Research Review By Dr. Joshua Plener©

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Date Posted:

February 2021

Study Title:

Current Evidence on Diagnostic Criteria, Relevant Outcome Measures, and Efficacy of Nonpharmacologic Therapy in the Management of Restless Legs Syndrome (RLS): A Scoping Review

Authors:

Guay A, Houle M, O’Shaughnessy J & Descarreaux M

Author's Affiliations:

University of Quebec at Trois-Rivieres, Canada

Publication Information:

Journal of Manipulative and Physiological Therapeutics 2020; 43: 930-41.

Background Information:

Restless legs syndrome (RLS), which has an estimated prevalence between 3.9% and 14.3% in the general population (1), is a hyperkinetic movement disorder that can lead to insomnia, impacting one’s sleep and overall quality of life (2, 3). Symptoms of RLS typically include paresthesia and an urge to move their limbs, generally following a circadian pattern (4). Furthermore, the lower limbs are affected to a greater degree, but the upper limbs can be impacted as well. Other symptoms associated with RLS can include mood swings, anxiety and even depression (5). In fact, RLS has been associated with a high risk of self-harm and even suicide.

RLS is classified as primary or secondary RLS. Primary, also termed idiopathic, is diagnosed when RLS is believed to be the primary disease. Currently, the pathophysiology underlying primary RLS is unclear, and this diagnosis is classified under the category of “other specified extrapyramidal and movement disorders” (3). Research investigating the primary etiology of RLS ranges from genetics to cortical-spinal excitability and the dopaminergic system (6). Secondary RLS, also termed acquired, can arise due to pregnancy, renal pathologies or polyneuropathy (7-9). Secondary RLS has been linked to conditions such as diabetes, hypertension, obesity, and metabolic syndrome (10).

Currently, there is no curative treatment available for RLS and treatments are provided to reduce symptoms and improve one’s sleep quality (11). Mild to moderate RLS commonly is managed through lifestyle changes aimed at addressing modifiable risk factors such as obesity, physical activity, and smoking (12). In addition, pharmacological treatments have demonstrated short-term symptom relief, but long-term use may result in worsening side effects, such as around-the-clock restlessness and decreased drug efficacy (13, 14). Pharmacological treatments include dopaminergic agents, as well as anti-epileptic drugs, opioids, and benzodiazepines (15).

Pregnancy is regarded as a common cause of secondary RLS. The prevalence of RLS during pregnancy is 2 to 3 times higher than in the general population and is considered the most common movement disorder during pregnancy (16). Typically, RLS symptoms resolve following delivery, however effective pharmacological treatments during pregnancy are limited due to a lack of good-quality studies (17). Furthermore, the risk-benefit ratio for nonpharmacological treatments such as manual therapy, exercises, and alternative treatments are generally safe during pregnancy (18).

The objective of this scoping review is to synthesize the evidence regarding non-pharmacological approaches used in the management of RLS. Examples of conservative treatments investigated will include exercises, manual therapy, physical therapy devices, and light therapy. To categorize the efficacy of conservative approaches in reducing RLS symptoms, this study sought to identify and summarize the current evidence on diagnostic criteria and relevant outcome measures, informing researchers and guiding clinical practice.

Summary:

Literature Search and Included Studies:
3046 articles were identified from the literature, with 23 articles fulfilling the inclusion criteria.

With respect to the clinical studies, 3 articles investigated exercise interventions, 2 discussed yoga, 1 assessed manual therapies such as massage, 1 assessed acupuncture and 1 assessed traction straight leg raise. Cryotherapy, pneumatic devices, vibrations, transcranial and transcutaneous stimulation, and light therapy were also investigated. Non-RCT studies discussed treatments targeting the hallux pressure, enhanced external counter pulsations, and sensory stimuli.

Methodological Quality:
Out of the 13 included RCTs, the methodological quality was excellent for 6 trials, good for 5, and 2 scored fair on PEDro rating scale. Most studies failed to blind the assessor.

Diagnostic Criteria for RLS:
All clinical trials except two utilized the International Restless Legs Syndrome Study Group diagnostic criteria. Other objective assessment tools used to diagnose RLS in the studies included actigraphy (a non-invasive method of monitoring human rest/activity cycles), blood test, suggested immobilisation test, electromyography, polysomnography, sleep laboratory measurements and electroneurography. To confirm the idiopathic nature of RLS, other tests were performed to exclude possible secondary causes such as an analysis of serum levels for iron.

