Restless legs syndrome: Over 50 years of European contribution.

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

10-year anniversary of the European Somnologist examination - A historic overview and critical appraisal

The European Somnologist certification programme was developed by the European Sleep Research Society to improve patient care in sleep medicine by providing an independent evaluation of theoretical and practical knowledge. The examination of eligible experts plays a key role in this procedure. A process was started more than 15 years ago to create the European sleep medicine curriculum, eligibility criteria for certification, and sleep centre accreditation criteria. The process was characterised by interdisciplinary collaboration, consensus, and achieving new solutions. During the past 10 years, experience has been gained by the examination and certification of more than 1000 sleep medicine experts from more than 50 countries. The process has continuously been improved. However, as the programme was designed and administered mainly by medical experts in the field, systematic influence from teaching and pedagogic experts was partially underrepresented. The current critical appraisal pinpoints several missing links in the process - mainly as a missing constructive alignment between learning objectives, learning and teaching activities, and the final assessment. A series of suggestions has been made to further improve the ESRS certification programme.Peer reviewe

The long-term treatment of restless legs syndrome/Willis–Ekbom disease: evidence-based guidelines and clinical consensus best practice guidance: a report from the International Restless Legs Syndrome Study Group

AbstractA Task Force was established by the International Restless Legs Syndrome Study Group (IRLSSG) to develop evidence-based and consensus-based recommendations for the long-term pharmacologic treatment of restless legs syndrome/Willis–Ekbom disease (RLS/WED). The Task Force reviewed the results of all studies of RLS/WED treatments with durations of 6months or longer presented at meetings over the past 2years, posted on Web sites of pharmaceutical companies, or published in peer-reviewed journals, asking the questions, “What is the efficacy of this treatment in patients with RLS/WED?” and “What is the safety of this treatment in patients with RLS/WED?”The Task Force developed guidelines based on their review of 61 papers meeting inclusion criteria, and using a modified evidence-grading scheme. Pregabalin has been established as effective for up to 1year in treating RLS/WED (Level A evidence). Pramipexole, ropinirole, and rotigotine have been established as effective for up to 6months in treating RLS/WED (Level A). The following drugs have been established as probably effective (Level B) in treating RLS/WED for durations ranging from 1 to 5years: gabapentin enacarbil, pramipexole, and ropinirole (1year); levodopa (2years); and rotigotine (5years). Because of associated safety concerns, pergolide and cabergoline should not be used in the treatment of RLS/WED unless the benefits clearly outweigh the risks. Other pharmacologic therapies have insufficient evidence to support their long-term use in treating RLS/WED.The IRLSSG Task Force also developed consensus-based strategies for the prevention and treatment of complications (such as augmentation, loss of efficacy, excessive daytime sleepiness, and impulse control disorders) that may develop with the long-term pharmacologic treatment of RLS/WED. The use of either a dopamine-receptor agonist or α2δ calcium-channel ligand is recommended as the first-line treatment of RLS/WED for most patients, with the choice of agent dependent on the patient’s severity of RLS/WED symptoms, cognitive status, history, and comorbid conditions

Progressive development of augmentation during long-term treatment with levodopa in restless legs syndrome: results of a prospective multi-center study

The European Restless Legs Syndrome (RLS) Study Group performed the first multi-center, long-term study systematically evaluating RLS augmentation under levodopa treatment. This prospective, open-label 6-month study was conducted in six European countries and included 65 patients (85% treatment naive) with idiopathic RLS. Levodopa was flexibly up-titrated to a maximum dose of 600 mg/day. Presence of augmentation was diagnosed independently by two international experts using established criteria. In addition to the augmentation severity rating scale (ASRS), changes in RLS severity (International RLS severity rating scale (IRLS), clinical global impression (CGI)) were analyzed. Sixty patients provided evaluable data, 35 completed the trial and 25 dropped out. Augmentation occurred in 60% (36/60) of patients, causing 11.7% (7/60) to drop out. Median time to occurrence of augmentation was 71 days. The mean maximum dose of levodopa was 311 mg/day (SD: 105). Patients with augmentation compared to those without were significantly more likely to be on higher doses of levodopa (≥300 mg, 83 vs. 54%, P = 0.03) and to show less improvement of symptom severity (IRLS, P = 0.039). Augmentation was common with levodopa, but could be tolerated by most patients during this 6-month trial. Patients should be followed over longer periods to determine if dropout rates increase with time

Algorithms for the diagnosis and treatment of restless legs syndrome in primary care

<p>Abstract</p> <p>Background</p> <p>Restless legs syndrome (RLS) is a neurological disorder with a lifetime prevalence of 3-10%. in European studies. However, the diagnosis of RLS in primary care remains low and mistreatment is common.</p> <p>Methods</p> <p>The current article reports on the considerations of RLS diagnosis and management that were made during a European Restless Legs Syndrome Study Group (EURLSSG)-sponsored task force consisting of experts and primary care practioners. The task force sought to develop a better understanding of barriers to diagnosis in primary care practice and overcome these barriers with diagnostic and treatment algorithms.</p> <p>Results</p> <p>The barriers to diagnosis identified by the task force include the presentation of symptoms, the language used to describe them, the actual term "restless legs syndrome" and difficulties in the differential diagnosis of RLS.</p> <p>Conclusion</p> <p>The EURLSSG task force reached a consensus and agreed on the diagnostic and treatment algorithms published here.</p

