Publications by authors named "Karin Stiasny-Kolster"

61 Publications

DTI and VBM reveal white matter changes without associated gray matter changes in patients with idiopathic restless legs syndrome.

Brain Behav 2015 Sep 30;5(9):e00327. Epub 2015 Jul 30.

Department of Neurology, Philipps-University Marburg Baldingerstrasse, Marburg, 35043, Germany.

Background And Purpose: We evaluated cerebral white and gray matter changes in patients with iRLS in order to shed light on the pathophysiology of this disease.

Methods: Twelve patients with iRLS were compared to 12 age- and sex-matched controls using whole-head diffusion tensor imaging (DTI) and voxel-based morphometry (VBM) techniques. Evaluation of the DTI scans included the voxelwise analysis of the fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD).

Results: Diffusion tensor imaging revealed areas of altered FA in subcortical white matter bilaterally, mainly in temporal regions as well as in the right internal capsule, the pons, and the right cerebellum. These changes overlapped with changes in RD. Voxel-based morphometry did not reveal any gray matter alterations.

Conclusions: We showed altered diffusion properties in several white matter regions in patients with iRLS. White matter changes could mainly be attributed to changes in RD, a parameter thought to reflect altered myelination. Areas with altered white matter microstructure included areas in the internal capsule which include the corticospinal tract to the lower limbs, thereby supporting studies that suggest changes in sensorimotor pathways associated with RLS.
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http://dx.doi.org/10.1002/brb3.327DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4589804PMC
September 2015

Diagnostic value of the REM sleep behavior disorder screening questionnaire in Parkinson's disease.

Sleep Med 2015 Jan 13;16(1):186-9. Epub 2014 Nov 13.

Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria. Electronic address:

Objective: We aimed to validate the rapid eye movement (REM) sleep behavior disorder (RBD) screening questionnaire (RBDSQ) in 2 independent samples of patients with Parkinson's disease (PD) using different settings when performing the investigations.

Methods: The RBDSQ was administered to two independent samples of 52 and 75 consecutive PD patients investigated with video-polysomnography (vPSG).

Results: In sample A, the RBDSQ identified 46/52 (88.5%) patients correctly. In sample B, 50/75 (66.7%) patients were identified correctly. Considering a cut-off score of ≥ 5 as a positive test result, sample A showed a sensitivity of 0.90 and a specificity of 0.87, sample B showed a sensitivity of 0.68 and a specificity of 0.63. Main differences between both groups were that patients of sample A underwent a sleep history including RBD assessment prior to administration of the RBDSQ, whereas in sample B the RBDSQ was administered during routine work-up.

Conclusions: The diagnostic value of the RBDSQ strongly depends on the clinical setting and may be influenced by the individual's awareness on RBD. This finding is a critical issue which deserves clarification before use of this and other questionnaires can be recommended in epidemiological studies.
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http://dx.doi.org/10.1016/j.sleep.2014.08.014DOI Listing
January 2015

Blood cis-eQTL analysis fails to identify novel association signals among sub-threshold candidates from genome-wide association studies in restless legs syndrome.

PLoS One 2014 29;9(5):e98092. Epub 2014 May 29.

Neurologische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany; Institut für Humangenetik, Helmholtz Zentrum München, Munich, Germany; Institut für Humangenetik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany; Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.

Restless legs syndrome (RLS) is a common neurologic disorder characterized by nightly dysesthesias affecting the legs primarily during periods of rest and relieved by movement. RLS is a complex genetic disease and susceptibility factors in six genomic regions have been identified by means of genome-wide association studies (GWAS). For some complex genetic traits, expression quantitative trait loci (eQTLs) are enriched among trait-associated single nucleotide polymorphisms (SNPs). With the aim of identifying new genetic susceptibility factors for RLS, we assessed the 332 best-associated SNPs from the genome-wide phase of the to date largest RLS GWAS for cis-eQTL effects in peripheral blood from individuals of European descent. In 740 individuals belonging to the KORA general population cohort, 52 cis-eQTLs with pnominal<10(-3) were identified, while in 976 individuals belonging to the SHIP-TREND general population study 53 cis-eQTLs with pnominal<10(-3) were present. 23 of these cis-eQTLs overlapped between the two cohorts. Subsequently, the twelve of the 23 cis-eQTL SNPs, which were not located at an already published RLS-associated locus, were tested for association in 2449 RLS cases and 1462 controls. The top SNP, located in the DET1 gene, was nominally significant (p<0.05) but did not withstand correction for multiple testing (p = 0.42). Although a similar approach has been used successfully with regard to other complex diseases, we were unable to identify new genetic susceptibility factor for RLS by adding this novel level of functional assessment to RLS GWAS data.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0098092PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4038519PMC
January 2015

The PD-associated alpha-synuclein promoter Rep1 allele 2 shows diminished frequency in restless legs syndrome.

Neurogenetics 2014 Aug 27;15(3):189-92. Epub 2014 May 27.

Neurodegeneration Research Laboratory, Molecular Biology and Genetics Department, Bogazici University, 34342, Istanbul, Turkey.

Gain-of-function mutations of alpha-synuclein (SNCA) are known to trigger Parkinson's disease (PD) with striatal dopaminergic deficits and a reduction of spontaneous movements. The longest size variant (allele 2) of the complex microsatellite repeat Rep1 within the SNCA gene promoter is known to confer a PD risk. We now observed this Rep1 allele 2 to show significantly decreased frequency in restless legs syndrome (RLS) in a genotyping study of 258 patients versus 235 healthy controls from Germany. Given that RLS is a disease with increased spontaneous movements and with increased striatal dopamine signaling, these novel data appear plausible. The scarcity of this alpha-synuclein gain-of-function variant in RLS might suggest that a low alpha-synuclein function via the SNARE complex in presynaptic vesicle release and neurotransmission of the striatum contributes to RLS pathogenesis.
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http://dx.doi.org/10.1007/s10048-014-0407-zDOI Listing
August 2014

Autonomic symptoms in idiopathic REM behavior disorder: a multicentre case-control study.

