Search

Pain in the legs belongs to the five most frequent regional pain symptoms. Restless legs syndrome (RLS) presents a particular differential diagnosis for pain in the legs, which is characterized by a nocturnal urge to move the legs often associated with painful sensations in the legs. It is one of the most common neurological disorders and probably the leading cause of nocturnal pain in the legs. In this overview, the diagnosis and therapy of RLS as well as aspects of pain therapy of the disorder are presented. In addition, the differential diagnoses for exclusion of other specific causes of nocturnal pain in the legs are discussed.

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. peerReviewed

Depressive Storungen sind eine haufige Komorbiditat beim Restless-legs-Syndrom (RLS). Vergleichbare Pravalenzraten von Begleitdepressionen finden sich zwar auch bei anderen Erkrankungen, die Assoziation zwischen RLS und Depression ist jedoch durch die RLS-bedingten erheblichen Schlafstorungen besonders komplex. Klinisch von Bedeutung ist zudem, dass verfugbare Daten, uberwiegend aus Fallberichten, zeigen, dass eine Vielzahl antidepressiver Medikamente die RLS-Symptomatik verstarken kann. Eine komorbide Depression beeinflusst den Therapieerfolg der Grunderkrankung und sollte deshalb berucksichtigt werden. Bislang gibt es keine systematischen Untersuchungen und daher keine evidenzbasierten Empfehlungen zur pharmakologischen Therapie von depressiven Symptomen bei RLS. In der vorliegenden Ubersicht werden die klinische Relevanz von depressiven Storungen bei RLS und die Auswirkung einer antidepressiven Behandlung auf die RLS-Symptomatik diskutiert sowie ein Therapiealgorithmus (Evidenzklasse C) zur Behandlung einer komorbiden Depression bei RLS vorgestellt.

Background Although the diagnosis of restless legs syndrome (RLS) is largely based on the presence of the four essential criteria, no validated diagnostic questionnaire exists for use in epidemiological studies or clinical practice.

Restless legs syndrome (RLS) is a frequent neurological disorder characterized by an imperative urge to move the legs during night, unpleasant sensation in the lower limbs, disturbed sleep and increased cardiovascular morbidity. In a genome-wide association study we found highly significant associations between RLS and intronic variants in the homeobox gene MEIS1, the BTBD9 gene encoding a BTB(POZ) domain as well as variants in a third locus containing the genes encoding mitogen-activated protein kinase MAP2K5 and the transcription factor LBXCOR1 on chromosomes 2p, 6p and 15q, respectively. Two independent replications confirmed these association signals. Each genetic variant was associated with a more than 50% increase in risk for RLS, with the combined allelic variants conferring more than half of the risk. MEIS1 has been implicated in limb development, raising the possibility that RLS has components of a developmental disorder.

Gutachterliche Fragestellungen bei Patienten mit einem Restless-Legs-Syndrom (RLS) nehmen stetig zu. Darum hat die “AG Motorik und Schlaf” der DGSM erstmals Empfehlungen zur Begutachtung und sozialmedizinischen Einschatzung des RLS erarbeitet. Im Folgenden werden die spezifischen Empfehlungen zur Beurteilung des RLS im Rahmen gutachterlicher Verfahren zusammengefasst (aus [5]). Diese Konsensusleitlinie soll eine Grundlage zur Vereinheitlichung und Qualitatssicherung in der Begutachtung des RLS darstellen und nicht in individuelle Begutachtungen eingreifen.

The term ‘sleep attack’ is used in patients with Parkinson's disease (PD) to designate a sudden onset of sleep (SOS) without any prior sleepiness. Clinically, sleep attacks can be distinguished from unintended sleep episodes, i.e. SOS with prior sleepiness. This study aimed to assess the prevalence of SOS and to identify its predictors in patients with sleep-disordered breathing (SDB). A total of 114 consecutive patients with the clinical suspicion of obstructive sleep apnoea syndrome (OSAS) and a respiratory disturbance index (RDI) of >5/h were examined using a questionnaire and polysomnography (PSG). Altogether 57.7% reported SOS, with 5.2% of the total population describing exclusively sleep attacks. SOS was observed in both patients with obstructive sleep apnoea-hypopnoea (OSAH) or increased upper airway resistance (UAR). Increased scores on the Epworth Sleepiness Scale (ESS) were the best predictor of SOS. Logistic regression showed a possible association of SOS with a low PLMS index, while no definite effect was observed for other PSG parameters. Our data show that SDB is frequently associated with SOS. Future studies should address in more detail whether SDB patients with sleep attacks pose an increased accident risk.

