless Legs Syndrome Study Group Rating Scale (IRLSSG-RS) score and anemia.
 Material and Methods It was a case-control study that included 106 patients with AS and 106 age- and sex-matched healthy controls in the rheumatology clinic of a training and research hospital. The patients were divided into two groups according to their hemoglobin levels. A hemoglobin level lower than 12 g/dL in women and less than 13 g/dL in men was the criterion for anemia.
 Results Although the frequency of RLS was higher in AS patients than in control groups, there was no significant difference in the IRLSSG-RS score between AS patients and control groups. 23 (57.5%) of the AS patients with anemia had RLS, and the IRLSSG-RS score was 21.3±5.7. Of the AS patients without anemia, 11 (16.7%) had RLS, and the IRLSSG-RS score was 15±6. Statistically significant differences between AS patients with and without anemia regarding RLS frequency and IRLSSG-RS score were found. The IRLSSG-RS scores of AS patients were negatively correlated with serum iron and hemoglobin level.
 Conclusions Patients with AS had a higher RLS frequency than the control group; AS patients with anemia had a higher RLS and IRLSSG-RS score than AS patients without anemia. Also, a negative and significant correlation was found between the IRLSS-RS score and serum iron and hemoglobin levels in AS patients.

Association of Decreased Serum BDNF With Restless Legs Syndrome in Parkinson's Disease Patients.

Objective: To objective of the study was to investigate whether serum brain-derived neurotrophic factor (BDNF) levels are associated with the severity of restless legs syndrome (RLS) in Parkinson's disease (PD).Methods: A total of 249 PD patients with (n = 53) and without RLS (n = 196) and 326 age-matched controls were included in this study. All the serum BDNF levels of the participants were measured. The International Restless Legs Syndrome Study Group Rating Scale (IRLSSG-RS) was administered for the severity of RLS. The severity of PD patients were assessed by the Unified PD Rating Scale (UPDRS) and the Hoehn and Yahr (H-Y) stage.Results: The prevalence of RLS was significantly higher in PD patients (21.3%) than in the controls group (7.4%) (p < 0.05). The IRLSSG-RS score in PD patients with RLS (16.25 ± 5.24) was significantly increased than in controls with RLS (12.08 ± 3.99) (p < 0.01). The serum BDNF levels were significantly decreased in PD patients with RLS than in PD patients without RLS, controls without RLS, and controls with RLS (p < 0.001). BDNF levels were negatively associated with IRLSSG-RS in both PD patients with RLS and controls with RLS group (both p < 0.01). Multiple regression analysis confirmed that in either PD with RLS or controls with RLS group, BDNF was an independent contributor to IRLSSG-RS (both p < 0.01).Conclusions: Decreased serum BDNF levels may be involved in the pathophysiology of RLS in PD, suggesting that it may serve as a potential blood biomarker of diagnostic value for RLS in PD.

Restless legs syndrome in Parkinson's disease: relationship with quality of life and medication.

We aimed to disclose the relationship between restless leg syndrome (RLS) and antiparkinsonian treatment, and its effect on quality of life (QoL) in patients with Parkinson's disease (PD). Previous studies documented the prevalence of RLS among patients with PD to be higher than in the general population, but conclusions regarding the aetiology and impact were contradictory. We examined 101 patients with idiopathic PD. All participants completed the five-dimension/five-level-EuroQoL questionnaire (EQ-5D-5L) and the International Restless-Legs-syndrome-study-group rating Scale (IRLS). The prevalence of RLS was 22.77 %. There were no statistically significant differences in levodopa or dopamine agonists (DA) doses between RLS-positive and negative participants. However, the use of levodopa as the last night-time medication was connected with a higher risk of RLS (OR=2.049, p=0.041). There was significantly lower prevalence of RLS in patients after surgical treatment for PD (p=0.024). Participants with RLS were at a greater risk for sleep disturbances (OR=3.866, p=0.023) and excessive daytime sleepiness (OR=7.202, p<0.001). Greater RLS symptoms were associated with worse QoL (higher IRLS score predicted higher EQ5D5L score, p=0.023). RLS is prevalent among PD patients and night-time dopaminergic over-excitation with levodopa plays an important role in its pathogenesis. Since the symptoms of RLS are associated with decreased QoL, early accurate diagnosis and appropriate adjustment of dopaminergic therapy can lead to immediate relief from RLS symptoms and to QoL improvement (Tab. 4, Fig. 1, Ref. 34).