J Neurol 2014 Jun 1;261(6):1112-8. Epub 2014 Apr 1.

Department of Clinical Neuroscience, Sleep Disorders Center, Università Vita-Salute San Raffaele, Via Stamira d' Ancona 20, 20127, Milan, Italy,

Patients with idiopathic REM sleep behavior disorder (iRBD) are at very high risk of developing neurodegenerative synucleinopathies, which are disorders with prominent autonomic dysfunction. Several studies have documented autonomic dysfunction in iRBD, but large-scale assessment of autonomic symptoms has never been systematically performed. Patients with polysomnography-confirmed iRBD (318 cases) and controls (137 healthy volunteers and 181 sleep center controls with sleep diagnoses other than RBD) were recruited from 13 neurological centers in 10 countries from 2008 to 2011. A validated scale to study the disorders of the autonomic nervous system in Parkinson's disease (PD) patients, the SCOPA-AUT, was administered to all the patients and controls. The SCOPA-AUT consists of 25 items assessing the following domains: gastrointestinal, urinary, cardiovascular, thermoregulatory, pupillomotor, and sexual dysfunction. Our results show that compared to control subjects with a similar overall age and sex distribution, patients with iRBD experience significantly more problems with gastrointestinal, urinary, and cardiovascular functioning. The most prominent differences in severity of autonomic symptoms between our iRBD patients and controls emerged in the gastrointestinal domain. Interestingly, it has been reported that an altered gastrointestinal motility can predate the motor phase of PD. The cardiovascular domain SCOPA-AUT score in our study in iRBD patients was intermediate with respect to the scores reported in PD patients by other authors. Our findings underline the importance of collecting data on autonomic symptoms in iRBD. These data may be used in prospective studies for evaluating the risk of developing neurodegenerative disorders.
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http://dx.doi.org/10.1007/s00415-014-7317-8DOI Listing
June 2014

Response to letter to the editor.

Pain 2014 Jan 4;155(1):200-201. Epub 2013 Oct 4.

Chair of Neurophysiology, Center of Biomedicine and Medical Technology Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim 68167, Germany Department of Neurology, Philipps-University, Marburg, Germany Somnomar, Institute for Medical Research and Sleep Medicine, Marburg, Germany.

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http://dx.doi.org/10.1016/j.pain.2013.09.029DOI Listing
January 2014

Hyperalgesia and functional sensory loss in restless legs syndrome.

Pain 2013 Aug 10;154(8):1457-63. Epub 2013 May 10.

Department of Neurology, Philipps-University, Marburg, Germany.

Pain and other sensory signs in patients with restless legs syndrome (RLS) are still poorly understood, as most investigations focus on motor system dysfunctions. This study aimed to investigate somatosensory changes in patients with primary RLS and the restoration of somatosensory function by guideline-based treatment. Forty previously untreated RLS patients were investigated unilaterally over hand and foot using quantitative sensory testing (QST) and were compared with 40 age- and gender-matched healthy subjects. The predominant finding in RLS patients was 3- to 4-fold increase of sensitivity to pinprick stimuli in both extremities (hand: P<.05; foot: P<.001), a sensory pathway involved in withdrawal reflexes. Pinprick hyperalgesia was not paralleled by dynamic mechanical allodynia. Additional significant sensory changes were tactile hypoesthesia in both extremities (hand: P<.05; foot P<.01) and dysesthesia to non-noxious cold stimuli (paradoxical heat sensation), which was present in the foot in an unusually high proportion (14 of 40 patients; P<.01). In 8 patients, follow-up QST 2 to 20 months after treatment with l-DOPA (L-3,4-dihydroxyphenylalanine) revealed a significant reduction of pinprick hyperalgesia (-60%, P<.001), improved tactile detection (+50%, P<.05), and disappearance of paradoxical heat sensation in half of the patients. QST suggested a type of spinal or supraspinal central sensitization differing from neuropathic pain or human experimental models of central sensitization by the absence of dynamic mechanical allodynia. Reversal of pinprick hyperalgesia by l-DOPA may be explained by impaired descending inhibitory dopaminergic control on spinal nociceptive neurons. Restoration of tactile sensitivity and paradoxical heat sensations suggest that they were functional disturbances resulting from central disinhibition.
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http://dx.doi.org/10.1016/j.pain.2013.05.007DOI Listing
August 2013

Effectiveness and tolerability of rotigotine transdermal patch for the treatment of restless legs syndrome in a routine clinical practice setting in Germany.

Sleep Med 2013 Jun 11;14(6):475-81. Epub 2013 May 11.

Somnomar, Institute for Medical Research and Sleep Medicine, Marburger Str. 9a, Marburg 35043, Germany.

Objective: We aimed to assess effectiveness and tolerability of rotigotine in patients with moderate to severe idiopathic restless legs syndrome (RLS) under daily practice conditions in Germany.

Methods: In this 3-month noninterventional study, effectiveness was assessed using RLS-6 (primary variables were symptom severity when falling asleep [item 2] and during the night [item 3]). Data were collected at baseline and at the end of treatment. Safety assessments included adverse events (AEs).

