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Original Research |

Pneumatic Compression Devices Are an Effective Therapy for Restless Legs Syndrome: A Prospective, Randomized, Double-Blinded, Sham-Controlled Trial FREE TO VIEW

Christopher J. Lettieri, MD, FCCP*; Arn H. Eliasson, MD, FCCP
Author and Funding Information

*From Pulmonary, Critical Care, and Sleep Medicine, Walter Reed Army Medical Center, Washington, DC.

Correspondence to: Christopher J. Lettieri, MD, Pulmonary, Critical Care, and Sleep Medicine, Walter Reed Army Medical Center, 6900 Georgia Ave NW, Washington, DC 20307; e-mail: christopher.lettieri@us.army.mil

*Values are given as the mean ± SD, unless otherwise indicated.

*Values are given as No. (%), unless otherwise indicated. NA = not available.

*Values are given as the mean ± SD, unless otherwise indicated.

*Values are given as the mean ± SD, unless otherwise indicated.

*Values are given as the percentage of subjects in each randomization arm who reported any improvement in the measured variable.

The opinions expressed herein are those of the authors and should not to be construed as official or as reflecting the policies of either the Department of the Army or the Department of Defense.

Aircast LLC (Summit, NJ) supplied the VenaFlow system pneumatic compression devices and matching sham devices for use in the study. Aircast LLC was not involved in this study or the preparation of this article.

The authors have reported to the ACCP that no significant conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/misc/reprints.shtml).


The opinions expressed herein are those of the authors and should not to be construed as official or as reflecting the policies of either the Department of the Army or the Department of Defense.

The opinions expressed herein are those of the authors and should not to be construed as official or as reflecting the policies of either the Department of the Army or the Department of Defense.

Aircast LLC (Summit, NJ) supplied the VenaFlow system pneumatic compression devices and matching sham devices for use in the study. Aircast LLC was not involved in this study or the preparation of this article.

Aircast LLC (Summit, NJ) supplied the VenaFlow system pneumatic compression devices and matching sham devices for use in the study. Aircast LLC was not involved in this study or the preparation of this article.

The authors have reported to the ACCP that no significant conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

The authors have reported to the ACCP that no significant conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/misc/reprints.shtml).

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/misc/reprints.shtml).


Chest. 2009;135(1):74-80. doi:10.1378/chest.08-1665
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Published online

Background:  Pharmacotherapy for restless legs syndrome (RLS) may be ineffective or complicated by side effects. Uncontrolled series using pneumatic compression devices (PCDs) have been shown to reduce symptoms of RLS. We sought to assess the efficacy of PCDs as a nonpharmacologic treatment for RLS.

Methods:  We performed a prospective, randomized, double-blinded, sham-controlled trial of individuals with RLS. Subjects wore a therapeutic or sham device prior to the usual onset of symptoms for a minimum of 1 h daily. Measures of severity of illness, quality of life, daytime sleepiness, and fatigue were compared at baseline and after 1 month of therapy.

Results:  Thirty-five subjects were enrolled. Groups were similar at baseline. Therapeutic PCDs significantly improved all measured variables more than shams. Restless Legs Severity Score improved from 14.1 ± 3.9 to 8.4 ± 3.4 (p = 0.006) and Johns Hopkins Restless Legs Scale improved from 2.2 ± 0.5 to 1.2 ± 0.7 (p = 0.01). All quality of life domains improved more with therapeutic than sham devices (social function 14% vs 1%, respectively; p = 0.03; daytime function 21% vs 6%, respectively, p = 0.02; sleep quality 16% vs 8%, respectively, p = 0.05; emotional well-being 17% vs 10%, respectively, p = 0.15). Both Epworth sleepiness scale (6.5 ± 4.0 vs 11.3 ± 3.9, respectively, p = 0.04) and fatigue (4.1 ± 2.1 vs 6.9 ± 2.0, respectively, p = 0.01) improved more with therapeutic devices than sham devices. Complete relief occurred in one third of subjects using therapeutic and in no subjects using sham devices.

Conclusion:  PCDs resulted in clinically significant improvements in symptoms of RLS in comparison to the use of sham devices and may be an effective adjunctive or alternative therapy for RLS.

