Restless legs syndrome: Over 50 years of European contribution

Abstract

Summary Restless legs syndrome (RLS) is a sensorimotor neurological disorder characterised by an urge to move the limbs with a circadian pattern (occurring in the evening/at night), more prominent at rest, and relieved with movements. RLS is one of the most prevalent sleep disorders, occurring in 5%–10% of the European population. Thomas Willis first described RLS clinical cases already in the 17th century, and Karl‐Axel Ekbom described the disease as a modern clinical entity in the 20th century. Despite variable severity, RLS can markedly affect sleep (partly through the presence of periodic leg movements) and quality of life, with a relevant socio‐economic impact. Thus, its recognition and treatment are essential. However, screening methods present limitations and should be improved. Moreover, available RLS treatment options albeit providing sustained relief to many patients are limited in number. Additionally, the development of augmentation with dopamine agonists represents a major treatment problem. A better understanding of RLS pathomechanisms can bring to light novel treatment possibilities. With emerging new avenues of research in pharmacology, imaging, genetics, and animal models of RLS, this is an interesting and constantly growing field of research. This review will update the reader on the current state of RLS clinical practice and research, with a special focus on the contribution of European researchers.

Title: Dopamine-refractory restless arms syndrome: a case report

“…Several clinical ndings suggest that a presynaptic hyperglutamatergic state is present in RLS, which may be involved not only in spinal and supraspinal hyperstimulation, but also in the sensorimotor symptoms of RLS [20]. The therapeutic effects of α2δ ligands such as gabapentin and pregabalin are based on glutamatergic mechanisms, as α2δ ligands inhibit glutamate release by binding to the α2δ subunits of calcium channels located in glutamatergic terminals, leading to a reduction in neuronal activity [20,21].…”

“…Genetic risk factors have also been identi ed [2,16] A large number of publications have attributed an important role to peripheral and central neuronal hypoxia in the pathogenesis of RLS, associated with dysregulation of iron transport across the blood-brain barrier and reduced iron storage in the brain [17][18][19][20][21][22][23]. The frequent improvement of RLS symptoms following administration of dopaminergic agents suggests a relative dopaminergic de cit in the brain, presumably as a result of postsynaptic receptor downregulation [2,18].…”

Experiences of facilitators and barriers for fulfilment of human needs when living with restless legs syndrome: a qualitative study

“…Restless legs syndrome (RLS) is a highly prevalent sensory-motor disorder, impacting approximately 3% of the global population (Broström et al, 2023 ), with a circadian rhythm profile, characterized by an urge to move the arms and legs, usually associated with discomfort, pain, and motor restlessness. The complete pathophysiology is not known, but genetic variants, abnormal iron metabolism, dopaminergic and central opioid system dysfunction are seen as potential mechanisms (Khachatryan et al, 2022 ). The diagnosis, based on five essential criteria (IRLSSG; Allen et al, 2014 ) ( Table I ), is commonly made in primary care, but the variation and fluctuation in symptoms, signs, and symptom burden, also when treatment is initiated, make RLS a difficult condition to diagnose and treat (Garcia-Borreguero et al, 2018 ).…”

Restless Legs Syndrome in Parkinson’s Disease

“…In the general population, a high prevalence of RLS was reported (up to 10%) [ 4 ], RLS being more commonly encountered in females [ 5 ]. Secondary causes of RLS have also been identified: renal failure [ 6 ], hepatic cirrhosis [ 7 ] and pregnancy (generally with a tendency to decrease after delivery) [ 8 ].…”