Results: Six hundred and eighty-four patients were treated with rotigotine and 418 (61%) completed the study. The full analysis set (FAS) comprised 564 patients (106 de novo; 458 pretreated [454 had complete rotigotine dosing data]). Mean rotigotine dose of longest duration was 2.4±1.4 mg/24 h. Rotigotine improved all RLS-6 items (mean change from baseline [item 2], -2.4±3.6; [item 3], -2.7±3.4), with the most pronounced improvement observed in daytime symptoms while at rest (item 4, -2.9±3.2). AEs were typical of dopaminergic treatment and transdermal administration. De novo patients generally started rotigotine on 1 mg/24 h (85% [90/106]) and pretreated patients on 1 (50% [227/454]) or 2 mg/24 h (40% [183/454]). Most patients who were pretreated with levodopa (57%), pramipexole (84%), or ropinirole (78%) monotherapy discontinued these medications on initiation of rotigotine.

Conclusions: Rotigotine was effective and well-tolerated when used in routine clinical practice.
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http://dx.doi.org/10.1016/j.sleep.2013.02.013DOI Listing
June 2013

Unimpaired postprandial pancreatic polypeptide secretion in Parkinson's disease and REM sleep behavior disorder.

Mov Disord 2013 Apr 12;28(4):529-33. Epub 2012 Dec 12.

Department of Neurology, Philipps-University Marburg, Marburg, Germany.

Background: Pancreatic polypeptide is released immediately after food ingestion. The release is operated by vagal-abdominal projections and has therefore been suggested as a test for vagal nerve integrity. Pathoanatomical and clinical studies indicate vagal dysfunction in early Parkinson's disease (PD).

Methods: We assessed the postprandial secretion of pancreatic polypeptide and motilin in healthy controls (n = 18) and patients with idiopathic rapid-eye-movement sleep behavior disorder (iRBD, n = 10), a potential premotor stage of PD, as well as in drug-naive (n = 19) and treated (n = 19) PD patients.

Results: The postprandial pancreatic polypeptide secretion showed a physiological pattern in all groups and even an enhanced response in drug-naive PD and iRBD. Motilin concentrations correlated with pancreatic polypeptide concentrations.

Conclusions: Postprandial pancreatic polypeptide secretion is not a suitable test for vagal nerve integrity in PD. The unimpaired pancreatic polypeptide response in iRBD and PD might be explained by partially intact vagal-abdominal projections or compensatory mechanisms substituting a defective neuronal brain-gut axis.
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http://dx.doi.org/10.1002/mds.25246DOI Listing
April 2013

A single-question screen for rapid eye movement sleep behavior disorder: a multicenter validation study.

Mov Disord 2012 Jun 30;27(7):913-6. Epub 2012 May 30.

Department of Neurology, McGill University, Montreal General Hospital, Montreal, Québec, Canada.

Background: Idiopathic rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia that is an important risk factor for Parkinson's disease (PD) and Lewy body dementia. Its prevalence is unknown. One barrier to determining prevalence is that current screening tools are too long for large-scale epidemiologic surveys. Therefore, we designed the REM Sleep Behavior Disorder Single-Question Screen (RBD1Q), a screening question for dream enactment with a simple yes/no response.

Methods: Four hundred and eighty-four sleep-clinic-based participants (242 idiopathic RBD patients and 242 controls) completed the screen during a multicenter case-control study. All participants underwent a polysomnogram to define gold-standard diagnosis according to standard criteria.

Results: We found a sensitivity of 93.8% and a specificity of 87.2%. Sensitivity and specificity were similar in healthy volunteers, compared to controls or patients with other sleep diagnoses.

Conclusions: A single-question screen for RBD may reliably detect disease, with psychometric properties favorably comparable to those reported for longer questionnaires.
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http://dx.doi.org/10.1002/mds.25037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4043389PMC
June 2012

Patients with idiopathic rapid-eye-movement sleep behavior disorder show normal gastric motility assessed by the 13C-octanoate breath test.

Mov Disord 2011 Dec 24;26(14):2559-63. Epub 2011 Aug 24.

Department of Neurology, Philipps-University Marburg, Marburg, Germany.

Background: Delayed gastric emptying is a non-motor symptom of Parkinson's disease. Few data exist on gastric emptying in early-stage Parkinson's disease. In idiopathic rapid-eye-movement sleep behavior disorder, a presumable pre-motor stage of Parkinson's disease, gastric emptying has not yet been investigated.

Methods: Twenty healthy controls, 13 patients with idiopathic rapid-eye-movement sleep behavior disorder, and 39 patients with Parkinson's disease patients underwent standardized testing for gastric emptying with the (13)C-octanoate breath test.

Results: Gastric emptying was significantly delayed in drug-naïve (P < .001) and in treated Parkinson's disease patients (P < .001), but normal in patients with idiopathic rapid-eye-movement sleep behavior disorder.

Conclusions: Our study confirms delayed gastric emptying in drug-naïve, early-stage Parkinson's disease. Normal gastric emptying in idiopathic rapid-eye-movement sleep behavior disorder might be explained by the fact that neurodegenerative changes in structures modulating gastric motility are not severe enough to cause a functional deficit that can be detected by the (13)C-octanoate breath test.
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http://dx.doi.org/10.1002/mds.23933DOI Listing
December 2011

Genome-wide association study identifies novel restless legs syndrome susceptibility loci on 2p14 and 16q12.1.

PLoS Genet 2011 Jul 14;7(7):e1002171. Epub 2011 Jul 14.

Institute of Human Genetics, Technische Universität München, Munich, Germany.

