Secondary Restless Legs Syndrome Research Articles

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.

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

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

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.

Restless legs syndrome: An overview of pathophysiology, comorbidities and therapeutic approaches (Review).

The aim of this overview was to outline the pathophysiology, common comorbidities and current therapeutic modalities in the treatment/management of restless legs syndrome (RLS) a sensorimotor neurological disorder. The main symptom in RLS is a compelling compulsion to move the legs and a sense of restlessness at rest most commonly occurring during the night and improving with movement. The prevalence of secondary RLS among comorbid conditions such as idiopathic pulmonary fibrosis, end-stage renal disease, irritable bowel syndrome and attention deficit/hyperactivity disorder have further elucidated our understanding of the role of the iron-dopamine hypothesis as an etiopathogenetic hallmark in RLS and the efficacy of therapeutic approaches in milder to more severe forms. Currently, RLS treatment uses only symptomatic agents, since a disease-modifying therapy does not yet exist. The phenomena of rebound and augmentation have become central phenomena in overcoming the pharmacotherapeutic challenges when treating with dopaminergic agents in RLS. Considering alternative nonpharmacological therapies, especially for the treatment of RLS in pregnancy has a significant role and positive clinical outcome for patients in controlling symptoms.

Idiopathic and secondary restless legs syndrome during pregnancy in Japan: Prevalence, clinical features and delivery-related outcomes.

The aim of this study was to investigate prevalence of idiopathic and secondary restless legs syndrome (RLS) according to pregnancy trimester, and its effects on delivery-related outcomes among pregnant women in Japan. This was a single-center, prospective observational study. One hundred eighty-two consecutive pregnant women participated in the study from June 2014 to March 2016. Participants were interviewed and examined in the second and third trimesters of pregnancy and 1 month after delivery. At each term, RLS was identified by a research assistant and then specialist in sleep medicine based on the diagnostic criteria of the International Restless Legs Syndrome Study Group. Delivery-related data was collected from medical charts. RLS was classified as idiopathic RLS, which originally existed before the index pregnancy, or secondary RLS, which newly appeared during the index pregnancy. The prevalence of RLS was 4.9% (idiopathic 3.3%, secondary 1.6%) in the second trimester, 5.0% (idiopathic 0.0%, secondary 5.0%) in the third trimester, and 0.6% (idiopathic 0.0%, secondary 0.6%) after delivery. Prolonged labor, emergency Cesarean section, and arrest of labor tended to be more frequent in idiopathic and/or second RLS (all p<0.05). The prevalence of RLS during pregnancy was 4-5% and decreases after delivery in current Japan. The presence of RLS was associated with an increase in some delivery-related outcomes. Early detection and treatment of RLS during pregnancy may be beneficial to safe delivery for pregnant women.

The prevalence and clinical characteristics of restless legs syndrome in patients with iron deficiency anemia in Korea.

While the prevalence and clinical characteristics of restless legs syndrome (RLS) are known to vary according to ethnicity, a detailed evaluation of this condition among patients with iron deficiency anemia (IDA) has not yet been reported in an Asian population. We investigated the prevalence and clinical characteristics of RLS in patients with IDA in Korea compared with age- and sex-matched patients diagnosed with idiopathic RLS. This prospective single-center study was performed at a regional university hospital. Consecutive patients with IDA were enrolled over a 4-year period. Clinical interviews and laboratory tests were conducted at the first visit. RLS diagnosis was confirmed through face-to-face interviews. We randomly selected patients with idiopathic RLS without comorbid medical disorders from our sleep center dataset as control patients. The clinical characteristics of both groups were compared. We enrolled 124 patients with IDA. Fifty (40.3%) patients were diagnosed with RLS, with 82% exhibiting severe to very severe symptoms. Patients with IDA and RLS were older and reported more sleep deterioration than patients with IDA without RLS. Patients with IDA and RLS also had a more depressed mood and higher periodic limb movement index scores than patients with idiopathic RLS. The prevalence of RLS among patients with IDA in Korea was high, with the majority having severe to very severe symptoms. Patients with IDA and RLS had poorer sleep quality and more emotional problems than patients with IDA without RLS. Therefore, patients with IDA should be screened for RLS to prevent adverse effects on the quality of sleep and life.

Relation of serum hepcidin levels and restless legs syndrome in chronic hemodialysis patients.

