title: Abnormal medial thalamic metabolism in patients with idiopathic restless legs syndrome.
abstract: Pathophysiology of restless legs syndrome is poorly understood. A role of the thalamus, specifically of its medial portion which is a part of the limbic system, was suggested by functional magnetic resonance imaging and positron emission tomography studies. The aim of this study was to evaluate medial thalamus metabolism and structural integrity in patients with idiopathic restless legs syndrome using a multimodal magnetic resonance approach, including proton magnetic resonance spectroscopy, diffusion tensor imaging, voxel-based morphometry and volumetric and shape analysis. Twenty-three patients and 19 healthy controls were studied in a 1.5 T system. Single voxel proton magnetic resonance spectra were acquired in the medial region of the thalamus. In diffusion tensor examination, mean diffusivity and fractional anisotropy were determined at the level of medial thalamus using regions of interest delineated to outline the same parenchyma studied by spectroscopy. Voxel-based morphometry was performed focusing the analysis on the thalamus. Thalamic volumes were obtained using FMRIB's Integrated Registration and Segmentation Tool software, and shape analysis was performed using the FMRIB Software Library tools. Proton magnetic resonance spectroscopy study disclosed a significantly reduced N-acetylaspartate:creatine ratio and N-acetylaspartate concentrations in the medial thalamus of patients with restless legs syndrome compared with healthy controls (P < 0.01 for both variable). Lower N-acetylaspartate concentrations were significantly associated with a family history of restless legs syndrome (β = -0.49; P = 0.018). On the contrary, diffusion tensor imaging, voxel-based morphometry and volumetric and shape analysis of the thalami did not show differences between the two groups. Proton magnetic resonance spectroscopic findings in patients with restless legs syndrome indicate an involvement of medial thalamic nuclei of a functional nature; however, the other structural techniques of the same region did not show any changes. These findings support the hypothesis that dysfunction of the limbic system plays a role in the pathophysiology of idiopathic restless legs syndrome.
authors.affiliation: Department of Internal Medicine, Aging and Nephrology, University of Bologna, Via Massarenti 9, 40138 Bologna, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Rizzo
authors.forename: Caterina
authors.initials: C
authors.lastname: Tonon
authors.forename: Claudia
authors.initials: C
authors.lastname: Testa
authors.forename: David
authors.initials: D
authors.lastname: Manners
authors.forename: Roberto
authors.initials: R
authors.lastname: Vetrugno
authors.forename: Fabio
authors.initials: F
authors.lastname: Pizza
authors.forename: Sara
authors.initials: S
authors.lastname: Marconi
authors.forename: Emil
authors.initials: E
authors.lastname: Malucelli
authors.forename: Federica
authors.initials: F
authors.lastname: Provini
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Plazzi
authors.forename: Pasquale
authors.initials: P
authors.lastname: Montagna
authors.forename: Raffaele
authors.initials: R
authors.lastname: Lodi
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D016880:Anisotropy; D001224:Aspartic Acid / Q000031:analogs & derivatives; D001931:Brain Mapping; D003401:Creatine; D003430:Cross-Sectional Studies; D056324:Diffusion Tensor Imaging; D001330:Electronic Data Processing; D006801:Humans; D007294:Inositol; D009682:Magnetic Resonance Spectroscopy; D008875:Middle Aged; D011522:Protons; D012148:Restless Legs Syndrome / Q000378:metabolism* / Q000473:pathology*; D013788:Thalamus / Q000378:metabolism*
chemical_list: D011522:Protons; D001224:Aspartic Acid; D007294:Inositol; C000179:N-acetylaspartate; D003401:Creatine