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Trenkwalder, Claudia
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Trenkwalder, Claudia
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Trenkwalder, Claudia
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Trenkwalder, C.
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2019Journal Article [["dc.bibliographiccitation.firstpage","152"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Movement Disorders"],["dc.bibliographiccitation.lastpage","153"],["dc.bibliographiccitation.volume","34"],["dc.contributor.author","Salminen, Aaro V."],["dc.contributor.author","Allen, Richard P."],["dc.contributor.author","Högl, Birgit"],["dc.contributor.author","Inoue, Yuichi"],["dc.contributor.author","Oertel, Wolfgang"],["dc.contributor.author","Winkelman, John W."],["dc.contributor.author","Trenkwalder, Claudia"],["dc.contributor.author","Sampaio, Cristina"],["dc.contributor.author","Winkelmann, Juliane"],["dc.date.accessioned","2021-06-01T10:46:50Z"],["dc.date.available","2021-06-01T10:46:50Z"],["dc.date.issued","2019"],["dc.identifier.doi","10.1002/mds.27570"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/85400"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-425"],["dc.relation.eissn","1531-8257"],["dc.relation.issn","0885-3185"],["dc.title","Reply to: A note on rotigotine for restless legs syndrome after renal transplantation"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]Details DOI2017Journal Article [["dc.bibliographiccitation.firstpage","78"],["dc.bibliographiccitation.journal","Sleep Medicine"],["dc.bibliographiccitation.lastpage","85"],["dc.bibliographiccitation.volume","31"],["dc.contributor.author","Trenkwalder, Claudia"],["dc.contributor.author","Zieglgänsberger, Walter"],["dc.contributor.author","Ahmedzai, Sam"],["dc.contributor.author","Högl, Birgit"],["dc.date.accessioned","2018-10-10T06:53:44Z"],["dc.date.available","2018-10-10T06:53:44Z"],["dc.date.issued","2017"],["dc.description.abstract","Opioid receptor agonists are known to relieve restless legs syndrome (RLS) symptoms, including both sensory and motor events, as well as improving sleep. The mechanisms of action of opioids in RLS are still a matter of speculation. The mechanisms by which endogenous opioids contribute to the pathophysiology of this polygenetic disorder, in which there are a number of variants, including developmental factors, remains unknown. A summary of the cellular mode of action of morphine and its (partial) antagonist naloxone via α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors and the involvement of dendritic spine activation is described. By targeting pain and its consequences, opioids are the first-line treatment in many diseases and conditions with both acute and chronic pain and have thus been used in both acute and chronic pain conditions over the last 40 years. Addiction, dependence, and tolerability of opioids show a wide variability interindividually, as the response to opioids is influenced by a complex combination of genetic, molecular, and phenotypic factors. Although several trials have now addressed opioid treatment in RLS, hyperalgesia as a complication of long-term opioid treatment, or opioid-opioid interaction have not received much attention so far. Therapeutic opioids may act not only on opioid receptors but also via histamine or N-methyl-d-aspartate (NMDA) receptors. In patients with RLS, one of the few studies investigating opioid bindings found that possible brain regions involved in the severity of RLS symptoms are similar to those known to be involved in chronic pain, such as the medial pain system (medial thalamus, amygdala, caudate nucleus, anterior cingulate gyrus, insular cortex, and orbitofrontal cortex). The results of this diprenorphine positron emission tomography study suggested that the more severe the RLS, the greater the release of endogenous opioids. Since 1993, when the first small controlled study was performed with oxycodone in RLS, opioids have been considered an efficacious off-label therapy in patients with severe RLS. A recent trial has proved the efficacy of a combination of prolonged release oxycodone/naloxone in patients