Correlation of Anaemia and Restless Legs Syndrome in Elderly: A Cross-sectional Study

Introduction: Restless Legs Syndrome (RLS) also known as Willis Ekbom Disease (WED) which manifests as a neurologic disorder among patients with anaemia, particularly with iron deficiency anaemia. Aim: To find the association of anaemia with RLS in the elderly population. Materials and Methods: In this cross-sectional study, 100 patients of age ≥60 years were enrolled and categorised into mild, moderate, and severe anaemia as per World Health Organisation (WHO) criteria. Every participant was enquired about RLS via a questionnaire based on the International RLS Study Group Rating Scale (IRLSSGRS) for its Severity and for the diagnosis (Essential clinical criteria for the diagnosis of RLS). Results: The study showed that patients with anaemia had a statistically significant correlation with RLS (p=0.04) and severity of RLS (p=0.032). Serum ferritin levels too showed a statistically significant correlation with RLS (p=0.032). Conclusion: Patients with severe anaemia and lower serum ferritin levels were more prone to RLS and had more RLS severity.

Restless Legs Syndrome in Aircrew.

INTRODUCTION: Restless legs syndrome (RLS) is characterized by an uncomfortable sensation on the legs, which causes the urge to move the legs. The main cause is unknown but there are many risk factors, including geographical properties and high altitude. Our objective was to explore the frequency of RLS in aircrew.METHODS: There were 301 Turkish aircrew who were admitted to Istanbul Medipol University Hospital Neurology Department for periodic examinations and 272 healthy (non-aircrew) subjects included in the study. The International RLS Study Group's Questionnaire and the International RLS Study Group Rating Scale (IRLSSGRS) were used to evaluate RLS. The participants filled the RLS questionnaire and then both groups were divided into two subgroups as having RLS or not. The subjects years in the profession, average flight duration in a month, daily sleep duration, smoking, and coffee consumption were recorded. None of the subjects had previously been diagnosed with RLS.RESULTS: The frequency of RLS was 6.7% in the aircrew group and 7.9% in the control group, and there was no significant difference between the two groups. Age, gender, daily duration of sleep, smoking, coffee consumption, family history of RLS, being a pilot or a flight attendant, years in profession, and monthly flight hours were similar in aircrew with and without RLS.DISCUSSION: The RLS frequency in aircrew was similar to that of the control group. We can conclude flying at high altitude wasnt a risk factor for RLS.Düz OA, Yilmaz NH, Olmuscelik O. Restless legs syndrome in aircrew. Aerosp Med Hum Perform. 2019; 90(11):934937.

Screening questions for the diagnosis of restless legs syndrome in hemodialysis.

BackgroundRestless legs syndrome (RLS) is common in end-stage renal disease and is associated with reduced health-related quality of life. Simple and accurate screening instruments are needed since RLS is underdiagnosed and treatable. We examined the operating characteristics of screening questions and a disease-specific measurement tool for the diagnosis of RLS in hemodialysis.MethodsWe conducted a cohort study of prevalent adult hemodialysis patients in Hamilton, Canada. The diagnosis of RLS was made using the 2012 Revised International Restless Legs Syndrome Study Group (IRLSSG) criteria. All participants received three screening instruments: (i) a single screening question for RLS derived from a nondialysis population; (ii) a single question from the Edmonton Symptom Assessment System (ESAS); and (iii) the IRLSSG Rating Scale (IRLS). All instruments were compared with the reference standard using logistic regression from which receiver operating characteristics curves were generated. Cutoffs associated with maximum performance were identified.ResultsWe recruited 50 participants with a mean (SD) age of 64 (12.4) years, of whom 52% were male and 92% were on three times weekly hemodialysis. Using the reference standard, 14 (28%) had a diagnosis of RLS. The single screening question for RLS had an area under the receiver operating curve (AUROC) of 0.72 with a sensitivity of 85.7% and specificity of 58.3%. An ESAS cutoff of ≥1 had the highest AUROC at 0.65 with a sensitivity of 79% and specificity of 56%. An IRLS cutoff of ≥20 had the highest AUROC at 0.75 with a sensitivity of 71% and specificity of 81%.ConclusionIRLS had better specificity than the single question or ESAS for the diagnosis of RLS.

