title: New hypointense lesions on MRI in relapsing-remitting multiple sclerosis patients.
abstract: BACKGROUND
  Preliminary observational studies with multiple sclerosis (MS) patients have reported strong correlations between an increase in hypointense lesion load (black holes) on T1-weighted spin echo images, and an increase in disability.
  
  
  OBJECTIVE
  We assessed the relationship of hypointense lesions to the clinical course of disease among 50 relapsing-remitting MS patients in the controlled setting of a randomized clinical trial.
  
  
  METHODS
  Fifty patients with relapsing-remitting disease were enrolled in a randomized double-blind two-arm (cladribine vs. placebo) clinical trial of 1-year duration. All patients had monthly clinical evaluations and MRIs over the course of the trial. Multivariate techniques were used to identify predictors of clinical severity from information on exacerbations, MRIs, baseline clinical parameters, and demographics.
  
  
  RESULTS
  At baseline, clinical severity is weakly related to counts of black holes, with rank correlations between counts and clinical scores (EDSS and SNRS) of absolute magnitude 0.3. Rates of appearance of new black holes over the course of the trial are higher for patients with more severe disease at baseline (EDSS > or = 4) than for the less severe patients. Changes in clinical severity over the course of the trial are best predicted by baseline neurologic scores and numbers of exacerbations, with black holes adding no further improvement in prediction.
  
  
  CONCLUSIONS
  Numbers of exacerbations seem more critical to short-term clinical outcomes in relapsing-remitting MS, as reflected by patients' clinical scores, rather than black holes. Various imaging methods and MRI indices capture complementary information relating to MS disease processes. The determination of which processes are affected by different drugs should lead to more effective treatment of MS patients.
authors.affiliation: Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, Calif., USA. simone_wagner@med.uni-heidelberg.de
authors.forename: S
authors.initials: S
authors.lastname: Wagner
authors.forename: H
authors.initials: H
authors.lastname: Adams
authors.forename: D F
authors.initials: DF
authors.lastname: Sobel
authors.forename: L S
authors.initials: LS
authors.lastname: Slivka
authors.forename: J C
authors.initials: JC
authors.lastname: Sipe
authors.forename: J S
authors.initials: JS
authors.lastname: Romine
authors.forename: J A
authors.initials: JA
authors.lastname: Koziol
mesh_terms: D017338:Cladribine / Q000627:therapeutic use*; D004311:Double-Blind Method; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000175:diagnosis* / Q000188:drug therapy* / Q000503:physiopathology; D011379:Prognosis; D012720:Severity of Illness Index
chemical_list: D007166:Immunosuppressive Agents; D017338:Cladribine