Restless Legs Syndrome Patients Research Articles

Comparison of Cognitive Function between Patients with Restless Legs Syndrome and Healthy Controls

Recent studies have reported that moderate to severe restless legs syndrome (RLS) patients may have significant cognitive deficits, primarily in executive functioning, compared with healthy control subjects.1-4 Electrophysiological studies also support the existence of cognitive dysfunction in RLS patients. For example, a recent event-related potential (ERP) study showed that underlying cognitive dysfunction, associated with a working memory deficit characterized by increased reaction time and lower amplitude of the P300 component, was evident in patients with severe RLS.5,6 In contrast, other studies found no difference in cognitive function between RLS patients and controls. RLS subjects performed better than sleep-restricted controls on a test of verbal fluency.7 In middle-aged and elderly subjects, individuals with mild RLS were found to have no differences in multiple domains of cognitive functioning when compared to those without RLS.8,9 This discrepancy may be attributable to several factors, such as differences in study samples, the use of different age groups (patients of middle vs. older age), the types of neuropsychological tests administered (full batteries vs. selected tests of frontal function), and medication effects (unmedicated vs. medicated). It has been reported that comorbid psychiatric conditions such as depression and anxiety are common in patients with RLS.10-12 Epidemiological studies report a 2to 4-fold risk of a deReceived: November 22, 2014 Revised: December 10, 2014 Accepted: December 15, 2014

Effect of Pramipexole on Cognitive Functions in Restless Legs Syndrome

Address for correspondence Ki-Young Jung, MD, PhD Department of Neurology, Seoul National University Hospital, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 110-744, Korea Tel: +82-2-2072-4988 Fax: +82-2-2072-7424 E-mail: jungky10@gmail.com Objectives: Neuropsychological evaluations have revealed cognitive dysfunction in restless legs syndrome (RLS) patients, especially frontal lobe functions. Although dopamine agonists improve RLS sensory symptoms and periodic leg movements during sleep, there was no study regarding the effects of dopamine agonist on cognition in patients with RLS. Methods: Sixteen drug-naive RLS patients were enrolled. They underwent sleep questionnaires, Beck Depression Inventory, and neuropsychological evaluation, consisting of Rey Complex Figure Test and recognition trial (RCFT), Korean-California Verbal Learning Test, Controlled Oral Word Association Test (COWAT) before and after treatment with pramipexole (PMP). PMP was administered over a period of 12 weeks every night 1 h before bedtime. Paired Student’s t-test and Spearman’s correlation analysis were used for analyses. Results: After treatment with PMP, the International RLS Severity Scale score was significantly decreased. Sleep quality and depression also significantly improved after the treatment. RCFT immediate recall, COWAT phoneme word frequency, and digit symbol coding scores significantly improved compared to those before the treatment (17.72±7.84 vs. 20.13±7.33, p=0.05; 36.50±12.62 vs. 41.50±12.58, p=0.03; 68.19±21.11 vs. 73.81±21.11, p=0.02, respectively). There were no significant correlations between changes in clinical variables and in cognitive functions before and after the treatment. Conclusions: This study suggests that treatment with PMP in RLS patients improves not only RLS sensory symptoms, but also cognitive functions. J Korean Sleep Res Soc 2014;11(1):16-20

Gray matter anomalies in anterior cingulate cortex as a correlate of depressive symptoms in drug-naïve idiopathic restless legs syndrome

BackgroundDepressive symptoms are frequent in idiopathic restless legs syndrome (RLS). However, little is known, so far, about the neurological basis. The present study aimed to explore the neuroanatomical anomalies in depressed drug-naïve RLS patients using voxel-based morphometry (VBM) analysis. MethodsWe recruited 16 drug-naïve idiopathic RLS patients with depressive symptoms (RLS-D), 18 drug-naïve idiopathic RLS patients without depressive symptoms (RLS-ND), and 18 normal controls. All participants underwent structural MRI scans on a 3-T MR system. The differences in regional gray matter (GM) density were determined across groups by VBM8. Additional regression analysis was used to identify any associations between regional GM density and clinical symptoms. ResultsGM density of the bilateral anterior cingulate cortex (ACC) was significantly reduced in RLS-D patients when compared to RLS-ND patients or to the healthy controls. However, there were no significant differences of GM density either when the whole RLS group or the RLS-ND group was compared to healthy controls, respectively. Particularly, we found GM density of right ACC was negatively correlated with the severity and duration of depressive symptoms in RLS-D patients. ConclusionsDepressive symptoms are associated with GM anomalies in ACC in patients with RLS. We propose that ACC is perhaps an important neuroimaging marker for facilitating treatment strategies in patients with RLS when assessing depressive symptoms.