Iron deficiency anemia, pregnancy, and end-stage renal disease (ESRD) are common causes of secondary restless legs syndrome (RLS). Serum ferritin is considered the most specific test associated with the total amount of body iron stores. However, due to the increase of serum ferritin secondary to inflammation in chronic hemodialysis (HD) patients, serum ferritin test results do not fully reflect decreased iron stores in these patients. The present study evaluates the serum hepcidin levels, as the main regulator of iron metabolism, and its relationship with RLS in chronic HD patients. The present cross-sectional study involved 72 patients (36 with and 36 without RLS) who received chronic HD treatment between April 2014 and April 2015. Demographic and biochemical data were evaluated in all patients, and statistical analyses were performed. The mean age and mean dialysis vintage of all patients (56% women) included in the study were 65.3 ± 11.6years and 41.5 ± 36.5months, respectively. Serum hepcidin, hemoglobin A1C (HbA1C), and ferritin levels were significantly higher in patients with RLS (p= 0.001, p =0.032, p =0.042, respectively). In addition, a positive correlation was found between International Restless Legs Syndrome Study Group severity scale score and serum hepcidin levels, HbA1C, and ferritin (r =0.387, p =0.001; r =0.426, p =0.034; r =0.240, p =0.046, respectively). A multivariate linear regression analysis revealed hepcidin and HbA1C to be independently associated with the presence of RLS. A significant relationship was detected between RLS and increased serum hepcidin levels in chronic HD patients, and uncontrolled diabetes was noted to contribute to this association.

Correlates of Nonanemic Iron Deficiency in Restless Legs Syndrome.

Objective: Iron deficiency anemia (IDA) is a well-known cause of secondary restless legs syndrome (RLS). Iron deficiency without anemia (IDNA) is insidious, and its association with RLS is less evaluated. We investigate prevalence and features of IDNA in a consecutive cohort of patients with RLS.Methods: We included sequential primary RLS patients and RLS patients with IDA. We also recruited age- and gender-matched healthy controls. RLS mimics and other comorbidities were carefully excluded.Results: One-hundred and ninety-six RLS patients without anemia, 26 RLS patients with IDA, and 63 controls were included. 42.3% of RLS patients without anemia had iron deficiency. Women were much more susceptible for IDNA with a relative risk of 5.51 (p < 0.0001). Women with IDNA and RLS had younger age both at interview and at RLS onset compared to women with RLS without iron deficiency (NID) (P < 0.01). IDNA RLS patients showed a tendency to higher risk of severe/very severe tiredness or sleepiness during the day as compared to NID RLS patients. Furthermore, IDNA RLS patients had longer duration of RLS (P < 0.01 in men, P < 0.05 in women) and younger age at onset (only in men, P < 0.05) compared to IDA RLS patients.Conclusion: IDNA is frequent in RLS and iron deficiency may be severe despite a normal hemoglobin level. Women are at much higher risk for IDNA, and IDNA in women presents some specific clinical features. Features of IDNA RLS are different from IDA RLS. Regular screening of peripheral iron parameters even in patients with normal blood counts is recommended for timely optimal management.

Patient characteristics predicting responses to intravenous ferric carboxymaltose treatment of restless legs syndrome

BackgroundSignificant benefit of intravenous ferric carboxymaltose (FCM) treatment for restless legs syndrome (RLS) has been well-established. However, no clinical indicators predicting treatment response of RLS have been established. This study aimed to determine factors predicting outcome of clinical FCM treatment of RLS patients. MethodsData were retrospectively reviewed from all patients who received FCM treatment for RLS from April 2016 to April 2019. These data included: detailed history, international RLS scale score (IRLS), questionnaires, comorbidity, and previous RLS medication use. Morning fasting serum iron, ferritin, and total iron-binding capacity were measured before and at four weeks after treatment. RLS patients with possible secondary RLS were identified by reviewing the medical histories. This included patients with iron deficiency anemia, lumbosacral radiculopathy, and gastrectomy. Primary RLS included those with no indication of secondary medical factors contributing to RLS. Treatment response was assessed using the IRLS and clinical ratings at four weeks after FCM administration. Patients with a greater than 40% decrease in IRLS were classified as responders. ResultsThe study comprised 164 patients with IRLS and clinical ratings obtained before and at four weeks after intravenous (IV) iron. Treatment responses differed considerably between diagnostic groups of RLS. Percentage responding was: 64.7% (66 of 102) for patients with primary RLS, 90.9% (10 of 11) with gastrectomy, 91.3% (21 of 23) with iron deficiency anemia and 39.3% (11 of 28) with lumbosacral radiculopathy. When responders were compared to non-responders in primary RLS patients, responders had significantly lower serum iron (80.5 ± 26.7 vs. 95.8 ± 30.5 μg/dL, p = 0.022) and percentage transferrin saturation (%TSAT) (25.4 ± 9.6 vs. 30.5 ± 10.5%, p = 0.026) in females, but not males. Logistic regression controlling for major subject variables showed that %TSAT significantly predicted response. (odds ratio [OR]: 0.955, confidence interval: 0.913–0.998, p = 0.040). ConclusionIntravenous FCM in moderate to severe RLS patients is beneficial as a first-line or add-on treatment, particularly for patients with compromised peripheral iron state. Overall, lower %TSAT predicted better chance of responding to the IV iron treatment especially for females.

