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Sequential Compression Devices for Treatment of Restless Legs Syndrome

Eliasson, Arn H. MD; Lettieri, Christopher J. MD

doi: 10.1097/MD.0b013e31815b1319

Restless legs syndrome (RLS) is a common disorder that presents with irresistible urges to move the legs and motor restlessness, worsening in the evening. RLS commonly causes insomnia and associated daytime symptoms. Treatment of first choice for RLS is usually medication, but medications are often ineffective or poorly tolerated. An effective nonpharmacologic therapy would be highly desirable. Here we review RLS and its treatment and present data from a pilot study on the effect of a novel treatment for this condition. The objective of this study was to determine the therapeutic effect of pneumatic sequential compression devices (SCDs) on RLS symptoms.

We performed an uncontrolled, prospective interventional study using SCDs on a convenience sample of adults reliably diagnosed with RLS. Patients were asked to wear the SCD for an hour each evening before the usual time of onset of restless legs symptoms. Before and after 1-3 months of SCD therapy, patients completed validated questionnaires to assess RLS severity, daytime sleepiness, and impact of RLS on quality of life in the domains of social function, daily task function, sleep quality, and emotional well-being. Compliance with SCD therapy was measured using patient-recorded logs.

Of 10 patients (7 women; age range, 37-80 yr; mean age, 56 yr), symptomatic for a mean of 68 months (range, 12-360 mo), 1 could not tolerate wearing the SCD and withdrew from the protocol after 3 days. The remaining 9 patients complied with therapy 58%-100% of nights (mean, 82%). Three patients experienced complete resolution of RLS and 6 patients had improvement of symptoms. Group severity score improved from 24/40 to 8/40 (p = 0.001). Epworth Sleepiness Scale score improved from 12/24 to 8/24 (p = 0.05). Every quality of life score improved: social function from 74% to 96% (p = 0.04), daily task function 63% to 80% (p = 0.05), sleep quality 27% to 63% (p = 0.003), and emotional well-being from 49% to 83% (p = 0.02). In this group of patients, wearing the SCD in the evening for an hour improved symptoms of RLS and improved quality of life, with complete resolution of symptoms in 3 of 10 patients.

Abbreviations: ESS = Epworth Sleepiness Scale, PLMS = periodic limb movements in sleep, RLS = restless legs syndrome, RLS-QLI = Restless Legs Syndrome-Quality of Life Instrument, SCD = sequential compression device.

From Department of Medicine (AHE, CJL), Walter Reed Army Medical Center, Washington, DC; and Department of Medicine (AHE, CJL), Uniformed Services University of the Health Sciences, Bethesda, Maryland.

Aircast LLC (Summit, NJ) supplied 6 VenaFlow system sequential compression devices and 10 sets of leg wraps for use in the study at no cost to the patients. No monetary or other support was provided. Aircast was not involved in the preparation, review, or approval of the manuscript, its contents, or its conclusions.

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

Address reprint requests to: Arn H. Eliasson, MD, Pulmonary and Critical Care Medicine Service, Department of Medicine, Walter Reed Army Medical Center, 6900 Georgia Avenue, NW, Washington, DC 20307-5001. Fax: 202-782-9032; e-mail:

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Restless legs syndrome (RLS) is a common, highly vexing problem manifested by sensory and motor symptoms that disrupt sleep onset or sleep maintenance. The sleep disruption may result in daytime symptoms such as excessive daytime sleepiness and mood changes14,21. Available pharmacologic treatments are often ineffective or are associated with unacceptable side effects12. Furthermore, treatment of RLS with medications may be limited by tachyphylaxis of the therapeutic effect. Because there are no consistently reliable treatment alternatives, there is an urgent need for new, innovative treatment strategies. An effective nonpharmacologic treatment would be a highly attractive alternative.

RLS is the second most common sleep disorder and occurs with an estimated prevalence of 10% in the general population4,14,21. While uncommon in young people, the prevalence of RLS increases with advancing age, and RLS appears to be more common in women than in men12. One study documented an incidence of 29% in patients over 50 years and 44% in patients aged 65 years and older9.

