Restless Legs Syndrome Patients Research Articles

Difference in Sleep Characteristics between Restless Leg Syndrome With and Without Periodic Limb Movement during Wakefulness

Objectives Restless leg syndrome (RLS) is a common sensorimotor disorder and is frequently associated with periodic limb movement in sleep (PLMS). Also about one third of patient with RLS have periodic limb movement during wakefulness (PLMW). However there is little research on the correlation between PLMW and RLS. We aimed to evaluate difference in sleep characteristics between patients with RLS with PLMW and those without PLMW. Methods Our study included twenty eight RLS patients. Subjects underwent suggested immobilization test (SIT) prior to one full-night polysomnography study. Patients were classified into two groups according to the presence of PLMW based on SIT-PLMW index. Polysomnographic findings, subjective sleep quality, and hematologic results were analyzed and compared between the two groups. Results Mean age of patient with frequent PLMW (SIT-PLMW ≥40/hr) was significantly higher. RLS patients with frequent PLMW were also significantly related to insomnia severity. The PLMS index was higher in patients with PLMW and showed a significant correlation with the PLMW index. Conclusions PLMW influence sleep quality such as insomnia and is correlated with movement during sleep. Keywords: Restless legs syndrome, Periodic leg movement during sleep, Periodic leg movement during wakefulness, Polysomnography, Suggested immobilization test.

Zastosowanie pramipeksolu o natychmiastowym uwalnianiu w leczeniu zespołu niespokojnych nóg u pacjentów w praktyce psychiatrycznej – w pytaniach i odpowiedziach

Zastosowanie pramipeksolu o natychmiastowym uwalnianiu w leczeniu zespołu niespokojnych nóg u pacjentów w praktyce psychiatrycznej – w pytaniach i odpowiedziach

Clinical Characteristics and Efficacy of Iron Treatment for Restless Legs Syndrome Patients with Very Low Ferritin Levels

Clinical Characteristics and Efficacy of Iron Treatment for Restless Legs Syndrome Patients with Very Low Ferritin Levels

Disconnect between sensory and motor features of restless legs syndrome during the suggested immobilization test

The Suggested Immobilization Test (SIT) was developed as an objective diagnostic tool to quantify motor restlessness periodic limb movements during wakefulness (PLMW) associated with Restless Legs Syndrome (RLS). Limited research has explored the relationship between discomfort and pain associated with motor activity in RLS during the SIT. Twenty-five RLS patients and ten control participants completed the International Restless Legs Syndrome Study Group Severity Scale and the SIT with bilateral recordings of tibialis anterior EMG (PLMW index), as well as pain and discomfort visual analogue scales every 5 min for the 60-min SIT. The discomfort score had the ability to discriminate between RLS and control participants (P = 0.0001); however, the PLMW index did not (P = 0.67). The RLS patients also exhibited greater discomfort and pain in the latter half of the SIT (P < 0.05) compared to the initial phase of the SIT and compared to controls. Despite rating significant levels of discomfort, the majority of the RLS patients did not exhibit PLMW possibly suggesting a disconnect between the sensory and motor components of RLS. These sensory and motor features may be independent and as such presentation of PLMW during the SIT may not be a reliable objective measure of RLS.

Restless legs syndrome in end-stage renal disease patients undergoing hemodialysis.

Restless legs syndrome (RLS) is a frequent complication of hemodialysis that has been associated with poor quality of life and increased risk for complications. Nevertheless, few studies regarding this entity exist in resource-limited settings. To determine the prevalence of RLS among Mexican patients on hemodialysis; and compare these patients with a control group of the same population. We recruited 105 hemodialysis patients. Restless legs syndrome was diagnosed according to the updated criteria set out by the International RLS Study Group. We selected patients who did not meet the criteria, as controls. We found an RLS prevalence of 18%. The RLS patients had a significantly higher prevalence of iron deficiency anemia and uremic pruritus. None of the patients reported RLS symptoms prior to hemodialysis initiation. Restless legs syndrome is common among Mexican patients on hemodialysis. Larger studies are required to address the impact of RLS in hemodialysis patients.