Trial registration:  Clinicaltrials.gov Identifier: NCT00479531

Figures in this Article

Restless legs syndrome (RLS) is a common sensorimotor disorder manifested by unpleasant sensations in the limbs that occur at rest and produce an irresistible urge to move.18 These sensations frequently produce discomfort and may cause significant impairments in quality of life.24,79 RLS symptoms commonly delay sleep onset or disrupt sleep continuity, leading to excessive daytime sleepiness (EDS), fatigue, mood changes, social withdrawal,29 eroding daytime function and sense of well-being.412

It is estimated that 10% of adults have RLS, with women affected twice as often as men.2,410 Symptoms can occur at any age, and 12% of patients develop RLS before age 10.3,7 Prevalence rises with increasing age and may affect 29% of subjects > 50 years old and 44% > 65 years old.9,11

Pharmacologic agents used in RLS include dopamine agonists, benzodiazepines, opioids, and anti-epileptics. However, success rates are highly variable, and all of these drugs can cause intolerable side effects.7,9,1225 Iron administration has been shown to improve or resolve symptoms of RLS.24,25 However, iron therapy is not universally successful, and recurrences of symptoms may occur despite the achievement of elevated ferritin levels.8,24,25 In view of the variable success rates and potential for side-effects, a reliable nonpharmacologic option would have advantages over current medical therapies.

Prior experience has shown that pneumatic compressive devices (PCDs) may improve symptoms associated with RLS. In a pilot study26 of nine patients with moderate to severe RLS, we found that PCDs improved symptoms in all patients. Complete resolution of symptoms occurred in one third of subjects, and partial relief occurred in two thirds. No patients reported lack of response or worsening of their RLS symptoms.

We sought to validate the findings of our prior pilot study in a prospective, randomized, sham-controlled trial. We hypothesized that PCDs can effectively reduce the severity of RLS, improve sleep, decrease EDS, and improve quality of life measures.

Study Design

We conducted a prospective, randomized, double-blinded, sham-controlled trial assessing the therapeutic effect of PCDs for RLS. Patients were randomized in a 3:2 distribution according to a computer generated randomization table, to receive treatment with an Aircast VenaFlow PCD at therapeutic or sub-therapeutic (“sham”) pressures. Patients, referring physicians, and investigators were blinded to the randomization order and treatment group. The protocol was approved by the Scientific Research Review Committee of our institution. The trial was registered in the National Clinical Trials registry (NCT00479531). The study devices and matching sham devices were provided by Aircast LLC (Summit, NJ). Aircast was not involved in the design or completion of the study, nor in the preparation of this article.

Patients

Consecutive patients presenting to the sleep clinic for evaluation of RLS were approached for participation. All subjects were recruited from a single center, an academic, military referral hospital which serves military service members, retired members, and civilian dependents. Our patient population, therefore, is comprised of both men and women of all ages, and a wide spectrum of ethnic backgrounds.

We included subjects > 17 years old with a reliable diagnosis of RLS in accordance with the International Classification of Sleep Disorders, Revised Diagnostic and Coding Manual of the American Academy of Sleep Medicine.6 Subjects were required to report subjective sensations in their limbs that produced urges to move that began or worsened with rest, improved with movement, and demonstrated a circadian rhythm with evening or nighttime onset or exacerbation. We excluded individuals < 17 years old; those with mental or physical limitations that would preclude data collection on questionnaires; and those with medical conditions that would preclude the use of PCDs, such as known or suspected deep vein thrombosis, active skin infections, recent vein ligation or skin graft, or extreme deformity of the legs. We also excluded individuals if they had previously used PCDs for deep vein thrombosis prophylaxis, as this would have potentially unblinded subjects randomized to sham devices.

Subjects taking iron, antidepressants, or prescription medications for RLS were offered enrollment only if they had been on a stable dose of medications for more than two months and reported persistent symptoms. Antidepressant use, particularly selective serotonin reuptake inhibitors was assessed, as these agents are known to exacerbate symptoms of RLS. Subjects were asked to remain on stable medication regimens, and medication use was followed throughout the study period. We defined RLS agents as iron supplementation, dopamine agonists (eg, L-Dopa, pramipexole, and ropinirole), gabapentin, narcotics, and benzodiazepines. While we did not prevent alterations in medical therapy, the need for increasing doses of medications due to worsening of symptoms was grounds for disenrollment. This was done to prevent confounding. Additionally, reductions in doses and discontinuation of medications for RLS were discouraged.

