Primary Restless Legs Syndrome Research Articles

Targeting the adenosinergic system in restless legs syndrome: A pilot, "proof-of-concept" placebo-controlled TMS-based protocol.

Restless Legs Syndrome (RLS) is a common sleep disorder characterized by an urge to move the legs that is responsive to movement (particularly during rest), periodic leg movements during sleep, and hyperarousal. Recent evidence suggests that the involvement of the adenosine system may establish a connection between dopamine and glutamate dysfunction in RLS. Transcranial magnetic stimulation (TMS) is a non-invasive electrophysiological technique widely applied to explore brain electrophysiology and neurochemistry under different experimental conditions. In this pilot study protocol, we aim to investigate the effects of dipyridamole (a well-known enhancer of adenosinergic transmission) and caffeine (an adenosine receptor antagonist) on measures of cortical excitation and inhibition in response to TMS in patients with primary RLS. Initially, we will assess cortical excitability using both single- and paired-pulse TMS in patients with RLS. Then, based on the measures obtained, we will explore the effects of dipyridamole and caffeine, in comparison to placebo, on various TMS parameters related to cortical excitation and inhibition. Finally, we will evaluate the psycho-cognitive performance of RLS patients to screen them for cognitive impairment and/or mood-behavioral dysfunction, thus aiming to correlate psycho-cognitive findings with TMS data. Overall, this study protocol will be the first to shed lights on the neurophysiological mechanisms of RLS involving the modulation of the adenosine system, thus potentially providing a foundation for innovative "pharmaco-TMS"-based treatments. The distinctive TMS profile observed in RLS holds indeed the potential utility for both diagnosis and treatment, as well as for patient monitoring. As such, it can be considered a target for both novel pharmacological (i.e., drug) and non-pharmacological (e.g., neuromodulatory), "TMS-guided", interventions.

Clinical features, polysomnography, and genetics association study of restless legs syndrome in clinic based Chinese patients: A multicenter observational study

Study objectivesTo systemically describe the clinical features, polysomnography (PSG) finding, laboratory tests and single-nucleotide polymorphisms (SNPs) in a clinic based Chinese primary restless legs syndrome (RLS) population. MethodsThis observational study, conducted from January 2020 to October 2021 across 22 sleep labs in China, recruited 771 patients diagnosed with RLS following the 2014 RLSSG criteria. Clinical data, PSG testing, and laboratory examination and SNPs of patients with RLS were collected. A total of 32 SNPs in 24 loci were replicated using the Asian Screening Array chip, employing data from the Han Chinese Genomes Initiative as controls. ResultsIn this study with 771 RLS patients, 645 had primary RLS, and 617 has DNA available for SNP study. Among the 645 primary RLS, 59.7% were women. 33% had a family history of RLS, with stronger familial influence in early-onset cases. Clinical evaluations showed 10.4% had discomfort in body parts other than legs. PSG showed that 57.1% of RLS patients had periodic leg movement index (PLMI) of >5/h and 39.1% had PLMI >15/h, respectively; 73.8% of RLS patients had an Apnea-Hypopnea Index (AHI) > 5/h, and 45.3% had an AHI >15/h. The laboratory examinations revealed serum ferritin levels <75 ng/ml in 31.6%, and transferrin saturation (TSAT) of <45% in 88.7% of RLS patients. Seven new SNPs in 5 genes showed a significant allelic association with Chinese primary RLS, with one previously reported (BTBD9) and four new findings (TOX3, PRMT6, DCDC2C, NOS1). ConclusionsChinese RLS patients has specific characters in many aspects. A high family history with RLS not only indicates strong genetic influence, but also reminds us to consider the familial effect in the epidemiological study. Newly developed sequencing technique with large samples remains to be done.

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.

Structural and functional multilayer network analysis in restless legs syndrome patients.