Decline in dopamine agonists prescribing and characteristics of drugs prescribed during ambulatory office visits for restless legs syndrome: the National Ambulatory Medical Care Survey 2007–2015

ObjectiveTo examine prescribing of drugs treating or exacerbating restless legs syndrome (RLS) during U.S. physician office visits for RLS for the years 2007–2015; and to assess potential prescribing predictors of these drugs. MethodsUsing the National Ambulatory Medical Care Survey data, we conducted a retrospective cross-sectional study. We calculated weighted percentages of RLS-related office visits associated with RLS treatment drugs (alpha-2-delta ligands, dopamine agonists, and other drugs used for RLS) and exacerbating drugs. Using logistic regression, we examined the adjusted association between potential predictors and prescribing of major RLS treatment (dopamine agonists and alpha-2-delta ligands) and exacerbating drugs. ResultsA total of 456 RLS-related office visits were included for analysis, representing approximately 9.9 million visits. The weighted percentages of visits with dopamine agonists (excluding levodopa) decreased from 50% to 22% (RR 0.44; 95% CI 0.26, 0.77). A visit to a neurologist was associated with a 76% increase in prescribing of the major RLS treatment drugs compared with a visit to a family/general or internal medicine physician (RR 1.76; 95% CI 1.29, 2.42). RLS exacerbating drugs were listed in 28% (95% CI 21–36) of RLS-related visits, mostly for antidepressants (83%). Younger age groups (18–44 and 45–64) were predictors of RLS exacerbating drug prescribing, compared with the older age group (RR 2.46; RR 2.00, respectively). ConclusionPrescribing of dopamine agonists during RLS-related visits decreased during 2007–2015, but prescribing of RLS exacerbating drugs remained high. More investigation is necessary concerning whether clinicians assess the appropriateness of RLS exacerbating drugs for RLS patients before newly prescribing or continuing those drugs. Also, future research would need to investigate what factors contribute to the difference in the RLS treatment prescribing patterns between neurologists and family/general or internal medicine physicians.

Ih contributes to increased motoneuron excitability in restless legs syndrome.

Restless legs patients complain about sensory and motor symptoms leading to sleep disturbances. Symptoms include painful sensations, an urge to move and involuntary leg movements. The responsible mechanisms of restless legs syndrome are still not known, although current studies indicate an increased neuronal network excitability. Reflex studies indicate the involvement of spinal structures. Peripheral mechanisms have not been investigated so far. In the present study, we provide evidence of increased hyperpolarization-activated cyclic nucleotide-gated (HCN) channel-mediated inward rectification in motor axons. The excitability of sensory axons was not changed. We conclude that, in restless legs syndrome, an increased HCN current in motoneurons may play a pathophysiological role, such that these channels could represent a valuable target for pharmaceutical intervention. Restless legs syndrome is a sensorimotor network disorder. So far, the responsible pathophysiological mechanisms are poorly understood. In the present study, we provide evidence that the excitability of peripheral motoneurons contributes to the pathophysiology of restless legs syndrome. In vivo excitability studies on motor and sensory axons of the median nerve were performed on patients with idiopathic restless legs syndrome (iRLS) who were not currently on treatment. The iRLS patients had greater accommodation in motor but not sensory axons to long-lasting hyperpolarization compared to age-matched healthy subjects, indicating greater inward rectification in iRLS. The most reasonable explanation is that hyperpolarization-activated cyclic nucleotide-gated (HCN) channels open at less hyperpolarized membrane potentials, a view supported by mathematical modelling. The half-activation potential for HCN channels (Bq) was the single best parameter that accounted for the difference between normal controls and iRLS data. A 6mV depolarization of Bq reduced the discrepancy between the normal control model and the iRLS data by 92.1%. Taken together, our results suggest an increase in the excitability of motor units in iRLS that could enhance the likelihood of leg movements. The abnormal axonal properties are consistent with other findings indicating that the peripheral system is part of the network involved in iRLS.