Pneumatic Compressive Devices

Subjects were randomized to receive therapeutic or sub-therapeutic “sham” PCDs. Both devices were identical in appearance, weight, noise generation, and timing of air inflation of the leg wraps. The devices were programmed to inflate the leg wraps for 5 s every minute. The only difference between these devices was that therapeutic devices generated 40 cm H2O of air pressure with each inflation cycle, while sham devices generated a 3- to 4 cm H2O rise in pressure. Venous Doppler flow studies were conducted on normal individuals to confirm that sham devices did not result in vascular compression.

Devices were provided to subjects who were enrolled for home use. Each patient was instructed in detail on how to apply leg wraps and how to operate the device. Subjects were instructed to keep a daily log of PCD use, RLS symptoms, and estimates of sleep lost from RLS symptoms. This log served as a means to derive device compliance and adherence to the study protocol. Subjects were asked to wear the PCDs for at least 1 h each day for 4 weeks, starting prior to the time when symptoms typically began. Compliance was defined as the percentage of days PCDs were used for at least 1 h. Use of PCDs during sleep was not part of the instructions to patients but was not prevented.

Data Measurements

Subjects were evaluated in clinic by the investigators at the time of enrollment and after the treatment period. During the treatment period, subjects were contacted by phone on days 3, 14, and 28 by a study coordinator who was also blinded to the assigned treatment group. During these interval follow-ups, subjects were queried about device compliance, symptoms, medication use for RLS, and any potential adverse reactions to the devices, such as rash, discomfort, or worsening of symptoms.

Subjects completed a comprehensive medical questionnaire to document medical conditions, current medications with dosages, and previously prescribed medical treatments and home remedies for RLS. All subjects submitted serum samples for measurement of iron, iron saturation, ferritin levels, and soluble transferrin receptor levels. Subjects completed validated questionnaires designed to assess the severity of RLS and its impact on quality of life. We compared variables measured at the beginning and on completion of the study between those receiving therapeutic and sham devices. These variables included demographic data, severity of RLS symptoms, measures of health-related quality of life, and estimates of EDS and fatigue. The validated instruments were:

  • International Restless Legs Syndrome Study Group Severity Scale (IRLSSS)27;

  • The Johns Hopkins Restless Legs Severity Scale (JHRLSS)28;

  • The restless legs syndrome quality of life instrument (RLS-QLI)29;

  • The Epworth sleepiness scale (ESS)30; and

  • Fatigue Visual Analog Scale.

End Points

The primary end points were improvements in disease severity. Secondary end points included quality of life measures, ESS, and fatigue visual analog scale.

Statistical Analysis and Sample Size Determination

From our initial pilot study, we estimated that subjects receiving therapeutic devices would experience a 50% greater improvement in symptoms than subjects receiving sham devices. We assumed that no baseline differences would exist between the two treatment groups. In order to detect the estimated difference in treatment effect, a total of 35 subjects would be enrolled using a 3:2 randomization (21 treatment subjects and 14 control/sham subjects).

We performed a univariate analysis with continuous variables analyzed using Student t test and categorical variables using a χ2 analysis. Two-sample t tests were performed for the eight variables comparing values from the pretreatment questionnaires to those obtained at day 28, as follows: (1) RLS severity score or IRLSSS; (2) JHRLSS; (3) RLS-QLI in four dimensions; (4) ESS; and (5) fatigue scale. All tests were two tailed, and p values < 0.05 were assumed to represent statistical significance. Pearson correlation coefficients were used to evaluate associations between severity and duration of symptoms, as they relate to response to therapy. Data are presented as mean ± SD. All analyses were performed using a statistical software package (SPSS, version 12.0; SPSS Inc; Chicago, IL).

Forty-one subjects were approached for enrollment (Fig 1). The final cohort was comprised of 35 subjects, 21 randomized to therapeutic PCDs, and 14 randomized to subtherapeutic “sham” devices. No subjects reported a need to initiate or escalate medical therapy, none reported a worsening of their RLS symptoms, and none experienced any adverse reactions related to PCD use.

Figure Jump LinkFigure 1 Subject enrollment (consort flowchart).Grahic Jump Location

Groups were similar at baseline (Table 1). Prior to enrollment, the majority of subjects reported moderate or severe symptoms of RLS, mild to moderate daytime sleepiness, moderate daytime fatigue, and significant impairments on quality of life. Prior and current pharmacologic therapies for RLS were common but did not differ between groups (Table 2). No subjects were receiving narcotics for any indication. Selective serotonin reuptake inhibitor use did not differ between groups (14.3% vs 14.3% respectively). No subjects initiated new medical therapy for RLS or increased the dose of their RLS medications during the study period. None of the patients using placebo devices decreased or discontinued medical therapy, while five (23.8%) individuals using therapeutic devices self-decreased or self-discontinued medical therapy for RLS (p = 0.05). No subjects were found to have diminished iron stores at the time of enrollment. No subjects enrolled in this trial reported worsening of their symptoms during the treatment period.