Restless legs syndrome (RLS) is a sensorimotor disorder with an age-dependent prevalence of up to 10% in the general population above 65 years of age. Affected individuals suffer from uncomfortable sensations and an urge to move in the lower limbs that occurs mainly in resting situations during the evening or at night. Moving the legs or walking leads to an improvement of symptoms. Concomitantly, patients report sleep disturbances with consequences such as reduced daytime functioning. We conducted a genome-wide association study (GWA) for RLS in 922 cases and 1,526 controls (using 301,406 SNPs) followed by a replication of 76 candidate SNPs in 3,935 cases and 5,754 controls, all of European ancestry. Herein, we identified six RLS susceptibility loci of genome-wide significance, two of them novel: an intergenic region on chromosome 2p14 (rs6747972, P = 9.03 × 10(-11), OR = 1.23) and a locus on 16q12.1 (rs3104767, P = 9.4 × 10(-19), OR = 1.35) in a linkage disequilibrium block of 140 kb containing the 5'-end of TOX3 and the adjacent non-coding RNA BC034767.
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http://dx.doi.org/10.1371/journal.pgen.1002171DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3136436PMC
July 2011

Long-term safety and efficacy of rotigotine transdermal patch for moderate-to-severe idiopathic restless legs syndrome: a 5-year open-label extension study.

Lancet Neurol 2011 Aug 24;10(8):710-20. Epub 2011 Jun 24.

Philipps-Universität, Marburg, Germany.

Background: Safety and efficacy of non-ergot dopamine agonists for the treatment of idiopathic restless legs syndrome have been shown in short-term trials. We did a prospective open-label extension of a 6-week, double-blind randomised trial to assess the safety, tolerability, and efficacy of rotigotine transdermal patch for up to 5 years in patients with restless legs syndrome.

Methods: Patients (aged 18-75 years) with moderate-to-severe idiopathic restless legs syndrome were treated with once-daily rotigotine transdermal patch in 33 centres in Austria, Germany, and Spain between July 31, 2003, and April 15, 2009. The dose was titrated in weekly increments (up to 4 weeks) from 0·5 mg/24 h to a maximum of 4 mg/24 h, and was followed by up to 5 years of maintenance at the optimum dose. Primary safety outcomes included occurrence of adverse events and dropouts. Efficacy assessments were secondary and included the International Restless Legs Syndrome study group severity rating scale (IRLS). Augmentation of symptoms was assessed by means of standard diagnostic criteria and was confirmed by an international expert panel. All patients who received at least one dose of study drug were included in assessments. This study is registered with ClinicalTrials.gov, number NCT00498186.

Findings: 295 patients entered the open-label study, of whom 126 (43%) completed 5 years of follow-up. 169 (57%) patients discontinued treatment, 89 (30%) because of adverse events and 31 (11%) because of lack of efficacy. 70 patients (24%) discontinued during year 1 of maintenance. The most common adverse events were application site reactions, which occurred in 37% (106/290) of patients in year 1, 17% (38/220) of patients in year 2, 14% (27/191) of patients in year 3, and in less than 6% of patients during year 4 (8/159) and year 5 (8/147). 56 patients (19%) discontinued because of application site reactions. Mean rotigotine dose was 2·43 mg/24 h (SD 1·21) after initial titration and 3·09 mg/24 h (1·07) at the end of maintenance. Of 89 patients who discontinued because of adverse events, 28 (31%) were on 4 mg/24 h rotigotine. Mean IRLS score of patients entering the open-label study was 27·8 (SD 5·9) at baseline of the double-blind trial. In patients who completed the maintenance period, mean IRLS score was reduced from a baseline score of 27·7 (SD 6·0) by a mean of 18·7 points (SD 9·5) to a score of 9·0 (SD 9·2) at the end of maintenance. 39% (48/123) of patients who completed the trial were classified as symptom free according to the IRLS. Clinically significant augmentation was recorded in 39 patients (13%), of whom 15 (5%) were receiving a dose of rotigotine within the range approved by the European Medicines Agency (EMA; 1-3 mg/24 h) and 24 (8%) were receiving 4 mg/24 h rotigotine.

Interpretation: Rotigotine transdermal patch is generally well tolerated after 1 year and provides sustained efficacy for patients with moderate-to-severe restless legs syndrome at a stable dose for up to 5 years. Thus, rotigotine transdermal patch is an appropriate long-term treatment option for moderate-to-severe restless legs syndrome, a disorder that often requires lifelong treatment.

Funding: UCB BioSciences, on behalf of Schwarz Pharma, Ireland.
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http://dx.doi.org/10.1016/S1474-4422(11)70127-2DOI Listing
August 2011

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

BMC Neurol 2011 Feb 27;11:28. Epub 2011 Feb 27.

Sleep Research Institute, Madrid, Spain.

Background: 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.

Methods: 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 practitioners. 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.

Results: 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.

Conclusion: The EURLSSG task force reached a consensus and agreed on the diagnostic and treatment algorithms published here.
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http://dx.doi.org/10.1186/1471-2377-11-28DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3056753PMC
February 2011

Postprandial ghrelin response is reduced in patients with Parkinson's disease and idiopathic REM sleep behaviour disorder: a peripheral biomarker for early Parkinson's disease?

J Neurol 2011 Jun 24;258(6):982-90. Epub 2010 Dec 24.

Department of Neurology, Philipps-Universität Marburg, Rudolf-Bultmann-Strasse 8, 35033, Marburg, Germany.