Outcome Measures:
The patient-reported outcome measure used in all studies (except two) was symptom severity determined by the International RLS Rating Scale which contains 10 items, with each question being rated on a 4-point scale. Mild is classified as 1-10, moderate as 11-20, severe as 21-30 and very severe as 31—40. Eleven other questionnaires assessing quality of life and function of patients with RLS were also reported.

Management of RLS
 
Exercise and Yoga:
Aerobic resistance exercise appears to be effective in improving RLS symptom severity. One study demonstrated a reduction of symptoms when aerobic lower body resistance training was performed 3 times per week, but that study also revealed a ceiling effect at 6 weeks (19). This reduction of treatment efficacy over the course of time mirrors pharmacological treatment interventions. Secondary outcomes such as sleep quality and depression scores also improved with exercise training. Furthermore, stretching exercise and yoga appears to be beneficial for RLS, however, this is based on class 3 evidence and more research is required (20).

Manual Therapy:
Foot reflexology massage 3 times per week for 30-40 minutes appears to be beneficial in reducing RLS symptoms (21). Compared to stretching exercises however, there was no difference in effect (21).

One study assessed standard acupuncture and the results suggest that this intervention is effective in the treatment of RLS (22).

Traction straight leg raise technique consists of stretching the posterior leg and increasing the hip range of motion to influence mobility of the sciatic nerve in the lower extremity. One case series demonstrated a reduction of RLS symptoms with this intervention.

Physical Therapy Devices:
The rationale for cryotherapy is to decrease neuronal activity, however local cryotherapy in one study didn’t lead to clinically relevant improvements. Conversely, whole-body cryotherapy demonstrated improved symptom severity. These studies had short treatment periods and follow-ups, therefore no long-term conclusions can be drawn at this time (23).

Pneumatic compression devices were assessed based on the vascular hypothesis that RLS symptoms can result from a decrease in blood flow which can be relieved by vasodilators. Pneumatic compression devices are applied to the thigh and leg regions, with the goal of stimulating the release of nitric oxide and/or enhancing venous and lymphatic draining. Two studies have demonstrated that this intervention can improve quality of life scores, daytime sleepiness and fatigue (24, 25).

Another treatment intervention based on the vascular hypothesis, which states that vascular disturbances lead to tissue hypoxia, resulting in RLS, is whole body vibration, which is hypothesized to increase skin blood flow. One study found that whole body vibration didn’t normalize skin blood flow in a 2-week clinical trial, but it did lead to clinically significant symptom improvements (26).

Transcranial Stimulation:
Transcranial direct current stimulation can increase or decrease cortical excitability and repetitive transcranial magnetic stimulation induces dopamine release in the basal ganglia. One study which scored excellent for its methodological quality, demonstrated that there was no significant effect of transcranial direct current stimulation compared to sham groups. Another study assessed repetitive transcranial magnetic stimulation and showed statistically significant improvement in symptom severity scores compared to a sham group (27). These stimulations do not induce pain and no side effects were reported in either study.

Transcutaneous Spinal Direct Current Stimulation, Electrical Nerve Stimulation and Sensory Stimuli:
Transcutaneous spinal direct current stimulation works through a reduction of spinal cord excitability (28). In one pilot study, this stimulation showed a clinically significant, short-lasting decrease in the visual analog scale (28). However, a previous review suggested that a prolonged administration of transcutaneous electrical nerve stimulation is less effective due to the development of an analgesic tolerance (29).

Near-Infrared Light:
This treatment is believed to enhance blood circulation through increasing nitric oxide generation, leading to vasodilatation (30). Two RCTs demonstrated that when used 3 times a week for 4 weeks, there was a significant improvement in symptoms lasting at least 4 weeks post-treatment (30, 31). This treatment doesn’t result in any pain, but adverse skin reactions may occur at the treatment site.

Clinical Application & Conclusions:

This scoping review demonstrated that based on the current evidence, nonpharmacological options appear to reduce RLS symptom severity with no adverse effects. However, most alternative treatment interventions have limited evidence and we simply need more work in this area, including the potential for chiropractic care to influence this condition.