The diagnosis of RLS is made by historical information and relies on 4 cardinal manifestations: sensory symptoms of an irresistible urge to move the legs, onset or exacerbation of symptoms with rest, improvement or relief of symptoms with activity, and worsening of the symptoms in the evening or night3,4,14 (Table 1). Symptoms commonly associated with the syndrome but not required for diagnosis are periodic limb movements in sleep (PLMS), difficulty initiating or maintaining sleep, excessive daytime sleepiness, and difficulty concentrating or functioning at peak level4,14,21.



The core manifestation of RLS, the sensory symptom of the distressing need to move the legs (akathisia) can be very difficult for patients to describe. Commonly used phrases include leg aches or muscle tension, worms or soda water in the veins, bone itch, and "creepy crawlies." Frankly painful sensations may occasionally be associated with the akathisia, and ignoring the urge to move the legs can lead to involuntary leg jerks. PLMS may be reported by the patient's bed partner and are seen on polysomnography in up to 80% of RLS cases, but PLMS are neither necessary nor sufficient for the diagnosis of RLS4.

Patients frequently employ a variety of home remedies, usually with unsatisfying results, including leg massage, hot and cold baths, lotions and liniments, stretching exercises, and walking. Because the symptoms may strike patients on an intermittent basis and resolve just as unpredictably, patients often have the impression that their home remedy is at least partially effective. This mistaken impression may often delay the patient's decision to seek medical consultation for the problem of RLS.

When physicians are consulted, pharmacologic alternatives are ordinarily used. There are 4 classes of medications that have been used with varying success rates7,12,17,24. Dopaminergic agents (levodopa, ropinirole, and pramipexole) are considered to be the treatment of first choice and can provide substantial relief at least for a time6,8,15,23,28,33 (Table 2). The United States Food and Drug Administration approved ropinirole in 2005 and pramipexole in 2006 for the treatment of moderate to severe RLS. Dopaminergic medications commonly cause nausea and orthostatic hypotension. Treatment with dopaminergic agents is often limited by the development of rebound symptoms as the medication wears off, or augmentation of symptoms unrelated to dosing of the medication23. In January 2007, ergot-derived dopamine receptor agonists previously used off-label for RLS (pergolide and cabergoline) were shown to be associated with heart valve damage34. Pergolide has subsequently been withdrawn from the United States market. Because cabergoline is not approved in the United States for Parkinson Disease or RLS, but for hyperprolactinemia using lower doses, the drug remains on the market. The findings of heart valve problems with the ergot-derived drugs is disappointing since prior studies showed treatment efficacy for RLS of 58%-95%8,26,27,29,32.



Second-line agents14,24 include benzodiazepines (complicated by morning drowsiness and confusion as well as increased risk for falls)8, opiates (complicated by tolerance to the medication, precipitation of sleep apnea, constipation, confusion, and falls risk)8,31, and gabapentin (complicated by drowsiness and ataxia)8,16. It is evident that pharmacologic treatments of RLS may be only temporarily effective and are frequently complicated by intolerable side effects.

The pathophysiologic role of iron in RLS has been supported by studies linking iron deficiency to the prevalence and severity of RLS symptoms1,22; studies documenting diminished iron levels in the central nervous system20, especially the substantia nigra of RLS patients2,10; and by studies demonstrating the therapeutic effect of iron replacement13,25. Administration of iron has improved or resolved symptoms of RLS patients in small published series13,25. However, iron therapy is not universally successful, and recurrences of symptoms may occur even with sustained iron administration and achievement of high ferritin levels3,13,25.

Anecdotal experience has suggested therapeutic efficacy of sequential compression device (SCDs) prescribed for prophylaxis of deep vein thrombosis. Review of the literature reveals a case report of periodic limb movement disorder effectively treated with a lumbar corset18, but to our knowledge no cases of SCD therapy for RLS have been reported. We report a series of patients prospectively treated with SCDs for RLS.

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A convenience sample from the Sleep Disorders Center at Walter Reed Army Medical Center was studied. The study was reviewed and approved by the Department of Clinical Investigation at Walter Reed.

