title: Abnormalities in normal appearing tissues in early primary progressive multiple sclerosis and their relation to disability: a tissue specific magnetisation transfer study.
abstract: BACKGROUND
  Patients with primary progressive multiple sclerosis (PPMS) often develop severe disability despite low levels of abnormality on conventional magnetic resonance imaging (MRI). This may relate to diffuse pathological processes occurring in normal appearing brain tissue (NABT) involving both white matter (NAWM) and grey matter (NAGM). Magnetisation transfer imaging (MTI) is capable of identifying these processes and may be particularly informative when applied to patients with early PPMS.
  
  
  OBJECTIVE
  To assess the relationship between abnormalities in NABT identified by MTI and disability and other radiological data in patients with early PPMS.
  
  
  METHODS
  We studied 43 patients within 5 years of disease onset and 43 controls. The Expanded Disability Status Scale (EDSS) and the Multiple Sclerosis Functional Composite (MSFC) were scored. Magnetisation transfer ratios (MTR) of NABT, NAWM, and NAGM were calculated and the following MTR parameters were measured: mean, peak height, peak location, and MTR value at the 25th, 50th, and 75th percentiles. Proton density, T2, T1, and gadolinium enhancing lesion loads were also calculated.
  
  
  RESULTS
  Differences were found between patients and controls in mean, peak height, and peak location of NAWM and NAGM (p < or = 0.001). Weak to moderate correlations were found between MTR parameters and disability in both NAWM and NAGM. Strong correlations between MTR parameters and lesion loads were found, particularly in NAWM.
  
  
  CONCLUSIONS
  MTR abnormalities are seen in NAWM and NAGM in early PPMS and both are associated with disability. NAWM MTR abnormalities are more closely related to conventional MRI measures than those seen in NAGM.
authors.affiliation: Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK.
authors.forename: L
authors.initials: L
authors.lastname: Ramió-Torrentà
authors.forename: J
authors.initials: J
authors.lastname: Sastre-Garriga
authors.forename: G T
authors.initials: GT
authors.lastname: Ingle
authors.forename: G R
authors.initials: GR
authors.lastname: Davies
authors.forename: V
authors.initials: V
authors.lastname: Ameen
authors.forename: D H
authors.initials: DH
authors.lastname: Miller
authors.forename: A J
authors.initials: AJ
authors.lastname: Thompson
mesh_terms: D000328:Adult; D000368:Aged; D001921:Brain / Q000473:pathology; D004185:Disability Evaluation; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000473:pathology*; D012720:Severity of Illness Index; D011795:Surveys and Questionnaires