Investigating the Effect of Temperature Therapy on the Severity of Restless Legs Syndrome: Systematic Review and Meta-Analysis

Mohammad Mehdi MOHAMMADI; Ali Akbar VAISI RAYGANI

doi:10.3121/cmr.2023.1824

Abstract

Background: Restless legs syndrome (RLS) is a sensorimotor disorder leading to disturbance of resting, discomfort, stress, and impaired daytime activity in the sufferers. The present systematic review and meta-analysis was conducted to determine the effect of temperature therapy on the severity of RLS.

Methods: The electronic databases of Google Scholar, ProQuest, Scopus, PubMed, Web of Science, and State Inpatient Databases (SID) were searched from inception to August 2022. The Cochrane Collaboration’s Risk of Bias Tool was used to check the quality of included studies. Meta-analysis was performed by calculating standardized mean differences (SMDs), using random effects model, and running Comprehensive Meta-Analysis (CMA) software version 2.

Results: The included studies (n=6) comprised 177 participants, whose mean age was 49.85 years old. The results of the meta-analysis showed temperature therapy could reduce the severity of RLS (SMD=−1.520, 95% CI: −2.122 to −0.918). Regarding the source of heterogeneity, meta-regression results indicated the efficacy of the intervention in reducing the severity of RLS enhanced significantly by increasing the duration of the intervention in each session (β=−0.039, 95% CI −0.076 to −0.002, P<0.001). The results also showed increasing the duration (β=−0.039, 95% CI −0.076 to −0.002, P<0.001) and the temperature of the intervention in each session (β=−0.016, 95% CI −0.028 to −0.003, P<0.05) significantly enhanced the efficacy of the intervention in reducing the severity of RLS. The results also indicated that, among patients with underlying clinical conditions, the effectiveness of temperature therapy was higher in hemodialysis patients (β=−2.006, 95% CI −2.736 to −1.276, P<0.05).

Conclusion: The present study findings suggested temperature therapy could mildly reduce the severity of RLS symptoms. It was also found that the highest efficacy of this intervention could be achieved when the higher temperature was used in fewer treatment sessions in hemodialysis patients. Based on our findings, this intervention can be included in the care plan of patients with RLS considering the settings described to achieve the highest efficacy.

Keywords:

Restless legs syndrome (RLS) is a sensorimotor disorder manifested as a strong urge to move the legs. RLS can be associated with discomfort, pain, tingling, and numbness in the legs. This syndrome becomes more severe at rest and inactivity, but its symptoms are relieved by activity.^1,2 In 1945, Karl Ekbom introduced the term “RLS” into the medical literature. However, Thomas Willis had described its symptoms many years before.³ The prevalence of RLS in the general population has been estimated to vary between 2% and 20%.^4,5 The syndrome symptoms are mainly worsened at rest and relieved by movement of the end organs, especially the legs.⁶ In addition to the unpleasant feeling associated with RLS, this syndrome is the etiology of other disorders such as depression, loss of sleep, reduced quality of life, exhaustion during the day, weak physical functioning, impaired daily function, daytime over-drowsiness, stress, and anxiety.^7-9 Alternately, recent studies suggest that RLS is associated with the risk of cardiovascular diseases, musculoskeletal pain, osteoporosis, and ultimately increased mortality in hemodialysis patients.^10-14 Regarding RLS treatment, two therapeutic approaches can be suggested including pharmacological and non-pharmacological therapies.² Common pharmacological agents for the treatment of RLS include levodopa, opioids, anticoagulants, benzodiazepines, and drugs such as clonidine.¹⁵ However, long-term use of drugs such as dopamine agonists can lead to increase and worsening of RLS, and patients can develop tolerance to the drug. These drugs can also induce side effects such as sleepiness, disruption in blood pressure regulation, reversal of symptoms, exacerbation of RLS symptoms in the morning, increased syndrome severity compared with before treatment initiation, early initiation of RLS at night, and spreading of symptoms to the arms.^16,17 Non-pharmacological approaches often have less complications than pharmacological ones and are commonly recommended.¹⁸ One of the non-pharmacological interventions is temperature therapy. Temperature therapy involves the application of heat or cold to change the temperature of the skin and soft tissue. The application of heat is a common treatment for musculoskeletal pains. During this therapy, blood flow increases following the increase of cutaneous temperature, providing more nutrition and oxygen to the cells. Applying cold exposure increases leukocytes and decreases histamine concentration. Therefore, it can strengthen the immune system. It has been shown that body temperature-lowering techniques can have antioxidant effects on multiple sclerosis patients. Other studies also have shown this treatment can increase plasma norepinephrine, resulting in increased release of neurotransmitters.¹⁹ Over the years, nurses have had a long-standing relationship with temperature therapy. According to Nasiriani, nurses have traditionally used heat and cold therapies to relieve diseases, but it is necessary to prove the effectiveness of these interventions using valid scientific evidence.²⁰ Recent studies have reported findings regarding the effectiveness of temperature therapy on the severity of RLS. However, a clear result about the effect of this intervention on the severity of RLS has not been reported so far. In this regard, the present systematic review and meta-analysis was attempted to combine the results of clinical trial studies and thereby publish a robust result for healthcare providers. Considering that so far no systematic review and meta-analysis has been done in this field, the present study was conducted with the aim of determining the effect of temperature therapy on the severity of RLS.

