title: Intrinsic damage to the major white matter tracts in patients with different clinical phenotypes of multiple sclerosis: a voxelwise diffusion-tensor MR study.
abstract: OBJECTIVE
  To apply voxelwise analysis of diffusion-tensor (DT) magnetic resonance (MR) tractography and T2-weighted MR lesion measurements to characterize intrinsic damage to the brain white matter (WM) tracts and the relation of this damage to the presence and location of focal lesions among the main clinical phenotypes of multiple sclerosis (MS).
  
  
  METHODS
  The study was conducted with institutional review board approval. Written informed consent was obtained from each participant. Brain dual-echo and DT MR images were obtained in 172 patients with MS (22 [13%] with clinically isolated syndromes [CIS] suggestive of MS, 51 [30%] with relapsing-remitting [RR] MS, 44 [26%] with secondary progressive MS, 20 [12%] with benign MS, 35 [20%] with primary progressive MS) and 46 healthy control subjects. Probability maps of the major brain WM tracts were produced. Between-group comparisons were assessed by using analysis of covariance.
  
  
  RESULTS
  Compared with the healthy control subjects, the patients with CIS had significantly increased (P < .001) mean diffusivity, axial diffusivity, and radial diffusivity in the majority of WM tracts. The primary progressive MS group showed diffuse increases in mean, axial, and radial diffusivity, with fractional anisotropy (FA) damage involving the majority of WM tracts. No relevant difference in diffusivity measures was found between the CIS and RR-MS groups. Compared with the benign MS group, the RR-MS group had reduced FA values in all WM tracts and decreased axial diffusivity in the majority of tracts. The secondary progressive MS group had pronounced damage to the majority of tracts and, compared with the benign MS group, pronounced FA alteration of the tracts relevant for motor impairment.
  
  
  CONCLUSIONS
  Voxelwise assessment of DT MR index abnormalities is a rewarding strategy for understanding the heterogeneity of clinical MS phenotypes.
authors.affiliation: Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute and University Hospital, Via Olgettina 60, 20132 Milan, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Preziosa
authors.forename: Maria A
authors.initials: MA
authors.lastname: Rocca
authors.forename: Sarlota
authors.initials: S
authors.lastname: Mesaros
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Pagani
authors.forename: Tatjana
authors.initials: T
authors.lastname: Stosic-Opincal
authors.forename: Katarina
authors.initials: K
authors.lastname: Kacar
authors.forename: Martina
authors.initials: M
authors.lastname: Absinta
authors.forename: Domenico
authors.initials: D
authors.lastname: Caputo
authors.forename: Jelena
authors.initials: J
authors.lastname: Drulovic
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Comi
authors.forename: Massimo
authors.initials: M
authors.lastname: Filippi
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D004185:Disability Evaluation; D005260:Female; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000473:pathology*; D009413:Nerve Fibers, Myelinated / Q000473:pathology*; D010641:Phenotype