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Magnetisation transfer ratio in the normal appearing white matter predicts progression of disability over 1 year in early primary progressive multiple sclerosis
  1. Z Khaleeli1,
  2. J Sastre-Garriga1,
  3. O Ciccarelli1,
  4. D H Miller2,
  5. A J Thompson1
  1. 1
    Department of Brain Repair and Rehabilitation, Nuclear Magnetic Resonance Unit, Institute of Neurology, University College London, London, UK
  2. 2
    Department of Neuroinflammation, Nuclear Magnetic Resonance Unit, Institute of Neurology, University College London, London, UK
  1. Professor Alan Thompson, Department of Brain Repair and Rehabilitation, Institute of Neurology, Queen Square, London, WC1N 3BG, UK; a.thompson{at}


Background: Progression rates in primary progressive multiple sclerosis (PPMS) vary widely and brain magnetisation transfer imaging (MTI) has potential as an early prognostic indicator. We investigated the predictive value of MTI and the longitudinal changes developing over 1 year in early PPMS.

Aims: To determine (1) whether baseline brain MTI parameters in early PPMS predict clinical changes over 1 year, independent of brain volume and (2) whether a change in magnetisation transfer (MT) parameters occurs over 1 year, independent of atrophy.

Methods: 30 patients with PPMS within 5 years of symptom onset and 15 controls underwent MT and volumetric imaging studies, at baseline and at 1 year. Patients underwent clinical assessment using the Expanded Disability Status Scale (EDSS) and Multiple Sclerosis Functional Composite (MSFC), including the timed walk subtest (TWT). Normalised MT histograms were generated for whole brain, normal appearing brain tissue (NABT) and normal appearing white and grey matter (NAWM and NAGM) segments. Multiple regression analyses were performed to investigate whether baseline MTR parameters predicted clinical change over 1 year, adjusting for baseline brain volume. MTR changes over 1 year were assessed using paired t tests.

Results: In patients, lower baseline NAWM MTR predicted greater deterioration in EDSS and MSFC, particularly in walking ability measured by the TWT, independent of NAWM baseline volume (p = 0.001). NAGM MTR mean (p<0.001), and to a lesser extent NAWM mean (p = 0.011) and lesion MTR (p = 0.03), decreased over 1 year.

Conclusions: NAWM MTR may provide information on short term clinical prognosis in early PPMS. MTI is sensitive to brain tissue changes over 1 year in early PPMS, which were primarily seen in the NAGM.

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  • Competing interests: None.

  • Abbreviations:
    3D FSPGR
    three dimensional inversion prepared fast spoiled gradient recall
    brain parenchymal fraction
    Expanded Disability Status Scale
    grey matter
    multiple sclerosis
    Multiple Sclerosis Functional Composite
    magnetisation transfer
    magnetisation transfer imaging
    magnetisation transfer ratio
    normal appearing brain tissue
    normal appearing grey matter
    normal appearing grey matter fraction
    normal appearing white matter
    normal appearing white matter fraction
    nine hole peg test
    paced auditory serial addition test
    peak height
    peak location
    primary progressive multiple sclerosis
    per cent units
    timed walk test
    whole brain
    white matter
    z score for the nine hole peg test
    z score for the paced auditory serial addition test
    z score for the timed walk test