Table Graphic Jump Location
Table 1 Baseline Characteristics for Subjects Randomized to Therapeutic Pneumatic Compression Devices or Subtherapeutic Sham Control*

*Values are given as the mean ± SD, unless otherwise indicated.

Table Graphic Jump Location
Table 2 Medication Use at Time of Enrollment*

*Values are given as No. (%), unless otherwise indicated. NA = not available.

The use of therapeutic PCDs resulted in greater improvements in the means of all measured variables over the use of sham devices (Tables 35, Fig 2). Eight subjects (38.1%) using therapeutic PCDs experienced a complete resolution of symptoms, while none of those using sham devices experienced complete remission (p = 0.007). Subjects with more severe symptoms (higher baseline severity) had a greater reduction in symptoms (r = 0.65). Furthermore, those with more severe disease at baseline tended to have lower severity scores at the end of therapy. Subjects experiencing symptoms over a longer period of time (longer history of RLS symptoms) had a less robust response to therapy (r = − 0.32).

Table Graphic Jump Location
Table 3 Characteristics at 4 Weeks for Subjects Randomized to Therapeutic Pneumatic Compression Devices or Subtherapeutic Sham Control*

*Values are given as the mean ± SD, unless otherwise indicated.

Table Graphic Jump Location
Table 4 Comparison of Therapeutic Responses*

*Values are given as the mean ± SD, unless otherwise indicated.

Table Graphic Jump Location
Table 5 Percentage of Subjects Responding to Intervention*

*Values are given as the percentage of subjects in each randomization arm who reported any improvement in the measured variable.

Figure Jump LinkFigure 2 Changes in instrument scales from baseline.Grahic Jump Location

Thirteen subjects (12 therapeutic and 1 sham) requested continued use of PCDs after completion of the study period. After unblinding, therapeutic devices were provided to eight subjects, and three patients purchased commercially available, similar devices.

We found that PCDs effectively improved the symptoms associated with RLS. While a placebo effect was observed, therapeutic PCDs resulted in significantly greater improvements in disease severity, quality of life scores, measures of daytime sleepiness, and fatigue in comparison to the use of sham devices. Notably, one third of subjects using therapeutic PCDs experienced complete resolution of symptoms.

Similar to other studies, we found that the majority of subjects experienced moderate to severe disease, with all subjects reporting impaired sleep quality and diminished quality of life measures. Sleep disruption, daytime sleepiness, fatigue, and a negative impact on quality of life all paralleled the reported severity of disease. Many patients were symptomatic despite medical therapy. The observed daytime sleepiness may reflect sleep disruption associated with RLS or undesirable side effects of medications.

This randomized, sham-controlled trial was conducted to validate the findings in our prior prospective observational cohort study that showed PCD use was an effective therapy for RLS.26 Previously, in a pilot study, Rajaram et al31 reported that enhanced external counterpulsation (EECP), as an adjunctive means to improve coronary blood flow, improved the symptoms of RLS. Subsequently, these investigators initiated a randomized, double-blinded, sham-controlled study of EECP in RLS patients, but the study was terminated prematurely after enrollment of only six subjects (four therapeutic and two placebo) due to closure of the EECP laboratory.32 Both groups of subjects experienced improved severity scores, but statistical comparison was not possible.

Pharmacologic therapy remains the treatment of choice for most patients with RLS, and several classes of agents have been well established as effective therapies.4,9,1225 However, no medication is universally effective, and most agents are limited by troublesome or intolerable side effects.26 An effective nonpharmaceutical treatment either as a primary or adjunctive therapy would be an attractive option.

There are a number of possible explanations for the benefits of PCDs in RLS. While the specific pathophysiology of RLS is unknown, it is regarded to be a CNS disorder resulting from dysfunction of dopaminergic and opioidergic neurotransmission mediated by the metabolism of iron. This theory is supported by therapeutic effects of dopamine agonists, opioids, and iron. However, RLS may be a peripheral disorder. Chronic venous insufficiency has been shown to have a common association with RLS.33 Tissue hypoxia and ischemia may lead to peripheral neuronal dysfunction. Vascular compression from PCDs may stimulate the release of endothelial mediators that modulate symptoms. Additionally, PCDs may improve local perfusion by enhancing venous and lymphatic drainage with consequent relief of mild, otherwise subclinical ischemia.