Treatment standards or guidelines have been developed for most features of Parkinson's disease (PD). However, data on the actual treatment that is put into practice are scarce. In 2000, a nationwide survey on the topic of sudden onset of sleep (SOS) in PD was initiated among the members of the German patient support group (deutsche Parkinson-Vereinigung, dPV). A part of this mailed questionnaire survey covering the antiparkinsonian and concomitant medication of the participants is presented here. This study analyses data sets from more than 6,500 PD patients. The mean dopaminergic dose was equivalent to 599 +/- 387 mg levodopa/die. The most frequently administered drugs were levodopa (94.2 %), dopamine agonists (DA) (71.7 %), amantadine (40.1 %), selegiline (27.6 %), entacapone (20.4 %), budipine (12.3 %), and anticholinergics (11.8 %). Costs of pharmacotherapy were estimated to be approximatelyeuro399 million/year in Germany. PD drug therapy in general strongly depended on age, disease duration, and the level of care. The treatment guidelines were apparently not consistently followed underlining the need for their continuous propagation throughout the medical community. In addition our data suggest that non-motor symptoms in PD are not adequately treated and that concomitant sedative medication contributes to the occurrence of SOS.

Die selbstberichtete Pravalenz von Tagesmudigkeit und Schlafstorungen bei Parkinson-Patienten vor und seit ihrer Erkrankung sollte abgeschatzt und auf Zusammenhange zueinander uberpruft werden. Ferner sollte erhoben werden, worauf die Patienten diese Symptome attribuieren und wie diese mit der Menge an Tagschlaf korreliert sind. Ein Fragebogen zu Schlafstorungen, Schlafverhalten, Tagesmudigkeit etc. wurde an 12 000 Parkinson-Patienten verschickt. Bei einer Rucklaufquote von 63% konnten die Daten von 6620 Patienten analysiert werden. Die Pravalenz von Tagesmudigkeit (35% vs. 71%) und Schlafstorungen (23% vs. 76%) war akut signifikant hoher als vor der Parkinson-Krankheit (P

We identified association of restless legs syndrome (RLS) with PTPRD at 9p23-24 in 2,458 affected individuals and 4,749 controls from Germany, Austria, Czechia and Canada. Two independent SNPs in the 5' UTR of splice variants expressed predominantly in the central nervous system showed highly significant P values (rs4626664, P(nominal/lambda corrected) = 5.91 x 10(-10), odds ratio (OR) = 1.44; rs1975197, P(nominal/lambda corrected) = 5.81 x 10(-9), OR = 1.31). This work identifies PTPRD as the fourth genome-wide significant locus for RLS.

Luigi Ferini-Strambi • Wolfgang Oertel • Yves Dauvilliers • Ronald B. Postuma • Sara Marelli • Alex Iranzo • Isabelle Arnulf • Birgit Hogl • Raffaele Manni • Tomoyuki Miyamoto • Maria-Livia Fantini • Monica Puligheddu • Poul Jennum • Karel Sonka • Joan Santamaria • Marco Zucconi • Paola M. V. Rancoita • Smeranda Leu-Semenescu • Birgit Frauscher • Michele Terzaghi • Masayuki Miyamoto • Marcus Unger • Karin Stiasny-Kolster • Alex Desautels • Christina Wolfson • Amelie Pelletier • Jacques Montplaisir

Background Rotigotine is a unique dopamine agonist with activity across D1 through D5 receptors as well as select adrenergic and serotonergic sites. This study reports the 2-year follow-up safety and efficacy data of an ongoing open-label multicenter extension study (NCT00498186) of transdermal rotigotine in patients with moderate to severe restless legs syndrome (RLS). Methods Patients received a once-daily patch application of an individually optimized dose of rotigotine between 0.5 mg/24 h to 4 mg/24 h. Safety assessments included adverse events (AEs) and efficacy was measured by the International RLS Study Group Severity Rating Scale (IRLS), RLS-6 scales and Clinical Global Impression (CGI). Quality of life (QoL) was measured by QoL-RLS. Results Of 310 patients who completed a 6-week placebo-controlled trial (SP709), 295 (mean age 58 ± 10 years, 66% females) were included in the open-label trial SP710. 64.7% (190/295 patients) completed the 2-year follow-up; 29 patients discontinued during the second year. Mean daily rotigotine dose after 2 years was 2.93 ± 1.14 mg/24 h with a 2.9% dose increase from year 1. Rotigotine was generally well tolerated. The rate of typical dopaminergic side effects, nausea and fatigue, was low (0.9% and 2.3%, respectively) during the second year; application site reactions were frequent but lower than in year 1 (16.4% vs. 34.5%). The IRLS total score improved from baseline of SP709 (27.8 ± 5.9) by 17.2 ± 9.2 in year 2 completers. Similar improvements were observed in RLS-6 scales, CGI scores and QoL-RLS. The responder rate in the CGI change item 2 ("much" and "very much" improved) was 95% after year 2. Conclusions Transdermal rotigotine is an efficacious and well-tolerated long-term treatment option for patients with moderate to severe RLS with a high retention rate during 2 years of therapy. Trial registration NCT00498186