Restless legs syndrome in patients with sequelae of poliomyelitis.

No studies have examined the association between RLS and the sequelae of poliomyelitis (PM). We studied the frequency and severity of RLS in a group of consecutive patients with the sequelae of poliomyelitis (PM) and the effect of treatment with dopaminergic drugs. A diagnosis of RLS was made according to the criteria of the International RLS Study Group, and severity was assessed by the RLS rating scale. Information on sex, age, age at onset, site affected by PM, disease duration of PM, and history of post-polio syndrome (pPS) was obtained in a cohort of 52 PM patients. The mean age was 55.9 ± 6.5 years; 39 patients had post-polio syndrome (75%). RLS was diagnosed in 21 (40.4%) patients. Sixteen of the 21 patients (76.2%) with RLS had pPS, which was similar to the non-RLS group (74.2% patients with pPS). RLS symptoms were very severe in 5 patients, severe in 13, moderate in 2 and mild in 1. Nineteen of the 21 patients with RLS had symptoms predominantly in the more affected lower limb (90% of patients). Sixteen patients received dopaminergic agonist treatment with a significant reduction in their scores on the RLS severity scale from 28.3 ± 4.7 to 6.9 ± 7.3 (p < 0.001). RLS occurs frequently in patients with PM, both in those with and without pPS, and responds well to treatment with dopaminergic drugs.

Restless Legs Syndrome: Psychiatric Comorbidities Are More Important Than Neuroticism

Restless legs syndrome (RLS) is often associated with psychopathological symptoms. We compared psychiatric diagnoses, psychological complaints, sleep and personality traits in RLS patients and a control group The RLS patients also answered the IRLS, RLS-6, and QoL-RLS. The RLS patients showed more depressive disorders, psychopathological symptoms, and lower well-being than controls, but no differences in personality traits. The slightly, but not significantly, higher neuroticism found in RLS patients can be explained by the higher rates of depression among the patients. It is advisable to screen RLS patients for psychiatric comorbidities. The design using a matched control group without sleep disorders limits the conclusions that can be drawn regarding the frequency of psychiatric diagnoses and controls with sleep problems.

P993: Circadian hyperactivity of the lower limb nociceptive system in idiopathic restless legs syndrome: a CO2 laser evoked potential study

Aim of the study was to assess the A-delta nociceptive system during the night and afternoon in idiopathic Restless Legs Syndrome (RLS) patients, by recording the Laser Evoked Potentials (LEPs). We studied 11 patients (mean age 53.40 ± 18.59 years; 6 males, 5 females) affected by idiopathic RLS. LEPs were recorded to stimulation of the right foot, hand and perioral region. LEPs were recorded at night (between 9.00 PM and 11.00 PM) and in the early afternoon (between 1.00 PM and 3.00 PM). Two consecutive averages (20 trials each) were obtained for each stimulation site. LEPs were recorded from 3 recording electrodes placed at Cz, Fz, and T3 sites of the 10–20 International System. In RLS patients, we found a significant increase of N2–P2 amplitude after foot stimulation during nighttime session ( p = 0.008) when compared to daytime. The N2/P2 amplitude after hand and face stimulation was not significantly different during both sessions ( p > 0.05). We did not find any impairment of the Adelta-fiber system. However, there is a prevailing activity of the Adelta nociceptive system of lower limbs during nighttime. These findings suggest, in idiopathic RLS, a circadian disinhibition in the central processing of the lower limb Adelta-fiber inputs.

Ropinirole regulates emotionality and neuronal activity markers in the limbic forebrain.

