Yves Dauvilliers1,2, Sofiene Chenini1, Jérôme Vialaret3, Constance Delaby3, Lily Guiraud1, Audrey Gabelle2,4, Regis Lopez1,2, Christophe Hirtz3, Isabelle Jaussent2, Sylvain Lehmann3. 1. National Reference Centre for Orphan Diseases, Narcolepsy, Idiopathic hypersomnia and Kleine-Levin Syndrome, France. Sleep Disorders Center, Department of Neurology, Gui-de-Chauliac Hospital, Montpellier, France. 2. Inserm, U1061, Montpellier, France; Université Montpellier, Montpellier, France. 3. CHU Montpellier, Institut de Recherche en Biothérapie, hôpital St Eloi, Laboratoire de Biochimie Protéomique Clinique et CCBHM, INSERM U1040, Montpellier, France. 4. Memory Research Resources center, Department of Neurology, Gui-de-Chauliac Hospital, Montpellier University Hospital, Montpellier, France.
Abstract
BACKGROUND: To better understand the role of iron homeostasis dysregulation in restless legs syndrome, we compared serum hepcidin and ferritin levels in drug-free patients with primary restless legs syndrome and healthy controls and studied the relationship between hepcidin level and restless legs syndrome severity. METHODS: One hundred and eight drug-free patients with primary restless legs syndrome (65 women; median age, 61.5 years) and 45 controls (28 women; median age, 53.9 years) were enrolled. Inclusion criteria were: normal ferritin level (>50 ng/mL) and absence of iron disorders, chronic renal or liver failure, and inflammatory or neurological diseases. Each subject underwent a thorough clinical examination and a polysomnography assessment. Serum hepcidin-25 was quantified using a validated mass spectrometry method. Restless legs syndrome severity was evaluated according to the International Restless Legs Syndrome Study Group. RESULTS: Despite no group difference between normal ferritin levels and demographic features, serum hepcidin level and hepcidin/ferritin ratio were higher in patients than in controls. Hepcidin level and hepcidin/ferritin ratio, but not ferritin level, were positively correlated with periodic leg movements during sleep and wakefulness in the whole sample. Hepcidin level seem to be associated with restless legs syndrome severity in a complex U-shaped relationship, without relationship with age at restless legs syndrome onset, positive family history, sleep and depressive symptoms, genetic background, and polysomnographic measurements. No relationship was found between ferritin level and restless legs syndrome severity. CONCLUSION: In drug-free patients with primary restless legs syndrome, hepcidin level is higher than in controls and may be associated with restless legs syndrome clinical severity. This result emphasizes the complex peripheral iron metabolism deregulation in restless legs syndrome, opening potential perspectives for a personalized approach with a hepcidin antagonist.
BACKGROUND: To better understand the role of iron homeostasis dysregulation in restless legs syndrome, we compared serum hepcidin and ferritin levels in drug-free patients with primary restless legs syndrome and healthy controls and studied the relationship between hepcidin level and restless legs syndrome severity. METHODS: One hundred and eight drug-free patients with primary restless legs syndrome (65 women; median age, 61.5 years) and 45 controls (28 women; median age, 53.9 years) were enrolled. Inclusion criteria were: normal ferritin level (>50 ng/mL) and absence of iron disorders, chronic renal or liver failure, and inflammatory or neurological diseases. Each subject underwent a thorough clinical examination and a polysomnography assessment. Serum hepcidin-25 was quantified using a validated mass spectrometry method. Restless legs syndrome severity was evaluated according to the International Restless Legs Syndrome Study Group. RESULTS: Despite no group difference between normal ferritin levels and demographic features, serum hepcidin level and hepcidin/ferritin ratio were higher in patients than in controls. Hepcidin level and hepcidin/ferritin ratio, but not ferritin level, were positively correlated with periodic leg movements during sleep and wakefulness in the whole sample. Hepcidin level seem to be associated with restless legs syndrome severity in a complex U-shaped relationship, without relationship with age at restless legs syndrome onset, positive family history, sleep and depressive symptoms, genetic background, and polysomnographic measurements. No relationship was found between ferritin level and restless legs syndrome severity. CONCLUSION: In drug-free patients with primary restless legs syndrome, hepcidin level is higher than in controls and may be associated with restless legs syndrome clinical severity. This result emphasizes the complex peripheral iron metabolism deregulation in restless legs syndrome, opening potential perspectives for a personalized approach with a hepcidin antagonist.
Authors: Vincent Beliveau; Ambra Stefani; Christoph Birkl; Christian Kremser; Elke R Gizewski; Birgit Högl; Christoph Scherfler Journal: Neuroimage Clin Date: 2022-04-26 Impact factor: 4.891
Authors: Aaro V Salminen; Stefan Clemens; Diego García-Borreguero; Imad Ghorayeb; Yuqing Li; Mauro Manconi; William Ondo; David Rye; Jerome M Siegel; Alessandro Silvani; John W Winkelman; Richard P Allen; Sergi Ferré Journal: Dis Model Mech Date: 2022-08-10 Impact factor: 5.732