Our study has several limitations. We relied on the self-reported logs of the subjects to verify compliance. There were no objective measurements to report. Despite attempts to blind patients to type of intervention, patients in the sham group may have been able to determine that they were receiving sub-therapeutic pressures. This may explain the differences seen in compliance between the two groups. We believe the difference in compliance probably reflects the differences in perceived benefit between the groups, as those noting a positive effect would be more likely to comply with therapy. Our study did not attempt to investigate patients according to possible etiologic category, specifically a comparison between familial or early-onset RLS and sporadic or late-onset RLS. While we found no correlation between age at the onset of symptoms and response to therapy, our study was not adequately powered to investigate such an association. We did observe that longer duration of symptoms correlated with a less robust response to therapy, suggesting that familial RLS is less responsive to PCDs than sporadic RLS. This observation deserves further investigation.

While effective for RLS treatment, the role of PCDs may be limited. RLS medications are effective, relatively safe, and usually well tolerated. Additionally, medications are obviously easier to use than PCDs, which require patients to remain immobile for 1 h each day. However, PCDs are not entirely impractical. Most patients experience symptoms in the evening when they may be relaxing, thus minimizing the ambulatory limitations for the patient. In fact, in both this study and during our pilot study, patients were largely compliant with the prescribed therapy, especially if they experienced a therapeutic benefit. The most likely roles for PCDs would be in the following: (1) patients unresponsive or incompletely responsive to pharmaceutical agents, (2) patients intolerant of pharmacologic side effects, or (3) situations where it is advisable to avoid drug-drug interactions. However, before PCD therapy is ready for more wide-spread use, it will be important to see validating studies in various populations of RLS patients.

EDS

excessive daytime sleepiness

EECP

enhanced external counterpulsation

ESS

Epworth sleepiness scale

IRLSSS

International Restless Legs Syndrome Study Group severity scale

JHRLSS

Johns Hopkins restless legs severity scale

PCD

pneumatic compression device

RLS

restless legs syndrome

RLS-QLI

restless legs syndrome quality of life instrument

Ekbom KA. Toward a better definition of the restless legs syndrome. Mov Disord. 1995;10:634-642. [PubMed] [CrossRef]
 
Allen RP, Walters AS, Montplaisir J, et al. Restless legs syndrome prevalence and impact: REST general population study. Arch Intern Med. 2005;165:1286-1292. [PubMed] [CrossRef]
 
Bassetti C, Mauerhofer D, Gugger M, et al. Restless legs syndrome: a prospective clinical study of 55 patients. Eur Neurol. 2001;45:67-74. [PubMed] [CrossRef]
 
Gamaldo CE, Earley CJ. Restless legs syndrome: a clinical update. Chest. 2006;130:1596-1604. [PubMed] [CrossRef]
 
Montplaisir J, Nicolas A, Godbout R, et al;Kryger M, Roth T, Dement W. Restless legs syndrome and periodic limb movement disorder. Principles and practice of sleep medicine. 2000;3rd ed. New York, NY WB Saunders:742-749
 
American Academy of Sleep Medicine The international classification of sleep disorders. Diagnostic and coding manual. 2005;2nd ed. Westchester, IL American Academy of Sleep Medicine:178-181
 
Earley CJ. Clinical practice: restless legs syndrome. N Engl J Med. 2003;348:2103-2109. [PubMed] [CrossRef]
 
Allen RP, Picchietti D, Hening WA, et al. Restless legs syndrome: diagnostic criteria, special considerations, and epidemiology: a report from the restless legs syndrome diagnosis and epidemiology workshop at the National Institutes of Health. Sleep Med. 2003;4:101-119. [PubMed] [CrossRef]
 
Hening W, Walters AS, Allen RP, et al. Impact, diagnosis and treatment of restless legs syndrome (RLS) in a primary care population: the REST (RLS epidemiology, symptoms and treatment) primary care study. Sleep Med. 2004;5:237-246. [PubMed] [CrossRef]
 
Phillips B, Young T, Finn L, et al. Epidemiology of restless legs syndrome in adults. Arch Intern Med. 2000;160:2137-2141. [PubMed] [CrossRef]
 