Patterns of gray matter alterations in migraine and restless legs syndrome.

ObjectivesMigraine and restless legs syndrome (RLS) are often comorbid and share elements of pathology; however, their neuroanatomical underpinnings are poorly understood. This study aimed to identify patterns of gray matter volume (GMV) alteration specific to and common among patients with RLS, migraine, and comorbid migraine and RLS.MethodsHigh‐resolution T1‐weighted images were acquired from 116 subjects: 27 RLS patients, 22 migraine patients, 22 patients with comorbid migraine and RLS, and 45 healthy controls. Direct group comparisons and conjunction analysis were first used to localize the distinct and shared neural signatures of migraine and RLS. We also investigated whether the shared neural signature could be replicated in an additional comorbid migraine/RLS group.ResultsCompared with healthy controls, migraine patients showed GMV changes in the lateral occipital cortex, cerebellum, frontal pole, and middle frontal gyrus (MFG), and RLS patients showed GMV changes in the thalamus, middle temporal gyrus, anterior cingulate cortex, insular cortex, and MFG. In migraine, compared with RLS, GMV differences were found in the precuneus, lateral occipital and occipital fusiform cortex, superior frontal and precentral gyri, and cerebellum. Conjunction analyses for these disorders showed altered GMV in the MFG, also found in patients with comorbid migraine and RLS. The GMV of the MFG also correlated with sleep quality in patients with comorbid migraine and RLS.InterpretationMigraine and RLS are characterized by shared and distinctive neuroanatomical characteristics, with a specific role of the MFG. These findings may be related to shared pathophysiology of these two distinct disorders.

Association of mitochondrial iron deficiency and dysfunction with idiopathic restless legs syndrome.

Restless legs syndrome is a sensorimotor neurological disorder of the limbs that impairs quality of life and disturbs sleep. However, there has been progress in understanding the disease involving the dopaminergic system as well as iron metabolism. The exact pathophysiological mechanisms of restless legs syndrome remain elusive. We tried to elucidate the underlying mechanisms in iron metabolism in restless legs syndrome subjects on a systemic, cellular, and mitochondrial level. We conducted a study prospectively recruiting 168 restless legs syndrome patients and 119 age-matched healthy controls focusing on iron metabolism using human monocytes as surrogates. Evaluation of systemic iron metabolism parameters in the circulation showed no significant difference between patients and controls. We observed a significant reduction in mRNA levels of heme oxygenase 1 and mitochondrial iron genes like mitoferrin 1 and 2 in monocytes isolated from restless legs syndrome patients, indicating mitochondrial iron deficiency. Interestingly, we also observed reduced expression of iron regulatory protein 2 along with impaired activity of mitochondrial aconitase and reduced mitochondrial superoxide formation in restless legs syndrome subjects. Along this line, patients had reduced mitochondrial respiratory capacity that improved in restless legs syndrome subjects under treatment with dopaminergic drugs compared with untreated patients. Our data suggest that restless legs syndrome is linked to mitochondrial iron deficiency and associated impairment of mitochondrial function. This is partly corrected by treatment with dopaminergic drugs compared with untreated patients, which may be linked to an effect of dopamine on cellular iron homeostasis. © 2018 International Parkinson and Movement Disorder Society.