Material and Methods

Search Strategy

This research was implemented based on the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement.²¹ Initially, the following electronic databases were searched from inception to August 2022: Google Scholar, ProQuest, Scopus, PubMed, Web of Science, and State Inpatient Databases (SID). To find related studies, the reference lists of the extracted studies were also searched manually. In addition, clinical trials registered in databases of the Japan Primary Registries Network (JPRN), European Union Registry (EUCR), ClinicalTrials.gov, Cochrane Library, ISRCTN (International Standard Randomised Controlled Trial Number), Australia and New Zealand Clinical Trials Registry (ANZCTR), and Iranian Registry of Clinical Trials (IRCT) were searched. After finding any clinical trial in the aforementioned databases, it was first checked whether the article related to a clinical trial that had been published or not. If the article was not published, we contacted the corresponding author via e-mail to obtain the required information. All searches were conducted in Persian and English using the following keywords: (“temperature” OR “cold wrap” OR “water bottles” OR “Cryotherapy” OR “thermotherapy” OR “cold pack” OR “cold poultices” OR “heat lamp” OR “heat pack” OR “electric heat pads” OR “hydrotherapy” OR “cold water baths” OR “hot water baths” OR “stream” OR “heat wrap” OR “hot poultices” OR “sauna” OR “temperature therapy”) AND (“restless legs syndrome” OR “Willis-Ekbom Syndrome” OR “Willis-Ekbom disease” OR “RLS”).

For this purpose, the intervention and outcome keywords were combined. In other words, keywords based on MeSH and free-text terms were selected for intervention (temperature therapy) and outcome (RLS severity). See Appendix 1 (available online) for more details on the search strategy.

Exclusion and Inclusion Criteria

The inclusion criteria were as follows:

Type of study: clinical trials and semi-experimental studies.
Study population: patients with RLS who met the following four criteria: 1) repeated movement of the legs along with an unpleasant feeling in the legs, 2) temporary relief of unpleasant symptoms by moving the legs, 3) onset or exacerbation of symptoms at rest or inactivity of legs, and 4) onset or exacerbation of symptoms in the evening or at night.
Intervention: Using temperature therapy as an intervention during which a temperature between −100 °C and +100 °C is used locally. temperature therapy used in the following way: “hot or cold water bottles”, “heat or cold pack (grain)”, “electric heat pads”, “heat or cold wrap (wearable)”, “stream/sauna”, “hot or cold stone therapy”, “hot or cold poultices”, “hot or cold water baths”, “hydrotherapy”, and “heat lamp”.
Outcome: Studies reported the severity of RLS quantitatively as an outcome.