Restless legs syndrome (RLS) and Parkinson's disease (PD) are movement disorders usually accompanied by emotional and cognitive deficits. Although D3/D2 receptor agonists are effective against motor and non-motor deficits in RLS and PD, the exact behavioral and neurochemical effects of these drugs are not clearly defined. This study aimed to evaluate the effects of acute ropinirole (0, 0.1, 1 or 10 mg/kg, i.p.), a preferential D3/D2 receptor agonist, on intracranial self-stimulation (ICSS), spontaneous motor activity, anxiety- and depression-like behaviors, spatial reference and working memory in rats as well as on certain markers of neuronal activity, i.e. induction of immediate early genes, such as c-fos and arc, and crucial phosphorylations on GluA1 subunit of α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors and NA1, NA2A and NA2B subunits of N-methyl-D-aspartate (NMDA) receptors. Ropinirole decreased ICSS thresholds and induced anxiolytic- and antidepressive-like effects without affecting motor activity or spatial memory. The effects on emotionality were associated with a decrease in p-Ser897-NA1 and an increase in p-Tyr1472-NA2B in the ventral striatum as well as an increased induction of c-fos messenger RNA (mRNA) in the prefrontal cortex (PFC) and decreased expression of arc mRNA in the striatum and the shell of the nucleus accumbens. Our data indicate that ropinirole significantly affects emotionality at doses (1-10 mg/kg, i.p.) that exert no robust effects on locomotion or cognition. The data reinforce the use of D3/D2 receptor agonists in the treatment of RLS and PD patients characterized by emotional deficits and suggest that altered NMDA-mediated neurotransmission in the limbic forebrain may underlie some of ropinirole's therapeutic actions.

Prevalence of migraine in patients with restless legs syndrome: a case-control study.

To assess and compare the prevalence of migraine in patients with restless legs syndrome (RLS) and matched controls. Recent studies have suggested an association between migraine and RLS. Our work is the first case-control study on this subject performed in an RLS population. A case-control study was conducted in 47 RLS patients (27 women and 20 men aged between 18 and 65 years) and 47 age- and sex-matched controls. Validated questionnaires were used to investigate the presence of migraine, anxiety, and depression (Zung Self-Rating Anxiety and Depression scales), sleep quality (Pittsburgh Sleep Quality Index), and RLS severity (International RLS scale). RLS patients had higher lifetime prevalence of migraine than non-RLS controls (53.2% vs. 25.5%, P = .005; matched-OR 1.3 [P = .019]; adjusted odds ratio (OR) 3.8 [P = .03]). No significant associations were found between RLS and active migraine with aura or inactive migraine (no episodes in the previous year). However, active migraine without aura was significantly more prevalent in patients with RLS than in controls (40.4% vs. 12.8%, P = .001; matched OR 1.5 [P = .001]; adjusted OR 2.7 [P = .04]). Within the RLS group, patients with migraine had poorer sleep quality than those without migraine (Pittsburgh Sleep Quality Index >5:100 vs. 80.9%, P = .038) but did not differ in terms of RLS severity, anxiety and depression, use of dopaminergic agonists, and body mass index. There appears to be a relationship between RLS and migraine, in particular for active migraine without aura.

PND39 - The Humanistic And Economic Burden Of Restless Legs Syndrome

Objectives To evaluate the humanistic and economic burden of a restless legs syndrome (RLS) diagnosis with regard to health-related quality of life, work productivity loss, healthcare resource use, and direct and indirect costs. Study Design Self-reported data came from the 2012 National Health and Wellness Survey (NHWS), a large, annual, nationally representative cross-sectional general health survey of US adults. Methods RLS patients (n = 2,392) were matched on demographic and health characteristics to Non-RLS respondents via propensity score matching differences between groups were tested with Bivariate and multivariable analyses. Results RLS patients had significantly lower health-related quality of life scores: Mental Component Summary (44.60 vs. 48.92, p<.001), Physical Component Summary (40.57 vs. 46.78, p<.001), Health Utilities (.63 vs. .71, p<.001) and higher levels of work productivity loss in the past seven days including absenteeism (8.1% vs. 9.3%, p<.001), presenteeism (26.5% vs. 15.8%, p<.001), and overall productivity loss (30.1% vs. 18.1%, p<.001) as well as general activity impairment (46.1% vs. 29.7%, p<.001). RLS patients had significantly higher healthcare resource use in the past 6 months than non-RLS patients: healthcare provider visits (7.46 vs. 4.42%, p<.001), ER visits (0.45 vs. 0.24, p<.001), and hospitalizations (0.24 vs. 0.15, p<.001). RLS patients also had higher estimated direct and indirect costs than non-RLS patients. Finally, it was found that across outcomes increasing severity is associated with increased economic and humanistic burden for RLS patients. Conclusions RLS patients suffer a greater humanistic and economic burden than those without RLS. Moreover as severity increases so does the burden of RLS.