A study for the mechanism of sensory disorder in restless legs syndrome based on magnetoencephalography

In spite of the relatively high incidence rate, the etiology and pathogenesis of restless legs syndrome (RLS) are still unclear. Long-term drug treatments fail to achieve satisfying curative effects, which is reflected by rebound and augmentation of related symptoms. An electrophysiological endophenotype experiment was done to investigate the mechanism of somatosensory disorder among RLS patients. Together with 15 normal subjects as the control group, with comparable ages and genders to the RLS patients, 15 primitive RLS patients were scanned by Magnetoencephalography (MEG) under natural conditions; furthermore, the somatosensory evoked magnetic field (SEF) with single and paired stimuli, was also measured. Compared to the control group, the SEF intensities of RLS patients’ lower limbs were higher, and the paired-pulse depression (PPD) for SEF in RLS patients was attenuated. It was also revealed by time-frequency analysis of somatosensory induced oscillation (SIO) in RLS patients, that 93.3% of somatosensory induced Alpha (8–12 Hz) oscillations were successfully elicited, while 0% somatosensory induced Gamma (30–55 Hz) oscillations were elicited; which was significantly different from the control group. Additionally, in RLS patients exhibit increased excitability of the sensorimotor cortex, a remarkable abnormality existing in early somatosensory gating control (GC) and an attenuated inhibitory interneuron network, which consequently results in a compensatory mechanism through which RLS patients increase their attention-driven lower limb sensory gating control via somatosensory-induced Alpha (8–12 Hz) oscillation. This hyperexcitability, partially due to an electrocortical disinhibition, may have an important therapeutical implication, and become an important target of neuromodulatory interventions.

Discovery of restless legs syndrome plasmatic biomarkers by proteomic analysis.

ObjectivesRestless legs syndrome (RLS) can lead to severe clinical consequences, thus negatively impacts on patients’ overall health and quality of life. Nevertheless, the pathophysiology of RLS is still unclear, resulting in underestimate, incorrect, or ignored diagnosis and in limited management and treatment. The aim of this study was to compare the plasma proteome of RLS patients and healthy controls, in the search of diagnostic biomarkers related to the disease severity.Materials and MethodsTwo‐dimensional gel electrophoresis coupled with liquid chromatography‐mass spectrometry was employed to analyze plasma samples of 34 patients with primary RLS, divided into two subgroups according to the disease severity: MMS group (mild‐moderate symptoms) and HS group (severe and very severe symptoms), and 17 age‐ and sex‐matched control subjects. Sleep quality, daytime sleepiness, and the level of depression were also evaluated.ResultsWe identified eight upregulated spots, corresponding to five unique proteins, in both RLS group vs. controls (alpha‐1B‐glycoprotein, alpha‐1‐acid glycoprotein 1, haptoglobin, complement C4‐A, and immunoglobulin kappa constant); five increased spots, consistent with three unique proteins, only in HS‐RLS (kininogen‐1, immunoglobulin heavy constant alpha 1, and immunoglobulin lambda constant 2); one downregulated spot in both patient's groups (complement C3) and another one only in HS‐RLS (alpha‐1‐antitrypsin).ConclusionsThe significantly different plasma proteins detected in RLS were mainly associated with inflammation, immune response, and cardiovascular disorders. Particularly, the gradual increasing in immunoglobulins could be indicative of the disease severity and evolution. Accordingly, these proteins may represent a valid set of useful biomarkers for RLS diagnosis, progression and treatment.