with severe RLS as second-line therapy, with a mean dosage of 10/5 mg twice daily (mean difference of International Restless Legs Syndrome Study Group Rating Scale (IRLS) score between groups at 12 weeks: 8.15), and has now been licensed as the first opioid therapy in Europe. The current results from both short- and long-term trials and studies with opioids encourage optimism in alleviating RLS symptoms in patients with severe RLS, or possibly during or after augmentation."],["dc.fs.pkfprnr","47312"],["dc.identifier.doi","10.1016/j.sleep.2016.09.017"],["dc.identifier.fs","634111"],["dc.identifier.pmid","27964861"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/15914"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.relation.eissn","1878-5506"],["dc.title","Pain, opioids, and sleep: implications for restless legs syndrome treatment"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]Details DOI PMID PMC2018Journal Article [["dc.bibliographiccitation.firstpage","98"],["dc.bibliographiccitation.journal","Parkinsonism & Related Disorders"],["dc.bibliographiccitation.lastpage","101"],["dc.bibliographiccitation.volume","52"],["dc.contributor.author","Ouled Amar Bencheikh, Bouchra"],["dc.contributor.author","Ruskey, Jennifer A."],["dc.contributor.author","Arnulf, Isabelle"],["dc.contributor.author","Dauvilliers, Yves"],["dc.contributor.author","Monaca, Christelle Charley"],["dc.contributor.author","De Cock, Valérie Cochen"],["dc.contributor.author","Gagnon, Jean-François"],["dc.contributor.author","Spiegelman, Dan"],["dc.contributor.author","Hu, Michele T.M."],["dc.contributor.author","Högl, Birgit"],["dc.contributor.author","Stefani, Ambra"],["dc.contributor.author","Ferini-Strambi, Luigi"],["dc.contributor.author","Plazzi, Giuseppe"],["dc.contributor.author","Antelmi, Elena"],["dc.contributor.author","Young, Peter"],["dc.contributor.author","Heidbreder, Anna"],["dc.contributor.author","Mollenhauer, Brit"],["dc.contributor.author","Sixel-Döring, Friederike"],["dc.contributor.author","Trenkwalder, Claudia"],["dc.contributor.author","Oertel, Wolfgang"],["dc.contributor.author","Montplaisir, Jacques Y."],["dc.contributor.author","Postuma, Ronald B."],["dc.contributor.author","Rouleau, Guy A."],["dc.contributor.author","Gan-Or, Ziv"],["dc.date.accessioned","2020-12-10T15:20:41Z"],["dc.date.available","2020-12-10T15:20:41Z"],["dc.date.issued","2018"],["dc.identifier.doi","10.1016/j.parkreldis.2018.03.019"],["dc.identifier.issn","1353-8020"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/72760"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.title","LRRK2 protective haplotype and full sequencing study in REM sleep behavior disorder"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]Details DOI2020Journal Article [["dc.bibliographiccitation.firstpage","142.e5"],["dc.bibliographiccitation.journal","Neurobiology of Aging"],["dc.bibliographiccitation.lastpage","142.e7"],["dc.bibliographiccitation.volume","93"],["dc.contributor.author","Rudakou, Uladzislau"],["dc.contributor.author","Futhey, Naomi C."],["dc.contributor.author","Krohn, Lynne"],["dc.contributor.author","Ruskey, Jennifer A."],["dc.contributor.author","Heilbron, Karl"],["dc.contributor.author","Cannon, Paul"],["dc.contributor.author","Alam, Armaghan"],["dc.contributor.author","Arnulf, Isabelle"],["dc.contributor.author","Hu, Michele T.M."],["dc.contributor.author","Montplaisir, Jacques Y."],["dc.contributor.author","Gagnon, Jean-François"],["dc.contributor.author","Desautels, Alex"],["dc.contributor.author","Dauvilliers, Yves"],["dc.contributor.author","Toffoli, Marco"],["dc.contributor.author","Gigli, Gian Luigi"],["dc.contributor.author","Valente, Mariarosaria"],["dc.contributor.author","Högl, Birgit"],["dc.contributor.author","Stefani, Ambra"],["dc.contributor.author","Holzknecht, Evi"],["dc.contributor.author","Sonka, Karel"],["dc.contributor.author","Kemlink, David"],["dc.contributor.author","Oertel, Wolfang"],["dc.contributor.author","Janzen, Annette"],["dc.contributor.author","Plazzi, Giuseppe"],["dc.contributor.author","Antelmi, Elena"],["dc.contributor.author","Figorilli, Michela"],["dc.contributor.author","Puligheddu, Monica"],["dc.contributor.author","Mollenhauer, Brit"],["dc.contributor.author","Trenkwalder, Claudia"],["dc.contributor.author","Sixel-Döring, Friederike"],["dc.contributor.author","De