Deep brain stimulation improves restless legs syndrome in patients with Parkinson disease

To study the effect of subthalamic nucleus (STN) deep brain stimulation (DBS) in patients with Parkinson disease (PD) and moderate to severe restless legs syndrome (RLS) on their RLS symptoms. Patients undergoing STN DBS surgery for PD completed the International RLS Study Group Rating Scale (IRLS) and RLS Quality of Life (QoL) questionnaires preoperatively and postoperatively at 6 months, 1 year, and 2 years. The primary outcome measure was IRLS sum score and subscales (severity and impact) and the secondary measure was RLS QoL scores. Differences among the mean scores over time were analyzed using mixed model regression. Twenty-two patients were enrolled. The preoperative IRLS sum scores were 19.59 ± 6.95, severity subscale 12.91 ± 4.33, impact subscale 4.45 ± 2.72, and transformed RLS QoL score 68.30 ± 20.26. The differences between preoperative and averaged postoperative scores were IRLS sum score -7.80, severity subscale -5.50, impact subscale -1.20, and RLS QoL 4.73. The overall F tests demonstrated differences among the times for the means of the IRLS sum and subscales: p < 0.05. There were no correlations between RLS symptoms improvement and PD motor symptoms improvement or reduction in PD medications. Half of the patients had at least 50% improvement and 27% had resolution of their RLS symptoms (IRLS = 0). STN DBS significantly decreased RLS symptoms in patients with PD despite a decrease in dopaminergic treatment. This improvement was sustained over a 2-year period. This study provides Class IV evidence that for patients with PD and moderate to severe RLS, STN DBS improves RLS symptoms.

Polysomnographic findings in restless legs syndrome (RLS) patients with severe augmentation

Background and objectivesAugmentation can occur frequently in restless legs syndrome (RLS) patients treated with dopaminergic agents. Video-polysomnographic (PSG) data from augmented RLS patients are scant. The aim of this study was to evaluate PSG findings in augmented RLS patients and compare them with those of non-augmented RLS patients. Patients and methodsValid PSG data were analyzed from 99 augmented and 84 non-augmented RLS inpatients who underwent one night PSG. ResultsBoth patient groups showed a high subjective burden of RLS symptoms. The mean scores on the International RLS Study Group Rating Scale (IRLS) were significantly higher in the group with augmentation than in the group without. The periodic leg movement index (PLMI) was increased in both groups, mostly on account of the PLM in wakefulness (PLMW). Both groups presented a reduced sleep efficiency and an increased sleep latency. The levodopa equivalent dose (LED) was significantly higher in the augmented group. ConclusionsOur study confirms that RLS patients with augmentation have disturbed sleep due to high amount of leg movements and fragmented sleep. Overall, however, polysomnographic characteristics were not different between insufficiently treated RLS and severely augmented RLS patients, implying that augmentation could represent a severe form of RLS and not a different phenomenon.