Ghrelin, an orexigenic peptide, has multiple functions, which include promoting gastrointestinal motility and influencing higher brain functions. Experimental data suggest that ghrelin has neuroprotective potential in the MPTP mouse model of Parkinson's disease (PD). PD patients show delayed gastric emptying and other symptoms that may relate to disturbed excretion of ghrelin. No data are available on postprandial ghrelin response in patients with PD and idiopathic REM sleep behaviour disorder (iRBD)--a condition considered a putative preclinical stage of PD. We measured fasting and postprandial ghrelin serum concentrations in 20 healthy controls, 39 (including 19 drug-naïve) PD patients and 11 iRBD patients using a commercial radioimmunoassay for total ghrelin. For statistical analysis we employed ANCOVA and post-hoc testing with Bonferroni's method. Controls showed a decrease of mean fasting ghrelin serum concentrations in the early postprandial phase, followed by a recuperation starting 60 min after the test meal and reaching a maximum at 300 min. This recuperation was less pronounced in PD and iRBD; the slope of relative postprandial ghrelin recovery was different between the investigated groups (p = 0.007). Post-hoc testing showed a difference between controls and PD patients (p = 0.002) and between controls and iRBD patients (p = 0.037). The dynamic regulation of ghrelin in response to food intake is partially impaired in subjects at putative preclinical (iRBD) and clinical stages of PD. Reduced ghrelin excretion might increase the vulnerability of nigrostriatal dopaminergic neurons as suggested by animal studies. The impaired ghrelin excretion might qualify as a peripheral biomarker and be of diagnostic or therapeutic value.
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http://dx.doi.org/10.1007/s00415-010-5864-1DOI Listing
June 2011

Treatment of moderate to severe restless legs syndrome: 2-year safety and efficacy of rotigotine transdermal patch.

BMC Neurol 2010 Sep 28;10:86. Epub 2010 Sep 28.

Department of Neurology, Innsbruck Medical University, Innsbruck, Austria.

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.
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http://dx.doi.org/10.1186/1471-2377-10-86DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2958158PMC
September 2010

Rotigotine transdermal patch in moderate to severe idiopathic restless legs syndrome: a randomized, placebo-controlled polysomnographic study.

Sleep Med 2010 Oct 1;11(9):848-56. Epub 2010 Sep 1.

Department of Neurology, Philipps Universität, Rudolf-Bultmann-Str. 8, Marburg, Germany.

Objective: To assess the efficacy of rotigotine transdermal patch in subjects with moderate to severe idiopathic restless legs syndrome (RLS) and periodic limb movement (PLM) in sleep in a double-blind, randomized, placebo-controlled, multicenter study (NCT00275236).

Methods: Sixty-seven (46 rotigotine, 21 placebo) subjects applied rotigotine (maximum 3mg/24h) or placebo patches once-daily during a 4-week maintenance period; efficacy evaluations used polysomnographic measures and clinician/patient ratings.

Results: Mean PLM index (PLMI; PLM/h time in bed) decreased more with rotigotine (50.9/h to 8.1/h) than with placebo (37.4/h to 27.1/h; adjusted treatment ratio 4.25 (95% CI [2.48,7.28], p<0.0001). PLM during sleep with arousal index (PLMSAI; 8.57/h to 2.47/h under rotigotine, 6.5/h to 4.95/h under placebo; adjusted treatment difference: -3.12 (95% CI [-5.36, -0.88], p=0.0072) also improved more under rotigotine. At end of maintenance, 39% of rotigotine subjects had PLMI levels <5/h and 26% showed no RLS symptoms (IRLS=0), whereas no placebo subject met these criteria. Common drug-related adverse events for rotigotine and placebo included nausea (21.7%/4.8%), headache (17.4%/14.3%), application site reactions (17.4%/4.8%), and somnolence (10.9%/9.5%); most were mild to moderate in intensity.

Conclusions: Rotigotine transdermal patch was efficacious and well tolerated in the short-term treatment of RLS motor symptoms and associated sleep disturbances.
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http://dx.doi.org/10.1016/j.sleep.2010.02.014DOI Listing
October 2010

Diffusion tensor imaging in idiopathic REM sleep behavior disorder reveals microstructural changes in the brainstem, substantia nigra, olfactory region, and other brain regions.

Sleep 2010 Jun;33(6):767-73

Department of Neurology, Philipps-Universität Marburg, Marburg, Germany.

Study Objectives: Idiopathic rapid eye movement sleep behavior disorder (iRBD)--a parasomnia characterized by dream enactments--is a risk marker for the development of Parkinson disease (PD) and other alpha-synucleinopathies. The pathophysiology of iRBD is likely due to dysfunction of brainstem nuclei that regulate REM sleep. Diffusion tensor imaging (DTI) is a method for studying microstructural brain tissue integrity in vivo. We investigated whether DTI detects microstructural abnormalities in the brain of patients with iRBD--compared with age-matched control subjects--as an in vivo potential indicator for changes related to "preclinical (premotor)" neuropathology in PD.

Design: N/A.

Patients: Patients with iRBD (n = 12) and age-matched healthy control subjects (n = 12) were studied.

Interventions: At a 1.5T MRI maschine, whole-head DTI scans of fractional anisotropy, axial diffusivity (a potential marker of neuronal loss), and radial diffusivity (a potential marker of glial pathology) were analyzed using track-based spatial statistics, and 2 types of group analysis tools (FreeSurfer and FSL).

Measurements And Results: We found significant microstructural changes in the white matter of the brainstem (P < 0.0001), the right substantia nigra, the olfactory region, the left temporal lobe, the fornix, the internal capsule, the corona radiata, and the right visual stream of the patients with iRBD.

Conclusions: Changes were identified in regions known to be involved in REM-sleep regulation and/or to exhibit neurodegenerative pathology in iRBD and/or early PD. The study findings suggest that iRBD-related microstructural abnormalities can be detected in vivo with DTI, a widely available MRI technique.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2881532PMC
http://dx.doi.org/10.1093/sleep/33.6.767DOI Listing
June 2010

Health economic burden of patients with restless legs syndrome in a German ambulatory setting.

Pharmacoeconomics 2010 ;28(5):381-93

Department of Neurology, Philipps-University Marburg, Marburg, Germany.

