When sleep time isn't paradise - Restless Legs Syndrome

For most of us going to bed signals the end of a busy day and the chance to slip into a blissful period of rest and recovery. For some, however, it signals a period of frustration, pain and intense discomfort because they experience restless legs syndrome. 

What is it?

Restless legs syndrome (RLS) is a neurological and sleep disorder characterised by uncomfortable leg sensations and an irresistible urge to move the legs. Symptoms typically occur in the evening and at night, resulting in sleep disturbances but can also happen during quiet periods during the day. It mostly occurs in the legs, but can also affect the arms. Not only is it disruptive of nighttime sleep, but results in increased daytime sleepiness, impaired work performance, memory, and increased risk for suicide, and medical comorbidities [1-3]. Essentially, a reduction in quality of life and increased risk of mortality. Restless Legs Syndrome affects around 2 - 3% of adults in the US and Europe.

Treatments

First-line treatment for RLS involves the use of dopamine agonists and alpha-2-delta ligands, however around 30% don't achieve an adequate positive effect and 5-20% experience intolerable side effects, or worse still, an increase in symptoms [4]. In an attempt to explore alternative treatments, in 2020, the US Food and Drug Administration granted a Breakthrough Device designation for a therapeutic wearable device that produced increases in tonic muscle activation. With RLS often affecting the posterior leg muscles, the natural action is to dorsiflex the ankle. However, this involves waking up and disrupting the natural sleep cycle. The wearable device utilises a wave pattern/frequency that is proprietary. However, it is essentially causing a submaximal anterior tibial activation by placing electrode pads on either side of the common fibular nerve, just below the head of the fibular. The wave pattern is likely to be low frequency, biphasic and submaximal (see Intervention suggestions below).

Does it Work?

There have been two papers specifically examining the pros and cons of this treatment [5-6]. Both were multicenter, randomised, double-blind, sham-controlled trials in adults with medication-refractory moderate-to-severe primary RLS. Participants of the first study were randomised to treatment or sham for 4 weeks (stage 1), then all progressed into an open-label phase (i.e., knowing that treatment was provided) for 4 weeks (stage 2). The primary outcome was the Clinical Global Impressions-Improvement (CGI-I). After 4 weeks there was a significant improvement for the active versus sham group (45% vs. 16%; Difference = 28%; 95% CI 14% to 43%; p = .00011) and after stage 2 this further increased to 61% for the active group. There were no severe or serious device-related adverse events.

The subsequent study examined longer-term use benefits/harms out to 24 weeks followed by 8 weeks to examine the effect of cessation of treatment. The treatment group was an extension of those from the prior study's active group. CGI-I responder rate improved from 63.6% (95% CI, 49.4 to 77.9%) to 72.7% (95% CI, 58.2 to 83.7%) at week 24 for the treatment group versus 13.6% (95% CI, 7.0 to 24.5%) at week 24 for the control group (p < 0.0001). Again there were no significant adverse events. During the 8 weeks without treatment, in the treatment group (weeks 24-32) the CGI-I decreased from 72.7% to 31.8%, a rate of 5.1% per week but did not return to the prior intervention level.

Intervention Suggestions

While these products are not on the market at present, it would seem there is good merit in exploring this intervention type for clients with RLS who can't tolerate or are refractory to the benefits of first-line drugs. We can utilise our standard TNS or EMS machines, setting parameters appropriately and trialling with clients for effectiveness and comfort [7].

If you are looking for a quick set of parameters, you could try;

• pads: dual small pad placement distal to fibular head on either side of the common fibular nerve
• frequency: 30 - 50 Hz
• waveform: biphasic, 300 - 500μs
• amplitude: submaximal
• duration: start 60-120mins before bed and continue through the night

References

1. Simon GE, VonKorff M. Prevalence, burden, and treatment of insomnia in primary care. Am J Psychiatry. 1997;154(10):1417– 1423. doi: 10.1176/ajp.154.10.1417 4.
2. Sabia S, Fayosse A, Dumurgier J, et al. Association of sleep duration in middle and old age with incidence of dementia. Nat Commun. 2021;12(1):2289. doi: 10.1038/s41467-021-22354-2 5.
3. Pearson VE, Allen RP, Dean T, Gamaldo CE, Lesage SR, Earley CJ. Cognitive deficits associated with restless legs syndrome (RLS). Sleep Med. 2006;7(1):25–30. doi: 10.1016/j.sleep.2005.05.006
4. Winkelman JW. Treating severe refractory and augmented restless legs syndrome. Chest. 2022;162(3):693–700. doi: 10.1016/j. chest.2022.05.014
5. Bogan RK, Roy A, Kram J, et al. Efficacy and safety of tonic motor activation (TOMAC) for medication-refractory restless legs syndrome: a randomized clinical trial. Sleep. 2023;46(10)doi:10.1093/sleep/zsad190
6. Roy A, Ojile J, Kram J, et al. Long-term efficacy and safety of tonic motor activation for treatment of medication-refractory restless legs syndrome: A 24-Week Open-Label Extension Study. Sleep. 2023;46(10)doi:10.1093/sleep/zsad188
7. Nussbaum EL, Houghton P, Anthony J, Rennie S, Shay BL, Hoens AM. Neuromuscular Electrical Stimulation for Treatment of Muscle Impairment: Critical Review and Recommendations for Clinical Practice. Physiother Can. 2017;69(5):1-76. doi:10.3138/ptc.2015-88

These treatments and more are discussed in the sleep mastery course.