Pivotal Role of Adenosine Neurotransmission in Restless Legs Syndrome

The symptomatology of Restless Legs Syndrome (RLS) includes periodic leg movements during sleep (PLMS), dysesthesias, and hyperarousal. Alterations in the dopaminergic system, a presynaptic hyperdopaminergic state, seem to be involved in PLMS, while alterations in glutamatergic neurotransmission, a presynaptic hyperglutamatergic state, seem to be involved in hyperarousal and also PLMS. Brain iron deficiency (BID) is well-recognized as a main initial pathophysiological mechanism of RLS. BID in rodents have provided a pathogenetic model of RLS that recapitulates the biochemical alterations of the dopaminergic system of RLS, although without PLMS-like motor abnormalities. On the other hand, BID in rodents reproduces the circadian sleep architecture of RLS, indicating the model could provide clues for the hyperglutamatergic state in RLS. We recently showed that BID in rodents is associated with changes in adenosinergic transmission, with downregulation of adenosine A1 receptors (A1R) as the most sensitive biochemical finding. It was hypothesized that A1R downregulation leads to hypersensitive striatal glutamatergic terminals and facilitation of striatal dopamine release. Hypersensitivity of striatal glutamatergic terminals was demonstrated by an optogenetic-microdialysis approach in the rodent with BID, indicating that it could represent a main pathogenetic factor that leads to PLMS in RLS. In fact, the dopaminergic agonists pramipexole and ropinirole and the α2δ ligand gabapentin, used in the initial symptomatic treatment of RLS, completely counteracted optogenetically-induced glutamate release from both normal and BID-induced hypersensitive corticostriatal glutamatergic terminals. It is a main tenet of this essay that, in RLS, a single alteration in the adenosinergic system, downregulation of A1R, disrupts the adenosine-dopamine-glutamate balance uniquely controlled by adenosine and dopamine receptor heteromers in the striatum and also the A1R-mediated inhibitory control of glutamatergic neurotransmission in the cortex and other non-striatal brain areas, which altogether determine both PLMS and hyperarousal. Since A1R agonists would be associated with severe cardiovascular effects, it was hypothesized that inhibitors of nucleoside equilibrative transporters, such as dipyridamole, by increasing the tonic A1R activation mediated by endogenous adenosine, could represent a new alternative therapeutic strategy for RLS. In fact, preliminary clinical data indicate that dipyridamole can significantly improve the symptomatology of RLS

The European Insomnia Guideline : An update on the diagnosis and treatment of insomnia 2023

Publisher Copyright: © 2023 The Authors. Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.Progress in the field of insomnia since 2017 necessitated this update of the European Insomnia Guideline. Recommendations for the diagnostic procedure for insomnia and its comorbidities are: clinical interview (encompassing sleep and medical history); the use of sleep questionnaires and diaries (and physical examination and additional measures where indicated) (A). Actigraphy is not recommended for the routine evaluation of insomnia (C), but may be useful for differential-diagnostic purposes (A). Polysomnography should be used to evaluate other sleep disorders if suspected (i.e. periodic limb movement disorder, sleep-related breathing disorders, etc.), treatment-resistant insomnia (A) and for other indications (B). Cognitive-behavioural therapy for insomnia is recommended as the first-line treatment for chronic insomnia in adults of any age (including patients with comorbidities), either applied in-person or digitally (A). When cognitive-behavioural therapy for insomnia is not sufficiently effective, a pharmacological intervention can be offered (A). Benzodiazepines (A), benzodiazepine receptor agonists (A), daridorexant (A) and low-dose sedating antidepressants (B) can be used for the short-term treatment of insomnia (≤ 4 weeks). Longer-term treatment with these substances may be initiated in some cases, considering advantages and disadvantages (B). Orexin receptor antagonists can be used for periods of up to 3 months or longer in some cases (A). Prolonged-release melatonin can be used for up to 3 months in patients ≥ 55 years (B). Antihistaminergic drugs, antipsychotics, fast-release melatonin, ramelteon and phytotherapeutics are not recommended for insomnia treatment (A). Light therapy and exercise interventions may be useful as adjunct therapies to cognitive-behavioural therapy for insomnia (B).Peer reviewe

Restless legs syndrome.

Restless legs syndrome (RLS) is a common sensorimotor disorder characterized by an urge to move that appears during rest or is exacerbated by rest, that occurs in the evening or night and that disappears during movement or is improved by movement. Symptoms vary considerably in age at onset, frequency and severity, with severe forms affecting sleep, quality of life and mood. Patients with RLS often display periodic leg movements during sleep or resting wakefulness. RLS is considered to be a complex condition in which predisposing genetic factors, environmental factors and comorbidities contribute to the expression of the disorder. RLS occurs alone or with comorbidities, for example, iron deficiency and kidney disease, but also with cardiovascular diseases, diabetes mellitus and neurological, rheumatological and respiratory disorders. The pathophysiology is still unclear, with the involvement of brain iron deficiency, dysfunction in the dopaminergic and nociceptive systems and altered adenosine and glutamatergic pathways as hypotheses being investigated. RLS is poorly recognized by physicians and it is accordingly often incorrectly diagnosed and managed. Treatment guidelines recommend initiation of therapy with low doses of dopamine agonists or α2δ ligands in severe forms. Although dopaminergic treatment is initially highly effective, its long-term use can result in a serious worsening of symptoms known as augmentation. Other treatments include opioids and iron preparations