The combination of brain structural and functional connectivity offers complementary insights into its organisation. Multilayer network analysis explores various relationships across different layers within a single system. We aimed to investigate changes in the structural and functional multilayer network in 69 patients with primary restless legs syndrome (RLS) compared with 50 healthy controls. Participants underwent diffusion tensor imaging (DTI) and resting state-functional magnetic resonance imaging (rs-fMRI) using a three-tesla MRI scanner. We constructed a structural connectivity matrix derived from DTI using a DSI program and made a functional connectivity matrix based on rs-fMRI using an SPM program and CONN toolbox. A multilayer network analysis, using BRAPH program, was then conducted to assess the connectivity patterns in both groups. At the global level, significant differences there were between the patients with RLS and healthy controls. The average multiplex participation was lower in patients with RLS than in healthy controls (0.804 vs. 0.821, p = 0.042). Additionally, several regions showed significant differences in the nodal level in multiplex participation between patients with RLS and healthy controls, particularly the frontal and temporal lobes. The regions affected included the inferior frontal gyrus, medial orbital gyrus, precentral gyrus, rectus gyrus, insula, superior and inferior temporal gyrus, medial and lateral occipitotemporal gyrus, and temporal pole. These results represent evidence of diversity in interactions between structural and functional connectivity in patients with RLS, providing a more comprehensive understanding of the brain network in RLS. This may contribute to a precise diagnosis of RLS, and aid the development of a biomarker to track treatment effectiveness.

Correlation of Diffusion Tensor Tractography with Restless Legs Syndrome Severity.

This prospective study investigated white matter tracts associated with restless legs syndrome (RLS) severity in 69 patients with primary RLS using correlational tractography based on diffusion tensor imaging. Fractional anisotropy (FA) and quantitative anisotropy (QA) were analyzed separately to understand white matter abnormalities in RLS patients. Connectometry analysis revealed positive correlations between RLS severity and FA values in various white matter tracts, including the left and right cerebellum, corpus callosum forceps minor and major, corpus callosum body, right cingulum, and frontoparietal tract. In addition, connectometry analysis revealed that the FA of the middle cerebellar peduncle, left inferior longitudinal fasciculus, left corticospinal tract, corpus callosum forceps minor, right cerebellum, left frontal aslant tract, left dentatorubrothalamic tract, right inferior longitudinal fasciculus, left corticostriatal tract superior, and left cingulum parahippocampoparietal tract was negatively correlated with RLS severity in patients with RLS. However, there were no significant correlations between QA values and RLS severity. It is implied that RLS symptoms may be potentially reversible with appropriate treatment. This study highlights the importance of considering white matter alterations in understanding the pathophysiology of RLS and in developing effective treatment strategies.

Evaluation of the relationship between idiopathic restless legs syndrome and serum hepcidin levels.

The relationship between restless legs syndrome (RLS) and iron deficiency is a well-known topic. However, the etiology of the disease has not been determined. As the central iron deficiency is the most critical biological abnormality for RLS, we planned a study examining the relationship between RLS and hepcidin, which is the only regulatory hormone of iron metabolism known so far. International Restless Legs Syndrome Study Group diagnostic criteria (2014) were taken as a basis. A total of 40 RLS patients and 40 healthy controls were included in the study. To avoid the potential variables that might cause secondary RLS, all the participants were asked to provide hemogram, ferritin, iron, thyroid function tests, and sedimentation analysis. The hepcidin levels were measured with a Human Hepcidin (Hepc 25) ELISA kit (MyBioSource). The statistically significant results of our analysis show that the red blood cell count, the neutrophil count, the percentage of lymphocytes and neutrophils, and, more distinctively, hepcidin levels were higher in RLS patients in comparison with the control group. In this study, no differences were found in iron and ferritin values. High levels of hepcidin, the main regulator of iron metabolism, in those with primary RLS support the possibility that hepcidin may play a role in the pathogenesis of RLS. We think that larger studies on this subject can give clearer ideas.

Glymphatic system dysfunction in restless legs syndrome: evidenced by diffusion tensor imaging along the perivascular space.