Sleep disturbances in restless legs syndrome

Background/Aim. Resteless legs syndrome (RLS) is chronical neurological disorder characterized by urge to move legs that is usually accompanied by unpleasant sensations in the lower extremities. Sleep disturbance is one of the main accompanying symptoms of RLS which exists in approximatelly 90% of patients. Impairment of sleep is related to daily sleepiness, depressive and anxiety disorders. The aim of this study was to detect frequency and characterisitics of sleep-related symptoms in patients with RLS, and its impairrment to daily sleepiness, fatique, anxiety and depression. Methods. We have examinated 94 patients with RLS. The diagnose of RLS was based on questionnaire with 4 specific questions according to the International Restless Legs Syndrome Study Group (IRLSSG) criteria updated in 2003. Severity of symptoms was astimated with IRLSSG Rating Scale, depression and anxiety with Hamilton Depression Rating Scale (HDRS) and Hamilton Anxiety Rating Scale (HARS) and sleepiness with Epworth Sleepiness scale (ESS). We astimated sleep characteristics and disturbances with specific questionnaire. Results. In our study 79.9% of patients had sleep-related symptoms. Average sleep duration was 6.50 ? 1.42 hours, with average frequency of awakening 2.34 ? 1.69 times per night. Average ESS score was 5.12 ? 4.08 (0?17). Patients with more severe symptoms had higher degree of sleepiness (p = 0.005). Patients with higher symptoms frequency, significantly more often had sleep disturbance (p = 0.016), tiredness and daily sleepiness (p = 0.001). Daily sleepiness (ESS) also significantly correlates with depression (p &lt; 0.05) and anxiety (p = 0.012). Conclusion. Our results confirm that sleep disturbances are one of the key accompanying symptoms of RLS which cause daily sleepiness, tiredness, depression and anxiety. Therefore, their early recognition and appropriate treatment must be a priority in RLS patients.

Efficacy of Intravenous Iron Sucrose in Hemodialysis Patients with Restless Legs Syndrome (RLS): A Randomized, Placebo-Controlled Study.

BackgroundRestless legs syndrome (RLS) is a common disorder in hemodialysis (HD) patients that causes sleep disturbances and diminished quality of life. Because iron deficiency has been implicated in the pathogenesis of RLS, we sought to investigate the effects of intravenous (IV) iron sucrose on symptoms of RLS in HD patients.Material/MethodsThe study was a randomized, placebo-controlled study of 1000 mg iron sucrose versus normal saline as placebo. Patients were evaluated at baseline and 2 weeks after the last injection. The severity of RLS was assessed using the International RLS Study Group rating scale (IRLS). Blood samples were taken to measure iron parameters reflecting the iron status, including serum ferritin (SF) concentration, percentage transferrin saturation (TSAT%) and hemoglobin (Hb), and other biochemical parameters as safety assessments, including creatinine (Cr), urea, intact parathyroid hormone (iPTH), and the index of urea clearance (Kt/V). Adverse events were monitored in all subjects during the period of infusion.ResultsAfter 2 weeks, IRLS scores decreased more in the IV-iron group (−7.38±2.03) than in the placebo group (−0.81±2.61) (P=0.000). Serum ferritin, TSAT, and hemoglobin increased more in the IV-iron group (227.63±77.64 μg/L; 26.06±7.77%; 13.98±3.62g/L, respectively) than in the placebo group (SF, p=0.000; TSAT, p=0.000; Hb, p=0.000, respectively). There were no significant differences between IV-iron and placebo groups in Cr, urea, iPTH, and Kt/V. No adverse effects were observed in the study.ConclusionsIV iron sucrose is a safe and effective treatment for reducing RLS symptoms in HD patients over the short-term.

Relationship between prevalence and severity of restless legs syndrome and anemia in patients with systemic lupus erythematosus.

