Disease concept of restless legs syndrome

<p>Restless legs syndrome (RLS), also known as Willis–Ekbom disease (named after the physicians Thomas Willis and Karl–Axel Ekbom, who established its concept), is a neurological and sleep–related disorder. This sensorimotor disorder is characterized by an urge to move associated with an unpleasant sensation in the lower limbs that is present at rest and is resolved or improved by movement ; these symptoms occur in a circadian pattern, with onset in the evening or at night. Although the complete pathophysiology of RLS remains unresolved, several studies utilizing imaging, genetics, and animal models have made progress in elucidating the underlying mechanisms. Magnetic resonance imaging studies have linked RLS with reduced iron concentrations in specific brain regions, while positron emission tomography and single–photon emission computed tomography studies have demonstrated functional abnormalities in dopaminergic nerves and the mesolimbic system. Additionally, functional magnetic resonance imaging studies have demonstrated abnormalities in brain regions belonging to both the sensorimotor system and the limbic network. Recent studies have suggested that abnormalities of adenosine, dopamine, and glutamatergic innervation in the striatum could be downstream of impaired iron utilization in the brain, leading to brain iron deficiency. RLS has numerous comorbidities and may be classified as secondary. It is a complex condition in which predisposing genetic, environmental, and comorbid factors contribute to the development of the disorder. The current treatment guidelines recommend treatment initiation with low–dose dopamine agonists or gabapentin enacarbil. Although dopamine agonists are very effective during induction, their long–term use can lead to serious worsening of the disease, known as augmentation. Other treatment options include opioids, iron supplements, and other new therapeutic candidates. Nevertheless, some patients still experience poor long–term symptom management. A better understanding of the pathological mechanisms of RLS can aid new therapeutic possibilities with the emergence of new avenues of research in pharmacology.</p>