Inclusion criteria included age greater than 17 years 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 Medicine4. Exclusion criteria included the following:

  1. Age less than 18 years,
  2. Unstable medical conditions that could interfere with the requirements of the study, such as uncontrolled diabetes mellitus or symptomatic asthma,
  3. Mental or physical limitations (including dementia) that would preclude data collection on questionnaires or wearing the SCD,
  4. Medical conditions where increased venous or lymphatic return was undesirable, such as severe congestive heart failure and pulmonary edema,
  5. Medical conditions where direct pressure of the SCD was undesirable or contraindicated, such as known or suspected deep vein thrombosis, thrombophlebitis, severe arteriosclerosis, active infection such as gangrene, recent vein ligation or skin graft, or extreme deformity of the legs.

Patients with medical disorders that could present with symptoms suggesting or overlapping with RLS could be included in the study. These potentially confounding conditions included chronic myelopathy, peripheral neuropathy, uremia, and anemia14.

After informed consent, patients completed a medical questionnaire to document medical conditions and medications. Patients were queried about previously tried therapies, both home remedies and medically prescribed treatments.

RLS severity of illness and impact on other parameters of daily living were measured using 3 tools:

  1. The RLS Rating Scale-a previously validated tool studied and published by the International RLS Study Group30. This tool uses 10 items on a degree of severity scale from 0 to 4, such that patients who are symptom free will score 0 and patients who are maximally symptomatic will score 40.
  2. The Restless Legs Syndrome-Quality of Life Instrument (RLS-QLI)5. This tool uses 17 questions relating to common activities of daily living and asks the subject to score the impact that RLS has on performing or attempting to perform these activities. The RLS-QLI scores quality of life in 4 dimensions: a) social function, b) daily function, c) sleep quality, and d) emotional well-being. The tool provides arithmetic rules to convert the raw scores to percentages with higher percentages reflecting better quality of life in each dimension.
  3. The Epworth Sleepiness Scale (ESS)-an 8-item questionnaire that attempts to place an objective number on the subjective symptoms of daytime sleepiness19. This questionnaire is the most commonly used tool worldwide to assess daytime sleepiness. Subjects can score from 0 to 24 points, with normal subjects scoring 10 or less while sleepy subjects score from 11 to 24. General divisions of severity are mild sleepiness (11-14 points), moderate sleepiness (15-19 points), and severe sleepiness (20-24 points).

Patients were given an AIRCAST SCD (Aircast LLC, Summit, NJ) for use at home. Each patient was instructed in detail on how to apply the leg wraps and how to operate the device. The AIRCAST SCD is an air pressure generator approximately the size of a large toaster that is placed on the floor or suspended with hooks from a bed frame. Flexible hoses carry compressed air to plastic bladders embedded in soft cloths that wrap around each lower leg. The cloth wraps are gently held in place with Velcro tabs and require 20-30 seconds to put on the legs. The AIRCAST SCD generates approximately 40 cm H2O air pressure and is programmed to inflate the leg wraps for 5 seconds every minute. Inflation and deflation are not generally regarded by patients as uncomfortable although the motion may awaken people from sleep. For this reason, patients were asked to wear the SCD for at least 1 hour each day before the period when symptoms typically began to occur. Use of the SCD during sleep was not proscribed but it was not part of the instructions to patients. Patients were instructed to keep a daily log of SCD use and of RLS symptoms. Adherence to treatment was derived from the daily logs kept by each patient while at home. No objective measurement device was used.

Patients were asked to complete the 3 tools measuring severity of illness, daytime sleepiness, and impact on quality of life at 2 weeks, 1 month, and 3 months.

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Statistical Methods

Two sample T-tests were performed for the 6 variables (1. RLS Rating, 2. RLS-QLI in 4 dimensions, and 3. ESS) comparing values from the pretreatment questionnaires to those obtained at subsequent intervals. Statistical significance was set at the 95% confidence interval with p < 0.05.