Coleman RM, Bliwise DL, Sajben N, et al;Guilleminault C, Lugaresi E. Epidemiology of periodic movements during sleep. Sleep/wake disorders: natural history, epidemiology and long term evolution. 1988; New York, NY Raven Press:217-229
 
Chesson AL Jr, Wise M, Davila D, et al. Practice parameters for the treatment of restless legs syndrome and periodic limb movement disorder: an American Academy of Sleep Medicine report. Sleep. 1999;22:961-968. [PubMed]
 
Hening W, Allen R, Earley C, et al. The treatment of restless legs syndrome and periodic limb movement disorder. Sleep. 1999;22:970-999. [PubMed]
 
Silber MH, Ehrenberg BL, Allen RP, et al. An algorithm for the management of restless legs syndrome. Mayo Clin Proc. 2004;79:916-922. [PubMed] [CrossRef]
 
Bogan RK, Fry JM, Schmidt MH, et al. Ropinirole in the treatment of patients with restless legs syndrome: a US-based randomized, double-blind, placebo-controlled clinical trial. Mayo Clin Proc. 2006;81:17-27. [PubMed] [CrossRef]
 
Clavadetscher SC, Gugger M, Bassetti CL. Restless legs syndrome: clinical experience with long-term treatment. Sleep Med. 2004;5:495-500. [PubMed] [CrossRef]
 
Garcia-Borreguero D, Larrosa O, de la Llave Y, et al. Treatment of restless legs syndrome with gabapentin: a double-blind, cross-over study. Neurology. 2002;59:1573-1579. [PubMed] [CrossRef]
 
Silber M, Girish M, Izurieta R. Pramipexole in the management of restless legs syndrome: an extended study. Sleep. 2003;26:910-921
 
Trenkwalder C, Garcia-Borreguero D, Montagna P, et al. Ropinirole in the treatment of restless legs syndrome: results from the TREAT RLS 1 study, a 12 week, randomized, placebo controlled study in 10 European countries. J Neurol Neurosurg Psychiatry. 2004;75:92-97. [PubMed]
 
Trenkwalder C, Hundemer HP, Lledo A, et al. Efficacy of pergolide in treatment of restless legs syndrome: the PEARLS Study. Neurology. 2004;62:1391-1397. [PubMed] [CrossRef]
 
Walters AS, Wagner ML, Hening WA, et al. Successful treatment of the idiopathic restless legs syndrome in a randomized double-blind trial of oxycodone versus placebo. Sleep. 1993;16:327-332. [PubMed]
 
Wetter TC, Stiasny K, Winkelmann J, et al. A randomized controlled study of pergolide in patients with restless legs syndrome. Neurology. 1999;52:944-950. [PubMed] [CrossRef]
 
Winkelman JW, Sethi KD, Kushida CA, et al. Efficacy and safety of pramipexole in restless legs syndrome. Neurology. 2006;67:1034-1039. [PubMed] [CrossRef]
 
Earley CJ, Heckler D, Allen RP. The treatment of restless legs syndrome with intravenous iron dextran. Sleep Med. 2004;5:231-235. [PubMed] [CrossRef]
 
Sloand JA, Shelly MA, Feigin A, et al. A double-blind, placebo-controlled trial of intravenous iron dextran therapy in patients with ESRD and restless legs syndrome. Am J Kidney Dis. 2004;43:663-670. [PubMed] [CrossRef]
 
Eliasson AH, Lettieri CJ. Sequential compression devices for treatment of restless legs syndrome. Medicine. 2007;86:317-323. [PubMed] [CrossRef]
 
Walters AS, LeBrocq C, Dhar A, et al. Validation of the International Restless Legs Syndrome Study group rating scale for restless legs syndrome. Sleep Med. 2003;4:121-132. [PubMed] [CrossRef]
 
Allen RP, Earley CJ. Validation of the Johns Hopkins restless legs severity scale. Sleep Med. 2001;3:239-242. [CrossRef]
 
Atkinson MJ, Allen RP, DuChane J, et al. Validation of the restless legs syndrome quality of life instrument (RLS-QLI): findings of a consortium of national experts and the RLS foundation. Qual Life Res. 2004;13:679-693. [PubMed] [CrossRef]
 
Johns MW. A new method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep. 1991;14:540-545. [PubMed]
 
Rajaram SS, Shanahan J, Ash C, et al. Enhanced external counter pulsation (EECP) as a novel treatment for restless legs syndrome (RLS): a preliminary test of the vascular neurologic hypothesis for RLS. Sleep Med. 2005;6:101-106. [PubMed] [CrossRef]
 
