title: Cortical lesions and atrophy associated with cognitive impairment in relapsing-remitting multiple sclerosis.
abstract: BACKGROUND
  Neuropsychological deficits in patients with multiple sclerosis (MS) have been shown to be associated with the major pathological substrates of the disease, ie, inflammatory demyelination and neurodegeneration. Double inversion recovery sequences allow cortical lesions (CLs) to be detected in the brain of patients with MS. Modern postprocessing techniques allow cortical atrophy to be assessed reliably.
  
  
  OBJECTIVE
  To investigate the contribution of cortical gray matter lesions and tissue loss to cognitive impairment in patients with relapsing-remitting MS.
  
  
  METHODS
  Cross-sectional survey.
  
  
  METHODS
  Referral, hospital-based MS clinic. Patients Seventy patients with relapsing-remitting MS.
  
  
  METHODS
  Neuropsychological performance was tested using the Rao Brief Repeatable Battery of Neuropsychological Tests, version A. Patients who scored 2 SDs below the mean normative values on at least 1 test of the Rao Brief Repeatable Battery of Neuropsychological Tests, version A, were considered to be cognitively impaired. A composite cognitive score (the cognitive impairment index) was computed. T2 hyperintense white matter lesion volume, contrast-enhancing lesion number, CL number and volume, normalized brain volume, and normalized neocortical gray matter volume were also assessed.
  
  
  RESULTS
  Twenty-four patients with relapsing-remitting MS (34.3%) were classified as cognitively impaired. T2 hyperintense white matter lesion volume and contrast-enhancing lesion number were not different between cognitively impaired and cognitively unimpaired patients. Cognitively impaired patients had a higher CL number (P = .01) and volume (P < .001) and decreased normalized brain volume (P = .02) and normalized neocortical gray matter volume (P = .002) when compared with cognitively unimpaired patients. Multivariate analysis revealed that age (beta = 0.228; P = .02), CL volume (beta = 0.452; P < .001), and normalized neocortical gray matter volume (beta = 0.349; P < .001) were independent predictors of the cognitive impairment index (r(2) = 0.55; F = 23.903; P < .001).
  
  
  CONCLUSIONS
  The burden of CLs and tissue loss are among the major structural changes associated with cognitive impairment in relapsing-remitting MS.
authors.affiliation: Multiple Sclerosis Centre of Veneto Region, First Neurology Clinic, Department of Neurosciences, University Hospital of Padua.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Calabrese
authors.forename: Federica
authors.initials: F
authors.lastname: Agosta
authors.forename: Francesca
authors.initials: F
authors.lastname: Rinaldi
authors.forename: Irene
authors.initials: I
authors.lastname: Mattisi
authors.forename: Paola
authors.initials: P
authors.lastname: Grossi
authors.forename: Alice
authors.initials: A
authors.lastname: Favaretto
authors.forename: Matteo
authors.initials: M
authors.lastname: Atzori
authors.forename: Valentina
authors.initials: V
authors.lastname: Bernardi
authors.forename: Luigi
authors.initials: L
authors.lastname: Barachino
authors.forename: Luciano
authors.initials: L
authors.lastname: Rinaldi
authors.forename: Paola
authors.initials: P
authors.lastname: Perini
authors.forename: Paolo
authors.initials: P
authors.lastname: Gallo
authors.forename: Massimo
authors.initials: M
authors.lastname: Filippi
mesh_terms: D000293:Adolescent; D000328:Adult; D001284:Atrophy / Q000453:epidemiology / Q000473:pathology* / Q000503:physiopathology; D001931:Brain Mapping; D002540:Cerebral Cortex / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology; D003072:Cognition Disorders / Q000453:epidemiology / Q000473:pathology* / Q000503:physiopathology; D015897:Comorbidity; D003430:Cross-Sectional Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000453:epidemiology / Q000473:pathology* / Q000503:physiopathology; D009413:Nerve Fibers, Myelinated / Q000473:pathology; D009483:Neuropsychological Tests; D011237:Predictive Value of Tests; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D014855:Wallerian Degeneration / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D055815:Young Adult