Exercise demonstrated promising results through 3 good quality RCTs, but evidence regarding manual therapy modalities such as massage, acupuncture and traction straight leg raise is less conclusive. Overall, larger scale studies are needed to assess the long-term effects of these interventions. Whole body cryotherapy and vibration appear to be beneficial but, long term efficacy cannot be established as more studies are required. The current evidence demonstrates that pneumatic compression devices may be effective in reducing RLS symptom severity but there are challenges to this intervention such as the length of time patients need to remain immobile during treatment (up to 1 hour per day). Transcranial and transcutaneous stimulation are non-invasive and painless, but larger studies are needed. Furthermore, near-infrared light therapy appears to reduce RLS symptom severity.

The primary outcome assessment tool in studies is the International RLS Rating Scale which assesses symptom severity. As well, quality of life and sleep are common secondary outcome measures.

Other reviews on RLS demonstrate similar results to this scoping review that non-drug related treatments yield fewer side effects, fewer symptom increases and lower costs (32). For example, a previous review on RLS during pregnancy revealed beneficial treatment outcomes with leg stretching before sleep, massage of the legs and pneumatic compression devices (33).

Study Methods:

As a result of the broad research question, a scoping review was the most appropriate methodology. This scoping review was conducted with a 5-step process based on a pre-existing framework (34).

For this review, the following question was answered: What is the current evidence regarding the diagnostic criteria, efficacy of nonpharmacological intervention and relevant outcome measures in the management of RLS?

Five electronic databases were searched using the MeSH term “Restless Legs Syndrome” and relevant key words such as Restless Legs Syndrome, RLS, and Willis-Ekbom disease: National Centre for Biotechnology Information (NCBI); EBSCO; The Manual and Alternative and Natural Therapy Index System (MANTIS); the Cumulative Index to Nursing & Allied Health Literature (CINAHL); and Scopus. All databases were searched from inception to July 2017.

Of the articles meeting the inclusion criteria, two reviewers extracted, screened and reviewed independently the title and abstract with a third reviewer used to resolve any disagreements. To be included in this scoping review, studies had to have an “alternative therapy” category. Randomized and non-randomized clinical trials, observational studies, case series, scoping reviews, systematic reviews, and guidelines were included in this review.

Excluded articles:
Editorials, pictorials, letters, comments, erratum, or other articles that were less than a page in length such as summaries or responses to the author(s). Articles that didn’t discuss RLS properly such as articles dedicated to insomnia or periodic limb movement disorder were also excluded.

Data Extraction:
Data was extracted by the lead author and double-checked by a research assistant. The lead author reviewed all full text articles evaluating exercises, manual therapy, and alternative treatment for idiopathic RLS and RLS during pregnancy. Study design, intervention, duration of study, group allocation, primary outcome measures, secondary outcome measures, and diagnostic criteria were extracted from each article.

Quality Assessment:
The Physiotherapy Evidence Database (PEDro) scale was used to rate the methodological quality of the included randomized clinical trials. PEDro is an 11-item tool to assess criteria relevant to internal validity in addition to statistical reporting or the size of the treatment effect. Criteria in the tool includes random allocation, concealment of allocation, comparability of groups at the baseline, blinding of patients, therapists, and assessor, analysis by intention to treatment, and adequacy of the follow-up. The 2 included systematic reviews were rated using the SIGN checklist which is a 14-item tool. Nonrandomized clinical trials, literature reviews, and clinical practice guidelines were not formally rated for quality.

Study Strengths / Weaknesses:

Strengths:
  • The PEDro scale was used, which is an efficient tool to categorize the quality of the evidence.
  • This scoping review assessed a broad range of literature in order to find relevant studies. Even though non-RCTs were included, this broader inclusion strategy allowed for further evaluation of modalities such as yoga, traction straight leg raise and whole-body vibration.
Weaknesses:
  • The studies included generally had small sample sizes.
  • The studies were heterogenous, which weakens the overall evidence quality and generalizability of the results.
  • Many included studies had participants taking ongoing medication, which could have interfered with treatment effects of the interventions under study.
  • A scoping review was the most appropriate methodology for this study, but it does not employ the same methodological rigour as a systematic review.

Additional References:

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