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Background Restless legs syndrome (RLS) with insomnia is presumed to be associated with antenatal depression. RLS without insomnia, however, has not been investigated in association with antenatal depression. We aimed to examine whether RLS without insomnia during pregnancy is associated with antenatal depressive symptoms. Methods This cross-sectional study used data from a randomized controlled trial (RCT) assessing antenatal depressive symptoms among Japanese pregnant women. The participants were 2,108 women who attended the RCT at 16–20 weeks of pregnancy. RLS, insomnia, and antenatal depressive symptoms were assessed using the Cambridge-Hopkins questionnaire short form, Insomnia Severity Index, and Edinburgh Postnatal Depression Scale, respectively. Associations of antenatal depressive symptoms with RLS and insomnia were examined using logistic regression analysis, adjusting for age, partner, education, children, and planned pregnancy. Results Of the total participants, 206 (9.8%) had antenatal depressive symptoms; 80 (3.8%) had RLS. The mean age (standard deviation) was 30.4 (4.6) years. RLS was positively associated with antenatal depressive symptoms: the odds ratio was 2.30 (95% confidence interval, 1.28–4.16). RLS without insomnia was positively associated with antenatal depressive symptoms, as well as insomnia without RLS and RLS with insomnia: the odds ratio was 2.44 (95% confidence interval, 1.09–5.46) for RLS without insomnia, 3.83 (2.78–5.28) for insomnia without RLS, and 5.80 (2.42–13.92) for RLS with insomnia, compared to neither RLS nor insomnia. Conclusions We observed the positive association between RLS without insomnia and antenatal depressive symptoms, suggesting the importance of assessing and treating RLS without insomnia during pregnancy for the reduction of antenatal depressive symptoms.

This study evaluated the efficacy and safety of limb ischemic preconditioning (LIPC) in treating restless leg syndrome (RLS) in maintenance hemodialysis (MHD) patients. A total number of 45 patients participated in the study. They were randomly divided into LIPC group and control group. The LIPC was performed by inflating the limb ischemic preconditioning training device in the patient's thigh to 200 mmHg to create transient ischemia, whereas control group inflated the device to 20 mmHg. International Restless Legs Syndrome (IRLS), Clinical Global Impression Scale (CGI-S), and Medical Outputs Study Sleep Scale were employed to evaluate LIPC effectiveness. The primary endpoint was the 'rate of clinical improvement in RLS severity', defined as the percentage of patients who had an IRLS score decrease of ≥5 points in each group. After intervention, the rate of clinical improvement in RLS severity was 56.5% in the LIPC group and 13.6% in the control group (13 (56.5) 3 (13.6),  = 0.003). In addition, the LIPC group's IRLS, CGI-S scores, the sleep disturbance and somnolence scores showed a significant downward trend compared to the control group (-5.5 ± 5.3  - 1.0 ± 3.8,  = 0.002; -1.7 ± 1.2  - 0.5 ± 1.4,  = 0.003; -15.5 ± 17.8 3.7 ± 12.0,  < 0.001; -9.9 ± 18.8  - 2.4 ± 8.6,  = 0.003). During the study, there were no serious adverse event in any of the patients. LIPC could be employed to effectively and safely alleviate the RLS symptoms in MHD patients.

Apart from the legs, restless legs syndrome (RLS) also affects the arms, head, neck, face, oral cavity, genital area, abdomen, intestines and bladder. RLS is also linked to several comorbid diseases, including headache disorders. Its association with dizziness has never been explored. We are reporting on two patients with RLS who also had a history of chronic dizziness. The treatment with levodopa or dopamine agonists completely alleviated both RLS and dizziness. We propose that RLS-like symptoms in the head may be experienced as dizziness and that dizziness may be part of the symptom complex of RLS. A large number of patients with chronic dizziness remain undiagnosed in clinical practice. We suggest exploring the history of RLS in patients presenting with chronic dizziness. Such patients may respond to levodopa or dopamine agonists. Because the response was seen in only two patients, a prospective placebo-controlled trial is needed to confirm these findings.

Comorbid depressive symptoms in restless legs syndrome (RLS) remain a treatment challenge, as some antidepressants aggravate RLS symptoms. Preliminary data in depressive patients suggest antidepressant properties of ropinirole. The present study investigates the effects of ropinirole immediate release (IR) on depressive symptoms and RLS severity. A multicenter, placebo-controlled, double-blind randomized (3:1) study was performed including patients with moderate to severe idiopathic RLS and at least mild depressive symptoms. Ropinirole IR (in flexible doses up to 4 mg/day) or placebo was given for 12 weeks including an uptitration phase of 7 weeks. Visits were scheduled at screening, baseline, and weeks 1, 4, and 12 with additional telephone contacts for dosing decisions. The modified intent to treat population comprised 231 patients (171 ropinirole, 60 placebo). The MADRS (Montgomery–Asberg Depression Rating Scale) scores decreased from baseline to week 12 from 18.8 to 8.7 in the ropinirole group and from 18.4 to 12.1 in the placebo group (primary endpoint, adjusted mean treatment difference −3.6 (95% CI: −5.6 to −1.6, significance in favor of ropinirole: P  < 0.001). The superiority of ropinirole compared to placebo was confirmed by the Hamilton Scale for Depression and Beck Depression Inventory-II scores. RLS severity scores (IRLS) decreased by 14.7 (ropinirole) and by 9.9 (placebo, P  < 0.001) points. Three out of four subdomains of the Medical Outcomes Study Sleep Scale improved significantly. The findings indicate that mild to moderate depressive symptoms should not be treated before sufficient therapy for RLS. Antidepressant medication can be necessary if depression symptoms still persist even if RLS symptoms are ameliorated.