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Twelve consecutive patients visiting the Sleep Disorders Center with all 4 essential diagnostic features of RLS were approached for participation in the study. Two patients deferred participation, the first a 42-year-old man because he would not be able to return for planned re-evaluations in a timely manner, and the second a 45-year-old woman because she did not think she could wear the SCD for the suggested amount of time each day. These patients did not complete the study intake questionnaires for detailed assessment of their RLS, but they were clinically assessed as mildly and moderately afflicted by their RLS symptoms and they were satisfied with their medical regimens.

Ten patients (7 women) who met clinical criteria for RLS were enrolled in the study. No patients were lost to follow-up. One patient was intolerant of SCD therapy and 9 (90%) completed the study protocol. The average age of the cohort was 56.1 years (range, 37-80 yr), and the mean duration of symptoms was 67.8 months (range, 12-360 mo). The majority of patients had received prior pharmacologic therapy for RLS (80%), and only 2 reported adequate symptom control (20%). At the time of enrollment, 70% of patients were still using prescription medications for RLS. All individuals included in the cohort had chronic medical conditions other than RLS and were receiving prescription medications. Coexisting conditions not previously associated with RLS were observed in this cohort. Specifically, headache disorders were present in 70%, hypertension and gastroesophageal reflux disease in 60%, hypothyroidism (on corrective therapy) in 50%, and underlying sleep-disordered breathing in 40%. It is noteworthy that iron deficiency or low transferrin levels were observed in only a minority of patients; see Table 3 for a summary of baseline clinical characteristics.



The patient who could not tolerate SCD therapy was a 51-year-old man whose RLS was extremely severe and had worsened over 10 years. His symptoms involved all 4 limbs and the muscles of his back and trunk. His symptoms evolved to the point where they were present 24 hours per day. He had been treated with every effective class of pharmacologic agent and was being managed with periodic intramuscular injections of botulinum toxin supplemented with oral acetaminophen/oxycodone as needed for relief. Three attempts at wearing the SCD were unsuccessful, and the patient refused further participation in the study. Since this patient was intolerant of therapy, he had no post-therapeutic data to include in an efficacy analysis. In a follow-up telephone interview, this patient reported that his RLS symptoms were stable and his overall condition and performance capacity were unchanged while on his regimen as described.

The remaining 9 patients complied with therapy 82% of days (range, 58%-100% of days). While asked to wear the SCD for an hour each day, patients were considered to be compliant with therapy for a certain day if they recorded at least 30 minutes of SCD use on that day on the daily log kept by the patient at home. Patients were followed at monthly intervals for 3 months.

Most patients had moderate or severe symptoms of RLS at the time of enrollment. The mean severity of RLS symptoms, as measured by the RLS Rating Scale, was 24 ± 6.8 (range, 14-33) out of a maximum score of 40. Mean ESS at baseline was 12.0 ± 6.9 (range, 0-17) out of a maximum of 24. RLS had significant impacts on the quality of life among the enrolled patients. Higher percentage values on the RLS-QLI indicate a better experience of quality of life, and mean values for the RLS-QLI at the time of enrollment were 74% ± 29% for social function; 63% ± 29% for daily function; 27% ± 25% for sleep quality; and 49% ± 32% for emotional well-being.

Use of the SCD resulted in a significant reduction of RLS severity and improvements in measures of quality of life in 90% of patients. The patient who was intolerant of the SCD did not experience a change in the severity of his symptoms. No patient experienced worsening symptoms following the application of SCD therapy. Among the 9 tolerant patients, all reported improvements in every measured parameter. These improvements were both clinically and statistically significant (Table 4). Three of the 9 tolerant patients (33.3%), with baseline severity scores of 28, 27, and 14, respectively, out of a possible 40, reported complete resolution of symptoms. Improvements occurred during the first month of SCD use (including resolution of symptoms), and plateaus in improvements were seen by 3 months. SCD use resulted in a significant reduction in the severity of RLS symptoms and improvements in all quality of life measures. In particular, sleep quality was significantly improved, and patients reported less daytime sleepiness as measured by ESS.



Data were analyzed for correlation between degree of improvement and the presence of chronic medical conditions, severity and duration of symptoms, and rate of compliance with therapy. No patient demographic or severity or duration of symptoms predicted response to therapy.