Restless legs syndrome in type 2 diabetes mellitus

AimsThis study aimed to investigate the prevalence of restless leg syndrome (RLS) in type-2 diabetes mellitus (DM) patients and to determine the risk factors. MethodsPatients were recruited from the Dr. Lütfi Kırdar Kartal Training and Research Hospital Diabetes Center. Patients between 18–80 years of age and meeting a minimum 5 years diagnosis of type-2 DM were included. All patients were examined by the same neurologist in terms of having RLS. The diagnosis was made according to the updated International Restless Legs Syndrome Study Group consensus criteria. Mimicking conditions such as myalgia, venous stasis, leg edema, arthritis, leg cramps, positional discomfort and habitual foot tapping were carefully investigated and excluded. Laboratory data, insulin use, family history and other related co-morbidities connected to RLS patients were recorded. RLS severity assessment was scored and recorded. Results318 patients were included in the study. The prevalence of RLS in type-2 DM patients was found to be 28.3%. RLS prevalence in females was 33.3% and 20.6% in males. 39 patients (43.3%) had a family history of RLS. 43 patients with RLS had a co-morbidity link with RLS. Any co-morbidity linked to RLS was not seen in 47 patients. The prevalence rate of RLS in patients without co-morbidities was 17.1%. Mean duration of DM in patients with RLS was 15.6±6.7years while in DM patients without RLS was 13.7±6.3years. The relationship between RLS and the duration of diabetes was found to be statically significant. (p=0.025). 68 (75.6%) of patients diagnosed with RLS were treated with insulin. A statistical significance was found in the development of RLS and insulin usage (p=0.035). ConclusionsThis is the first study which shows the RLS prevalence and risk factors in Turkish type-2 diabetes mellitus patients. The results indicated that RLS is much more frequent in DM patients even after excluding polyneuropathy than in general Turkish population. The duration of diabetes and insulin use are related to RLS.

Differential Dopamine D1 and D3 Receptor Modulation and Expression in the Spinal Cord of Two Mouse Models of Restless Legs Syndrome.

Restless Legs Syndrome (RLS) is often and successfully treated with dopamine receptor agonists that target the inhibitory D3 receptor subtype, however there is no clinical evidence of a D3 receptor dysfunction in RLS patients. In contrast, genome-wide association studies in RLS patients have established that a mutation of the MEIS1 gene is associated with an increased risk in developing RLS, but the effect of MEIS1 dysfunction on sensorimotor function remain unknown. Mouse models for a dysfunctional D3 receptor (D3KO) and Meis1 (Meis1KO) were developed independently, and each animal expresses some features associated with RLS in the clinic, but they have not been compared in their responsiveness to treatment options used in the clinic. We here confirm that D3KO and Meis1KO animals show increased locomotor activities, but that only D3KO show an increased sensory excitability to thermal stimuli. Next we compared the effects of dopaminergics and opioids in both animal models, and we assessed D1 and D3 dopamine receptor expression in the spinal cord, the gateway for sensorimotor processing. We found that Meis1KO share most of the tested behavioral properties with their wild type (WT) controls, including the modulation of the thermal pain withdrawal reflex by morphine, L-DOPA and D3 receptor (D3R) agonists and antagonists. However, Meis1KO and D3KO were behaviorally more similar to each other than to WT when tested with D1 receptor (D1R) agonists and antagonists. Subsequent Western blot analyses of D1R and D3R protein expression in the spinal cord revealed a significant increase in D1R but not D3R expression in Meis1KO and D3KO over WT controls. As the D3R is mostly present in the dorsal spinal cord where it has been shown to modulate sensory pathways, while activation of the D1Rs can activate motoneurons in the ventral spinal cord, we speculate that D3KO and Meis1KO represent two complementary animal models for RLS, in which the mechanisms of sensory (D3R-mediated) and motor (D1R-mediated) dysfunctions can be differentially explored.

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.

Investigation of alexithymia and levels of anxiety and depression among patients with restless legs syndrome.