Progress in diagnosis and treatment of restless legs syndrome

Restless legs syndrome (RLS) is defined as a sleep-wake disorder, with the key feature being an urge to move, which can be classified as two types as primary RLS and secondary RLS. Iron deficiency is a key role of RLS, low levels of serum ferritin is noted in RLS lab tests. Pathophysiology of RLS is complex, genetic variants, anatomical network vulnerability, neurotransmission abnormalities and abnormal dopaminergic neurotransmission may all contribute to its pathogenesis. The mild RLS can choose non-drug therapy, but most of the patients need drug therapy especially the severe cases. The aboved aspects are discussed in this review based on recent literatures. Key words: Restless legs syndrome; Sleeping disorder; Dopa; Iron

Increased Risk for New-Onset Psychiatric Adverse Events in Patients With Newly Diagnosed Primary Restless Legs Syndrome Who Initiate Treatment With Dopamine Agonists: A Large-Scale Retrospective Claims Matched-Cohort Analysis.

Published literature documents increased risk for psychiatric adverse events (P-AEs) following dopamine agonist (DA) initiation for treatment of primary restless legs syndrome (RLS). We examined the association between DA initiation and subsequent new-onset P-AEs among patients with a new diagnosis of RLS who had no history of psychiatric disorder or DA use. Selected were adults (age 18 years or older) enrolled through United States employer-sponsored plans and Medicare Advantage from 7/1/2008-12/31/2014, with ≥ 2 years of claims data preceding their first RLS diagnosis ("preindex period"). Excluded were those with psychiatric diagnoses (International Classification of Diseases, Ninth Revision [ICD-9] 290-319) or DA use during the preindex period, and those with possible secondary RLS. Patients who initiated (DA+) versus did not initiate (DA-) DAs were matched 1:1 on age at index RLS diagnosis, sex, geographic region, and employment status, and preindex period comorbid illness burden and number of non-DA drug fills. Using a validated ICD-9-based severity-of-illness psychiatric disorder classification system, we compared likelihoods of new-onset P-AEs between matched pairs during parallel follow-up periods. Identified were 889 matched pairs. Compared with their DA- counterparts, DA+ patients were nearly two times more likely to experience development of any P-AE (odds ratio [OR] 1.71, 95% confidence interval [CI] 1.31-2.24, P < .0001); and similarly more likely to experience the development of a severe (OR 1.68, 95% CI 1.03-2.86, P = .04), moderately severe (OR 1.63, 95% CI 1.17-2.29, P = .004), or mild (OR 1.72, 95% CI 1.12-2.65, P = .01) P-AE. Compared to DA- matched control patients, patients in whom RLS was newly diagnosed and who initiated de novo DAs demonstrated significantly increased risk for subsequent development of P-AEs of any severity. Hankin C, Lee D, Garcia-Borreguero D, Wang Z. Increased risk for new-onset psychiatric adverse events in patients with newly diagnosed primary restless legs syndrome who initiate treatment with dopamine agonists: a large-scale retrospective claims matched-cohort analysis. J Clin Sleep Med. 2019;15(9): 1225-1232.

Aumento de los depósitos cerebrales de hierro en una familia de donantes de sangre con síndrome de piernas inquietas

The pathophysiology of restless legs syndrome (RLS) is complex. Secondary RLS with iron deficiency -which suggests disturbed iron homeostasis- remains to be elucidated. We report the findings from a unique blood donor family with RLS. Three blood donors family members were diagnosed with RLS defined by the International RLS Study Group and without history of neurologic diseases and RLS symptoms in the last 3-5 years (range of blood donation: 10-40 years). The neurological examination and electromyographies were normal. A polisomnography showed disturbed nocturnal sleep with a reduction in sleep efficiency and an increased periodic limbs movement index. The cranial MRI showed brain iron deposits in basal ganglia, substantia nigra, red nuclei and dentate nuclei. Phenotypic and genotypic studies rule out genetic haemochromatosis or iron overload. The abnormal iron accumulation in the basal ganglia indicated a complex iron metabolism disorder of the central nervous system. Further studies are warranted to confirm our findings and its role in the pathophysiology of RLS.