Rajaram SS, Rudzinskiy P, Walters AS. Enhanced external counter pulsation (EECP) for restless legs syndrome (RLS): preliminary negative results in a parallel double-blind study [letter]. Sleep Med. 2006;7:390-391. [PubMed] [CrossRef]
 
McDonagh B, King T, Guptan RC. Restless legs syndrome in patients with chronic venous disorders: an untold story. Phlebology. 2007;22:156-163. [PubMed] [CrossRef]
 

Figures

Figure Jump LinkFigure 1 Subject enrollment (consort flowchart).Grahic Jump Location
Figure Jump LinkFigure 2 Changes in instrument scales from baseline.Grahic Jump Location

Tables

Table Graphic Jump Location
Table 1 Baseline Characteristics for Subjects Randomized to Therapeutic Pneumatic Compression Devices or Subtherapeutic Sham Control*

*Values are given as the mean ± SD, unless otherwise indicated.

Table Graphic Jump Location
Table 2 Medication Use at Time of Enrollment*

*Values are given as No. (%), unless otherwise indicated. NA = not available.

Table Graphic Jump Location
Table 3 Characteristics at 4 Weeks for Subjects Randomized to Therapeutic Pneumatic Compression Devices or Subtherapeutic Sham Control*

*Values are given as the mean ± SD, unless otherwise indicated.

Table Graphic Jump Location
Table 4 Comparison of Therapeutic Responses*

*Values are given as the mean ± SD, unless otherwise indicated.

Table Graphic Jump Location
Table 5 Percentage of Subjects Responding to Intervention*

*Values are given as the percentage of subjects in each randomization arm who reported any improvement in the measured variable.

References

Ekbom KA. Toward a better definition of the restless legs syndrome. Mov Disord. 1995;10:634-642. [PubMed] [CrossRef]
 
Allen RP, Walters AS, Montplaisir J, et al. Restless legs syndrome prevalence and impact: REST general population study. Arch Intern Med. 2005;165:1286-1292. [PubMed] [CrossRef]
 
Bassetti C, Mauerhofer D, Gugger M, et al. Restless legs syndrome: a prospective clinical study of 55 patients. Eur Neurol. 2001;45:67-74. [PubMed] [CrossRef]
 
Gamaldo CE, Earley CJ. Restless legs syndrome: a clinical update. Chest. 2006;130:1596-1604. [PubMed] [CrossRef]
 
Montplaisir J, Nicolas A, Godbout R, et al;Kryger M, Roth T, Dement W. Restless legs syndrome and periodic limb movement disorder. Principles and practice of sleep medicine. 2000;3rd ed. New York, NY WB Saunders:742-749
 
American Academy of Sleep Medicine The international classification of sleep disorders. Diagnostic and coding manual. 2005;2nd ed. Westchester, IL American Academy of Sleep Medicine:178-181
 
Earley CJ. Clinical practice: restless legs syndrome. N Engl J Med. 2003;348:2103-2109. [PubMed] [CrossRef]
 
Allen RP, Picchietti D, Hening WA, et al. Restless legs syndrome: diagnostic criteria, special considerations, and epidemiology: a report from the restless legs syndrome diagnosis and epidemiology workshop at the National Institutes of Health. Sleep Med. 2003;4:101-119. [PubMed] [CrossRef]
 
Hening W, Walters AS, Allen RP, et al. Impact, diagnosis and treatment of restless legs syndrome (RLS) in a primary care population: the REST (RLS epidemiology, symptoms and treatment) primary care study. Sleep Med. 2004;5:237-246. [PubMed] [CrossRef]
 
Phillips B, Young T, Finn L, et al. Epidemiology of restless legs syndrome in adults. Arch Intern Med. 2000;160:2137-2141. [PubMed] [CrossRef]
 
Coleman RM, Bliwise DL, Sajben N, et al;Guilleminault C, Lugaresi E. Epidemiology of periodic movements during sleep. Sleep/wake disorders: natural history, epidemiology and long term evolution. 1988; New York, NY Raven Press:217-229
 
Chesson AL Jr, Wise M, Davila D, et al. Practice parameters for the treatment of restless legs syndrome and periodic limb movement disorder: an American Academy of Sleep Medicine report. Sleep. 1999;22:961-968. [PubMed]
 
Hening W, Allen R, Earley C, et al. The treatment of restless legs syndrome and periodic limb movement disorder. Sleep. 1999;22:970-999. [PubMed]
 
