Restless Legs Syndrome: From Pathophysiology to Clinical Diagnosis and Management

Abstract

Restless legs syndrome (RLS), a common neurological sensorimotor disorder in western countries, has gained more and more attention in Asian countries. The prevalence of RLS is higher in older people and females. RLS is most commonly related to iron deficiency, pregnancy and uremia. The RLS symptoms show a significant circadian rhythm and a close relationship to periodic limb movements (PLMs) in clinical observations, while the pathophysiological pathways are still unknown. The diagnostic criteria have been revised in 2012 to improve the validity of RLS diagnosis. Recent studies have suggested an important role of iron decrease of brain in RLS pathophysiology. Dopaminergic (DA) system dysfunction in A11 cell groups has been recognized long ago from clinical treatment and autopsy. Nowadays, it is believed that iron dysfunction can affect DA system from different pathways and opioids have a protective effect on DA system. Several susceptible single nucleotide polymorphisms such as BTBD9 and MEIS1, which are thought to be involved in embryonic neuronal development, have been reported to be associated with RLS. Several pharmacological and non-pharmacological treatment are discussed in this review. First-line treatments of RLS include DA agents and α2δ agonists. Augmentation is very common in long-term treatment of RLS which makes prevention and management of augmentation very important for RLS patients. A combination of different types of medication is effective in preventing and treating augmentation. The knowledge on RLS is still limited, the pathophysiology and better management of RLS remain to be discovered.

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“…Other studies have similarly found high a prevalence of RLS [32, 33]. Ethnicity is also a factor in RLS prevalence [30, 31], as it is more common in the west and less so in Eastern Asia [34]. …”

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“…RLS also affects other parts of the body as well. 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).…”

“…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).…”

“…The lack of proper sleep (insomnia) that accompanies RLS is the main reason behind a patient looking for medical consultation. Struggle to initiate sleep is the most common insomnia-related issues associated with RLS (Guo et al, 2017). …”

“…Patients with severe RLS symptoms show obvious deficits in general health, vitality, physicality, emotional and social stability amongst other features (Trenkwalder et al, 2005). Mostly, these patients complain of having trouble in normal life schedules almost on daily basis, including poor performance on their jobs and social functions (Guo et al, 2017). Diagnosis of RLS is based on symptoms reported by patients.…”