Our aim was to evaluate the relationship between the prevalence and severity of restless legs syndrome (RLS) and the anemia in patients with systemic lupus erythematosus (SLE). This was a case-control study which was conducted at the rheumatology clinic of a university affiliated hospital, including 62 patients with SLE and 62 age- and sex-matched healthy controls. The patients were divided into two groups in terms of their hemoglobin levels. The criterion for anemia was hemoglobin level lower than 12 g/dL in females and 13 g/dL in males. Nineteen patients (30.6%) in the patient group were diagnosed with RLS, and International RLS Study Group Rating Scale (IRLSSG-RS) score was 10.7 ± 9.5 (median:10.0 [range:0.0-30.0]). Three subjects (4.8%) in the control group had RLS, and the IRLSSG-RS score was 0.7 ± 3.3 (median:0.0 [range:0.0-18.0]). The prevalence of RLS and the IRLSSG-RS score were higher in the patient group than those in the control group (P < 0.001). Ten SLE patients (50%) with anemia had RLS, and their IRLSSG-RS score was 14.5 ± 9.9 (median:21.0 [range:11.0-30.0]). Nine SLE patients (21.4%) without anemia had RLS and their IRLSSG-RS was 9.0 ± 8.9 (median:21.0 [range:11.0-24.0]). Significant differences were present in the prevalence of RLS and the IRLSSG-RS score between SLE patients with and without anemia (P = 0.024, P = 0.044, respectively). The present study demonstrated that the prevalence of RLS was higher in patients with SLE than that of the normal population. Results of this study also suggested that anemia was associated with higher frequency of and more severe RLS in patients with lupus.

Management of augmentation of restless legs syndrome with rotigotine: a 1-year observational study

AimThe aim of this study is to assess the effect of switching to rotigotine transdermal patch on severity of restless legs syndrome (RLS) in patients who experienced acute augmentation with previous oral dopaminergics. MethodsIn this 13-month observational study, adults with moderate-to-severe RLS and augmentation were switched to rotigotine per the physician’s independent decision. Assessments included Clinical Global Impression severity score (CGI-1); (primary), treatment regimen for switching (secondary), RLS-6, International RLS Study Group Rating Scale (IRLS), and augmentation severity rating scale (ASRS). ResultsA total of 99 patients received rotigotine, of whom 46 completed observational period, and 43 were assessed for effectiveness. A total of 5 patients switched to rotigotine after a >1-day drug holiday, 23 switched overnight, 9 had an overlapping switch, and 6 received ongoing oral dopaminergics with rotigotine for ≥28 days. Of the 99 patients, 57 took concomitant RLS medications (excluding switching medications) on at least 1 day. At the final visit, median change in CGI-1 (Hodges–Lehman estimate [95% CI]) was −2.0 (–2.5, −1.50); 37 of the 43 patients improved by ≥1 CGI-1 category, and 16 of 43 were responders (≥50% improvement). RLS-6 and IRLS scores also improved. Patients had median ASRS of 0 at the final visit indicating “no worsening/occurrence of augmentation.” ASRS item 1 showed a shift in mean time of symptom onset (24-h clock) from 12:38 (baseline) to 18:25 (final visit). Most common reasons for withdrawal of rotigotine were adverse events (26 patients) and lack of efficacy (14 patients). ConclusionsSwitching from oral therapies to rotigotine was effective in improving RLS symptoms in 37 of the 43 patients (from the original population of 99 patients) who remained in the study over 13 months. Clinical trial registrationClinicalTrials.govNCT01386944.

Restless legs syndrome in Egyptian medical students using a validated Arabic version of the Restless Legs Syndrome Rating Scale

ObjectiveRestless legs syndrome (RLS) is a common movement disorder that has a variable prevalence and impact reported from different countries and specific populations. The current study validated an Arabic version of the International Restless Legs Syndrome Study Group (IRLSSG) rating scale (IRLS) and investigated the prevalence and impact of RLS in medical students at Ain Shams University in Cairo. MethodsTranslation of IRLS was done according to standard recognized guidelines provided by the publisher. A total of 389 medical students (217 female and 172 male) participated in the study and answered four questions to detect RLS as proposed by the IRLSSG. Subjects who answered positively the first three questions were recruited for face-to-face interview to exclude RLS mimics and to answer the IRLS. ResultsA total of 46 subjects (11.8%; 27 female and 19 male) met the four criteria for RLS. Of these, 39 subjects (10%) had idiopathic RLS. Five subjects (1.3%) and two subjects (0.5%) reported association with history of anemia and diabetes mellitus respectively. Their mean total IRLS score was 16.33 ± 5.3, with moderate severity (11.62 ± 3.9) and low impact (3.1 ± 1.8). The prevalence of individuals who had two or more episodes of RLS of at least moderate severity per week was 5.9%. ConclusionIn this specific population of Egyptian medical students, a within-average prevalence of RLS was found with low impact on quality of life similar to worldwide reported populations. RLS sufferers were of high prevalence among this cohort. The Arabic version of IRLS is reliable and valid for further research in Arabic countries.