Cock, Valérie Cochen"],["dc.contributor.author","Monaca, Christelle Charley"],["dc.contributor.author","Heidbreder, Anna"],["dc.contributor.author","Ferini-Strambi, Luigi"],["dc.contributor.author","Dijkstra, Femke"],["dc.contributor.author","Viaene, Mineke"],["dc.contributor.author","Abril, Beatriz"],["dc.contributor.author","Boeve, Bradley F."],["dc.contributor.author","Postuma, Ronald B."],["dc.contributor.author","Rouleau, Guy A."],["dc.contributor.author","Gan-Or, Ziv"],["dc.date.accessioned","2021-04-14T08:23:22Z"],["dc.date.available","2021-04-14T08:23:22Z"],["dc.date.issued","2020"],["dc.identifier.doi","10.1016/j.neurobiolaging.2020.04.005"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/80887"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.relation.issn","0197-4580"],["dc.title","SMPD1 variants do not have a major role in rapid eye movement sleep behavior disorder"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]Details DOI2020Journal Article [["dc.bibliographiccitation.firstpage","235"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Movement Disorders"],["dc.bibliographiccitation.lastpage","240"],["dc.bibliographiccitation.volume","36"],["dc.contributor.author","Mufti, Kheireddin"],["dc.contributor.author","Rudakou, Uladzislau"],["dc.contributor.author","Yu, Eric"],["dc.contributor.author","Krohn, Lynne"],["dc.contributor.author","Ruskey, Jennifer A."],["dc.contributor.author","Asayesh, Farnaz"],["dc.contributor.author","Laurent, Sandra B."],["dc.contributor.author","Spiegelman, Dan"],["dc.contributor.author","Arnulf, Isabelle"],["dc.contributor.author","Hu, Michele T.M."],["dc.contributor.author","Montplaisir, Jacques Y."],["dc.contributor.author","Gagnon, Jean‐François"],["dc.contributor.author","Desautels, Alex"],["dc.contributor.author","Dauvilliers, Yves"],["dc.contributor.author","Gigli, Gian Luigi"],["dc.contributor.author","Valente, Mariarosaria"],["dc.contributor.author","Janes, Francesco"],["dc.contributor.author","Högl, Birgit"],["dc.contributor.author","Stefani, Ambra"],["dc.contributor.author","Holzknecht, Evi"],["dc.contributor.author","Šonka, Karel"],["dc.contributor.author","Kemlink, David"],["dc.contributor.author","Oertel, Wolfgang"],["dc.contributor.author","Janzen, Annette"],["dc.contributor.author","Plazzi, Giuseppe"],["dc.contributor.author","Antelmi, Elena"],["dc.contributor.author","Figorilli, Michela"],["dc.contributor.author","Puligheddu, Monica"],["dc.contributor.author","Mollenhauer, Brit"],["dc.contributor.author","Trenkwalder, Claudia"],["dc.contributor.author","Sixel‐Döring, Friederike"],["dc.contributor.author","Cochen De Cock, Valérie"],["dc.contributor.author","Monaca, Christelle Charley"],["dc.contributor.author","Heidbreder, Anna"],["dc.contributor.author","Ferini‐Strambi, Luigi"],["dc.contributor.author","Dijkstra, Femke"],["dc.contributor.author","Viaene, Mineke"],["dc.contributor.author","Abril, Beatriz"],["dc.contributor.author","Boeve, Bradley F."],["dc.contributor.author","Postuma, Ronald B."],["dc.contributor.author","Rouleau, Guy A."],["dc.contributor.author","Gan‐Or, Ziv"],["dc.date.accessioned","2021-04-14T08:23:40Z"],["dc.date.available","2021-04-14T08:23:40Z"],["dc.date.issued","2020"],["dc.identifier.doi","10.1002/mds.28318"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/81008"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.relation.eissn","1531-8257"],["dc.relation.issn","0885-3185"],["dc.title","Comprehensive Analysis of Familial Parkinsonism Genes in Rapid‐Eye‐Movement Sleep Behavior Disorder"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]Details DOI2020Journal Article [["dc.bibliographiccitation.firstpage","e1008"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","Neurology"],["dc.bibliographiccitation.lastpage","e1016"],["dc.bibliographiccitation.volume","95"],["dc.contributor.author","Krohn, Lynne"],["dc.contributor.author","Ruskey, Jennifer A."],["dc.contributor.author","Rudakou, Uladzislau"],["dc.contributor.author","Leveille, Etienne"],["dc.contributor.author","Asayesh, Farnaz"],["dc.contributor.author","Hu, Michele