New concepts in the management of restless legs syndrome

Abstract

Restless legs syndrome (RLS), also known as Willis-Ekbom disease (WED) is a neurological condition with an overall prevalence in adults of 5-10% in Europe and North America. It is characterised by strong feelings of restlessness and distressing paraesthesia-like sensations in the lower legs, particularly when at rest. The symptoms vary considerably in severity and frequency. RLS/WED has a variable clinical expression influenced by genetic, environmental, and medical factors. Research into the pathophysiology of RLS/WED has found that various genetic markers and existing dysfunctions in dopaminergic mechanisms and iron mechanisms play a central role. Until recently, the first line treatment of RLS/WED was with low dose dopamine agonists, with three drugs having been approved by the US Food and Drug Administration and the European Medicines Agency. However, the occurrence of dopaminergic augmentation and an overall increase in severity of symptoms during long term treatment with dopamine agonists is leading to a shift towards non-dopaminergic alternatives as initial treatments, and particularly to αδ ligands. Recent international guidelines recommend, whenever possible, to start treatment with these drugs (αδ ligands) to avoid augmentation from the start. Other (eg, glutamatergic or adenosine) neurotransmitters might also play an important role in causing RLS/WED and might thus lead to new treatments.

Prevalence and Characteristics of Restless Legs Syndrome in Korean Adults: A Study in Two Independent Samples of the General Population

“…It is known that RLS has a higher prevalence in women and older individuals [1,4,8,10]. As population 1 was a stratified population sample that included relatively young subjects, population 1 may have had more primary RLS cases than population 2, leading to a predominance of young and female cases, and long disease durations in population 1.…”

“…RLS can profoundly disturb sleep and cause significant reductions in health-related quality of life. Currently, the key pathomechanisms underlying RLS are thought to be dopaminergic and glutamatergic dysfunction, as well as iron imbalance [4].…”

Caenorhabditis elegans and its applicability to studies on restless legs syndrome

“…The number of DA transporters may be decreased in RLS, as shown by a PET study (Earley et al, 2011). Additionally, lesion of the area where DAergic pathway projects to spinal cord (area A11) led to overactivity in a rodent model, although this could not be corroborated in autopsy study of RLS patients (Garcia-Borreguero & Cano-Pumarega, 2017; Guo et al, 2017). …”

“…It is known that the longer the condition persists, the more likely the arms or the other regions of the body become symptomatic (Guo et al, 2017). These symptoms are said to typically become evident when patients are at rest, with a higher possibility of symptoms occurring during a relaxed or cosy state (Garcia-Borreguero & Cano-Pumarega, 2017; Guo et al, 2017; Trenkwalder et al, 2005). RLS symptoms commonly show a circadian rhythm, with symptoms being worse in the evenings, followed by short lessening after waking up in the morning (Garcia-Borreguero & Cano-Pumarega, 2017).…”

“…Several studies have reported robust association between onset of RLS and predisposing genetics. Genome-wide association studies (GWAS) have demonstrated several single nucleotide polymorphisms associated with RLS, including BTBD9 (on chromosome6p21.2), MEIS1 (on chromosome 2p14), MAP2K5/SCOR1 (on chromosome 15q23), PTPRD (on chromosome 9p24.1-p23), and chromosome 16q12.1 (Garcia-Borreguero & Cano-Pumarega, 2017; Guo et al, 2017). Deficiency in Fe has been repeatedly demonstrated to involved in RLS pathogenesis.…”