Silber MH, Ehrenberg BL, Allen RP, et al. An algorithm for the management of restless legs syndrome. Mayo Clin Proc. 2004;79:916-922. [PubMed] [CrossRef]
 
Bogan RK, Fry JM, Schmidt MH, et al. Ropinirole in the treatment of patients with restless legs syndrome: a US-based randomized, double-blind, placebo-controlled clinical trial. Mayo Clin Proc. 2006;81:17-27. [PubMed] [CrossRef]
 
Clavadetscher SC, Gugger M, Bassetti CL. Restless legs syndrome: clinical experience with long-term treatment. Sleep Med. 2004;5:495-500. [PubMed] [CrossRef]
 
Garcia-Borreguero D, Larrosa O, de la Llave Y, et al. Treatment of restless legs syndrome with gabapentin: a double-blind, cross-over study. Neurology. 2002;59:1573-1579. [PubMed] [CrossRef]
 
Silber M, Girish M, Izurieta R. Pramipexole in the management of restless legs syndrome: an extended study. Sleep. 2003;26:910-921
 
Trenkwalder C, Garcia-Borreguero D, Montagna P, et al. Ropinirole in the treatment of restless legs syndrome: results from the TREAT RLS 1 study, a 12 week, randomized, placebo controlled study in 10 European countries. J Neurol Neurosurg Psychiatry. 2004;75:92-97. [PubMed]
 
Trenkwalder C, Hundemer HP, Lledo A, et al. Efficacy of pergolide in treatment of restless legs syndrome: the PEARLS Study. Neurology. 2004;62:1391-1397. [PubMed] [CrossRef]
 
Walters AS, Wagner ML, Hening WA, et al. Successful treatment of the idiopathic restless legs syndrome in a randomized double-blind trial of oxycodone versus placebo. Sleep. 1993;16:327-332. [PubMed]
 
Wetter TC, Stiasny K, Winkelmann J, et al. A randomized controlled study of pergolide in patients with restless legs syndrome. Neurology. 1999;52:944-950. [PubMed] [CrossRef]
 
Winkelman JW, Sethi KD, Kushida CA, et al. Efficacy and safety of pramipexole in restless legs syndrome. Neurology. 2006;67:1034-1039. [PubMed] [CrossRef]
 
Earley CJ, Heckler D, Allen RP. The treatment of restless legs syndrome with intravenous iron dextran. Sleep Med. 2004;5:231-235. [PubMed] [CrossRef]
 
Sloand JA, Shelly MA, Feigin A, et al. A double-blind, placebo-controlled trial of intravenous iron dextran therapy in patients with ESRD and restless legs syndrome. Am J Kidney Dis. 2004;43:663-670. [PubMed] [CrossRef]
 
Eliasson AH, Lettieri CJ. Sequential compression devices for treatment of restless legs syndrome. Medicine. 2007;86:317-323. [PubMed] [CrossRef]
 
Walters AS, LeBrocq C, Dhar A, et al. Validation of the International Restless Legs Syndrome Study group rating scale for restless legs syndrome. Sleep Med. 2003;4:121-132. [PubMed] [CrossRef]
 
Allen RP, Earley CJ. Validation of the Johns Hopkins restless legs severity scale. Sleep Med. 2001;3:239-242. [CrossRef]
 
Atkinson MJ, Allen RP, DuChane J, et al. Validation of the restless legs syndrome quality of life instrument (RLS-QLI): findings of a consortium of national experts and the RLS foundation. Qual Life Res. 2004;13:679-693. [PubMed] [CrossRef]
 
Johns MW. A new method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep. 1991;14:540-545. [PubMed]
 
Rajaram SS, Shanahan J, Ash C, et al. Enhanced external counter pulsation (EECP) as a novel treatment for restless legs syndrome (RLS): a preliminary test of the vascular neurologic hypothesis for RLS. Sleep Med. 2005;6:101-106. [PubMed] [CrossRef]
 
Rajaram SS, Rudzinskiy P, Walters AS. Enhanced external counter pulsation (EECP) for restless legs syndrome (RLS): preliminary negative results in a parallel double-blind study [letter]. Sleep Med. 2006;7:390-391. [PubMed] [CrossRef]
 
McDonagh B, King T, Guptan RC. Restless legs syndrome in patients with chronic venous disorders: an untold story. Phlebology. 2007;22:156-163. [PubMed] [CrossRef]
 
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    Print ISSN: 0012-3692
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