There is growing evidence pointing at glymphatic system dysfunction in diseases with circadian disruption, such as sleep disorders. Lower diffusivity in the direction of perivascular space has been shown in several neurological and sleep-related disorders; however, its role in restless legs syndrome (RLS) is unclear. We hypothesized that similarly, in RLS the diffusivity in glymphatic system is decreased. Here, we aimed to evaluate glymphatic system functionality in patients with RLS, compare it to healthy controls, and analyze the correlation between its function and clinical characteristics. Sixty-nine patients with primary RLS and 51 healthy controls were recruited at a tertiary hospital. All participants underwent diffusion tensor imaging (DTI) and magnetic resonance imaging (MRI) using a 3T MRI scanner, and the DTI along the perivascular space (DTI-ALPS) index was calculated using DTI data. We compared the DTI-ALPS index between the patients with RLS and healthy controls. We also conducted the correlation analysis between the DTI-ALPS index and clinical characteristics, including age, age of onset, symptom duration, and RLS severity. DTI-ALPS index differed significantly between the patients with RLS and healthy controls; the DTI-ALPS index in the patients with RLS was lower than that in the healthy controls (1.48 vs. 0.60, p = 0.008). There was no significant correlation between the DTI-ALPS index and clinical characteristics. A significantly lower DTI-ALPS index in patients with RLS suggests that the glymphatic system function is impaired in patients with RLS.

Treatment of primary restless legs syndrome with Fu's subcutaneous needling: A case report

RationaleFu's subcutaneous needling (FSN) is a novel acupuncture technique developed based on traditional needling principles that aims to alleviate diseases by improving local muscle conditions and blood supply. FSN have been widely used for the treatment of various diseases. Restless legs syndrome (RLS) is a common central nervous system disorder characterized by intense discomfort in the legs, particularly at night, leading to an urge to move the legs for relief. In this study, we report a case in which FSN was used to treat primary RLS. Patient concernsA 67-year-old patient complained of nocturnal discomfort in the right leg for over 4 months, the symptoms occurred 2–3 times, with uncontrollable movement impulses in the right leg during the onset, accompanied by a burning sensation, lasting about 2 h, accompanied by anxiety and insomnia. Imaging examinations revealed no spinal stenosis or history of kidney disease, rheumatic disease, diabetes, or Parkinson's disease. DiagnosesThe patient was diagnosed with primary RLS, and the International Restless Legs Syndrome Study Group rating scale (IRLS) score was 26. InterventionsFSN was successfully performed three times per week on different days. No adverse and unanticipated events while the treatment. The total treatment course lasted for six weeks. OutcomesAfter the treatment, the patient reported that the recent onset interval was approximately 10 days, each time lasting approximately 15 min. The patient's IRLS score was 5, After a follow-up of 2 months following the end of treatment, the patient reported that the incidence of RLS was approximately one episode within two weeks,each lasting approximately 10 min. LessonsFSN significantly improved leg discomfort and desire for leg movement in patients with RLS. FSN may exert its therapeutic effects by influencing connective and muscular tissues, thereby improving the condition of the central nervous system and the local blood supply in the legs. However, due to the limitation of a single clinical observation case, a randomized clinical trial with a sufficient follow-up time is needed.

Effects of Different Exercise Programs on Symptoms, Sleep, and Quality of Life in Patients with Primary Restless Legs Syndrome.

Restless legs syndrome (RLS) is a sensorimotor disorder that can have a significant detrimental impact on the quality of life and sleep. Our aim was to examine the effects of aerobic exercise and stretching exercise programs on symptom severity, sleep, and quality of life in patients with primary RLS. A total of 18 patients between the ages of 22 and 61 were randomly divided into 3 groups as aerobic exercise, stretching exercises, and control. All exercise programs were applied 3 times a week for 8 weeks. Evaluations were performed before and after treatment. Symptom severity of the patients was evaluated by the International Restless Legs Syndrome Study Group Rating Scale, sleep was evaluated with the Pittsburgh Sleep Quality Index and actigraphy, and quality of life was evaluated with the John Hopkins Restless Legs Syndrome Quality of Life Questionnaire. Recovery status of the patients was determined using the post treatment global change scale. Aerobic exercise and the stretching exercise program were found to be effective in decreasing RLS symptoms (P = 0.025, P = 0.034) and improving subjective sleep quality (P = 0.034, P = 0.025), overall sleep quality (P < 0.001, P = 0.034), and quality of life (P = 0.009, P = 0016). Aerobic exercises were found to be more effective in reducing wake after sleep onset of sleep (P = 0.048), whereas stretching exercises reduced sleep disorders (P = 0.025). Both exercise approaches have been identified as highly effective approaches in patients with RLS. The treatment can be planned according to the choice of the available facilities, patient and clinician preference, and the advantages of the 2 exercise approaches.