Exclusion criteria included non-human studies and those that combined temperature therapy with other effective interventions to treat RLS.

Selection of Studies

To search each of the databases, first the search strategy was defined for each database. Then, theses and dissertations, registered clinical trials, conference proceedings, and bibliography or reference lists were evaluated. After that, duplicates were removed manually and by using Endnote software. The remaining studies entered the initial screening stage. To do an initial screening, the title and abstract of each study were evaluated to check its eligibility for inclusion in the study. Then, we entered the secondary screening stage. For this purpose, the full text of the selected articles was reviewed, and eligible ones were chosen. All the searches were done by two researchers independently. In case of disagreement, the third researcher was consulted to resolve disagreements.

Evaluating the Quality of Articles

The quality of the studies was assessed using the Cochrane Collaboration’s Risk of Bias Tool.²² To do this, two independent researchers rated the risk of bias as ‘low risk’, ‘high risk’, or ‘unclear risk’ (Table 1). Random sequence generation was done in two studies using computer, through which a randomization list was developed.^23,24 In another study, randomized block design was used.²⁵ In three studies, this item was not clearly reported.^19,20,26 Allocation concealment was done in one study by using sealed envelopes.²⁴ In this regard, one of the studies used central randomization.²⁵ In other studies, there was no clear report about allocation concealment.^19,20,23,26 In addition, blinding was clearly reported only in one study.²⁴ Moreover, in all extracted studies, there was no incomplete outcome data due to reporting the number, nature, and management of incomplete outcome data.^19,20,23-26 Other information is reported in Table 1.

View this table:

Table 1.

Risk of bias in included studies

Data Extraction

Data extraction was done by two researchers independently. In this regard, a data extraction form was used, which included information about the name of the country, year of publication, author’s name, study design, duration of intervention, the temperature of intervention, sample size, study population, duration of intervention, participants’ age, comparison group, the study tool, and the measured outcome.

Data Analysis

Meta-analysis in this research was done by using comprehensive meta-analysis software (CMA, Version 2.0, New England, NJ, USA). For this purpose, the effect size was calculated based on the standardized mean difference and considering 95% confidence interval. The calculations were based on the random-effects model. Heterogeneity analysis of studies was done using I² value. To find the source of heterogeneity, subgroup analysis, and meta-regression were performed. To do so, the included studies were assigned to subgroups based on the type of study design, country, underlying medical conditions, and comparison group. To perform meta-regression, the participant’s age, the year of publication, duration of the intervention, the number of treatment sessions, and the temperature of the intervention (in °C) were considered as moderators. There were no false reports in the included studies regarding pre-post correlation or standard deviation of changes (SD_change). Therefore, the pre-post correlation was calculated based on sensitivity measures. To do so, meta-analysis was run separately with 0, 0.5, and 0.99 correlations, and in all cases, the overall result of the calculations was estimated to be the same. Therefore, the researchers finally estimated the pre-post correlation at 0.5. The publication bias was also investigated using the funnel plot and Egger’s test. In this study, sensitivity analysis was performed to check the robustness of the study results.

Results

Study Selection

In the process of selecting studies, 445 studies were initially found by searching electronic databases. In addition to electronic databases, other sources, including theses and dissertations, registered clinical trials, conference proceedings, and bibliographies or reference lists were searched. Accordingly, eight studies were found. Five studies were found by a manual search of reference lists, and three studies were found in the clinical trial registration databases. After removing duplicate studies (141 studies), 312 studies remained. In the next step, primary screening of the studies was done. For this purpose, the titles and abstracts were examined to identify potentially relevant studies (24 studies). Then, secondary screening was conducted by examining the full text of retrieved studies. In this step, six studies were considered eligible, and 18 studies were excluded (Appendix 2; available online). Accordingly, the present study was conducted on six studies by performing qualitative and quantitative analysis (Figure 1).

