Restless Legs Syndrome and Sleep-Related Movement Disorders

Chu

et al. 2020

Sci Rep

Both of periodic limb movements during sleep (pLMS) and tinnitus were related with dopaminergic system dysfunction. However, it was still unclear whether PLMS, one kind of sleep disturbances, was associated with chronic tinnitus or not. Thus, we aimed to investigate this issue in humans. Clinical and overnight polysomnographic data of 2849 adults from a community hospital during Nov. 2011 to Jun 2017 in Taiwan was collected retrospectively. The association of PLMS and chronic tinnitus was analyzed by Student's t-test, Pearson's Chi-Square test, and multivariate logistic regression. The results showed that the mean age was 50.6 years old (standard deviation, SD = 13.3, range = 18~91) for all subjects. There were 1886 subjects without tinnitus and 963 subjects with tinnitus in this study. The PLMS was not significantly different between subjects without tinnitus (mean = 1.0/h, SD = 3.5/h) and subjects with tinnitus mean = 1.1/h, SD = 3 .4/h) by Student's t-test. The severity of PLMS was not significantly between non-tinnitus and tinnitus subjects by Pearson's Chi-Square test. Multivariate logistic regression also showed that PLMS was not significantly associated with tinnitus after adjusting age, sex, subjective hearing loss, Parkinson's disease, and insomnia. In conclusion, PLMS was not associated with chronic tinnitus in humans.Tinnitus is a phantom auditory perception. There were many types of tinnitus, for example auditory tinnitus, somatic tinnitus, vascular origin tinnitus, muscular origin tinnitus, etc. And, the prevalence of tinnitus depends on the type and/or definition for it. A nationwide survey of South Korea reported that the prevalence of any tinnitus was 20.7% among adults aged 20 to 98 years 1 . The prevalence of all types of tinnitus was higher in women than in men, and it increased with age 1 . The contributing factors and/or etiologies of tinnitus were numerous, including hearing impairment, cardiometabolic disorders, sleep disturbances and sleep apnea, migraine, and non-migraine headache, etc. 2-4 . And, tinnitus often comorbided with other diseases, such as anxiety, depression, brain tumors or stroke, and some symptoms including irritability, inability to concentration, and sleep disturbances [5][6][7] .Dysfunction in the cochlea, and neural reorganization in the auditory and non-auditory cortices have been reported to be associated with auditory tinnitus 8 . In addition to neuroinflammation and/or oxidative stress damages 9-13 , increased expression of N-methyl D-aspartate (NMDA) receptor (NR) gene 14 , decreasedγ-amino butyric acid (GABA) receptor (GR) and cannabinoid receptor genes were found in the cochlea and some brain areas 9,15 . Increased expresssion of K + -Cl − cotransporter (KCC2) gene was also found in salicylate-induced tinnitus 16 . Besides, dysfunction of dopaminergic system was reported to be related with tinnitus formation 17,18 . On the other hand, the pathophysiology of periodic limb movements during sleep (PLMS) was reported to be related with dysfunction of dopaminergic sy...

Section: Discussioncontrasting

confidence: 79%

“…In the aspect of dopaminergic systemTrotti (2017), reported that dopamine agonists could reduce the severity of PLMS 19 . On the other hand, the results about tinnitus-related dopaminergic pathway dysfunction varied.…”

Section: Discussionmentioning

confidence: 99%

Association of periodic limb movements during sleep and tinnitus in humans

Chu

et al. 2020

Sci Rep

“…Restless legs syndrome (RLS), also called Willis–Ekbom disease, is a neurological sensorimotor condition characterized by unpleasant sensations in the legs, which leads to the pressing need to move the limbs, thus relieving the associated discomforts, such as paresthesias and dysesthesias (Allen et al., ). These symptoms occurring at rest and their intensity increase in the evening or night, often inducing spontaneous episodic jolting of the legs that, in turn, cause serious sleep disruption and impairs quality of life (Trotti, ).…”

Section: Introductionmentioning

confidence: 99%

Discovery of restless legs syndrome plasmatic biomarkers by proteomic analysis

et al. 2018

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.

“…Partitioning of heritability across tissue types 25,26 showed enrichment in the central nervous system, adrenal/pancreas tissue lineages and skeletal muscle (p<10 -5 ) (Supplementary Table 17 [29][30][31][32] . Furthermore, the restless legs syndrome gene BTBD9 has been implicated as a substrate adaptor for the Cullin-3 class of E3 ubiquitin ligases 33 .…”

mentioning

confidence: 99%

Biological and clinical insights from genetics of insomnia symptoms

Lane

Jones

Dashti

et al. 2018

Preprint

Insomnia is a common disorder linked with adverse long-term medical and psychiatric outcomes, but underlying pathophysiological processes and causal relationships with disease are poorly understood. Here we identify 57 loci for self-reported insomnia symptoms in the UK Biobank (n=453,379) and confirm their impact on self-reported insomnia symptoms in the HUNT study (n=14,923 cases, 47,610 controls), physician diagnosed insomnia in Partners Biobank (n=2,217 cases, 14,240 controls), and accelerometer-derived measures of sleep efficiency and sleep duration in the UK Biobank (n=83,726). Our results suggest enrichment of genes involved in ubiquitin-mediated proteolysis, phototransduction and muscle development pathways and of genes expressed in multiple brain regions, skeletal muscle and adrenal gland. Evidence of shared genetic factors is found between frequent insomnia symptoms and restless legs syndrome, aging, cardio-metabolic, behavioral, psychiatric and reproductive traits. Evidence is found for a possible causal link between insomnia symptoms and coronary heart disease, depressive symptoms and subjective well-being.