Clinical presentation of restless legs syndrome: Does the gender matter?

This study was conducted to find out whether higher prevalence of females among restless legs syndrome (RLS) patients in a clinical setting is related to clinical presentation and co-morbid conditions. A total of 173 consecutive patients with idiopathic RLS were included in this study after obtaining permission from the institutional ethics committee. Their demographic data, history of RLS, associated sleep problems and family history were gathered. Severity of RLS was also measured with the help of IRLS. Results have shown that out of 173 subjects, 29.6% were males. Male subjects in this study were nearly 4 years older than females (P = 0.04). Symptoms were experienced in both legs in all subjects except 3% of females who reported involvement of one leg. Some of the patients reported symptoms in other parts of body as well! 27.5% of males and 33.6% of females reported involvement of other parts of body in addition to the legs (χ2 = 0.62; P = 0.27). Explanations of sensory symptoms e.g., “tingling”, “restlessness”, “tickling” were two times more common in females while males reported “pricking”, “just pain” and “stretching” twice as commonly as females. Severity of RLS did not differ between groups (χ2 = 1.51; P =0.67). Similarly, sleep problems were comparable across genders (88.2% males vs. 93.4% females; χ2 = 1.31; P = 0.25). Family history was comparable across genders. In conclusion, clinical presentation of RLS did not differ across genders. The observed female predominance in the RLS is not related to clinical presentation.

Working memory deficit in patients with restless legs syndrome: an event-related potential study

ObjectiveThe aim of this study was to investigate whether there is a working memory (WM) deficit in restless legs syndrome (RLS) patients, by studying the Sternberg WM task of event-related potential (ERP). MethodsThirteen drug-naive RLS patients and 13 healthy age-matched controls with no sleep disturbances participated in the present study. P300 ERP was recorded during Sternberg WM task using digits as mnemonic items. P300 amplitudes and reaction times were compared between groups (RLS vs control) considering brain regions (frontal, central, and parietal) and memory load sizes (two, three, and four) as within-subject factors. Clinical and sleep-related variables were correlated with P300 amplitude. ResultsThe reaction time in RLS patients was significantly longer than controls over all memory load sizes. The P300 amplitude at parietal regions in RLS patients was significantly lower than in controls regardless of memory load sizes, which was significantly negatively correlated with duration of RLS history in RLS patients. ConclusionOur study suggests that patients with severe RLS have WM deficits. Furthermore, negative correlation of P300 amplitudes with the duration of RLS illness suggests that cerebral cortical dysfunction in RLS patients results from repeated RLS symptom attacks.

Reduced daytime intramuscular blood flow in patients with restless legs syndrome/Willis–Ekbom disease

The aim of this study was to examine possible signs of impairment of the microcirculation in the lower extremities of female patients suffering from primary restless legs syndrome (RLS)/Willis-Ekbom disease. This study was performed in eight female patients, mean age 48 years (range 21-65), diagnosed with primary RLS but otherwise healthy. Eight healthy female control subjects, mean age 47 years (range 27-64), were also included in the study. Laser Doppler flowmetry was used to determine intramuscular blood flow by placing an optical single fiber in the tibialis anterior muscle belly. The studies were performed between 08.00 and 10.00 hours and 20.00 and 22.00 hours. Blood flow was expressed in perfusion units. The median intramuscular blood flow in the RLS patients' tibialis anterior muscles, recorded from both legs, was significantly higher in the morning, at 17.9 perfusion units, than in the evening, at 12.1 perfusion units (P = 0.004). Corresponding values for the healthy controls were 13.1 perfusion units and 12.0 perfusion units, a non-significant difference. The relative fold changes of microcirculation in the RLS group compared to healthy age-matched controls were 0.7 ± 0.3 and 1.1 ± 0.6, respectively (P = 0.04). Our results suggest that in female patients with primary RLS, the microcirculation in the tibialis anterior muscle is higher in the morning compared with in the evening.

Restless Leg Syndrome in Patients with Chronic Liver Disease

Background: Restless leg syndrome (RLS), characterized by irresistible urge to move limbs at rest which improves with limb movement, is observed in patients with iron deficiency anemia, diabetes mellitus, hypothyroidism, and chronic kidney disease (CKD). Recently two studies from Milwaukee and Japan showed that 62 % and 16.8 % of patients with chronic liver disease (CLD) had RLS.

