A meta-analysis identifies a potential polysomnographic signal of RLS more sensitive and specific than the PLMS index.

Interview by Alyx Arnett

A new meta-analysis refines the understanding of polysomnographic differences between individuals with idiopathic restless legs syndrome (RLS) and healthy controls. 

The study also clarifies specific characteristics of leg movements in RLS, potentially distinguishing them from periodic limb movements of sleep (PLMS) seen in people with narcolepsy or REM sleep behavior disorder, and suggests a more sensitive, specific marker of RLS than the PLMS index.

“The meta-analysis allowed us to state with much more confidence the exact polysomnographic changes associated with RLS,” says meta-analysis investigator Michael V. Vitiello, PhD.

By comparing polysomnographic data between individuals with RLS and control subjects in 31 studies, Vitello and co-investigators uncovered abnormalities—including lighter sleep, increased sleep fragmentation, and more significant sleep-related breathing disruption and limb movements—in people with RLS. 

The meta-analysis also found that PLMS in RLS are concentrated in non-REM sleep. In contrast, PLMS in REM sleep behavior disorder and narcolepsy are concentrated in REM sleep—which may be because of an impaired mechanism responsible for motor inhibition during REM sleep in the latter sleep disorders. So a periodicity index may be a more sensitive and specific marker of RLS than the more general PLMS index.

The research opens up potential avenues for improved diagnostic methods and tailored treatment approaches and emphasizes the critical role of sleep evaluation in understanding the complex pathophysiology of RLS. 

Vitiello, professor emeritus of psychiatry and behavioral sciences at the University of Washington, discussed the study with Sleep Review over email. The transcript has been lightly edited for clarity and style.

[Editor’s Note: Read the full study, Polysomnographic features of idiopathic restless legs syndrome: a systematic review and meta-analysis of 13 sleep parameters and 23 leg movement parameters, in the Journal of Clinical Sleep Medicine.]

Your study found that markers other than the PLMS index could be more sensitive and specific markers of RLS. Can you elaborate on this?

Characterizing the number of periodic leg movements as a function of hours of sleep (PLMS index) has traditionally been a way of quantifying the presence and severity of RLS. Our findings indicate that the simple index—reflecting the number of movements per hour—may not be as informative as a periodicity index, which breaks out leg movements occurring during NREM, REM, and total sleep. Analysis of periodicity indices revealed that, compared to controls, RLS patients demonstrated a concentration of leg movements in NREM sleep.

What are the clinical implications of your study?

Our findings indicate that the RLS index during NREM is the most sensitive and specific polysomnographic measure distinguishing RLS patients from controls. This NREM index may prove to be a biomarker and potentially a useful measure of treatment efficacy in RLS.

Your study shows that RLS patients have fragmented sleep with deterioration of both REM and NREM sleep, putting them at risk for chronic sleep loss. What’s the significance of this finding?

As with any sleep disorder, RLS patients experience chronic poor sleep quality, which can result in compromised daytime function, including excessive daytime sleepiness, poor concentration, moodiness, etc, and in the long term may adversely impact physical health.

What further research should be done?

RLS index during NREM and its relationship to other polysomnographic measures, as well as its potential as a biomarker for and measure of treatment efficacy in RLS, needs to be further explored.

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