PurposeThe purpose of this study was to examine alexithymia among restless legs syndrome (RLS) patients, compare with healthy controls, and argue the clinical inferences of this relationship. We searched for anxiety and depression and their clinical outcomes among patients and searched whether the results are similar to previous studies.Patients and methodsEighty-seven RLS patients and 88 age, gender, and educationally matched healthy controls were assessed in Bezmialem Foundation University Hospital. RLS patients and healthy controls were assessed with the Sociodemographic Data Form constructed for the present study, 20-item Toronto Alexithymia Scale (TAS-20), Beck Depression Inventory (BDI), and Beck Anxiety Scale (BAS). The patient group was also assessed with the International Restless Legs Syndrome Study Group (IRLSSG) RLS Severity Scale.ResultsRLS patients were found to have greater TAS-20, BDI, and BAS scores compared with the control group (P < 0.05). RLS severity score was positively correlated with the scores of anxiety and depression scales. However, no significant relationship was found between scores of IRLSSG RLS scale and TAS-20 total and subscale scores.ConclusionRLS patients were found to be more alexithymic than healthy controls, whereas no significant relationship was found between RLS severity and levels of alexithymia. Still, alexithymia might be a predictor for early diagnosis and may be considered in the treatment and follow-up of RLS. RLS patients have higher depression and anxiety scores than healthy individuals. Thus, depression and anxiety should be taken into consideration throughout the RLS treatment.

Effect of intravenous vitamin C supplementation on the quality of sleep, itching and restless leg syndrome in patients undergoing hemodialysis; A double-blind randomized clinical trial

Introduction: Poor sleep quality is common among hemodialysis patients and can potentially predict morbidity, mortality and quality of life in these patients. On the other hand, hemodialysis patients are encountered with vitamin C deficiency. Objectives: The purpose of this study was to determine the effect of intravenous vitamin C on sleep quality, itching and restless leg syndrome in hemodialysis patients. Patients and Methods: In this double-blind randomized clinical trial, 90 qualified hemodialysis patients were gone under investigation in Sanandaj in 2016. Patients randomly allocated in two equal intervention and control groups. The main measured outcome was the Pittsburg Sleep Quality Index (PSQI) which consists of seven components. At the end of each hemodialysis session, the intervention group received vitamin C vial (500 mg/5 cc) intravenously, three times a week for 8 weeks and the control group received normal saline as placebo in the same way. Data were collected at pretreatment and after 2 months of treatment. Additionally raises questions related to restless leg syndrome and was assessed by VAS scale for determining the incidence of pruritus. Data were analyzed by independent t test, paired t test, Wilcoxon and chi-square tests. Results: Around 52.2% of subjects were female and 47.8% were male and most of them were in the age group above 50 years old. Results showed a notable difference in the value of itching and restless leg syndrome between the two groups as these values decreased significantly in the intervention group (P=0.0001). There was also a great difference in the quality of sleep disorder in subjective sleep quality, sleep latency and daily function between the two groups and those disorders was significantly lower in the intervention group (P=0.0001). Conclusion: This study showed that intravenous vitamin C can effectively improve sleep quality, itching and restless legs syndrome in hemodialysis patients.

Impaired Sensorimotor Integration in Restless Legs Syndrome.

Objective: Restless legs syndrome (RLS) is a complicated sensorimotor syndrome that may be linked to changes in sensorimotor integration. The mechanism of such changes is unclear. The aim of this study was to investigate sensorimotor integration in patients with RLS through transcranial magnetic stimulation-motor evoked potentials (TMS-MEPs) preceded by peripheral electric stimulation.Methods: Fourteen RLS patients and 12 healthy, age-matched controls were investigated. The clinical severity of RLS was evaluated based on the International Criteria of the International Restless Legs Syndrome Study Group (IRLSSG) severity scores. The tibial and median H-reflexes and the resting motor threshold (RMT) of the abductor pollicis brevis (APB) were tested in all 26 subjects. The RMT of the tibialis anterior (TA) was tested in 8 patients and 7 controls. All 26 subjects underwent measurement of unconditioned MEPs of the APB. Electric pulses were applied to the right median nerve, followed by TMS pulses over the left motor cortex at interstimulus intervals (ISIs) of 20, 25, 30, 50, 100, 150, and 200 ms. Unconditioned MEPs of the TA were measured in 8 patients and 7 controls. Electric pulses were applied to the right peroneal nerve, followed by TMS pulses over the left motor cortex at ISIs of 30, 35, 45, 60, 100, and 200 ms. The degree of modulation of MEPs by electric stimulation was expressed as the ratio of the conditioned MEP amplitude to the unconditioned MEP amplitude. Ratios <1 indicated inhibition, and ratios >1 indicated facilitation.Results: No significant differences in RMT or H-reflex latencies or amplitudes were found between RLS patients and controls. A significant increase in unconditioned MEP amplitudes of the TA was observed in patients compared to controls (p = 0.03). Long-latency afferent inhibition (LAI) of the median nerve in RLS patients was decreased significantly at ISIs of 150 (p = 0.000) and 200 ms (p = 0.004). Upon peroneal nerve stimulation, no significant difference was observed between the two groups at any ISI.Conclusions: Our results suggest increased motor cortical excitability of the legs and disturbed sensorimotor integration in RLS patients; this disturbance might originate at the cortical level.