Alterations of the thalamic nuclei volumes and intrinsic thalamic network in patients with restless legs syndrome

We aimed to investigate the alterations of thalamic nuclei volumes and intrinsic thalamic network in patients with primary restless legs syndrome (RLS) compared to healthy controls. Seventy-one patients with primary RLS and 55 healthy controls were recruited. They underwent brain MRI using a three-tesla MRI scanner, including three-dimensional T1-weighted images. The intrinsic thalamic network was determined using graph theoretical analysis. The right and left whole thalamic volumes, and the right pulvinar inferior, left ventral posterolateral, left medial ventral, and left pulvinar inferior nuclei volumes in the patients with RLS were lower than those in healthy controls (0.433 vs. 0.447%, p = 0.034; 0.482 vs. 0.502%, p = 0.016; 0.013 vs. 0.015%, p = 0.031; 0.062 vs. 0.065%, p = 0.035; 0.001 vs. 0.001%, p = 0.034; 0.018 vs. 0.020%, p = 0.043; respectively). There was also a difference in the intrinsic thalamic network between the groups. The assortative coefficient in patients with RLS was higher than that in healthy controls (0.0318 vs. − 0.0358, p = 0.048). We demonstrated the alterations of thalamic nuclei volumes and intrinsic thalamic network in patients with RLS compared to healthy controls. These changes might be related to RLS pathophysiology and suggest the pivotal role of the thalamus in RLS symptoms.

Opioids and restless legs syndrome: a double-edged sword.

Opioids and restless legs syndrome: a double-edged sword.

Pharmacologic and Nonpharmacologic Treatment of Restless Legs Syndrome.

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

Structural brain connectivity in patients with restless legs syndrome: a diffusion tensor imaging study.

To evaluate alterations of global and local structural brain connectivity in patients with restless legs syndrome (RLS). Patients with primary RLS and healthy controls were recruited at a sleep center where they underwent diffusion tensor imaging (DTI) of the brain. We calculated the network measures of global and local structural brain connectivity based on the DTI in both groups using DSI studio program and a graph theory. A total of 69 patients with primary RLS and 51 healthy controls were included in the study. We found a significant difference in the global structural connectivity between the groups. The transitivity in the patients with RLS was lower than that in healthy controls (0.031 vs. 0.033, p = 0.035). Additionally, there were significant differences in the local structural connectivity between the groups. The characteristic path length (r = 0.283, p = 0.018), radius of graph (r = 0.260, p = 0.030), and diameter of graph (r = 0.280, p = 0.019) were all positively correlated with RLS severity, whereas the mean clustering coefficient (r = -0.327, p = 0.006), global efficiency (r = -0.272, p = 0.023), small-worldness index (r = -0.325, p = 0.006), and transitivity (r = -0.351, p = 0.003) were negatively correlated with RLS severity. We identified changes in the global structural connectivity of patients with RLS using graph theory based on DTI, which showed decreased segregation in the brain network compared to healthy controls. These changes are well correlated with RLS severity. We also found changes in local structural connectivity, especially in regions involved in sensorimotor function, which suggests that these areas play a pivotal role in RLS. These findings contribute to a better understanding of the pathophysiology of RLS symptoms.

Attention-deficit/hyperactivity and obsessive-compulsive symptoms in adult patients with primary restless legs syndrome

