title: Determinants of brain iron in multiple sclerosis: a quantitative 3T MRI study.
abstract: OBJECTIVE
  Abnormal high cerebral iron deposition may be implicated in chronic neurologic disorders, including multiple sclerosis (MS). R2* relaxometry has been recently validated in a postmortem study to indicate brain iron accumulation in a quantitative manner. We used this technique to assess brain iron levels in different stages of MS and healthy controls (HC) and determined their relation with demographic, clinical, neuropsychological, and other imaging variables.
  
  
  METHODS
  We studied 113 consecutive patients (35 clinically isolated syndrome [CIS], 78 MS) and 35 HC with 3 T MRI and clinical and neuropsychological examination. Iron deposition in subcortical gray matter structures was assessed by automated, regional calculation of R2* rates.
  
  
  RESULTS
  Basal ganglia (BG) R2* levels were significantly increased in MS compared to CIS (p < 0.001) and HC (p < 0.005). They were correlated with age (r = 0.5, p < 0.001), disease duration (r = 0.5, p < 0.001), Expanded Disability Status Scale (r = 0.3, p < 0.005), and the z values of mental processing speed (r = -0.3, p < 0.01). Stepwise linear regression analysis revealed gray matter atrophy as the strongest independent predictor of BG R2* levels (p < 0.001), followed by age (p < 0.001) and T2 lesion load (p < 0.005).
  
  
  CONCLUSIONS
  BG iron accumulation in MS occurs with advancing disease and is related to the extent of morphologic brain damage, which argues for iron deposition as an epiphenomenon. The absence of increased iron levels in patients with CIS indicates that iron accumulation does not precede the development of MS.
authors.affiliation: Department of Neurology, Medical University of Graz, Graz, Austria.
authors.forename: M
authors.initials: M
authors.lastname: Khalil
authors.forename: C
authors.initials: C
authors.lastname: Langkammer
authors.forename: S
authors.initials: S
authors.lastname: Ropele
authors.forename: K
authors.initials: K
authors.lastname: Petrovic
authors.forename: M
authors.initials: M
authors.lastname: Wallner-Blazek
authors.forename: M
authors.initials: M
authors.lastname: Loitfelder
authors.forename: M
authors.initials: M
authors.lastname: Jehna
authors.forename: G
authors.initials: G
authors.lastname: Bachmaier
authors.forename: R
authors.initials: R
authors.lastname: Schmidt
authors.forename: C
authors.initials: C
authors.lastname: Enzinger
authors.forename: S
authors.initials: S
authors.lastname: Fuchs
authors.forename: F
authors.initials: F
authors.lastname: Fazekas
mesh_terms: D000328:Adult; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000473:pathology* / Q000503:physiopathology*; D009483:Neuropsychological Tests; D055815:Young Adult
chemical_list: D007501:Iron