Background Adults with moderate-to-severe primary restless legs syndrome (RLS) often experience painful dysesthesias, which may lead to impaired quality of life. Objectives The aim of this study was to assess the effects of gabapentin enacarbil (GEn) on pain associated with moderate-to-severe primary RLS in adults. Methods Data were pooled from three double-blind, randomized, placebo-controlled, 12-week trials (NCT00298623, NCT00365352, NCT01332305) for adults receiving GEn or placebo once daily. Change in average daily RLS pain score and a combined International Restless Legs Scale (IRLS)–pain response were examined. Results The modified intention-to-treat population included 671 adults (placebo, n  = 244; GEn 600 mg, n  = 161; GEn 1200 mg, n  = 266). Both GEn doses significantly improved average daily RLS pain score at week 12 ( p  < 0.001 for GEn 600 mg vs. placebo and GEn 1200 mg vs. placebo). The combined IRLS–pain response subanalysis included 366 patients with a baseline IRLS total score ≥15 and pain score ≥4 (placebo, n = 133; GEn 600 mg, n = 86; GEn 1200 mg, n  = 147). Most patients were both IRLS and pain responders (placebo, 40 %; GEn 600 mg, 70 %; GEn 1200 mg, 67 %). Spearman rank correlations between IRLS total and pain score (change from baseline to week 12) were moderate or strong. The most frequent treatment-emergent adverse events were somnolence (placebo, 5 %; GEn 600 mg, 20 %; GEn 1200 mg, 23 %) and dizziness (placebo, 4 %; GEn 600 mg, 13 %; GEn 1200 mg, 22 %). Conclusions This post hoc pooled analysis suggests that GEn (600 and 1200 mg) once daily significantly improved pain associated with moderate-to-severe primary RLS in adults; however, the analysis was not powered to detect statistical differences between the two GEn doses. Numerically, more GEn-treated patients had a combined IRLS–pain response than placebo-treated patients.

Abstract Restless sleep disorder (RSD) is a newly defined sleep-related movement disorder characterized by large muscle movements (LMM) in sleep. We examined the sleep study, clinical characteristics, and daytime functioning in children with RSD and compared them to children with periodic limb movement disorder (PLMD) or restless legs syndrome (RLS). Video polysomnography from 47 children with restless sleep was retrospectively reviewed for LMM and age- and sex-matched to 34 children with PLMD and 12 children with RLS. Data examined included PSG characteristics, ferritin, Pediatric Quality of Life (PedsQL), and Epworth Sleepiness Scale (ESS). Fourteen children met the clinical criteria for RSD with an LMM index of 5 or more per hour of sleep. Mean ESS was elevated in patients with RSD compared to either the PLMD or RLS groups though the result did not reach statistical significance (RSD = 10.20 ± 6.81, PLMD = 6.19 ± 4.14, RLS = 6.25 ± 4.90). The PedsQL score was significantly decreased in the RLS group compared to RSD and was reduced overall in all three groups (PedsQL Total RSD = 70.76 ± 18.05, PLMD = 57.05 ± 20.33, RLS = 53.24 ± 16.97). Serum ferritin values were similar in all three groups (RSD = 26.89 ± 10.29, PLMD = 33.91 ± 20.31, RLS = 23.69 ± 12.94 ng/mL, p = ns). Children with RSD demonstrate increased daytime sleepiness compared to PLMD or RLS and all three disease groups showed decreased quality of life. Further studies are needed to examine long-term consequences of RSD.

We aimed to investigate the frequency of restless legs syndrome (RLS) and neuropathic pain (NeP) in patients with Takayasu arteritis (TAK), and their relationship with disease activity, and quality of life (QoL). In this prospective case-control study, we evaluated 30 patients with TAK and 28 healthy subjects. Demographic, clinical, and current treatment-related data were also recorded. RLS diagnosis was confirmed in both groups according to the International Restless Legs Study Group criteria. The Douleur neuropathic-4 questionnaire (DN4) confirmed the frequency of neuropathic pain, and the quality of life was confirmed by the Short Form 36 (SF-36) health survey questionnaire. Univariate logistic regression analyses were performed to estimate the odds ratio (OR) for factors associated with NeP in patients with TAK. There was no statistically significant difference in the diagnosis of RLS between the TAK group and the control group ( p  = 0.195). The prevalence of NeP was significantly higher in TAK patients than in healthy controls ( p  = 0.011). The SF-36 subscale scores for physical functioning ( p  = 0.01) and general health ( p  = 0.002) were significantly lower in the TAK group than in the control group. Vasculitis Damage Index (VDI) scores were considerably higher in patients with NeP ( p  = 0.004). In univariate analyses, VDI decreased unbound iron-binding capacity, and SF36 mental component summary were predictors associated with NeP. This study revealed that the frequency of NeP was higher in patients with TAK than in the healthy population, and the patients with TAK were negatively affected in terms of NeP and QoL rather than RLS.

