title: The normal appearing grey matter in primary progressive multiple sclerosis: a magnetisation transfer imaging study.
abstract: BACKGROUND
  In 10-15 % of patients with multiple sclerosis (MS), the clinical course is characterized by slow progression in disability without relapses (primary progressive (PP) MS). The mechanism of disability in this form of MS is poorly understood. Using magnetization transfer ratio (MTR) imaging, we investigated normal appearing white matter (NAWM) and normal appearing grey matter (NAGM) in PPMS and explored the relationship of MTR measures with disability.
  
  
  METHODS
  Thirty patients with PPMS and 30 age matched controls had spin echo based MTR imaging to study lesions and normal appearing tissues. The brain was segmented into NAWM and NAGM using SPM99 with lesions segmented using a semiautomated local thresholding technique. A 75% probability threshold for classification of NAWM and NAGM was used to diminish partial volume effects. From normalized histograms of MTR intensity values, six MTR parameters were measured. Mean lesion MTR and T2 lesion volume were also measured. Disability was assessed using Kurtzke's expanded disability status scale (EDSS).
  
  
  RESULTS
  Compared with controls, patients exhibited a significant reduction in mean NAWM (p = 0.001) and NAGM (p = 0.004) MTR. Spearman's rank correlation of EDSS with the six MTR parameters in NAWM and NAGM, mean lesion MTR, and T2 lesion volume, was only significant with mean NAGM MTR (r = -0.41, p = 0.02), the 25th percentile of NAGM MTR intensity (r = -0.37, p = 0.05), and T2 lesion volume (r = 0.39, p = 0.04). Multiple regression analysis of the relationship between EDSS and 4 MR parameters representing each tissue type (mean NAWM MTR, mean NAGM MTR, mean lesion MTR, T2 lesion volume) showed that the association of EDSS with mean NAGM MTR remained significant.
  
  
  CONCLUSIONS
  There appear to be significant abnormalities in the NAGM in PP MS. Further investigation of the pathological basis and functional significance of grey matter abnormality in PPMS is warranted.
authors.affiliation: Medicsight plc, 46 Berkley Square, London W1J 5AT, UK.
authors.forename: J
authors.initials: J
authors.lastname: Dehmeshki
authors.forename: D T
authors.initials: DT
authors.lastname: Chard
authors.forename: S M
authors.initials: SM
authors.lastname: Leary
authors.forename: H C
authors.initials: HC
authors.lastname: Watt
authors.forename: N C
authors.initials: NC
authors.lastname: Silver
authors.forename: P S
authors.initials: PS
authors.lastname: Tofts
authors.forename: A J
authors.initials: AJ
authors.lastname: Thompson
authors.forename: D H
authors.initials: DH
authors.lastname: Miller
mesh_terms: D000328:Adult; D001921:Brain / Q000473:pathology*; D004185:Disability Evaluation; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000473:pathology*; D012044:Regression Analysis