Restless legs syndrome in patients infected with Helicobacter pylori

ABSTRACTObjective Although the etiology of restless legs syndrome (RLS) is yet to be discovered, some studies have mentioned the effect of infectious diseases in occurrence of RLS. This study aims to determine the association between common Helicobacter pylori (H. pylori) infection and occurrence of RLS.Methods In this descriptive analytical cross-sectional study, patients with RLS who were referred to the Internal Medicine Clinic of Fayazbakhsh Hospital in Tehran from September to December 2016 were evaluated. Patients with underlying diseases that would lead to secondary RLS were excluded from the study. The control group were matched with the patients group regarding their age and gender, but did not have RLS or diseases that would lead to secondary RLS. All participants underwent serologic tests for evaluating serum levels of IgA and IgG antibodies against H. pylori. Data were analyzed using Chi-Square test and Logistic Regression with SPSS Software Version 20. The significance level was ≤0.05.Results Fifty-seven RLS patients and 64 healthy controls were included in the study. In the RLS group, 36 participants (29.8%) had H. pylori infection. This number was 27 participants (22.3%) in the control group. Data analysis using logistic regression showed a significant relation between H. pylori and occurrence of RLS (p value ≤ 0.05).Conclusions Results of the present study indicated that infection with H. pylori is related with the occurrence of RLS. It seems that releasing inflammatory factors, iron deficiency, and small intestinal bacterial overgrowth are some of the involved mechanisms in this pathogenesis.

Risk factors of primary and secondary restless legs syndrome among a middle-aged population in Saudi Arabia: A community-based study.

INTRODUCTION:Restless legs syndrome (RLS) is etiologically divided into primary and secondary syndromes. However, a comparative description of both types is lacking in the literature. We compared primary and secondary RLS with respect to demographic determinants, associated risk factors, and comorbidities.METHODS:Following a cross-sectional survey on the prevalence of RLS in a Saudi population, RLS cases were identified using the International RLS Study Group (IRLSSG) criteria. Cases were assessed with an interview-based questionnaire regarding baseline characteristics, risk factors, and comorbidities and with lower limb examinations and laboratory measurements. RLS severity was assessed using the IRLSSG Severity Rating Scale.RESULTS:In total, 78 patients with RLS, including 50 (64.1%) primary and 28 (35.9%) secondary cases, were examined. Of the primary cases, 35 (70%) were male; of the secondary cases, 25 (89.3%) were female (P < 0.001). Multivariate regression confirmed the association of male gender with primary RLS (odds ratio = 14.53, 95% confidence interval [2.9–75], P = 0.001). There were more dark- and black-skinned participants in the primary RLS group (38, 72%) than in the secondary group (15, 28%) (P = 0.042). Iron deficiency was observed in most (26, 92%) of the secondary cases. More severe symptoms were reported in secondary than in primary RLS cases (P < 0.05).CONCLUSIONS:Primary RLS is more common but less severe than secondary RLS. Male gender and ethnicity play significant roles in primary RLS, whereas female gender and iron deficiency may be the main risk factors associated with secondary RLS.

Restless legs syndrome and sleep quality among adult sickle cell disease patients.

The purpose of this study is to determine and compare the prevalence of restless legs syndrome (RLS) between adult patients with sickle cell disease (SCD) and non-SCD anemia. This cross-sectional study was conducted from December 2013 to July 2014. Patients with SCD and non-SCD anemia were recruited from a hematology clinic at a large university hospital. Patients with secondary RLS were excluded. Data were collected on demographic features, clinical evaluations, laboratory tests, sleep quality using the Pittsburgh Sleep Quality Index, RLS symptoms using the International Restless Legs Syndrome Study Group Criteria, severity of RLS using the International Restless Leg Syndrome Rating Scale, and daytime sleepiness using the Epworth Sleepiness Scale. The study sample consisted of 44 patients with SCD and 45 with non-SCD anemia. The two groups were comparable in age, gender, body mass index, smoking habit, and comorbidities. Poor sleep quality was found in 63% of the SCD group compared to 53% of the non-SCD group. The prevalence of RLS among SCD group and non-SCD group was 13.6% (6/44) and 8.8% (4/45), respectively. These differences, however, were not statistically significant, p > 0.05. Excessive daytime sleepiness was also similar in both groups, with the rate being 20.5 and 17.8% in the SCD and non-SCD groups, respectively. Our study revealed that poor sleep quality and RLS were both common among adult patients with SCD; however, they did not differ significantly from patients with non-SCD anemia.

