title: Posterior brain damage and cognitive impairment in pediatric multiple sclerosis.
abstract: OBJECTIVE
  We combined structural and functional MRI to better understand the mechanisms responsible for cognitive impairment in pediatric patients with multiple sclerosis (MS).
  
  
  METHODS
  Brain dual-echo, diffusion tensor, 3D T1-weighted, and resting-state (RS) fMRI scans were acquired from 35 consecutive pediatric patients with MS and 16 sex- and age-matched healthy controls. Patients with abnormalities in ≥2 neuropsychological tests were classified as cognitively impaired. The regional distribution of white matter (WM) and gray matter (GM) damage was assessed using voxel-wise analyses. Default mode network (DMN) RS functional connectivity (FC) was also measured.
  
  
  RESULTS
  Sixteen patients (45%) were classified as cognitively impaired. Compared to cognitively preserved (CP) patients, cognitively impaired patients with MS had higher occurrence of T2 lesions as well as more severe damage to the WM and GM, as measured by atrophy and diffusivity abnormalities, in the posterior regions of the parietal lobes close to the midline (precuneus, posterior cingulum, and corpus callosum). Compared to the other study groups, they also showed reduced RS FC of the precuneus, whereas CP patients experienced an increased RS FC of the anterior cingulate cortex. A multivariable model identified diffusivity abnormalities of the cingulum and corpus callosum and RS FC of the precuneus as the covariates more strongly associated with cognitive impairment (C-index = 0.99).
  
  
  CONCLUSIONS
  In pediatric patients with MS, cognitive dysfunction is associated with structural and functional abnormalities of the posterior core regions of the DMN. WM structural abnormalities co-occurring at this level are likely to be the substrate of such modifications.
authors.affiliation: From the Neuroimaging Research Unit (M.A.R., M.A., M.F.), Department of Neurology, Institute of Experimental Neurology, Division of Neuroscience (M.A.R., M.A., L.M., A. Fiorino, G.C., M.F.), and Department of Neurology (M.P.A., E.P.), University of Florence; the Multiple Sclerosis Center (A.G., L.P.), Ospedale di Gallarate; Fondazione "Istituto Neurologico Casimiro Mondino" (P.V., M.C.P.), Pavia; Multiple Sclerosis Center (R.C.), Spedali Civili of Brescia, Italy; Department of Cardiovascular Sciences (M.A.H.), University of Leicester, UK; and the Department of Neuroradiology (A. Falini), San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Rocca
authors.forename: Martina
authors.initials: M
authors.lastname: Absinta
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Amato
authors.forename: Lucia
authors.initials: L
authors.lastname: Moiola
authors.forename: Angelo
authors.initials: A
authors.lastname: Ghezzi
authors.forename: Pierangelo
authors.initials: P
authors.lastname: Veggiotti
authors.forename: Ruggero
authors.initials: R
authors.lastname: Capra
authors.forename: Emilio
authors.initials: E
authors.lastname: Portaccio
authors.forename: Agnese
authors.initials: A
authors.lastname: Fiorino
authors.forename: Lorena
authors.initials: L
authors.lastname: Pippolo
authors.forename: Maria Carmela
authors.initials: MC
authors.lastname: Pera
authors.forename: Mark A
authors.initials: MA
authors.lastname: Horsfield
authors.forename: Andrea
authors.initials: A
authors.lastname: Falini
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Comi
authors.forename: Massimo
authors.initials: M
authors.lastname: Filippi
mesh_terms: D000293:Adolescent; D001284:Atrophy / Q000473:pathology / Q000503:physiopathology; D001921:Brain / Q000473:pathology* / Q000503:physiopathology; D001931:Brain Mapping; D002648:Child; D003072:Cognition Disorders / Q000150:complications / Q000175:diagnosis* / Q000473:pathology / Q000503:physiopathology; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D009103:Multiple Sclerosis / Q000150:complications* / Q000473:pathology / Q000503:physiopathology; D009413:Nerve Fibers, Myelinated / Q000473:pathology; D059906:Neuroimaging; D009483:Neuropsychological Tests