Comorbidity between Restless Legs Syndrome and Attention-Deficit/Hyperactivity Disorder remains a matter of debate. This putative association, possibly reflecting a shared brain iron homeostasis and dopaminergic dysfunction, supports the hypothesis of a neurodevelopmental component in Restless Legs Syndrome pathogenesis. The aim of this study was to investigate Attention-Deficit/Hyperactivity Disorder and Obsessive-Compulsive Disorder symptoms prevalence in adult patients with primary Restless Legs Syndrome compared to another ill group of patients with obstructive sleep apnea syndrome to control for the disease specific effects on psychiatric symptoms and a healthy individuals control group. Clinical data were obtained through standardized and validated self-administrated questionnaires evaluating Attention-Deficit/Hyperactivity Disorder and Obsessive-Compulsive Disorder symptoms frequencies in 139 outpatients with idiopathic Restless Legs Syndrome, 111 patients with treated obstructive sleep apnea syndrome and 136 healthy subjects. Our findings demonstrate a higher prevalence of Attention-Deficit/Hyperactivity Disorder symptoms among both male and female patients with Restless Legs Syndrome, compared to obstructive sleep apnea syndrome patients and healthy subjects (33.3 and 43.5%, respectively, p < 0.001). Only women presented a strong relationship between Attention-Deficit/Hyperactivity Disorder and Restless Legs Syndrome severity (p < 0.001). Male and female in the three groups showed similar Obsessive-Compulsive Disorder symptom prevalence. These findings indicate that Attention-Deficit/Hyperactivity Disorder symptoms among adult patients with Restless Legs Syndrome populations are a robust phenomenon. These data provide arguments in favor of an enlargement of the clinical neuropsychological presentation of Restless Legs Syndrome and question the role of decreased brain iron of these psychiatric symptoms.

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

Background: Several studies have reported the efficacy of intravenous (IV) iron for patients with restless legs syndrome (RLS), but little is known about the efficacy or safety of repeated IV iron treatment. The aim of this study was to evaluate the effectiveness of repeated doses of IV ferric carboxymaltose (FCM) in treating RLS symptoms. Methods: Patients who received FCM more than twice for RLS from April 2016 to January 2020 were retrospectively reviewed. Patients who had shown positive response to initial IV FCM re-visited the clinic when their symptoms returned, and received repeated IV FCM (1000 mg). Blood iron panels were measured before initial and repeated IV FCM. We defined ‘responders’ as patients with a greater than 40% decrease in International Restless Legs Study Group Severity Scale (IRLS) compared with pre-treatment levels. Results: A total of 42 patients, including 26 with primary RLS, 5 with gastrectomy, and 11 with anemia, completed the evaluation. Patients received IV FCM infusion 2–4 times. A total of 21 of 26 (80.8%) primary cases of RLS, 4 of 5 (80.0%) patients with a history of gastrectomy, and 9 of 11 (81.8%) patients with anemia responded to repeated FCM treatment. Serum ferritin levels of patients with primary RLS were higher before the second treatment than the baseline levels. There were no serious adverse events observed in the study. Conclusions: Repeated IV FCM for recurring symptoms is an effective treatment for primary RLS and RLS associated with iron deficiency. Serum ferritin might not be a reliable factor to monitor the sustained effects of IV iron for RLS.

Restless Legs Syndrome and the Eyes: Spectral-Domain Optic Coherence Tomography Study.

Restless legs syndrome (RLS) is a movement disorder thought to be caused by impaired dopamine action. This study aimed to evaluate possible changes in ocular biometric and optic coherence tomography (OCT) parameters in RLS patients. This is a prospective, cross-sectional comparative study. Consecutive primary and secondary (with iron-deficiency anemia) RLS patients and age-matched and sex-matched controls were enrolled in the study. All participants underwent comprehensive neurological and ophthalmological examinations. Ocular biometric and OCT parameters, such as choroidal thickness, macular thickness, macular volume, ganglion cell layer thickness, inner nuclear cell layer thickness, and retinal nerve fiber layer thickness, were compared. Fifty-one RLS patients and 50 healthy controls were included in this study. There was no difference between the groups' refraction status, ocular biometric data (axial length, anterior chamber depth, central corneal thickness), or OCT parameters (choroidal thickness, macular thickness, macular volume, ganglion cell layer thickness, inner nuclear cell layer thickness). Primary and secondary (with only iron-deficiency anemia) RLS patients were compared, and there was no difference in their axial length, anterior chamber depth, central corneal thickness or OCT parameters. No significant relationship was found between disease severity or duration and OCT parameters. Disease severity and disease duration do not affect OCT parameters in primary or secondary RLS patients. OCT data do not seem to provide information about the course of this disease.

