title: Relevance of brain lesion location to cognition in relapsing multiple sclerosis.
abstract: OBJECTIVE
  To assess the relationship between cognition and brain white matter (WM) lesion distribution and frequency in patients with relapsing-remitting multiple sclerosis (RR MS).
  
  
  METHODS
  MRI-based T2 lesion probability map (LPM) was used to assess the relevance of brain lesion location for cognitive impairment in a group of 142 consecutive patients with RRMS. Significance of voxelwise analyses was p<0.05, cluster-corrected for multiple comparisons. The Rao Brief Repeatable Battery was administered at the time of brain MRI to categorize the MS population into cognitively preserved (CP) and cognitively impaired (CI).
  
  
  RESULTS
  Out of 142 RRMS, 106 were classified as CP and 36 as CI. Although the CI group had greater WM lesion volume than the CP group (p = 0.001), T2 lesions tended to be less widespread across the WM. The peak of lesion frequency was almost twice higher in CI (61% in the forceps major) than in CP patients (37% in the posterior corona radiata). The voxelwise analysis confirmed that lesion frequency was higher in CI than in CP patients with significant bilateral clusters in the forceps major and in the splenium of the corpus callosum (p<0.05, corrected). Low scores of the Symbol Digit Modalities Test correlated with higher lesion frequency in these WM regions.
  
  
  CONCLUSIONS
  Overall these results suggest that in MS patients, areas relevant for cognition lie mostly in the commissural fiber tracts. This supports the notion of a functional (multiple) disconnection between grey matter structures, secondary to damage located in specific WM areas, as one of the most important mechanisms leading to cognitive impairment in MS.
authors.affiliation: Department of Neurological and Behavioral Sciences, University of Siena, Siena, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Rossi
authors.forename: Antonio
authors.initials: A
authors.lastname: Giorgio
authors.forename: Marco
authors.initials: M
authors.lastname: Battaglini
authors.forename: Maria Laura
authors.initials: ML
authors.lastname: Stromillo
authors.forename: Emilio
authors.initials: E
authors.lastname: Portaccio
authors.forename: Benedetta
authors.initials: B
authors.lastname: Goretti
authors.forename: Antonio
authors.initials: A
authors.lastname: Federico
authors.forename: Bahia
authors.initials: B
authors.lastname: Hakiki
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Amato
authors.forename: Nicola
authors.initials: N
authors.lastname: De Stefano
mesh_terms: D000293:Adolescent; D000328:Adult; D001921:Brain / Q000473:pathology* / Q000503:physiopathology*; D003071:Cognition; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000473:pathology* / Q000503:physiopathology*; D055815:Young Adult