title: MRI phenotypes based on cerebral lesions and atrophy in patients with multiple sclerosis.
abstract: BACKGROUND
  While disease categories (i.e. clinical phenotypes) of multiple sclerosis (MS) are established, there remains MRI heterogeneity among patients within those definitions. MRI-defined lesions and atrophy show only moderate inter-correlations, suggesting that they represent partly different processes in MS. We assessed the ability of MRI-based categorization of cerebral lesions and atrophy in individual patients to identify distinct phenotypes.
  
  
  METHODS
  We studied 175 patients with MS [age (mean ± SD) 42.7 ± 9.1 years, 124 (71%) women, Expanded Disability Status (EDSS) score 2.5 ± 2.3, n = 18 (10%) clinically isolated demyelinating syndrome (CIS), n=115 (66%) relapsing-remitting (RR), and n = 42 (24%) secondary progressive (SP)]. Brain MRI measures included T2 hyperintense lesion volume (T2LV) and brain parenchymal fraction (to assess whole brain atrophy). Medians were used to create bins for each parameter, with patients assigned a low or high severity score.
  
  
  RESULTS
  Four MRI phenotype categories emerged: Type I = low T2LV/mild atrophy [n = 67 (38%); CIS = 14, RR = 47, SP = 6]; Type II = high T2LV/mild atrophy [n = 21 (12%); RR = 19, SP = 2]; Type III = low T2LV/high atrophy [n = 21 (12%); CIS = 4, RR = 16, SP = 1]; and Type IV = high T2LV/high atrophy [n = 66 (38%); RR = 33, S P = 33]. Type IV was the most disabled and was the only group showing a correlation between T2LV vs. BPF and MRI vs. EDSS score (all p < 0.05).
  
  
  CONCLUSIONS
  We described MRI-categorization based on the relationship between lesions and atrophy in individual patients to identify four phenotypes in MS. Most patients have congruent extremes related to the degree of lesions and atrophy. However, many have a dissociation. Longitudinal studies will help define the stability of these patterns and their role in risk stratification.
authors.affiliation: Department of Neurology, Brigham and Women's Hospital, Laboratory for Neuroimaging Research, Partners MS Center, Harvard Medical School, Boston, MA, USA.
authors.forename: Shahamat
authors.initials: S
authors.lastname: Tauhid
authors.affiliation: Department of Neurology, Brigham and Women's Hospital, Laboratory for Neuroimaging Research, Partners MS Center, Harvard Medical School, Boston, MA, USA.
authors.forename: Mohit
authors.initials: M
authors.lastname: Neema
authors.affiliation: Department of Neurology, Brigham and Women's Hospital, Laboratory for Neuroimaging Research, Partners MS Center, Harvard Medical School, Boston, MA, USA.
authors.forename: Brian C
authors.initials: BC
authors.lastname: Healy
authors.affiliation: Department of Neurology, Brigham and Women's Hospital, Laboratory for Neuroimaging Research, Partners MS Center, Harvard Medical School, Boston, MA, USA.
authors.forename: Howard L
authors.initials: HL
authors.lastname: Weiner
authors.affiliation: Department of Neurology, Brigham and Women's Hospital, Laboratory for Neuroimaging Research, Partners MS Center, Harvard Medical School, Boston, MA, USA. Electronic address: rbakshi@bwh.harvard.edu.
authors.forename: Rohit
authors.initials: R
authors.lastname: Bakshi
mesh_terms: D000328:Adult; D001284:Atrophy / Q000473:pathology*; D001921:Brain / Q000473:pathology*; D003711:Demyelinating Diseases / Q000473:pathology; D004185:Disability Evaluation; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000473:pathology*; D020528:Multiple Sclerosis, Chronic Progressive / Q000473:pathology; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000473:pathology; D010641:Phenotype; D012720:Severity of Illness Index; D055815:Young Adult
keywords: Atrophy; Disability; Lesions; MRI; Multiple sclerosis; Phenotypes