T.M."],["dc.contributor.author","Arnulf, Isabelle"],["dc.contributor.author","Dauvilliers, Yves"],["dc.contributor.author","Högl, Birgit"],["dc.contributor.author","Stefani, Ambra"],["dc.contributor.author","Monaca, Christelle Charley"],["dc.contributor.author","Abril, Beatriz"],["dc.contributor.author","Plazzi, Giuseppe"],["dc.contributor.author","Antelmi, Elena"],["dc.contributor.author","Ferini-Strambi, Luigi"],["dc.contributor.author","Heidbreder, Anna"],["dc.contributor.author","Boeve, Bradley F."],["dc.contributor.author","Espay, Alberto J."],["dc.contributor.author","De Cock, Valérie Cochen"],["dc.contributor.author","Mollenhauer, Brit"],["dc.contributor.author","Sixel-Döring, Friederike"],["dc.contributor.author","Trenkwalder, Claudia"],["dc.contributor.author","Sonka, Karel"],["dc.contributor.author","Kemlink, David"],["dc.contributor.author","Figorilli, Michela"],["dc.contributor.author","Puligheddu, Monica"],["dc.contributor.author","Dijkstra, Femke"],["dc.contributor.author","Viaene, Mineke"],["dc.contributor.author","Oertel, Wolfgang"],["dc.contributor.author","Toffoli, Marco"],["dc.contributor.author","Gigli, Gian Luigi"],["dc.contributor.author","Valente, Mariarosaria"],["dc.contributor.author","Gagnon, Jean-François"],["dc.contributor.author","Desautels, Alex"],["dc.contributor.author","Montplaisir, Jacques Y."],["dc.contributor.author","Postuma, Ronald B."],["dc.contributor.author","Rouleau, Guy A."],["dc.contributor.author","Gan-Or, Ziv"],["dc.date.accessioned","2021-04-14T08:23:55Z"],["dc.date.available","2021-04-14T08:23:55Z"],["dc.date.issued","2020"],["dc.identifier.doi","10.1212/WNL.0000000000010042"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/81098"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.relation.eissn","1526-632X"],["dc.relation.issn","0028-3878"],["dc.title","GBA variants in REM sleep behavior disorder"],["dc.title.alternative","A multicenter study"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]Details DOI2020Journal Article [["dc.bibliographiccitation.firstpage","740"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","Journal of Neurology, Neurosurgery & Psychiatry"],["dc.bibliographiccitation.lastpage","749"],["dc.bibliographiccitation.volume","91"],["dc.contributor.author","Videnovic, Aleksandar"],["dc.contributor.author","Ju, Yo-El S"],["dc.contributor.author","Arnulf, Isabelle"],["dc.contributor.author","Cochen-De Cock, Valérie"],["dc.contributor.author","Högl, Birgit"],["dc.contributor.author","Kunz, Dieter"],["dc.contributor.author","Provini, Federica"],["dc.contributor.author","Ratti, Pietro-Luca"],["dc.contributor.author","Schiess, Mya C"],["dc.contributor.author","Schenck, Carlos H"],["dc.contributor.author","Trenkwalder, Claudia"],["dc.date.accessioned","2021-04-14T08:25:19Z"],["dc.date.available","2021-04-14T08:25:19Z"],["dc.date.issued","2020"],["dc.identifier.doi","10.1136/jnnp-2020-322875"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/81594"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.relation.eissn","1468-330X"],["dc.relation.issn","0022-3050"],["dc.title","Clinical trials in REM sleep behavioural disorder: challenges and opportunities"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]Details DOI2020Journal Article [["dc.bibliographiccitation.firstpage","584"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Annals of Neurology"],["dc.bibliographiccitation.lastpage","598"],["dc.bibliographiccitation.volume","87"],["dc.contributor.author","Krohn, Lynne"],["dc.contributor.author","Wu, Richard Y. J."],["dc.contributor.author","Heilbron, Karl"],["dc.contributor.author","Ruskey, Jennifer A."],["dc.contributor.author","Laurent, Sandra B."],["dc.contributor.author","Blauwendraat, Cornelis"],["dc.contributor.author","Alam, Armaghan"],["dc.contributor.author","Arnulf, Isabelle"],["dc.contributor.author","Hu, Michele T. M."],["dc.contributor.author","Gan‐Or, Ziv"],["dc.contributor.author","Dauvilliers, Yves"],["dc.contributor.author","Högl, Birgit"],["dc.contributor.author","Toft, Mathias"],["dc.contributor.author","Bjørnarå, Kari Anne"],["dc.contributor.author","Stefani, Ambra"],["dc.contributor.author","Holzknecht, Evi"],["dc.contributor.author","Monaca, Christelle