Figure 1.

PRISMA flow diagram of the study

Study Characteristics

The included studies comprised six studies, three of which were clinical trials,^23-25 and the other three were semi-experimental.^19,20,26 The publication dates for the studies were between 2016 and 2022. The total samples of these studies were 177 individuals, whose mean age was 49.85 years. The studies were done in Iran,^19,20,26 the United States,²⁵ Turkey,²³ and Germany.²⁴ Five studies were published in the English language,^19,23-26 and one was published in the Persian language²⁰ (Table 2).

View this table:

Table 2.

Characteristics of included studies

The Effect of Temperature Therapy on the Severity of RLS

In the present study, the results of the meta-analysis indicated that temperature therapy reduced the severity of RLS (SMD = −1.520, 95%CI: −2.122 to −0.918). However, Park et al.²⁵ reported no significant association in this regard (SMD = −0.277, 95%CI: −1.373 to 0.818) (Figure 2). In addition, the results revealed the heterogeneity of the included studies (I² = 80.55%, P < 0.001).

Figure 2.

Effect of temperature therapy on RLS severity

Investigating the Source of Heterogeneity

Subgroup analysis and meta-regression were used in this study to explore the source of heterogeneity. The results of the subgroup analysis showed the source of heterogeneity was not the type of study design, country, and comparison group. Subgroup analysis based on the participants’ underlying clinical conditions, including pregnancy, hemodialysis, and without specific clinical conditions, revealed studies with a hemodialysis population (I2=68.76%, P = 0.074) and without the underlying disease (I2=0%, P = 0.552) were not heterogeneous. However, in studies where the study population was pregnant, there was significant heterogeneity (I²=83.03%, P = 0.015) (Figure 3). Moreover, the results indicated that among underlying clinical conditions, the effectiveness of temperature therapy was higher in hemodialysis patients than in other groups (β = −2.006, 95% CI −2.736 to −1.276, P < 0.05).

Figure 3.

Subgroup analysis based on underlying clinical conditions

In the present study, the meta-regression results demonstrated the efficacy of the intervention in reducing the severity of RLS decreased with the increase in the number of temperature therapy sessions (β = 0.122, 95% CI 0.054 to 0.189, P < 0.001) (Figure 4). Accordingly, it was found the greatest effectiveness occurred when the number of intervention sessions was eight.

Figure 4.

Meta-regression based on the number of temperature therapy sessions

Alternately, meta-regression results also indicated the efficacy of the intervention in reducing the severity of RLS enhanced significantly by increasing the duration of the intervention in each session, (β =−0.039, 95% CI −0.076 to −0.002, P < 0.001). (Figure 5). Hence, it was found the greatest effectiveness occurred when the duration of the intervention in each session was 20 minutes.

Figure 5.

Meta-regression based on the duration of intervention in each session

The meta-regression results also revealed that the efficacy of the intervention in reducing the severity of RLS improved when the temperature of intervention was increased (β =−0.016, 95% CI −0.028 to −0.003, P < 0.05) (Figure 6). It was found the greatest effective intervention occurred at temperatures of 38.5 and 41.5 °C. However, based on meta-regression, the publication years of the studies and the participants’ age were not able to significantly explain the heterogeneity between the studies.

Figure 6.

Meta-regression based on the temperature of intervention

Publication Bias

In the present study, to identify potential publication bias, the funnel plot was first visually checked, suggesting the absence of bias in the publication (Figure 7). Similarly, the results of Egger’s test revealed no publication bias (Egger’s test, P = 0.917).

Figure 7.

Publication bias

Sensitivity Analysis

To verify the robustness of the results, sensitivity analysis was used. For this purpose, the robust estimate of the overall effect size in the meta-analysis was done by removing each of the studies from the analysis. The sensitivity analysis results revealed that the exclusion of each study did not have a significant effect on the overall results (Figure 8).

