Magnetisation transfer ratio in the normal appearing white matter predicts progression of disability over 1 year in early primary progressive multiple sclerosis

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.