Charley"],["dc.contributor.author","Abril, Beatriz"],["dc.contributor.author","Plazzi, Giuseppe"],["dc.contributor.author","Antelmi, Elena"],["dc.contributor.author","Young, Peter"],["dc.contributor.author","Heidbreder, Anna"],["dc.contributor.author","Cochen De Cock, Valérie"],["dc.contributor.author","Mollenhauer, Brit"],["dc.contributor.author","Sixel‐Döring, Friederike"],["dc.contributor.author","Trenkwalder, Claudia"],["dc.contributor.author","Sonka, Karel"],["dc.contributor.author","Kemlink, David"],["dc.contributor.author","Puligheddu, Monica"],["dc.contributor.author","Dijkstra, Femke"],["dc.contributor.author","Viaene, Mineke"],["dc.contributor.author","Oertel, Wolfang"],["dc.contributor.author","Toffoli, Marco"],["dc.contributor.author","Gigli, Gian Luigi"],["dc.contributor.author","Valente, Mariarosaria"],["dc.contributor.author","Gagnon, Jean‐François"],["dc.contributor.author","Nalls, Mike A."],["dc.contributor.author","Singleton, Andrew B."],["dc.contributor.author","Desautels, Alex"],["dc.contributor.author","Montplaisir, Jacques Y."],["dc.contributor.author","Cannon, Paul"],["dc.contributor.author","Ross, Owen A."],["dc.contributor.author","Boeve, Bradley F."],["dc.contributor.author","Dupré, Nicolas"],["dc.contributor.author","Fon, Edward A."],["dc.contributor.author","Postuma, Ronald B."],["dc.contributor.author","Pihlstrøm, Lasse"],["dc.contributor.author","Rouleau, Guy A."],["dc.contributor.authorgroup","23andMe Research Team"],["dc.date.accessioned","2021-04-14T09:58:36Z"],["dc.date.available","2021-04-14T09:58:36Z"],["dc.date.issued","2020"],["dc.identifier.doi","10.1002/ana.25687"],["dc.identifier.eissn","1531-8249"],["dc.identifier.issn","0364-5134"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/84130"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.relation.eissn","1531-8249"],["dc.relation.issn","0364-5134"],["dc.title","Fine‐Mapping of SNCA in Rapid Eye Movement Sleep Behavior Disorder and Overt Synucleinopathies"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]Details DOI2018Journal Article [["dc.bibliographiccitation.firstpage","994"],["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","The Lancet Neurology"],["dc.bibliographiccitation.lastpage","1005"],["dc.bibliographiccitation.volume","17"],["dc.contributor.author","Trenkwalder, Claudia"],["dc.contributor.author","Allen, Richard"],["dc.contributor.author","Högl, Birgit"],["dc.contributor.author","Clemens, Stefan"],["dc.contributor.author","Patton, Stephanie"],["dc.contributor.author","Schormair, Barbara"],["dc.contributor.author","Winkelmann, Juliane"],["dc.date.accessioned","2021-06-01T10:50:23Z"],["dc.date.available","2021-06-01T10:50:23Z"],["dc.date.issued","2018"],["dc.identifier.doi","10.1016/S1474-4422(18)30311-9"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/86639"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-425"],["dc.relation.issn","1474-4422"],["dc.title","Comorbidities, treatment, and pathophysiology in restless legs syndrome"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]Details DOI2019Journal Article [["dc.bibliographiccitation.firstpage","150"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Movement Disorders"],["dc.bibliographiccitation.lastpage","151"],["dc.bibliographiccitation.volume","34"],["dc.contributor.author","Salminen, Aaro V."],["dc.contributor.author","Allen, Richard P."],["dc.contributor.author","Högl, Birgit"],["dc.contributor.author","Inoue, Yuichi"],["dc.contributor.author","Oertel, Wolfgang"],["dc.contributor.author","Winkelman, John W."],["dc.contributor.author","Trenkwalder, Claudia"],["dc.contributor.author","Sampaio, Cristina"],["dc.contributor.author","Winkelmann, Juliane"],["dc.date.accessioned","2021-06-01T10:46:52Z"],["dc.date.available","2021-06-01T10:46:52Z"],["dc.date.issued","2019"],["dc.identifier.doi","10.1002/mds.27571"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/85411"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-425"],["dc.relation.eissn","1531-8257"],["dc.relation.issn","0885-3185"],["dc.title","Reply to: Safety of dopamine agonists for treating restless legs syndrome"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]Details DOI