Patients reported a durable response to SCD therapy upon termination of their daily use of the device. It was not within the scope of this study to measure the duration of the therapeutic response, although several patients reported anecdotally that they had no symptoms or continued with improved symptoms for 9 months after cessation of SCD use.

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Medical practitioners faced with the common problem of RLS have a broad array of pharmaceutical options to alleviate their patients' symptoms. Medications have a high likelihood of providing symptom relief, at least for a time, although patients may experience rebound, augmentation, tachyphylaxis, or untenable side effects. There is a need for nonpharmaceutical treatment options for RLS either as a primary or adjunctive therapy. The results of this pilot study demonstrate a remarkable response rate of RLS symptoms to the therapeutic use of SCDs worn for a portion of an hour each day. The 90% response rate and 30% resolution rate are powerful indicators of treatment efficacy. The fact that therapy appeared to have a positive impact on so many aspects of RLS symptoms, including severity of symptoms and a variety of spheres of quality of life, argues against the notion that these findings are merely due to a strong placebo effect.

The relative ease of taking a medication may explain why prior therapeutic measures for RLS have tended toward a pharmacologic remedy. It is notable that 9 of 10 patients were able to comply with SCD therapy at rates that were highly favorable when compared with known adherence rates for drug therapy11. Patients found it feasible to wear the SCD for 30-60 minutes during a variety of other activities, usually in the evening before the usual onset of RLS symptoms. The willingness of patients to use the SCD as outlined in this protocol is remarkable in that it requires much more discipline that taking a capsule of medication. A motivating factor for compliance with SCD therapy may also be the untenable side effects associated with pharmacologic interventions.

In view of the ease of taking an oral medication and the propensity many providers have toward pharmacologic remedies, it is perhaps surprising that a proportion (20%) of these patients with moderate to severe RLS had not received prior medical treatment for their condition. Our impression, derived from interviews with this cohort of patients, is that occasional patients have the notion that their symptoms are not "reportable," that is, not serious enough to bother the doctor, or that they would need to "live with jumpy legs like their mothers did." Elderly patients appear to be especially suspicious of medications, some having suffered from side effects from a range of other medications on prior occasions. We speculate that ignorance of the ability to get relief and wariness of medications in general may be prominent reasons that patients go unrecognized and untreated.

For clarity it is useful to emphasize that patients were not instructed to wear SCDs while sleeping. Rather, patients were encouraged to find a time in the afternoon or evening when they could be sedentary and wear the SCD before the usual onset time of their RLS symptoms. In fact, anecdotes from study patients included reports that inadvertent sleep that came while wearing the SCD was often interrupted by the squeezing action of the device on the legs.

One criticism of this study is the small number of patients studied. Additionally, there may be something unique about this small group of patients that makes them different from other sufferers of RLS. Perhaps some selection process such as lack of response to previously tried treatments brought these 10 patients to the study, and this selection process could account for the positive response to SCD therapy. This criticism is valid and justifies a larger study, preferably in a variety of settings, to substantiate these findings. However, while the exclusion criteria were extensive, they would likely apply to any study of expanded proportions. Furthermore, the investigator did not sift through lists of patients to find the 10 included in this report. This group of 10 patients represents very nearly consecutive patients presenting to the Sleep Clinic with the reliable diagnosis of RLS.

The pathophysiology of RLS and more specifically the mechanism of the effectiveness of SCD therapy were not evaluated in this trial. Several theories could be advanced as possible explanations of the efficacy of this treatment: a) release of humoral mediators from the endothelium that provide central feedback to modulate symptoms; b) improvement of local perfusion secondary to improved venous drainage of the limbs with consequent relief of mild, otherwise subclinical ischemia; and c) a temporary decrease in the amount of third space fluid that may enhance lymphatic flow and removal of symptom-causing substances from the lower limbs.

The fact that a relationship to iron or iron metabolism was not seen in this study does not diminish prior reports of a connection between RLS and iron metabolism. Future studies directed at SCD therapy in RLS would benefit from a careful evaluation of the role of iron metabolism in predicting response to therapy or providing a pathophysiologic explanation of the mechanisms involved.