Figure 8.

Exploring the robustness of the results based on sensitivity analysis

Discussion

The present study showed temperature therapy reduced the severity of RLS symptoms in the sufferers. However, desired changes should also be discussed from a clinical significance point of view. In this study, the severity of RLS decreased by 1.5 points. Based on Mitchell and Hilton’s study, this change in the severity of RLS symptoms was categorized as mild.²⁷ However, the cost-effectiveness of this method can be a starting point for its use in the future. Furthermore, in this study, findings showed this method can be used in a way that induces maximum effectiveness. For instance, the present study showed the efficacy of temperature therapy in reducing the symptoms of the syndrome enhanced when the temperature was increased. This finding can be justified by the fact that the increase in the temperature can lead to improved blood supply and nutrition in the feet cells. In other words, based on the findings of the present study, applying warm packs with a temperature equivalent to 38.5 to 41.5 °C, compared to other temperatures on the RLS patient’s foot led to greater efficacy of the intervention. Many other interventions that have been used to relieve RLS symptoms are also based on this mechanism (increasing limb blood flow). For instance, Guffey et al.,² in their study, emphasized the use of infrared light therapy in the leg area released nitrous oxide from the endothelium of the vessels, thus improving the blood supply to the leg and relieving the symptoms of RLS. In another study, Hosseini et al.²⁸ showed vibration was able to reduce the severity of RLS by increasing blood flow.

We also found that efficacy of the intervention did not enhance by increasing the number of treatment sessions, while the increased duration of the intervention in each session led to the highest efficacy. According to our findings, the ideal number of sessions to obtain greater effectiveness was eight sessions, and the ideal duration of intervention in each session was 20 minutes.

Moreover, it was revealed there was homogeneity in the studies where the participants were treated with hemodialysis. This homogeneity was also present in studies done on participants without an underlying disease. The findings of the present suggested RLS in hemodialysis patients probably had characteristics that may affect the effectiveness of temperature therapy. The efficacy of temperature therapy in reducing the severity of RLS symptoms was higher in hemodialysis patients compared to patients with other underlying clinical conditions. However, the justification of this issue requires further studies clarifying the pathophysiology of RLS based on hemodialysis. In justifying the occurrence of RLS in hemodialysis patients, de Menezes et al.²⁹ concluded the pathophysiology of RLS occurrence in patients with kidney disease had not yet been well established. Researchers have proposed several risk factors, but the reported results are contradictory.³⁰ For instance, some researchers have stated the dialysis modality does not seem to interfere with the pathophysiology and occurrence of this syndrome.³¹ However, recent studies report conflicting results, and there is still no clear consensus in this regard.^32,33 Fortunately, there was no publication bias in the present study, and the robustness of the results was reported based on sensitivity analysis. This means each study alone was not able to change the overall results, and the significance of the overall result had not been affected by the results of one study.

Temperature therapy, encompassing both thermotherapy and cryotherapy, may exert its effects on RLS symptoms through several mechanisms.²⁹ Thermotherapy can induce muscle relaxation, improve local circulation, and alter the transmission of pain signals, which may alleviate the discomfort associated with RLS.²⁸ Cryotherapy, by reducing inflammation and nerve conduction velocity, may also provide symptomatic relief.² The application of temperature therapy may influence the sensory pathways that are implicated in RLS, potentially modulating the abnormal sensations that drive the urge to move the legs.¹⁹ It is also worth considering that the sensory experience of RLS varies among individuals. Some patients may describe it as a creeping sensation that is relieved by movement, while others may experience it as an aching or throbbing pain.^28,32 The subjective nature of these symptoms could influence the perceived efficacy of temperature therapy, as the modality may be more effective in alleviating certain types of discomfort over others.

One of the limitations of the study was related to the small number of included studies. It is suggested to do further original studies in this field to elucidate the effect of temperature therapy on the severity of RLS symptoms.