Nerve Decompression and Restless Legs Syndrome: A Retrospective Analysis.

Restless legs syndrome (RLS) is a prevalent sleep disorder affecting quality of life and is often comorbid with other neurological diseases, including peripheral neuropathy. The mechanisms related to RLS symptoms remain unclear, and treatment options are often aimed at symptom relief rather than etiology. RLS may present in distinct phenotypes often described as "primary" vs. "secondary" RLS. Secondary RLS is often associated with peripheral neuropathy. Nerve decompression surgery of the common and superficial fibular nerves is used to treat peripheral neuropathy. Anecdotally, surgeons sometimes report improved RLS symptoms following nerve decompression for peripheral neuropathy. The purpose of this retrospective analysis was to quantify the change in symptoms commonly associated with RLS using visual analog scales (VAS). Forty-two patients completed VAS scales (0-10) for pain, burning, numbness, tingling, weakness, balance, tightness, aching, pulling, cramping, twitchy/jumpy, uneasy, creepy/crawly, and throbbing, both before and 15 weeks after surgical decompression. Subjects reported significant improvement among all VAS categories, except for "pulling" (P = 0.14). The change in VAS following surgery was negatively correlated with the pre-surgery VAS for both the summed VAS (r = -0.58, P < 0.001) and the individual VAS scores (all P < 0.01), such that patients who reported the worst symptoms before surgery exhibited relatively greater reductions in symptoms after surgery. This is the first study to suggest improvement in RLS symptoms following surgical decompression of the common and superficial fibular nerves. Further investigation is needed to quantify improvement using RLS-specific metrics and sleep quality assessments.

Epilepsy and restless legs syndrome

Restless legs syndrome (RLS) is a common neurological movement disorder occurring in approximately 10% of the general population. The prevalence of moderately severe RLS is 2.7% overall (3.7% for women and 1.7% for men). Epilepsy is also a common neurological disorder with significant associated morbidity and impact on quality of life. We evaluated the severity and frequency of primary RLS in patients with localization-related temporal lobe epilepsy (TLE) and investigated the role of prodromal RLS symptoms as a warning sign and lateralizing indicator. All epilepsy patients seen in the outpatient clinic were screened for movement disorders from 2005 to 2015. Ninety-eight consecutive patients with localization-related TLE (50 right TLE and 48 left TLE) who met inclusion criteria were seen in the outpatient clinic. The control group consisted of 50 individuals with no history or immediate family history of epilepsy. Each patient was evaluated with the International Restless Legs Study Group (IRLSSG) questionnaire, NIH RLS diagnostic criteria, ferritin level, and comprehensive sleep screening including polysomnography. Furthermore, patients with obstructive sleep apnea or a definite cause of secondary restless legs syndrome such as low serum ferritin or serum iron levels were also excluded from the study. There was a significant association between the type of epilepsy and whether or not patients had RLS χ2 (1)=10.17, p<.01, using the χ2 Goodness of Fit Test. Based on the odds ratio, the odds of patients having RLS were 4.60 times higher if they had right temporal epilepsy than if they had left temporal epilepsy, serving as a potential lateralizing indicator. A prodromal sensation of worsening RLS occurred in some patients providing the opportunity to intervene at an earlier stage in this subgroup. We identified frequent moderate to severe RLS in patients with epilepsy. The frequency of RLS was much more common than would typically be seen in patients of similar age. The restlessness was typically described as moderately severe. The RLS symptoms were more common and somewhat more severe in the right TLE group than the left TLE group.

Restless Legs Syndrome in Adults in Peking Union Medical College Hospital.