Higher Prevalence of Hypertension among Individuals with Restless Legs Syndrome: A Meta-Analysis.

Objective This study investigated the proposed association between restless legs syndrome (RLS) and the prevalence of hypertension. Methods A meta-analysis was conducted based on searches of the PUBMED, EMBASE, Cochrane Library, and Korean electronic databases. Cohort and cross-sectional studies reporting the incidence of hypertension in individuals with RLS were included. Dichotomous data were pooled to obtain an odds ratio (OR) and 95% confidence interval (CI) for the prevalence of hypertension in individuals with RLS. The main outcome measure of the study was prevalence of hypertension in patients with RLS compared with a control group. Results One cohort study and eight cross-sectional studies were included in the meta-analysis. Individuals with RLS had an increased prevalence of hypertension (all studies: OR=1.13, 95% CI=1.04–1.23; cross-sectional studies: OR=1.12, 95% CI=1.01–1.24). However, in subgroup analyses controlling for cardiovascular risk factors, such as diabetes mellitus and dyslipidemia, the differences in the prevalence of hypertension between RLS and control patients were no longer significant. Conclusion Patients with RLS may have a higher prevalence of hypertension, according to a pooled analysis, but the results remain to be confirmed in well-designed prospective studies.

Restless Legs Syndrome in Patients with Epilepsy Under Levetiracetam Monotherapy

Restless Legs Syndrome in Patients with Epilepsy Under Levetiracetam Monotherapy

Gabapentin and Pregabalin Use and Association with Adverse Outcomes among Hemodialysis Patients.

Background Gabapentin and pregabalin are used to manage neuropathic pain, pruritus, and restless legs syndrome in patients on hemodialysis. These patients may be especially predisposed to complications related to these agents, which are renally cleared, but data regarding the risk thereof are lacking.Methods From the US Renal Data System, we identified 140,899 Medicare-covered adults receiving hemodialysis with Part D coverage in 2011. Using Cox regression models in which we adjusted for demographics, comorbidities, duration of exposure, number of medications, and use of potentially confounding concomitant medications, we investigated the association between gabapentin and pregabalin, modeled as separate time-varying exposures, and time to first emergency room visit or hospitalization for altered mental status, fall, and fracture. We evaluated risk according to daily dose categories: gabapentin (>0-100, >100-200, >200-300, and >300 mg) and pregabalin (>0-100 and >100 mg).Results In 2011, 19% and 4% of patients received gabapentin and pregabalin, respectively. Sixty-eight percent of gabapentin or pregabalin users had a diagnosis of neuropathic pain, pruritus, or restless legs syndrome. Gabapentin was associated with 50%, 55%, and 38% higher hazards of altered mental status, fall, and fracture, respectively, in the highest dose category, but even lower dosing was associated with a higher hazard of altered mental status (31%-41%) and fall (26%-30%). Pregabalin was associated with up to 51% and 68% higher hazards of altered mental status and fall, respectively.Conclusions Gabapentin and pregabalin should be used judiciously in patients on hemodialysis, and research to identify the most optimal dosing is warranted.