Increased frequency of restless leg syndrome in patients with ankylosing spondylitis

To assess the prevalence of restless leg syndrome (RLS) in patients with ankylosing spondylitis (AS) and to investigate factors potentially associated with RLS. One hundred and thirty patients diagnosed with AS according to modified New York criteria and 91 age- and sex-matched healthy control subjects were included in this study. The diagnosis of RLS was made according to the criteria of the International RLS Study Group. The factors associated with RLS were evaluated. Electrophysiological procedures were performed in a group of patients with RLS. RLS was significantly more common in patients with AS (30.8%) than in healthy controls (13.2%). When AS patients with RLS were compared with AS patients without RLS, it was seen that peripheral arthritis, uveitis, anemia, smoking and polyneuropathy were significantly higher in the former group. RLS is common in patients with AS and iron deficiency, smoking and small fiber neuropathy seem to be possible causes.

Altered white matter integrity in primary restless legs syndrome patients: diffusion tensor imaging study

Objectives:A prior diffusion tensor imaging (DTI) of restless legs syndrome (RLS) subjects found alterations in brain white matter (WM). The aim of this study was to explore the possible mechanism of altered integrity of brain WM in RLS patients.Methods:The DTI measurement was performed in 22 subjects with RLS and 22 age-matched control subjects. Using a voxel-based analysis, fractional anisotropy (FA) and axial and radial diffusivities (AD and RD) were compared between RLS and control subjects with a two-sample t-test, and correlation analysis was performed in RLS subjects.Results:RLS subjects demonstrated decreased FA in the genu of the corpus callosum and frontal WM adjacent to the inferior frontal gyrus compared with the control subjects. For areas of decreased FA, both the AD and RD were higher than that in the control subjects.Discussion:Our findings suggest that loss of axonal density and myelin may account for WM changes seen in a prior study of RLS subjects.

Gabapentin enacarbil for the treatment of moderate to severe primary restless legs syndrome (Willis-Ekbom disease): 600 or 1,200 mg dose?

Gabapentin enacarbil is a prodrug of the anticonvulsant gabapentin. The efficacy and safety of gabapentin enacarbil for the treatment of moderate to severe primary restless legs syndrome (RLS) has been evaluated in several clinical trials in the United States and Japan. Although most clinical trials assessed gabapentin enacarbil at doses greater than 600 mg/day and demonstrated the overall safety and efficacy (defined as improvements in the coprimary endpoints of the international RLS rating scale [IRLS] total score and Clinical Global Impression-Improvement response), the US Food and Drug Administration approved the 600 mg once-daily dosage because doses higher than 600 mg/day were considered to provide no additional benefits and were associated with higher rates of adverse events, such as somnolence and dizziness. Nonetheless, the results of clinical trials and post hoc meta-analyses have indicated that the 1,200 mg once-daily dosage was the most validated gabapentin enacarbil treatment for not only subjective RLS symptoms but also severe sleep disturbance associated with RLS. A Japanese dose-finding study showed that 900 mg/day, the intermediate dose between 600 and 1,200 mg, failed to show a significant improvement in IRLS total score, probably because many of the patients who discontinued treatment did so early, suggesting that a half-landing dose may cause more adverse effects than favorable ones in some RLS patients early in the treatment. Gabapentin enacarbil may have two distinct therapeutic doses for the treatment of RLS: 600 mg/day or lower doses for the treatment of subjective RLS symptoms and 1,200 mg/day or higher doses for the treatment of both subjective RLS symptoms and associated problems such as severe sleep disturbances.