The primary characteristics of restless legs syndrome (RLS), including severe sleep disorders, restlessness in the evening and discomfort while at rest, have substantial impact on normal daily activities. Because of the high prevalence of RLS in the general population, it is necessary to evaluate the economic impact of RLS. To determine the health economic burden of patients with RLS in Germany. A total of 519 RLS patients (mean age: 65.2 +/- 11.1 years) in different stages of disease were recruited in five health centres (university hospitals, district hospitals and office-based neurologists) by applying the diagnostic criteria of the International Restless Legs Syndrome Study Group. A questionnaire was administered that assessed healthcare resource consumption as well as socioeconomic, demographic, clinical and health status. In addition, the International RLS severity scale (IRLS), Epworth Sleepiness Scale (ESS), EQ-5D and Beck Depression Inventory (BDI) were addressed in the assessment. Direct and indirect costs (euro, year 2006 values) were derived from various German economic resources and calculated from the perspective of the healthcare and transfer payment providers. We calculated average total costs over the 3-month observation period. It was determined that average total costs were euro2090 for this period. The average direct medical and non-medical costs from the perspective of the health insurance provider were determined to be euro780, with euro300 attributed to drug costs and euro354 to hospitalization costs. Average total indirect costs amounted to euro1308 and were calculated based on productivity loss, using the human capital approach. As cost-driving factors we identified disease severity according to the IRLS (p < 0.01) and ESS (p < 0.04). Health-related quality of life was determined to be substantially affected by RLS; the mean EQ-5D visual analogue scale (VAS) was 55.6, considerably lower than that of the age-matched general population. RLS places a notable financial burden on society as well as on patients and their families. More detailed studies are needed to evaluate the health economic impact of this disorder.
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http://dx.doi.org/10.2165/11531030-000000000-00000DOI Listing
January 2011

Normal regional brain iron concentration in restless legs syndrome measured by MRI.

Nat Sci Sleep 2010 22;2:19-22. Epub 2009 Dec 22.

Department of Neurology, Center of Nervous Diseases, Marburg, Germany.

Using a T2* gradient echo magnetic resonance imaging (MRI) sequence, regional T2 signal intensity (SI) values, a surrogate marker for T2 values, were determined in 12 regions of interest (substantia nigra, pallidum, caudate head, thalamus, occipital white matter, and frontal white matter bilaterally) and in two reference regions (cerebrospinal fluid and bone) in 12 patients suffering from moderate to severe idiopathic restless legs syndrome (RLS; mean age 58.5 ± 8.7 years) for 12.1 ± 9.1 years and in 12 healthy control subjects (mean age 56.8 ± 10.6 years). Iron deposits shorten T2 relaxation times on T2-weighted MRI. We used regional T2* SI to estimate regional T2-values. A T2-change ratio was calculated for each region of interest relative to the reference regions. We did not find significant differences in any of the investigated brain regions. In addition, serum measures involved in iron metabolism did not correlate with T2 SI values. We could not replicate earlier findings describing reduced regional brain iron concentrations in patients with RLS. Our results do not support the view of substantially impaired regional brain iron in RLS.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3630928PMC
April 2013

Differential diagnosis of unpleasant sensations in the legs: prevalence of restless legs syndrome in a primary care population.

Sleep Med 2010 Feb 22;11(2):161-6. Epub 2009 Dec 22.

Department of Neurology, J.W. Goethe-University, Frankfurt am Main, Germany; Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany.

Background: Restless legs syndrome (RLS) is a common neurological condition. We investigated the prevalence of RLS in patients suffering from unpleasant sensations in the legs.

Methods: We included 16,543 patients consulting one of 312 primary care practices in Germany on November 8, 2007. All patients filled out a self-assessment questionnaire. Patients who reported suffering from unpleasant sensations in the legs were then assessed by the physician. Main outcome measures were the overall prevalence of unpleasant sensations in the legs and the prevalence of RLS; the most common differential diagnoses in the subpopulation suffered from unpleasant leg sensations.

Results: Out of all participating patients 7704 (46.6%) suffered from unpleasant sensations in the legs and 1758 (10.6%) were diagnosed with RLS according to the four essential clinical criteria. Among patients with unpleasant leg sensations, the prevalence of RLS was considerably higher (22.7%) than in the total population. The most common differential diagnoses were osteoarthritis (21.5%), disc lesion (19.2%), varicose veins (18.8%) and muscle cramps (14.6%). Of the patients with RLS 53.4% had already consulted their physician about their leg problems in the past. Still, only 20.1% of the RLS patients had received the correct diagnosis. Comorbidity rates were significantly increased in RLS patients compared to patients suffering from leg symptoms of other origin.

Conclusions: This study showed a high prevalence of RLS in primary care patients with unpleasant sensations in the legs. Thus, in patients presenting with these symptoms the diagnosis of RLS should routinely be considered.
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http://dx.doi.org/10.1016/j.sleep.2009.04.009DOI Listing
February 2010

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

J Neurol 2010 Feb 11;257(2):230-7. Epub 2009 Sep 11.

Department of Neurology, Innsbruck Medical University, Anichstr. 35, 6020, Innsbruck, Austria.

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 (> or =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.
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http://dx.doi.org/10.1007/s00415-009-5299-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3085743PMC
February 2010

Restless Legs Syndrome (RLS) and Parkinson's disease (PD)-related disorders or different entities?

J Neurol Sci 2010 Feb 15;289(1-2):135-7. Epub 2009 Sep 15.

Department of Neurology, Philipps-University, Marburg, Germany.