Relation of Serum Hepcidin Levels and Restless Legs Syndrome in Patients Undergoing Peritoneal Dialysis.

Introduction: Restless legs syndrome is a common and severe complication in patients undergoing peritoneal dialysis (PD), which seriously affects the life quality and prognosis of patients undergoing PD. Unfortunately, there are still no effective prevention and treatment measures. Serum hepcidin was demonstrated to be related to primary restless legs syndrome (RLS), whereas there are no studies on the relationship between serum hepcidin and RLS in patients undergoing PD. We aimed to evaluate the role and function of serum hepcidin in patients undergoing PD with RLS.Methods: A total of 51 patients undergoing PD with RLS and 102 age-and gender-matched patients undergoing PD without RLS were included. We collected the clinical data including serum hepcidin of those patients undergoing PD. We scored the severity of RLS according to the International restless leg Syndrome Research Group rating scale (IRLS). We compared the clinical characteristics of the two groups and evaluated the determinant factors of RLS by Logistic regression analysis. In addition, we evaluated the diagnostic value of serum hepcidin in patients undergoing PD with RLS by receiver operating characteristic (ROC) curve. We also analyzed the influencing factors of IRLS by multivariate linear regression analysis.Results: The duration of PD, serum hepcidin, and calcium were found to be significantly higher in patients undergoing PD with RLS than those patients undergoing PD without RLS (P < 0.001, P < 0.001, and P = 0.002, respectively). The level of hemoglobin, albumin, and RKF were significantly lower in patients undergoing PD with RLS (P = 0.002, P = 0.042, and P < 0.001, respectively). The duration of PD [odds ratio (OR) 1.038, 95% CI: 1.017, 1.060, P < 0.001], hemoglobulin level (OR 0.969, 95% CI: 0.944, 0.995, P = 0.019), calcium level (OR 9.224, 95% CI: 1.261, 67.450, P = 0.029), albumin level (OR 0.835, 95% CI: 0.757, 0.921, P < 0.001), hepcidin level (OR 1.023, 95% CI: 1.009, 1.038, P = 0.001), and RKF (OR 0.65, 95% CI: 0.495, 0.856, P = 0.002) are independent determinant factors of RLS in patients undergoing PD. Multivariate linear regression analysis revealed that, in addition to albumin, they were also independently associated with the severity of RLS.Conclusion: A significant relation was detected between serum hepcidin level and RLS in patients undergoing PD.

Analysis of Serum Vitamin D Level and Related Factors in Patients With Restless Legs Syndrome.

Objective: This study aimed to detect serum vitamin D (VitD) levels in patients with primary restless legs syndrome (RLS). The further objective was to analyze the relationship of VitD levels with the severity of RLS symptoms, sleep, anxiety, and depression.Methods: The serum 25-hydroxyvitamin D [25(OH)D] levels of 57 patients with primary RLS and the healthy physical examinees in our hospital during the same period were detected. The International Restless Legs Syndrome Study Group (IRLSSG) rating scale for measuring RLS severity and Pittsburgh Sleep Quality Index (PSQI) Scale, 24-item Hamilton Depression Rating Scale (HAMD24), and 14-item Hamilton Anxiety Scale (HAMA14) were used to assess the severity of symptoms, sleep, and emotional state of patients with RLS. Based on VitD level and IRLSSG score, they were grouped for analysis.Results: The serum 25(OH)D level was significantly lower in patients with RLS than in healthy controls, and the incidence of insufficient serum VitD levels was significantly higher in patients with RLS than in healthy people (both P < 0.05). The serum VitD level was significantly lower in (extremely) severe patients with RLS than in mild to moderate patients with RLS (P < 0.05). The IRLSSG scale score and HAMD24 score were significantly higher in patients with RLS with insufficient serum VitD levels than those with normal serum VitD levels (both P < 0.05). Correlation analysis of IRLSSG scale score with serum VitD level and each scale score in patients with RLS showed that IRLSSG scale score was negatively correlated with VitD level, but positively correlated with PSQI, HAMA14, and HAMD24 scores. The results of correlation analysis between serum VitD levels and each scale score in patients with RLS indicated that serum VitD levels were negatively correlated with IRLSSG scale scores, PSQI scores, and HAMD24 scores.Conclusion: The serum VitD level is generally lower in patients with RLS than in healthy people, and lower serum VitD level is associated with more severe symptoms of RLS, worse quality of sleep, and worse depression.