Mapping intrinsic functional brain changes and repetitive transcranial magnetic stimulation neuromodulation in idiopathic restless legs syndrome: a resting-state functional magnetic resonance imaging study

ObjectiveThe objectives of this study were, first, to explore differences in brain activity between normal people and idiopathic restless legs syndrome (RLS) patients during asymptomatic periods; and, second, to determine whether administering repetitive transcranial magnetic stimulation (rTMS) to specific cortical regions would reverse any observed differences in brain activity and alleviate patient symptoms. MethodsFifteen idiopathic RLS patients (nine drug-naive patients) and 14 gender- and age-matched healthy controls were enrolled. Resting-state functional magnetic resonance imaging was used to measure the amplitude of low-frequency fluctuations (ALFF) in spontaneous brain activity during asymptomatic periods. Seven patients received high-frequency (5 Hz) rTMS directed toward the leg area of the primary motor cortex. Scores on the International Restless Legs Syndrome Study Group (IRLSSG) Rating Scale and ALFF values were measured before and after treatment. ResultsCompared with healthy controls, RLS patients showed lower ALFF in the sensorimotor and visual processing regions, and higher ALFF in the insula, parahippocampal and hippocampal gyri, left posterior parietal areas, and brainstem. These results were largely conserved when only drug-naive patients were considered. After rTMS treatment, ALFF in several sensorimotor and visual regions were significantly elevated and IRLSSG Rating Scale scores decreased, indicating improved RLS symptoms. ConclusionsHigh-frequency rTMS delivered to the leg area of the primary motor cortex may raise functional activity in the sensorimotor and occipital regions, leading to improve symptoms in RLS patients. These results provide novel insight into RLS pathophysiology and suggest a potential mechanism for rTMS therapy in idiopathic RLS patients.

A mixed treatment comparison of gabapentin enacarbil, pramipexole, ropinirole and rotigotine in moderate-to-severe restless legs syndrome

Objective:A mixed treatment comparison (MTC) was performed to investigate the relative efficacy and safety of licensed pharmaceuticals for moderate-to-severe restless legs syndrome (RLS).Methods:RLS trials published over the past 10 years were identified via systematic literature searches of MEDLINE, Embase, Cochrane CENTRAL, and manufacturers’ websites. MTC was performed with WinBUGS software using a Bayesian approach. Identified primary outcomes: change in International RLS Study Group Rating Scale (IRLS) at week 12 and end of maintenance (EoM). Secondary outcomes: IRLS and Clinical Global Impression – Improvement Scale (CGI-I) responders, RLS-6 items and adverse events (AEs).Results:Twenty-eight clinical trials were identified. Fifteen were included in the primary analysis. Indirect comparisons were established among gabapentin enacarbil, pramipexole, ropinirole, rotigotine and placebo. Overall, the four active treatments showed similar efficacies as assessed by changes in IRLS scores, IRLS responders, CGI-I responders, and RLS-6 scores. The sole exception was change in IRLS at week 12, for which rotigotine was likely more efficacious than ropinirole (mean difference: −2.52 [95% CrI: −4.74, −0.40]). Indirect comparisons on safety endpoints indicated ropinirole was associated with a higher risk of nausea than the other agents, and was more likely to result in discontinuations due to lack of efficacy than pramipexole. Nausea was likely more frequent with pramipexole than gabapentin enacarbil, and rotigotine was more likely to result in discontinuation due to AEs than ropinirole and pramipexole.Conclusions:This MTC confirmed the superiority of gabapentin enacarbil, pramipexole, ropinirole, and rotigotine above placebo in alleviating RLS symptoms. Compared to ropinirole, rotigotine showed some additional benefit in terms of change in IRLS at Week 12. Choice of RLS drugs requires careful evaluation of effectiveness and safety profiles in clinical practice. Due to lack of head-to-head trials, inconsistency could not be assessed in our analysis. Head-to-head trials on a more homogeneous population are needed to validate the MTC results.

