Magnetization transfer ratio abnormalities reflect clinically relevant grey matter damage in multiple sclerosis

Background In multiple sclerosis, grey matter (GM) damage appears more clinically relevant than either white matter damage or lesion load. Objective We investigated if normal-appearing white matter (NAWM) and grey matter tissue changes assessed by magnetization transfer ratio were associated with long-term disability. Methods Sixty-nine people were assessed 20 years after presentation with a clinically isolated syndrome (CIS) [28 still CIS, 31 relapsing-remitting multiple sclerosis, 10 secondary progressive multiple sclerosis], along with 19 healthy subjects. Mean magnetization transfer ratio, peak height (PH) and peak location of the normalized magnetization transfer ratio histograms were determined in NAWM and grey matter, as well as, white matter and GM Fraction (GMF) and T-2-weighted lesion load. Results Median expanded disability status scale for multiple sclerosis patients was 2.5 (range 1-8). GM-PH, and less so, NAWM mean and peak location, were lower in multiple sclerosis patients (P = 0.009) versus controls, relapsing-remitting multiple sclerosis versus CIS (P = 0.008) and secondary progressive multiple sclerosis versus relapsing-remitting multiple sclerosis (P = 0.002). GM-PH (as well as GMF) correlated with expanded disability status scale (r(s) = -0.49; P = 0.001) and multiple sclerosis functional score (r(s) = 0.51; P = 0.001). GM-PH independently predicted disability with similar strength to the associations of GMF with clinical measures. Conclusion Grey matter damage was related to long-term disability in multiple sclerosis cohort with a relatively low median expanded disability status scale. Markers of intrinsic grey matter damage (magnetization transfer ratio) and tissue loss offer clinically relevant information in multiple sclerosis. Multiple Sclerosis 2009; 15: 668-677. http://msj.sagepub.com