The relationship between Restless Legs Syndrome (RLS) and Parkinson's disease (PD) is still controversial. Most genetic, pathological, and imaging data argue against a close association of these two disorders. Still, many studies reported an increased prevalence of RLS in PD patients. These studies are difficult to interpret because the current diagnostic criteria for RLS have not been validated in PD patients. Although many PD patients suffer from motor restlessness due to parkinsonism and may thus mimic RLS, the risk for (secondary) RLS in PD patients is probably slightly increased. This review provides an overview of the current pertinent literature and discusses the possible association between RLS and PD.
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http://dx.doi.org/10.1016/j.jns.2009.08.035DOI Listing
February 2010

Transcranial midbrain sonography in narcoleptic subjects with and without concomitant REM sleep behaviour disorder.

J Neurol 2009 Jun 28;256(6):874-7. Epub 2009 Feb 28.

Department of Neurology, Philipps-Universität Marburg, Rudolf-Bultmann-Str. 8, 35039, Marburg, Germany.

Substantia nigra (SN) hyperechogenicity--a sonographic vulnerability marker for Parkinson's disease (PD)--has been recently described in patients with idiopathic REM sleep behaviour disorder (RBD). It is not known whether subjects with narcolepsy (who frequently have associated RBD) also show SN hyperechogenicity. The aim of this study was to (1) evaluate SN echogenicity in narcolepsy and (2) determine whether transcranial sonography (TCS) differs in narcoleptic subjects with and without RBD. A total of 16 patients with narcolepsy-cataplexy (7 had a concomitant, video-polysomnographically based diagnosis of RBD) were examined with TCS by two investigators blinded to the clinical data. The size of the SN echogenic area in both subgroups was within the range previously described for healthy subjects. The brainstem raphe, however, was reduced in five of seven narcoleptic subjects with RBD, whereas only two of nine narcoleptic subjects without RBD exhibited this TCS finding. We conclude that evaluation of SN echogenicity does not discriminate between both subgroups. The absence of SN hyperechogenicity in narcoleptic patients with RBD supports the hypothesis that SN hyperechogenicity in patients with presumed idiopathic RBD is an additional risk marker for subsequent evolvement of PD rather than an RBD-immanent finding. Reduced echogenicity of the brainstem raphe might indicate an involvement of the serotonergic system in narcoleptic subjects with RBD.
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http://dx.doi.org/10.1007/s00415-009-5032-7DOI Listing
June 2009

Treatment of restless legs syndrome: an evidence-based review and implications for clinical practice.

Mov Disord 2008 Dec;23(16):2267-302

Paracelsus-Elena Hospital, Center of Parkinsonism and Movement Disorders, Kassel, Germany.

Only in the last three decades, the restless legs syndrome (RLS) has been examined in randomized controlled trials. The Movement Disorder Society (MDS) commissioned a task force to perform an evidence-based review of the medical literature on treatment modalities used to manage patients with RLS. The task force performed a search of the published literature using electronic databases. The therapeutic efficacy of each drug was classified as being either efficacious, likely efficacious, investigational, nonefficacious, or lacking sufficient evidence to classify. Implications for clinical practice were generated based on the levels of evidence and particular features of each modality, such as adverse events. All studies were classed according to three levels of evidence. All Level-I trials were included in the efficacy tables; if no Level-I trials were available then Level-II trials were included or, in the absence of Level-II trials, Level-III studies or case series were included. Only studies published in print or online before December 31, 2006 were included. All studies published after 1996, which attempted to assess RLS augmentation, were reviewed in a separate section. The following drugs are considered efficacious for the treatment of RLS: levodopa, ropinirole, pramipexole, cabergoline, pergolide, and gabapentin. Drugs considered likely efficacious are rotigotine, bromocriptine, oxycodone, carbamazepine, valproic acid, and clonidine. Drugs that are considered investigational are dihydroergocriptine, lisuride, methadone, tramadol, clonazepam, zolpidem, amantadine, and topiramate. Magnesium, folic acid, and exercise are also considered to be investigational. Sumanirole is nonefficacious. Intravenous iron dextran is likely efficacious for the treatment of RLS secondary to end-stage renal disease and investigational in RLS subjects with normal renal function. The efficacy of oral iron is considered investigational; however, its efficacy appears to depend on the iron status of subjects. Cabergoline and pergolide (and possibly lisuride) require special monitoring due to fibrotic complications including cardiac valvulopathy. Special monitoring is required for several other medications based on clinical concerns: opioids (including, but not limited to, oxycodone, methadone and tramadol), due to possible addiction and respiratory depression, and some anticonvulsants (particularly, carbamazepine and valproic acid), due to systemic toxicities.
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http://dx.doi.org/10.1002/mds.22254DOI Listing
December 2008

One year open-label safety and efficacy trial with rotigotine transdermal patch in moderate to severe idiopathic restless legs syndrome.

Sleep Med 2008 Dec 26;9(8):865-73. Epub 2008 Aug 26.

Department of Neurology, Philipps Universität, Marburg, Germany.

Background: Long-term efficacy and tolerability data are not yet available for patch formulations of dopamine agonists in restless legs syndrome.

Methods: Efficacy and safety of rotigotine (0.5-4mg/24h), formulated as a once-daily transdermal system (patch), were investigated in an open extension (SP710) of a preceding 6-week placebo-controlled trial (SP709, 341 randomized patients) in patients with idiopathic restless legs syndrome. For efficacy assessment the international RLS severity scale (IRLS), the RLS-6 scales, the clinical global impressions (CGI) and the QoL-RLS questionnaire were administered. In addition, long-term tolerability and safety were assessed.

