title: Gray matter atrophy in multiple sclerosis: a longitudinal study.
abstract: OBJECTIVE
  To determine gray matter (GM) atrophy rates in multiple sclerosis (MS) patients at all stages of disease, and to identify predictors and clinical correlates of GM atrophy.
  
  
  METHODS
  MS patients and healthy control subjects were observed over 4 years with standardized magnetic resonance imaging (MRI) and neurological examinations. Whole-brain, GM, and white matter atrophy rates were calculated. Subjects were categorized by disease status and disability progression to determine the clinical significance of atrophy. MRI predictors of atrophy were determined through multiple regression.
  
  
  RESULTS
  Subjects included 17 healthy control subjects, 7 patients with clinically isolated syndromes, 36 patients with relapsing-remitting MS (RRMS), and 27 patients with secondary progressive MS (SPMS). Expressed as fold increase from control subjects, GM atrophy rate increased with disease stage, from 3.4-fold normal in clinically isolated syndromes patients converting to RRMS to 14-fold normal in SPMS. In contrast, white matter atrophy rates were constant across all MS disease stages at approximately 3-fold normal. GM atrophy correlated with disability. MRI measures of focal and diffuse tissue damage accounted for 62% of the variance in GM atrophy in RRMS, but there were no significant predictors of GM atrophy in SPMS.
  
  
  CONCLUSIONS
  Gray matter tissue damage dominates the pathological process as MS progresses, and underlies neurological disabillity. Imaging correlates of gray matter atrophy indicate that mechanisms differ in RRMS and SPMS. These findings demonstrate the clinical relevance of gray matter atrophy in MS, and underscore the need to understand its causes.
authors.affiliation: Department of Biomedical Engineering, Cleveland Clinic Foundation, Cleveland, OH 44195, USA. fishere@ccf.org
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Fisher
authors.forename: Jar-Chi
authors.initials: JC
authors.lastname: Lee
authors.forename: Kunio
authors.initials: K
authors.lastname: Nakamura
authors.forename: Richard A
authors.initials: RA
authors.lastname: Rudick
mesh_terms: D000328:Adult; D000368:Aged; D001284:Atrophy / Q000473:pathology* / Q000503:physiopathology; D001921:Brain / Q000473:pathology* / Q000503:physiopathology; D015331:Cohort Studies; D004185:Disability Evaluation; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000473:pathology* / Q000503:physiopathology; D020528:Multiple Sclerosis, Chronic Progressive / Q000473:pathology / Q000503:physiopathology; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000473:pathology / Q000503:physiopathology; D009410:Nerve Degeneration / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology; D009413:Nerve Fibers, Myelinated / Q000473:pathology; D009474:Neurons / Q000473:pathology*; D011237:Predictive Value of Tests; D012044:Regression Analysis; D012720:Severity of Illness Index