Conclusion

The present study findings suggested temperature therapy could mildly reduce the severity of RLS symptoms. It was also found that the highest efficacy of this intervention could be achieved when the temperature was 38.5 or 41.5 °C, there were eight treatment sessions (each session lasted 20 minutes), and it was performed in hemodialysis patients. Based on our findings, this intervention can be included in the care plan of patients with RLS by nurses and other treatment personnel, considering the settings described to achieve the highest efficacy.

Authors’ Contributions

MMM, and AVR conceptualized, analyzed, and interpreted the data, and drafted the manuscript. MMM designed the study and participated in the analysis and interpretation of data. MMM and AVR coordinated the study, revised the manuscript, edited and approved the final version to be submitted for publication, and helped in the analysis and interpretation of data. All authors read and approved the final manuscript. Any disagreement between the two researchers (MMM and AVR) in the process of selecting studies were resolved by a researcher named HS (His full name is mentioned in the acknowledgment section); However, only in a few limited cases, differences arose between MMM and AVR.

Acknowledgments

We are extremely grateful to Dr. Habib Shareinia for his guidance in selecting studies.

Footnotes

Disclosures: The authors declare that they have no competing interests and that this research did not receive any specific grant from funding agencies. The datasets used during the current study are available from the corresponding author upon reasonable request.

Received January 1, 2023.
Revision received November 10, 2023.
Accepted December 11, 2023.