The response to SCD therapy in this group of RLS sufferers is especially hopeful since there appear to be no serious consequences of wearing SCDs, even on a daily basis for up to 3 months. Furthermore, side effects from medications may be precluded if SCD therapy alone is effective. It is also encouraging that SCD therapy is relatively affordable, with cost comparison being favorable to medication. However, before SCD therapy is ready for more widespread use, validating studies in various populations of RLS patients are necessary. If validated in other studies of RLS patients, SCD therapy may soon be considered a useful adjunctive treatment when medications do not resolve the symptoms or when dosages must be reduced due to side effects.

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1. Akyol A, Kiylioglu N, Kadikoylu G, Bolaman AZ, Ozgel N. Iron deficiency anemia and restless legs syndrome: is there an electrophysiological abnormality? Clin Neurol Neurosurg. 2003;106:23-27.
2. Allen RP, Barker PB, Wehrl F, Song HK, Earley CJ. MRI measurement of brain iron in patients with restless legs syndrome. Neurology. 2001;56:263-265.
3. Allen RP, Picchietti D, Hening WA, Trenkwalder C, Walters AS, Montplaisir J. Restless legs syndrome: diagnostic criteria, special considerations, and epidemiology. Sleep Med. 2003;4:101-119.
4. American Academy of Sleep Medicine. The International Classification of Sleep Disorders. Diagnostic and Coding Manual. 2nd ed. Westchester, IL: American Academy of Sleep Medicine; 2005:178-181.
5. Atkinson MJ, Allen RP, DuChane J, Murray C, Kushida C, Roth T. 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.
6. Bogan RK, Fry JM, Schmidt MH, Carson SW, Ritchie SY. 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.
7. Chesson AL Jr, Wise M, Davila D, Johnson S, Littner M, Anderson WM, Hartse K, Rafecas J. 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.
8. Clavadetscher SC, Gugger M, Bassetti CL. Restless legs syndrome: clinical experience with long-term treatment. Sleep Med. 2004;5:495-500.
9. Coleman RM, Bliwise DL, Sajben N, Boomkamp A, de Bruyn LM, Dement WC. Epidemiology of periodic movements during sleep. In: Guilleminault C, Lugaresi E, eds. Sleep/Wake Disorders. Natural History, Epidemiology and Long Term Evolution. New York: Raven Press; 1988:217-229.
10. Connor JR, Wang SX, Patton SM, Menzies SL, Troncoso JC, Earley CJ, Allen RP. Decreased transferrin receptor expression by neuromelanin cells in restless legs syndrome. Neurology. 2004;62:1563-1567.
11. DiMatteo MR. Variations in patients' adherence to medical recommendations: a quantitative review of 50 years of research. Med Care. 2004;42:197-199.
12. Earley CJ. Restless legs syndrome. N Engl J Med. 2003;348:2103-2109.
13. Earley CJ, Heckler D, Allen RP. The treatment of restless legs syndrome with intravenous iron dextran. Sleep Med. 2004;5:231-235.
14. Gamaldo CE, Earley CJ. Restless legs syndrome: a clinical update. Chest. 2006;130:1596-1604.
15. Garcia-Borreguero D, Grunstein R, Sridhar G, Dreykluft T, Montagna P, Dom R, Lainey E, Moorat A, Roberts J. A 52-week open-label study of the long-term safety of ropinirole in patients with restless legs syndrome. Sleep Med. May 17 2007, doi:10.1016/j.sleep.2006.09.009. [epub ahead of print, in press.]
16. Garcia-Borreguero D, Larrosa O, de la Llave Y, Verger K, Masramon X, Hernandez G. Treatment of restless legs syndrome with gabapentin: A double-blind, cross-over study. Neurology. 2002;59:1573-1579.
