The Neurobiology and Treatment of Restless Legs Syndrome

Abstract

Background: Restless legs syndrome (RLS) is a relatively common neurological disorder affecting sleep and health-related quality of life. Neuroimaging studies, autopsy investigations and experimental studies using animal models have been conducted to investigate the potential causes of RLS, resulting in the generation of multiple pathophysiological hypotheses. Methods: This paper reviews the neurobiology and pharmacotherapy of RLS, with a critical analysis of the heterogeneity and methodological limitations of the existing scientific literature. Results: Although several neurotransmitter systems dysfunction and neuroanatomical abnormalities have been implicated in RLS pathogenesis, dopamine dysfunction within basal ganglia pathways, iron deficiency and opioid system abnormalities have consistently been found to be involved. Their involvement is further strengthened by the therapeutic effectiveness of dopaminergic agents, iron supplementation and opioid medications. Discussion: Converging evidence from neuroimaging, autoptic and animal studies points towards dopamine dysregulation and iron metabolism alterations as the main contributors to RLS pathophysiology. The possible interactions between different neurotransmitter systems should guide further neuropharmacological research in order to improve therapeutic efficacy for this disabling condition.

Prevalence, severity, and impact on quality of life of restless leg syndrome in patients with liver cirrhosis in India

“…The scores of individual questions are aggregated to yield a total score ranging from 0 to 40. Based on the IRLS score, RLS was graded as mild (0-10), moderate (11)(12)(13)(14)(15)(16)(17)(18)(19)(20), severe (21)(22)(23)(24)(25)(26)(27)(28)(29)(30), and very severe (31-40). All the subjects diagnosed with RLS were provided the standard-of-care management by the neurologist (VP) in the research team [22].…”

Mood Disorders in Restless Legs Syndrome (Willis-Ekbom Disease)

“…13,[63][64][65] A dopaminergic deficiency has also been implicated in the pathophysiology of depression. [66][67][68] Dopamine-containing circuits in the central nervous system are thought to be involved in the regulation of motivation, concentration, and the ability to experience pleasure, all 3 of which are impaired in patients with depression.…”

The Prevalence of Fibromyalgia in Patients with Restless Legs Syndrome

“…Headache, fatigue, sleep disturbances, depression and anxiety are common in patients with FM and/or RLS and quality of life is adversely affected (10,34,35,45,46). Looking at the data from our study, the addition of FM symptoms on RLS symptoms causes significantly worse responses to questions ("How do you think your overall health is?"…”

“…Although the pathogenesis of RLS is not fully understood, a decreased amount of iron in the central nervous system and perturbation in the dopaminergic system were thought to play important roles (34). It is suggested that dopamine activity decreases at night as a result of postsynaptic receptor desensitization due to hyperdopaminergia (35). The use of dopamine-containing drugs in the treatment supports this hypothesis (36,37).…”