Restless legs syndrome is a common but still underdiagnosed neurologic disorder, characterized by peculiar symptoms typically occurring in the evening and at night, and resulting in sleep disruption and daily functioning impairment. This disease can affect subjects of all age ranges and of both sexes, manifesting itself with a broad spectrum of severity and deserving special attention in certain patient categories, in order to achieve a correct diagnosis and an effective treatment. The diagnosis of restless legs syndrome can be challenging in some patients, especially children and elderly people, and an effective treatment might be far from being easy to achieve after some years of drug therapy, notably when dopaminergic agents are used. Moreover, the pathophysiology of this disorder offers an interesting example of interaction between genetics and the environment, considering strong iron metabolism involvement and its interaction with recognized individual genetic factors. Therefore, this syndrome allows clinicians to verify how lifespan and time can modify diagnosis and treatment of a neurological disorder.

Study Objectives: Sleep disturbance is common in long-COVID (LC). Restless legs syndrome (RLS) is characterized by sleep disturbance and has been reported after viral infections. Therefore, we evaluated RLS symptoms cross-sectionally in individuals with LC at both current and pre–coronavirus disease 2019 (pre-COVID-19) time points. Methods: Adults on LC-focused Facebook pages were recruited for an online assessment of symptoms before COVID-19 infection and during their present LC state in a cross-sectional manner. The LC group documented baseline symptoms retrospectively. Questions were included about the presence/severity of RLS symptoms and assessments of fatigue, quality of life, and sleep apnea. A control group was recruited and included individuals ≥ 18 years of age who never had overt symptoms of COVID-19. Pregnancy was an exclusion criterion for both groups. Results: There were 136 participants with LC (89.7% females, age 46.9 ± 12.9 years) and 136 controls (65.4% females, age 49.2 ± 15.5). RLS prevalence in females with LC was 5.7% pre-COVID-19 and 14.8% post-COVID-19 ( P < .01) vs 6.7% in control females. Severity of RLS was moderate in both groups. Logistic regression predicting post-COVID-19 RLS among females with LC failed to find significant effects of hospitalization, sleep apnea, neuropathic pain severity, or use of antihistamines and antidepressants. Conclusions: The baseline prevalence of RLS in females with LC was similar to the general population group as well as to patients in epidemiological studies. The prevalence significantly increased in the LC state. Postinfectious immunological mechanisms may be at play in the production for RLS symptoms. Citation: Weinstock LB, Brook JB, Walters AS, Goris A, Afrin LB, Molderings GJ. Restless legs syndrome is associated with long-COVID in women. J Clin Sleep Med . 2022;18(5):1413–1418.

Study Objectives To report at a population level the prevalence of restless legs syndrome, insomnia, and the risk of obstructive sleep apnea in multiple sclerosis patients. Sleep patterns and associations with fatigue and daytime sleepiness were identified. Methods A cross-sectional study was performed using a written survey that was mailed to 11,400 individuals from the Northern California Chapter of the National Multiple Sclerosis (MS) Society Database who self-identified as having MS. The survey included individual questions relating to demographics as well as several standard validated questionnaires related to primary sleep disorders, sleepiness, fatigue severity, and sleep patterns. Results Among the 11,400 surveys mailed out, 2,810 (24.6%) were returned. Of these, 2,375 (84.5%) met the inclusion criteria. Among the completed surveys, 898 (37.8%) screened positive for obstructive sleep apnea, 746 (31.6%) for moderate to severe insomnia, and 866 (36.8%) for restless legs syndrome. In contrast, only 4%, 11%, and 12% of the cohort reported being diagnosed by a health care provider with obstructive sleep apnea, insomnia, and restless legs syndrome, respectively. Excessive daytime sleepiness was noted in 30% of respondents based on the Epworth Sleepiness Scale. More than 60% of the respondents reported an abnormal level of fatigue based on the Fatigue Severity Scale. Both abnormal fatigue and sleepiness scores were associated with screening positive for obstructive sleep apnea, insomnia, and restless legs syndrome. Conclusion A significant percentage of MS subjects in our sample screened positive for one or more sleep disorders. The vast majority of these sleep disorders were undiagnosed. Greater attention to sleep problems in this population is warranted, especially in view of fatigue being the most common and disabling symptom of MS. Citation Brass SD, Li CS, Auerbach S. The underdiagnosis of sleep disorders in patients with multiple sclerosis. J Clin Sleep Med 2014;10(9):1025–1031.