Sleep improvement for restless legs syndrome patients. Part IV: meta-analysis comparison of effect sizes of vibratory stimulation sham pads and placebo pills

Sleep improvement for restless legs syndrome patients. Part IV: meta-analysis comparison of effect sizes of vibratory stimulation sham pads and placebo pills

Functional connectivity alternation of the thalamus in restless legs syndrome patients during the asymptomatic period: a resting-state connectivity study using functional magnetic resonance imaging

BackgroundRestless legs syndrome (RLS) is a primary sensory disorder with a secondary motor component (e.g., urge to move), and the thalamus is known to play a central role in RLS. The purpose of our study was to explore the intrinsic changes in the thalamocortical circuit in RLS patients using a resting-state functional magnetic resonance imaging (fMRI) paradigm. MethodsResting-state fMRIs were obtained in the morning from 25 idiopathic RLS patients who were not using RLS medications and 25 controls. Resting-state connectivity was analyzed by a seed-based method using Analysis of Functional NeuroImages (AFNI) software with the bilateral thalami (ventroposterolateral nucleus [VPLN]). The connectivity characteristics of RLS patients were compared to those of the controls. ResultsWe found that RLS patients showed reduced thalamic connectivity with the right parahippocampal gyrus, right precuneus, right precentral gyrus, and bilateral lingual gyri; however, the right superior temporal gyrus, bilateral middle temporal gyrus, and right medial frontal gyrus showed enhanced connectivity with the thalamus. RLS severity was negatively correlated with connectivity between the thalamus and right parahippocampal gyrus (r=−0.414; P=.040). ConclusionsOur results suggest that the characteristics of the connectivity changes may reflect the pathways involved in producing RLS symptoms and indicate that RLS patients may have deficits in controlling and managing sensory information, which supports the act of viewing RLS as a disorder disrupting somatosensory processing.

The Prevalence of Migraine in Restless Legs Syndrome

While previous studies have investigated the prevalence of restless legs syndrome (RLS) in patients with migraine, we aimed to explore the prevalence and characteristics of migraine in adult patients diagnosed with RLS. The association of primary headaches, especially of migraine, with RLS has recently attracted much attention. Migraine prevalence was reported to be higher in patients with RLS than in the general population, and the role of dopamine was strengthened. We evaluated 265 consecutive adult RLS patients (137 males and 128 females) followed up in a Sleep Disorders Unit and diagnosed according to criteria defined by the International Restless Legs Syndrome Study Group (IRLSSG). RLS characteristics, and the severity, were performed by using the IRLSSG severity scale. The diagnosis of headache subtypes was defined by the International Classification of Headache Disorders. Gender, age, age at RLS onset, duration of RLS, family history of RLS, family history of headache, presence of depression, any treatments given for RLS, and the change in headache following RLS treatment were questioned. The mean age of the study population was 50.4 ± 12.8 years, mean age at RLS onset was 41.6 ± 13.2 years, and mean disease duration was 8.40 ± 8.6 years. Of these, 163 patients had headache; 40 of them were diagnosed to have migraine-type headache (15.1%). The presence of migraine-type headache was 9.4% in males with RLS, and 21.1% in female RLS patients. In RLS patients with migraine, 67.5% were females, while 48.0% of RLS patients with other types of headache were females (P = .032), and only 41.2% of RLS patients without headache were females (P = .005). The severity of RLS was significantly higher in patients with migraine compared with those without headache (P < .001). The presence of depression, the family history of RLS, and headache were also higher in patients with migraine compared with RLS patients with other types of headache or those without headache. Thirty-six patients with headache reported partial or substantial benefit from RLS treatment. Our results did not suggest higher rates of migraine-type headache in RLS patients when compared with population-based prevalence studies from Turkey. Alternatively, the severity of RLS was significantly higher in patients with migraine. Although the increase in these scores does not constitute a relationship etiopathogenetic, it suggests a correlation between the type cross-model nociceptive systems. Moreover, the family history of RLS was higher in patients with migraine. The prevalence of migraine in patients with RLS, however, waits to be better demonstrated.

The Impact of Restless Legs Syndrome/Willis-Ekbom Disorder on Quality of Life

Restless legs syndrome (RLS), also known as Willis–Ekbom Disorder (WED), is a condition associated with nocturnal sensorimotor symptoms that can result in significant sleep disruption. RLS is a prevalent condition, affecting an estimated 3.9–14.3 % of the US population. Despite the most recently reported prevalence studies, many experts in the field still believe RLS is a generally underdiagnosed condition. RLS can negatively affect a patient’s quality of life (QoL) across several domains, such as daytime sleepiness, decreased general health, decreased immune function, stress, and mood. Of those patients with moderate-to-severe symptoms that require treatment, the currently available therapeutic options (e.g. iron supplements, dopamine agonists, benzodiazepines, opioids, and anticonvulsants) can also come with adverse side effects that can further impact QoL. The purpose of this article is to examine the QoL deficits experienced by RLS patients.