References

1.
↵
Perez-Diaz H, Iranzo A, Rye DB, Santamaria J. Restless abdomen: a phenotypic variant of restless legs syndrome. Neurology. 2011;77(13):1283-6. doi:10.1212/WNL.0b013e318230207a
Google Scholar CrossRef PubMed
2.
↵
Guffey JS, Motts S, Barymon D, Using near infrared light to manage symptoms associated with restless legs syndrome. Physiother Theory Pract. 2016;32(1):34-44. doi:10.3109/09593985.2015.1087613.
Google Scholar CrossRef
3.
↵
Einollahi B, Izadianmehr N. Restless leg syndrome: a neglected diagnosis. Nephrourol Mon. 2014;6(5):e22009. doi:10.5812/numonthly.22009.
Google Scholar CrossRef
4.
↵
Bidaki R, Dabestani-Tafti T, Mirhosseni H, Amiri-Hosseini M, Pourrashidi-Boshrabadi A, Arab-Baniasad F. Prevalence of Restless Leg Syndrome and Related Factors in Patients under Chronic Hemodialysis. Zahedan Journal of Research in Medical Sciences. 2014;16(9):95-97.
Google Scholar
5.
↵
Cirillo DJ, Wallace RB. Restless legs syndrome and functional limitations among American elders in the Health and Retirement Study. BMC Geriatr. 2012;12(1):39. doi:10.1186/1471-2318-12-39.
Google Scholar CrossRef PubMed
6.
↵
Stefanidis I, Vainas A, Giannaki CD, Restless legs syndrome does not affect 3-year mortality in hemodialysis patients. Sleep Med. 2015;16(9):1131-1138. doi:10.1016/j.sleep.2015.04.023.
Google Scholar CrossRef
7.
↵
Naini AE, Masoumi M, Mortazavi M, Gholamrezaei A, Amra B. Restless legs syndrome in patients on maintenance hemodialysis and peritoneal dialysis. Journal of research in Medical Sciences. 2012;17(2):264-271.
Google Scholar
8.
Gade K, Blaschke S, Rodenbeck A, Becker A, Anderson-Schmidt H, Cohrs S. Uremic restless legs syndrome (RLS) and sleep quality in patients with end-stage renal disease on hemodialysis: potential role of homocysteine and parathyroid hormone. Kidney Blood Press Res. 2013;37(4-5):458-463. doi:10.1159/000355727.
Google Scholar CrossRef
9.
↵
Goffredo Filho GS, Gorini CC, Purysko AS, Silva HC, Elias IEF. Restless legs syndrome in patients on chronic hemodialysis in a Brazilian city: frequency, biochemical findings and comorbidities. Arq Neuropsiquiatr. 2003;61(3B)(3b):723-727. doi:10.1590/S0004-282X2003000500004.
Google Scholar CrossRef PubMed
10.
↵
Rodrigues RN, Rodrigues AA, Corso JT, Peixoto TF. Restless legs syndrome associated with cardiac failure and aggravated after valvular replacement: Vesper’s curse? Arq Neuropsiquiatr. 2008;66(3A):539-541. doi:10.1590/S0004-282X2008000400019.
Google Scholar CrossRef PubMed
11.
Winter AC, Berger K, Glynn RJ, Buring JE, Gaziano JM, Schurks M, Vascular risk factors, cardiovascular disease, and restless legs syndrome in men. Am J Med. 2013;126(3):228-35, 35.e1-2. doi:10.1016/j.amjmed.2012.06.039
Google Scholar CrossRef
12.
Hershey LA. Do women with restless legs syndrome have less bone loss? Neurology. 2016;86(13):e144-e146. doi:10.1212/WNL.0000000000002580.
Google Scholar CrossRef Abstract/Full Text PubMed
13.
Hoogwout SJ, Paananen MV, Smith AJ, Musculoskeletal pain is associated with restless legs syndrome in young adults. BMC Musculoskelet Disord. 2015;16:294. Published 2015 Oct 14. doi:10.1186/s12891-015-0765-1
Google Scholar CrossRef
14.
↵
Sahli ZT, Jo J, Mousa SA, Tarazi FI. Clinical management of restless legs syndrome in end-stage renal disease patients. CNS Spectr. 2017;22(1):14-21. doi:10.1017/S109285291600064X
Google Scholar CrossRef PubMed
15.
↵
Aurora RN, Kristo DA, Bista SR, The treatment of restless legs syndrome and periodic limb movement disorder in adults--an update for 2012: practice parameters with an evidence-based systematic review and meta-analyses: an American Academy of Sleep Medicine Clinical Practice Guideline. Sleep. 2012;35(8):1039-1062. doi:10.5665/sleep.1988
Google Scholar CrossRef PubMed Web of Science
16.
↵
Winkelman JW, Johnston L. Augmentation and tolerance with long-term pramipexole treatment of restless legs syndrome (RLS). Sleep Med. 2004;5(1):9-14. doi:10.1016/j.sleep.2003.07.005
Google Scholar CrossRef PubMed
17.
↵
Ferini-Strambi L, Aarskog D, Partinen M, Effect of pramipexole on RLS symptoms and sleep: a randomized, double-blind, placebo-controlled trial. Sleep Med. 2008;9(8):874-881. doi:10.1016/j.sleep.2008.09.001
