title: Hyperdopaminergism in lenticulostriate stroke-related restless legs syndrome: an imaging study.
abstract: The pathophysiology of restless legs syndrome (RLS) involves a dopaminergic dysregulation that remains poorly understood, with controversial data from the literature. Stroke-related RLS is a rare condition that involves primarily the basal ganglia, the paramedian pons, and the thalamus. Given these elements, we studied dopaminergic metabolism in patients with RLS secondary to lenticulostriate infarction using structural and nuclear imaging in the striatum ipsilateral to the infarction area, as compared to the contralateral side. We hypothesized that dopaminergic metabolism would be impaired in the striatum ipsilateral to stroke.
  
  
  
  In this observational case-control study, we aimed to prospectively include patients with RLS secondary to lenticulo-striate infarction, for analyses of dopamine dysfunction ipsilateral to stroke as compared to the contralateral striatum and to a control population. Four patients fulfilled inclusion criteria with either de novo RLS or major exacerbation of RLS existing prior to stroke, and all four patients were included. Structural imaging was performed using brain magnetic resonance imaging, and the stroke-induced metabolic modifications were assessed by18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET). Dopamine reuptake via DAT was explored using123I-FP-CIT SPECT. PET with18F-FDOPA was used to evaluate the functional integrity of the presynaptic dopaminergic synthesis.
  
  
  
  The only structure damaged in all patients was the body of the caudate nucleus, right-sided for three and left-sided for one, as illustrated by magnetic resonance imaging.18F-FDG PET showed a hypometabolism in the infarcted area, the ipsilateral thalamus, and the contralateral cerebellum. All patients displayed, in the ipsilateral putamen, increased dopaminergic tone.
  
  
  
  The present findings suggest that increased dopaminergic tone in the striatum may participate in the pathogenesis of RLS. These observations should encourage further research on RLS symptomatic with well-defined lesions as a promising way to further improve our understanding of its pathophysiology.
authors.affiliation: Department of Neurology, Sleep Disorders Center - CIRCSom, Hôpitaux Universitaires de Strasbourg, Strasbourg, France; CNRS UPR 3212, Institute for Cellular and Integrative Neurosciences, Strasbourg, France; Fédération de Médecine Translationnelle de Strasbourg (FMTS), University of Strasbourg, Strasbourg, France. Electronic address: elisabeth.ruppert@chru-strasbourg.fr.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Ruppert
authors.affiliation: Department of Neurology, Sleep Disorders Center - CIRCSom, Hôpitaux Universitaires de Strasbourg, Strasbourg, France; CNRS UPR 3212, Institute for Cellular and Integrative Neurosciences, Strasbourg, France; Fédération de Médecine Translationnelle de Strasbourg (FMTS), University of Strasbourg, Strasbourg, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Bataillard
authors.affiliation: Fédération de Médecine Translationnelle de Strasbourg (FMTS), University of Strasbourg, Strasbourg, France; Department of Biophysics and Nuclear Medicine, Hôpitaux Universitaires de Strasbourg, Strasbourg, France; ICube, CNRS, UMR 7237, University of Strasbourg, Strasbourg, France.
authors.forename: Izzie Jacques
authors.initials: IJ
authors.lastname: Namer
authors.affiliation: Department of Anatomy, UFR Sciences Médicales et Pharmaceutiques, University of Franche-Comté, Besançon, France; Department of Neuromuscular Diseases, CHU Besançon, Besançon, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Tatu
authors.affiliation: Department of Neurology, Sleep Disorders Center - CIRCSom, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
authors.forename: Aurélien
authors.initials: A
authors.lastname: Hacquard
authors.affiliation: Department of Neurology, Sleep Disorders Center - CIRCSom, Hôpitaux Universitaires de Strasbourg, Strasbourg, France; CNRS UPR 3212, Institute for Cellular and Integrative Neurosciences, Strasbourg, France; Fédération de Médecine Translationnelle de Strasbourg (FMTS), University of Strasbourg, Strasbourg, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Hugueny
authors.affiliation: Department of Neurology, Sleep Disorders Center - CIRCSom, Hôpitaux Universitaires de Strasbourg, Strasbourg, France; CNRS UPR 3212, Institute for Cellular and Integrative Neurosciences, Strasbourg, France; Fédération de Médecine Translationnelle de Strasbourg (FMTS), University of Strasbourg, Strasbourg, France.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Hubbard
authors.affiliation: Department of Neurology, Sleep Disorders Center - CIRCSom, Hôpitaux Universitaires de Strasbourg, Strasbourg, France; CNRS UPR 3212, Institute for Cellular and Integrative Neurosciences, Strasbourg, France; Fédération de Médecine Translationnelle de Strasbourg (FMTS), University of Strasbourg, Strasbourg, France.
authors.forename: Ulker
authors.initials: U
authors.lastname: Kilic-Huck
authors.affiliation: Fédération de Médecine Translationnelle de Strasbourg (FMTS), University of Strasbourg, Strasbourg, France; ICube, CNRS, UMR 7237, University of Strasbourg, Strasbourg, France; Department of Neurology, Stroke Unit, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Wolff
authors.affiliation: Department of Neurology, Sleep Disorders Center - CIRCSom, Hôpitaux Universitaires de Strasbourg, Strasbourg, France; CNRS UPR 3212, Institute for Cellular and Integrative Neurosciences, Strasbourg, France; Fédération de Médecine Translationnelle de Strasbourg (FMTS), University of Strasbourg, Strasbourg, France.
authors.forename: Patrice
authors.initials: P
authors.lastname: Bourgin
mesh_terms: D000368:Aged; D020144:Basal Ganglia Cerebrovascular Disease / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D016022:Case-Control Studies; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D012148:Restless Legs Syndrome / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D020521:Stroke / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology
chemical_list: D004298:Dopamine
keywords: Basal ganglia; Caudate nucleus; Dopamine dysregulation; Post stroke RLS; RLS pathophysiology; Restless legs syndrome