Objective To investigate the clinical characteristics of restless legs syndrome (RLS) in adults in Peking Union Medical College Hospital and explore the sleep quality,fatigue degree,daytime sleepiness,disease severity,depression and anxiety of RLS patients.Methods Totally 4739 consecutive patients who visited the outpatient departments with any sleep complaint or leg discomforts were recruited in the study. Patients under 18 years were excluded. All participants answered RLS questionnaire. The subjects fulfilled all four criteria would be followed up and given advanced examinations to rule out secondary RLS and RLS mimics. Primary RLS patients were evaluated with International Restless Legs Scale (IRLS),Pittsburgh Sleep Quality Index (PSQI),Fatigue Severity Scale (FSS),Epworth Sleepiness Scale (ESS),and Hospital Anxiety and Depression Scale for depression and anxiety (HADD and HADA). Another two groups of age-and gender-matched healthy subjects and non-RLS insomnia patients were served as normal and non-RLS insomnia controls.Results There were 162 (3.42%,162/4739) subjects fulfilling all four criteria for RLS; 42 (0.89%,42/4739) subjects were diagnosed as primary RLS and 33 (0.70%,33/4739) as RLS mimics. In primary RLS patients,41(97.6%) were found to be with poor sleep,13 (31.0%) with anxiety,and 4(9.5%) with depression. The scores of PSQI(q=11.69,P=0.000),HADA(q=8.02,P=0.000),and HADD(q=6.60,P=0.000)in primary RLS patients were significantly higher than those in normal controls. The scores of FSS(q=3.74,P=0.001),ESS(q=2.97,P=0.012),and HADD(q=4.15,P=0.000) in primary RLS patients were significantly lower than those in non-RLS insomnia controls. The scores of HADA and HADD were significantly correlated with those of PSQI(r=0.340,P=0.028;r=0.383,P=0.012),FSS(r=0.445,P=0.003;r=0.511,P=0.001),and IRLS(r=0.477,P=0.001;r=0.578,P=0.000). Conclusions RLS should be considered in the patients with any sleep-related complaint or leg discomforts. Primary RLS patients suffer from bad sleep and are more susceptible to anxiety and depression. Secondary RLS and RLS mimics should be excluded before the diagnosis of primary RLS.

Restless legs syndrome associated with major diseases: A systematic review and new concept.

Recent publications on both the genetics and environmental factors of restless legs syndrome (RLS) defined as a clinical disorder suggest that overlapping genetic risk factors may play a role in primary (idiopathic) and secondary (symptomatic) RLS. Following a systematic literature search of RLS associated with comorbidities, we identified an increased prevalence of RLS only in iron deficiency and kidney disease. In cardiovascular disease, arterial hypertension, diabetes, migraine, and Parkinson disease, the methodology of studies was poor, but an association might be possible. There is insufficient evidence for conditions such as anemia (without iron deficiency), chronic obstructive pulmonary disease, multiple sclerosis, headache, stroke, narcolepsy, and ataxias. Based on possible gene-microenvironmental interaction, the classifications primary and secondary RLS may suggest an inappropriate causal relation. We recognize that in some conditions, treatment of the underlying disease should be achieved as far as possible to reduce or eliminate RLS symptoms. RLS might be seen as a continuous spectrum with a major genetic contribution at one end and a major environmental or comorbid disease contribution at the other.

Restless legs syndrome: associated non-motor symptoms and medical comorbidities: a controlled study

Introduction: Restless legs syndrome (RLS) is a chronic sensorimotor disorder characterized by discomfort or pain, predominantly in the legs, resulting in an urge to move during times of rest. These disturbances are often accompanied by sleep fragmentation, which can significantly increase medical comorbidities over time and can have a detrimental effect on a patient’s overall quality of life. In this retrospective study, we examined the temporal relationship between the time of RLS diagnosis and the onset of non-motor symptoms (NMS) and medical comorbidities. Patients and methods: Thirty-six RLS patients were evaluated for age at: symptom onset, time of diagnosis, time of occurrence of NMS, and medical comorbidities. We used structured interviews, validated questionnaires, and past medical records to aggregate and verify patient data. There was no clinical evidence to suggest secondary RLS in any patient at time of diagnosis. Results: Twenty-five patients were diagnosed as having RLS alone and eleven were diagnosed with RLS and Parkinson’s disease (RLS + PD). In the RLS + PD group, irrespective of which disorder presented first, we found that patients exhibited symptoms of RLS at a significantly later age than those patients with RLS alone (P,0.05). The incidence and severity of NMS were significantly higher in the RLS + PD group compared to RLS alone and controls (P,0.001). Increased risk of RLS was identified in patients exhibiting mood changes and sleep deficits, and these risk factors manifested 5 and 10 years prior, respectively, to their diagnosis. Conclusion: Primary RLS develops earlier in those patients who only have RLS compared to those who later also develop PD. Mood and sleep impairment can be present years prior to the diagnosis of RLS. Other medical comorbidities associated with RLS included hypertension, hyperlipidemia, arthritis, chronic pain, and diabetes.