The effectiveness of short-term cognitive behavioral therapy in the complex treatment of idiopathic restless legs syndrome with chronic insomnia

Aim. To investigate the effectiveness of the short-term protocol of cognitive behavioral therapy RELEGS M. Hornyak et al. in complex treatment to improve the quality of sleep, reduce the symptoms of depression, anxiety, suicidal thoughts in patients with primary SBN comorbid with chronic insomnia.&#x0D; Methods. Study participants: 68 patients with primary restless legs syndrome with comorbid chronic insomnia. Women 56 (average age 52.110.3 years), men 12 (average age 50.39.4 years). The severity of restless legs syndrome is moderate to severe. The average age of the onset of the disease is 1848 years, the duration of the course of the disease is on average 1415 years. Taking various medications for the management of SBN for an average of 45 years. Study design: a randomized controlled trial, after screening 26 patients were assigned to the main group, underwent combined treatment, took a prolonged form of Pramipexole (Mirapex-PD, 1.5 mg.) and underwent the RELEGS CBT protocol (Restless Legs Skills program, Hornyak, Grossmann, 2018), which integrates the cognitive behavioral insomnia protocol (Morin, 2007) and Mindfulness-Based Stress therapy (Mindfulness-Based Stress Reduction, Bablas, 2016). The control group consisted of 24 people who received only general recommendations on sleep hygiene once. Both groups were treated with dopaminergic agonists under the supervision of a neurologist. Research methods: IRLS, ISI, DBAS-16, sleep diary analysis, actigraphy, BDI, SBQ-R, BAI.&#x0D; Results. The use of the CBT protocol in combination therapy with prolonged-acting dopaminergic agonists in patients with primary restless leg syndrome (mild and moderate severity) with comorbid chronic insomnia, in contrast to simple one-time general recommendations on sleep hygiene, is more effective for reducing dysfunctional behaviors, the spectrum of reinsurance and avoidance behavior both in relation to sleep and symptoms of restless legs. In patients with primary restless legs syndrome who underwent CBT, greater mental well-being was observed, which was expressed in a decrease in the severity of symptoms of insomnia, anxiety, and suicidal behavior after completion and persisted after 3 months of follow-up.&#x0D; Conclusion. As part of a personalized comprehensive approach, along with a drug-based approach and general recommendations for sleep hygiene, the use of short-term CBT (4 sessions, 60 minutes each) can significantly improve mental well-being, improve the quality of sleep of patients with restless legs syndrome with comorbid chronic insomnia.

White matter tract-specific alterations in patients with primary restless legs syndrome

Prior diffusion tensor imaging (DTI) studies have investigated white matter (WM) changes in patients with primary restless legs syndrome (RLS), but the results were inconsistent. Here, we proposed using tract-specific statistical analysis (TSSA) to find alterations in specific WM tracts to clarify the pathophysiological mechanisms of RLS. We enrolled 30 patients with RLS and 31 age- and sex- matched controls who underwent brain magnetic resonance imaging, neuropsychological tests, and polysomnography. Fractional anisotropy (FA) maps obtained from whole-brain diffusion tensor imaging and TSSA were used to localize WM changes in patients with RLS. Subsequently, a comparison of FA values for each tract between patients and controls was performed. The associations between FA values and clinical, polysomnographic, and neuropsychological parameters in RLS patients were assessed. RLS patients demonstrated decreased FA values in the left corticospinal tract (CST) and cingulum, and in the right anterior thalamic radiation (ATR) and inferior fronto-occipital fasciculus (IFO). Patients’ attention/executive function and visual memory scores positively correlated with FA values in the right ATR, and anxiety levels negatively correlated with FA values in the right IFO. Additionally, the number of periodic leg movements and movement arousal index were negatively correlated with FA values in the left CST. The TSSA method identified previously unknown tract-specific alterations in patients with RLS and significant associations with distinct clinical manifestations of RLS.