J Clin Neurol.  2017 Oct;13(4):340-350. 10.3988/jcn.2017.13.4.340.

Abnormal Sleep Delta Rhythm and Interregional Phase Synchrony in Patients with Restless Legs Syndrome and Their Reversal by Dopamine Agonist Treatment

• Choi JW
• Jeong MH
• Her SJ
• Lee BU
• Cha KS
• Jung KY
• Kim KH

• KMID: 2392129
• DOI: http://doi.org/10.3988/jcn.2017.13.4.340

Abstract

BACKGROUND AND PURPOSE
The purpose of this study was to characterize abnormal cortical activity during sleep in restless legs syndrome (RLS) patients and to determine the effects of treatment with a dopamine agonist. Based on whole-brain electroencephalograms, we attempted to verify alterations in the functional network as well as the spectral power of neural activities during sleep in RLS patients and to determine whether the changes are reversed by treatment with pramipexole.
METHODS
Twelve drug-naïve RLS patients participated in the study. Overnight polysomnography was performed before and after treatment: the first recording was made immediately prior to administering the first dose of pramipexole, and the second recording was made 12-16 weeks after commencing pramipexole administration. Sixteen age-matched healthy participants served as a control group. The spectral power and interregional phase synchrony were analyzed in 30-s epochs. The functional characteristics of the cortical network were quantified using graph-theory measures.
RESULTS
The delta-band power was significantly increased and the small-world network characteristics in the delta band were disrupted in RLS patients compared to the healthy controls. These abnormalities were successfully treated by dopaminergic medication. The delta-band power was significantly correlated with the RLS severity score in the RLS patients prior to treatment.
CONCLUSIONS
Our findings suggest that the spectral and functional network characteristics of neural activities during sleep become abnormal in RLS patients, and these abnormalities can be successfully treated by a dopamine agonist.

Keyword

restless legs syndrome; polysomnography; delta rhythm; spectral power; functional network; dopamine agonist treatment

MeSH Terms

Delta Rhythm*
Dopamine Agonists*
Dopamine*
Electroencephalography
Healthy Volunteers
Humans
Polysomnography
Restless Legs Syndrome*
Dopamine
Dopamine Agonists

Figure

• 

  Fig. 1 Spectral powers in electroencephalograms (EEGs). A: Comparison of spectral powers in EEGs among groups. The spectral power was obtained by averaging the log-transformed power for every sleep stage (awake, N1, N2, N3, and REM) and nine electrodes (F3, Fz, F4, C3, Cz, C4, P3, Pz, and P4). The error bars indicate standard errors (*p<0.05, †p<0.01, and ‡p<0.001, respectively, in Mann-Whitney U-tests and Wilcoxon signed-rank tests). B: Correlation between delta-band power and IRLS scores in RLS patients (baseline condition). Delta-band power was obtained by averaging the log-transformed power for the nine electrodes and all sleep stages. Spearman's rank correlation coefficient (r) was 0.606 (p=0.037). IRLS: International Restless Legs Syndrome Severity Scale, REM: rapid eye movement, RLS: restless legs syndrome.

• 

  Fig. 2 SWI as a function of degree K in each sleep stage. A: Comparison between the control (black dashed lines) and RLS baseline (denoted by red solid lines). B: Comparison between the RLS baseline (denoted by red lines) and RLS follow-up (denoted by blue lines). The SWI was plotted as the number of identical connections for the three groups. Shading indicates standard errors. Black downward triangles indicate p<0.05 in Mann-Whitney U-tests and Wilcoxon signed-rank tests for (A) and (B), respectively. REM: rapid eye movement, RLS: restless legs syndrome, SWI: smallworldness index.

• 

  Fig. 3 Graph-theory measures for each sleep stage in each group. Normalized clustering coefficient (A), normalized characteristic path length (B), and SWI (C). Each graph-theory measure was obtained by averaging the values from K=3.5 to K=6.5. Error bars indicate standard errors (*p<0.05 and †p<0.01, respectively, in Wilcoxon signed-rank tests with Bonferroni correction). REM: rapid eye movement, RLS: restless legs syndrome.

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