Prevalence and associated features of restless legs syndrome in a population of Iranian women during pregnancy

ObjectiveTo investigate the prevalence of restless legs syndrome (RLS) during pregnancy and to evaluate factors associated with RLS in a population of Iranian pregnant women. MethodsIn the present cross-sectional study, 443 consecutive pregnant women admitted for delivery underwent an interview within 2days of parturition. The diagnosis of RLS was established by the 4 criteria of the International Restless Legs Syndrome Study Group (IRLSSG). The severity of RLS was assessed through the IRLSSG Rating Scale. ResultsSeventy-nine (17.8%) women met the RLS diagnostic criteria, with most (74.7%) having RLS of moderate severity. The mean RLS duration before delivery was 3.1±2.1months among 69 (87.3%) women; 10 (12.7%) had RLS onset before pregnancy. Sleep disturbances including insomnia and early awakening were significantly more common among women with RLS than among those without (P<0.001), and the frequency of cesarean delivery was also significantly higher (58.2% versus 44.5%, P=0.027; odds ratio 2.4). There were no significant differences between the 2 groups in terms of age, number of pregnancies, folate and iron supplementation, hemoglobin level, and neonatal anthropometric data. ConclusionRestless legs syndrome is common during pregnancy and is associated with poor sleep and an increased risk of cesarean delivery.

2012 Emerging Science Abstracts

The Emerging Science abstracts were originally presented at the 2012 AAN Annual Meeting. Abstracts qualify for Emerging Science presentations by having key aspects of research conducted after the October 24th abstract submission deadline and must be new and of sufficient scientific importance to warrant expedited presentation and publication. Diego Garcia-Borreguero, MD, Crystal Chen, MD, Richard Allen, PhD, John Winkelman, Sarah Dubrava, MS, Jeffrey Miceli, PhD, Lloyd Knapp, PharmD OBJECTIVE: To assess pregabalin efficacy vs placebo and pramipexole, and augmentation vs pramipexole, in restless legs syndrome (RLS). BACKGROUND: Dopamine agonists (e.g. pramipexole) are currently first-line treatment for RLS; however long-term use is limited by augmentation and they only partly improve sleep. Pregabalin has shown efficacy in improving RLS symptoms and sleep and, with its non-dopaminergic mechanism-of-action, might induce less augmentation. METHODS: This was a 12-week placebo-controlled, 52-week active-comparator, randomized, double-blinded, multicenter trial. Participants with moderate-to-severe RLS received pregabalin 300mg/day, pramipexole 0.25mg/day or pramipexole 0.5mg/day for 52 weeks, or placebo for the first 12 weeks followed by randomization to one of the 3 active treatments for 40 weeks. Co-primary endpoints were efficacy of pregabalin vs placebo in reducing RLS symptoms over 12 weeks and augmentation with pregabalin vs pramipexole over 40 or 52 weeks. RESULTS: 719 participants received treatment: 182 pregabalin, 178 pramipexole 0.25mg/day, 180 pramipexole 0.5mg/day, and 179 placebo. RLS symptoms were significantly improved with pregabalin vs placebo, as measured by International RLS Study Group Rating Scale (IRLS) score (change from baseline vs placebo, −4.5; p<0.0001) and Clinical Global Impression-Improvement (CGI-I) scale (71.4% vs 46.8% with symptoms “very much” or “much” improved; p<0.0001). Pregabalin also demonstrated superior short- and long-term efficacy to pramipexole in reducing RLS symptoms (IRLS). Incidence of augmentation over 40/52 weeks was significantly lower with pregabalin vs pramipexole 0.5mg/day (2.1% vs 8.3%;p=0.0012) and numerically lower vs pramipexole 0.25mg/day …