17. Hening W, Allen R, Earley C, Kushida C, Picchietti D, Silber M. The treatment of restless legs syndrome and periodic limb movement disorder. Sleep. 1999;22:970-999.
18. Ishizu T, Ohyagi Y, Furuya H, Araki T, Tobimatsu S, Yamada T, Kira J. [A patient with restless legs syndrome/periodic limb movement successfully treated by wearing a lumbar corset.] Rinsho Shinkeigaku. 2001;41:438-441.
19. Johns MW. A new method for measuring daytime sleepiness: the Epworth Sleepiness Scale. Sleep. 1991;14:540-545.
20. Mizuno S, Mihara T, Miyaoka T, Inagaki T, Horiguchi J. CSF iron, ferritin and transferrin levels in restless legs syndrome. J Sleep Res. 2005;14:43-47.
21. Montplaisir J, Nicolas A, Godbout R, Walters A. Restless legs syndrome and periodic limb movement disorder. In: Kryger M, Roth T, Dement W, eds. Principles and Practice of Sleep Medicine. 3rd ed. New York: WB Saunders; 2000:742-749.
22. O'Keefe ST, Gavin K, Lavan JN. Iron status and restless legs syndrome in the elderly. Age Ageing. 1994;23:200-203.
23. Silber M, Girish M, Izurieta R. Pramipexole in the management of restless legs syndrome: an extended study. Sleep. 2003;26:819-821.
24. Silber MH, Ehrenberg BL, Allen RP, Buchfuhrer MJ, Earley CJ, Hening WA, Rye DB. An algorithm for the management of restless legs syndrome. Mayo Clin Proc. 2004;79:916-922.
25. Sloand JA, Shelly MA, Feigin A, Bernstein P, Monk RD. 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.
26. Staedt J, Wassmuth F, Ziemann U, Hajak G, Ruether E, Stoppe G. Pergolide: treatment of choice in restless legs syndrome and nocturnal myoclonus syndrome. J Neural Transm. 1997;104:461-468.
27. Stiasny-Kolster K, Benes H, Peglau I, Hornyak M, Holinka B, Wessel K, Emser W, Leroux M, Kohnen R, Oertel WH. Effective cabergoline treatment in idiopathic restless legs syndrome. Neurology. 2004;63:2272-2279.
28. Trenkwalder C, Garcia-Borreguero D, Montagna P, Lainey E, de Weerd AW, Tidswell P, Saletu-Zyhlarz G, Telstad W, Ferini-Strambi L; Therapy with Ropiunirole; Efficacy and Tolerability in RLS 1 Study Group. Ropinirole in the treatment of restless legs syndrome: results from the TREAT RLS 1 study, a 12 week, randomised, placebo controlled study in 10 European countries. J Neurol Neurosurg Psychiatry. 2004;75:92-97.
29. Trenkwalder C, Hundemer HP, Lledo A, Swieca J, Polo O, Wetter TC, Ferini-Strambi L, de Groen H, Quail D, Brandenburg U; PEARLS Study Group. Efficacy of pergolide in treatment of restless legs syndrome: the PEARLS Study. Neurology. 2004;62:1391-1397.
30. Walters AS, LeBrocq C, Dhar A, Hening W, Rosen R, Allen RP, Trenkwalder C; International Restless Legs Syndrome Study Group. Validation of the International Restless Legs Syndrome Study Group rating scale for restless legs syndrome. Sleep Med. 2003;4:121-132.
31. Walters AS, Wagner ML, Hening WA, Grasing K, Mills R, ChokrovertyS, Kavey N. Successful treatment of the idiopathic restless legs syndrome in a randomized double-blind trial of oxycodone versus placebo. Sleep. 1993;16:327-332.
32. Wetter TC, Stiasny K, Winkelmann J, Buhlinger A, Brandenburg U, Penzel T, Medori R, Rubin M, Oertel WH, Trenkwalder C. A randomized controlled study of pergolide in patients with restless legs syndrome. Neurology. 1999;52:944-950.
33. Winkelmann JW, Sethi KD, Kushida CA, Becker PM, Koester J, Cappola JJ, Reess J. Efficacy and safety of pramipexole in restless legs syndrome. Neurology. 2006;67:1034-1039.
34. Zanettini R, Antonini A, Gatto G, Gentile R, Tesei S, Pezzoli G. Valvular heart disease and the use of dopamine agonists for Parkinson's disease. N Engl J Med. 2007;356:39-46.
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