Google Scholar CrossRef PubMed Web of Science
18.
↵
Mitchell UH. Use of near-infrared light to reduce symptoms associated with restless legs syndrome in a woman: a case report. J Med Case Rep. 2010;4:286. Published 2010 Aug 23. doi:10.1186/1752-1947-4-286
Google Scholar CrossRef
19.
↵
Jafarimanesh H, Vakilian K, Mobasseri S. Thermo-therapy and cryotherapy to decrease the symptoms of restless leg syndrome during the pregnancy: A randomized clinical trial. Complement Ther Med. 2020;50:102409. doi:10.1016/j.ctim.2020.102409
Google Scholar CrossRef
20.
↵
Nasiriani K, Eftekhari A. Effect of Hot Water Bag on Severity of Restless Legs Syndrome in Hemodialysis Patients. Majallah-i Danishgah-i Ulum-i Pizishki-i Mazandaran. [Journal of Mazandaran University of Medical Sciences] 2016;26(142):23-30.
Google Scholar
21.
↵
Liberati A, Altman DG, Tetzlaff J, The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ. 2009;339:b2700. doi:10.1136/bmj.b2700
Google Scholar CrossRef Abstract/Full Text PubMed
22.
↵
Higgins JP, Altman DG, Gøtzsche PC, The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ. 2011;343:d5928. doi:10.1136/bmj.d5928
Google Scholar CrossRef Full Text PubMed
23.
↵
Kaplan ö, Başer M, Müderris İ. The effect of hot water application in pregnant women with restless legs syndrome: A randomised controlled study. Authorea. Preprint (not peer reviewed); 2021. DOI: 10.22541/au.162935801.10999591/v1
Google Scholar CrossRef
24.
↵
Happe S, Evers S, Thiedemann C, Bunten S, Siegert R. Whole body and local cryotherapy in restless legs syndrome: A randomized, single-blind, controlled parallel group pilot study. J Neurol Sci. 2016;370:7-12. doi:10.1016/j.jns.2016.09.006
Google Scholar CrossRef
25.
↵
Park A, Ambrogi K, Hade EM. Randomized pilot trial for the efficacy of the MMF07 foot massager and heat therapy for restless legs syndrome. PLoS One. 2020;15(4):e0230951. doi:10.1371/journal.pone.0230951
Google Scholar CrossRef
26.
↵
Eftekhari A, Nasiriani K, Baghian N. Investigating the Effect of Cold Water Bags on the Severity of Restless Leg Syndrome and Sleep Quality in Hemodialysis Patients. Nephro-Urology Monthly. 2021;In press. doi:10.5812/numonthly.119463.
Google Scholar CrossRef
27.
↵
Mitchell U, Hilton S. Change of international Restless Legs Syndrome Study group Rating Scale subscales with treatment and placebo: a pilot study. Research and Reviews in Parkinsonism. 2014;4:27-33. doi:10.2147/JPRLS.S53015.
Google Scholar CrossRef
28.
↵
Hosseini H, Kazemi M, Azimpour S. The effect of vibration on the severity of restless legs syndrome in hemodialysis patients. J Renal Inj Prev. 2016;6(2):113-116. Published 2016 Nov 21. doi:10.15171/jrip.2017.22
Google Scholar CrossRef
29.
↵
de Menezes AF, Motta DRMS, de Carvalho FO, Restless Legs Syndrome in Dialysis Patients: Does the Dialysis Modality Influence Its Occurrence and Severity?. Int J Nephrol. 2018;2018:1414568. doi:10.1155/2018/1414568
Google Scholar CrossRef
30.
↵
Kavanagh D, Siddiqui S, Geddes CC. Restless legs syndrome in patients on dialysis. Am J Kidney Dis. 2004;43(5):763-771. doi:10.1053/j.ajkd.2004.01.007
Google Scholar CrossRef PubMed Web of Science
31.
↵
Janzen L, Rich JA, Vercaigne LM. An overview of levodopa in the management of restless legs syndrome in a dialysis population: pharmacokinetics, clinical trials, and complications of therapy. Ann Pharmacother. 1999;33(1):86-92. doi:10.1345/aph.18024
Google Scholar CrossRef PubMed
32.
↵
Merlino G, Lorenzut S, Romano G, Restless legs syndrome in dialysis patients: a comparison between hemodialysis and continuous ambulatory peritoneal dialysis. Neurol Sci. 2012;33(6):1311-1318. doi:10.1007/s10072-012-0953-9
Google Scholar CrossRef PubMed
33.
↵
Al-Jahdali H. A comparison of sleep disturbances and sleep apnea in patients on hemodialysis and chronic peritoneal dialysis. Saudi J Kidney Dis Transpl. 2011;22(5):922-930.
Google Scholar PubMed

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Investigating the Effect of Temperature Therapy on the Severity of Restless Legs Syndrome: Systematic Review and Meta-Analysis

Abstract