Results: Of 310 patients who finished the controlled trial, 295 (mean age 58+/-10 years, 66% females) with a mean IRLS score of 27.8+/-5.9 at baseline of SP709 were included. We report results after one year of this ongoing long-term trial. Two hundred twenty patients (retention rate=74.6%) completed the 12-month follow-up period. The mean daily dose was 2.8+/-1.2mg/24h with 4mg/24h (40.6%) being the most frequently applied dose; 14.8% were sufficiently treated with 0.5 or 1.0mg/24h. The IRLS total score improved by ?17.4+/-9.9 points between baseline and end of Year 1 (p<0.001). The other measures of severity, sleep satisfaction and quality of life supported the efficacy of rotigotine (p<0.001 for pre-post-comparisons of all efficacy variables). The tolerability was described as "good" or "very good" by 80.3% of all patients. The most common adverse events were application site reactions (40.0%), which led to withdrawal in 13.2%. Further relatively frequent adverse events were nausea (9.5%) and fatigue (6.4%). Two drug-related serious adverse events, nausea and syncope, required hospitalization. Symptoms of augmentation were not reported by the patients.

Conclusion: Rotigotine provided a stable, clinically relevant improvement in all efficacy measures throughout one year of maintenance therapy. The transdermal patch was safe and generally well tolerated by the majority of patients. Comparable to any transdermal therapy, application site reactions were the main treatment complication.
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http://dx.doi.org/10.1016/j.sleep.2008.04.012DOI Listing
December 2008

PTPRD (protein tyrosine phosphatase receptor type delta) is associated with restless legs syndrome.

Nat Genet 2008 Aug 27;40(8):946-8. Epub 2008 Jul 27.

Institute of Human Genetics, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg 85764, Germany.

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.
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http://dx.doi.org/10.1038/ng.190DOI Listing
August 2008

Continuous sleep EEG monitoring in PD patients with and without sleep attacks.

Parkinsonism Relat Disord 2009 Mar 10;15(3):238-41. Epub 2008 Jul 10.

Department of Neurology, Philipps-University Marburg, Rudolf-Bultmann-Strasse 8, 35039 Marburg, Germany.

The pathogenesis of sleep attacks in Parkinson's disease (PD) is still unresolved. We investigated seven matched pairs of PD patients with and without a history of sleep attacks using continuous sleep EEG recording. According to the event marker altogether 12 sleep attacks were identified in three patients with a history of sleep attacks. All sleep attacks were characterized by NREM stage 1 and 2 sleep, whereas no sleep onset REM episodes were recorded. Five sleep attacks fulfilled our criteria for microsleep episodes lasting less than 120 s. The cumulative duration of microsleep episodes during the day was 27.7+/-20 min in patients with a history of sleep attacks vs. 6.4+/-4.1 min in patients without a history of sleep attacks (p=0.03), i.e., the majority of microsleep episodes were not perceived by the patients. In summary, our study suggests that sleep attacks are intrusions of NREM stage 1 and 2 sleep into wakefulness and can be identical to microsleep episodes. Future studies should systematically address the awareness of short sleep episodes in patients with PD and other disorders with increased daytime sleepiness.
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http://dx.doi.org/10.1016/j.parkreldis.2008.05.009DOI Listing
March 2009

Efficacy of rotigotine for treatment of moderate-to-severe restless legs syndrome: a randomised, double-blind, placebo-controlled trial.

Lancet Neurol 2008 Jul;7(7):595-604

Paracelsus-Elena Hospital, Kassel, Germany.

Background: Continuous administration of a dopamine agonist could be used to treat patients with restless legs syndrome. Our aim was to investigate the efficacy of transdermal rotigotine in the treatment of idiopathic restless legs syndrome.

Methods: In this randomised, double-blind, placebo-controlled trial, 458 patients with moderate-to-severe idiopathic restless legs syndrome (average baseline International Restless Legs Syndrome Study Group severity rating scale [IRLS] sum score of 28.1) were randomly assigned to receive transdermal rotigotine 1 mg over 24 h (n=115), 2 mg over 24 h (n=112), or 3 mg over 24 h (n=114), or to receive placebo (n=117). Study medication was delivered via patches, applied once a day for 6 months. Randomisation was done with a computer-generated randomisation list, stratified by centre. Primary efficacy outcomes were absolute change from baseline to end of maintenance in IRLS sum score and in the clinical global impressions (CGI) item 1 score, assessed by analysis of covariance in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT00136045.

Findings: Efficacy analyses were done on 112 patients in the 1 mg group, 109 in the 2 mg group, 112 in the 3 mg group, and 114 in the placebo group. Mean change in IRLS sum score from baseline at the end of the maintenance phase was -13.7 (SE 0.9) in the 1 mg group, -16.2 (0.9) in the 2 mg group, -16.8 (0.9) in the 3 mg group, and -8.6 (0.9) in the placebo group (p<0.0001 for treatment difference vs placebo with each dose). Mean change in CGI item 1 score from baseline at the end of the maintenance phase was -2.09 (0.14) in the 1 mg group, -2.41 (0.14) in the 2 mg group, -2.55 (0.14) in the 3 mg group, and -1.34 (0.14) in the placebo group (p<0.0001 for treatment difference vs placebo with each dose). Skin reactions, mostly mild or moderate, were seen in 145 (43%) of 341 patients who received rotigotine and in two (2%) of 117 who received placebo. Ten patients had serious adverse event that were deemed to be related to rotigotine: elevation of liver enzymes (one patient), worsening of tinnitus (one patient), non-response to anticoagulation (one patient), electrocardiogram changes (one patient), and application-site reactions (six patients). No admissions to hospital were needed for the application-site reactions, and they all resolved within a short time of patch removal without any other therapeutic intervention. The rate of typical dopaminergic side-effects in patients who received rotigotine was low; no signs of augmentation were noted.

Interpretation: 24 h transdermal delivery of low-dose rotigotine could be used to relieve the night-time and daytime symptoms of restless legs syndrome.

Funding: Schwarz Biosciences.
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http://dx.doi.org/10.1016/S1474-4422(08)70112-1DOI Listing
July 2008