MEIS1 variant as a determinant of autonomic imbalance in Restless Legs Syndrome

Thireau, Jérôme; Farah, Charlotte; Molinari, Nicolas; Bouilloux, Fabrice; Torreilles, Lucas; Winkelmann, Juliane; Scholz, Sabine; Richard, Sylvain; Dauvilliers, Yves; Marmigère, Frédéric

doi:10.1038/srep46620

Cited by 24 publications

(11 citation statements)

References 59 publications

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“…These results may support the hypothesis that other factors, such as genetic profiles and individual vulnerability to PLMS, may confer susceptibility to RLS/PLMS [38] and autonomic dysfunction and cardiovascular disorders [39].…”

Section: Discussionsupporting

confidence: 77%

Determinants of Nocturnal Cardiovascular Variability and Heart Rate Arousal Response in Restless Legs Syndrome (RLS)/Periodic Limb Movements (PLMS)

Sforza

Roche

Pichot

2019

JCM

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Recent studies have suggested that restless legs syndrome is associated with an increased prevalence of cardiovascular diseases mediated by sympathetic activation occurring during periodic limb movements. The aim of this study was to establish which factors affect the degree of sympathetic activation during the basal condition and during periodic limb movements that may contribute to increased vascular risk. Fifty untreated restless legs syndrome patients aged 62.6 ± 11.1 y, free of cardiovascular diseases, were examined. Heart rate variability was calculated during wakefulness and all sleep stages, during periods with and without periodic limb movements. Heart rate changes before and after periodic limb movement onset were analyzed to assess the arousal response to periodic limb movements. Both analyses took into account the effects of age, gender, periodic limb movement duration, periodic limb movement index, periodic limb movement interval and periodicity, and magnitude of muscular activity (electromyogram power). Compared to periods without periodic limb movements, a significant increase in sympathetic activity occurred in periods with periodic limb movements, independent of age, sex and periodic limb movement characteristics. Data obtained from the cardiac arousal response to periodic limb movements showed that electromyogram power is the factor affecting sympathetic tonus. These results suggest that other factors, such as electromyogram power and individual susceptibility, should be considered in the assessment of the vascular risk related to restless legs syndrome.

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Section: Discussionsupporting

confidence: 77%

Determinants of Nocturnal Cardiovascular Variability and Heart Rate Arousal Response in Restless Legs Syndrome (RLS)/Periodic Limb Movements (PLMS)

Sforza

Roche

Pichot

2019

JCM

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“…For example, it is well known that the MEIS1 gene variant significantly influences HRV in RLS in adults. 26 Further studies that evaluate these interactions during development and aging are needed.…”

Section: Discussionmentioning

confidence: 99%

Heart rate variability during sleep in children and adolescents with restless sleep disorder: a comparison with restless legs syndrome and normal controls

DelRosso

Bruni

Ferri

2020

Journal of Clinical Sleep Medicine

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Study Objectives: Restless sleep disorder (RSD) has recently been characterized clinically and polysomnographically in children and differentiated from restless legs syndrome (RLS). Heart rate variability is a reliable method to quantify autonomic changes during sleep. The aim of this study was to characterize heart rate variability in children with RSD, RLS, and individuals without these disorders, with the hypothesis that children with RSD have a shift toward sympathetic predominance during sleep. Methods: We analyzed polysomnographic recordings from 32 children who fulfilled RSD diagnostic criteria (19 boys and 13 girls), 32 children with RLS (20 boys and 12 girls), and 33 individuals without disorders (17 boys and 16 girls). Four electrocardiographic epochs were chosen, 1 for each stage, and were analyzed for automatic detection of R waves. Time domain and frequency domain heart rate variability parameters were obtained and analyzed. Results: In terms of time domain, only the standard deviation of the average interval between successive R waves during stage N3 was slightly but significantly higher in patients with RSD than in patients with RLS. In terms of frequency domain, in patients with RSD, the very-low-frequency and low-frequency bands were increased (vs patients with RLS and individuals without disorders, respectively), whereas low-frequency/high-frequency ratio tended to be increased in both patients with RSD and with RLS. In rapid eye movement sleep, low-frequency/high-frequency ratio was increased in both patients with RSD and with RLS. The low-frequency/high-frequency ratio increased in patients with RLS during quiet wakefulness preceding sleep. Conclusions: Children with RSD have increased sympathetic activation during sleep, particularly N3 and rapid eye movement sleep, compared with individuals without disorders but, as expected, not during wakefulness. Differently, children with RLS have sympathetic activation during relaxed wakefulness preceding sleep and during sleep.

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“…In the last few years, substantial progress has been made also in understanding the genetic basis of RLS, with focus on the identification of genes that may give rise to the disease (Winkelmann et al., ). Genomewide association studies (GWAS), meta‐analysis, twin, and family large‐scale studies have successfully contributed to identify significant association between RLS and common variants in MEIS1, BTBD9, and MAP2K5 genes (Thireau et al., ; Winkelmann et al., ). It should be noted that our patients were not sequenced for these allelic variations that however might be of relevant interest for the study.…”

Section: Discussionmentioning

confidence: 99%

Discovery of restless legs syndrome plasmatic biomarkers by proteomic analysis

et al. 2018

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ObjectivesRestless legs syndrome (RLS) can lead to severe clinical consequences, thus negatively impacts on patients’ overall health and quality of life. Nevertheless, the pathophysiology of RLS is still unclear, resulting in underestimate, incorrect, or ignored diagnosis and in limited management and treatment. The aim of this study was to compare the plasma proteome of RLS patients and healthy controls, in the search of diagnostic biomarkers related to the disease severity.Materials and MethodsTwo‐dimensional gel electrophoresis coupled with liquid chromatography‐mass spectrometry was employed to analyze plasma samples of 34 patients with primary RLS, divided into two subgroups according to the disease severity: MMS group (mild‐moderate symptoms) and HS group (severe and very severe symptoms), and 17 age‐ and sex‐matched control subjects. Sleep quality, daytime sleepiness, and the level of depression were also evaluated.ResultsWe identified eight upregulated spots, corresponding to five unique proteins, in both RLS group vs. controls (alpha‐1B‐glycoprotein, alpha‐1‐acid glycoprotein 1, haptoglobin, complement C4‐A, and immunoglobulin kappa constant); five increased spots, consistent with three unique proteins, only in HS‐RLS (kininogen‐1, immunoglobulin heavy constant alpha 1, and immunoglobulin lambda constant 2); one downregulated spot in both patient's groups (complement C3) and another one only in HS‐RLS (alpha‐1‐antitrypsin).ConclusionsThe significantly different plasma proteins detected in RLS were mainly associated with inflammation, immune response, and cardiovascular disorders. Particularly, the gradual increasing in immunoglobulins could be indicative of the disease severity and evolution. Accordingly, these proteins may represent a valid set of useful biomarkers for RLS diagnosis, progression and treatment.

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MEIS1 variant as a determinant of autonomic imbalance in Restless Legs Syndrome

Cited by 24 publications

References 59 publications

Determinants of Nocturnal Cardiovascular Variability and Heart Rate Arousal Response in Restless Legs Syndrome (RLS)/Periodic Limb Movements (PLMS)

Determinants of Nocturnal Cardiovascular Variability and Heart Rate Arousal Response in Restless Legs Syndrome (RLS)/Periodic Limb Movements (PLMS)

Heart rate variability during sleep in children and adolescents with restless sleep disorder: a comparison with restless legs syndrome and normal controls

Discovery of restless legs syndrome plasmatic biomarkers by proteomic analysis

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