Objective To investigate whether T2 lesion load and magnetisation transfer ratio (MTR) in the normal-appearing white matter (NAWM) and grey matter (GM) at study entry are independent predictors of progression and whether their changes correlate with the accrual of disability, over 5 years in early primary progressive multiple sclerosis (PPMS).
Methods Forty-seven patients with early PPMS and 18 healthy controls were recruited at baseline and invited to attend clinical 6-monthly assessments for 3 years, and after 5 years. Patients were scored on the Expanded Disability Status Scale and multiple sclerosis functional composite subtests (25-foot timed walk test (TWT), nine-hole peg test and paced auditory serial addition test). At each time point, all subjects underwent brain MRI including T2-weighted, magnetisation transfer and volumetric sequences. T2 lesion load (T2LL), MTR histogram parameters and volumes for NAWM and GM were calculated. Statistical analyses identified predictors of progression and correlations between MRI changes and clinical changes over time.
Results Baseline T2LL and GM peak location and peak height MTR were independent predictors of progression, as measured by TWT; a model including these three predictors explained 91% of the variance of the progression on TWT, a significantly higher percentage than that obtained when the predictors were modelled individually (80%, 74% and 68%, respectively). A greater progression rate correlated with a steeper increase in T2LL and a faster decline in GM mean and peak location MTR.
Conclusions The combined assessment of both visible white matter damage and GM involvement is useful in predicting progression in PPMS.
- Multiple sclerosis
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Statistical analysis DRA and CT. CT had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Funding CT was funded by the Multiple Sclerosis International Federation (McDonald Fellowship) and has received honoraria and support for travel from Serono Foundation and Sanofi-Aventis. ZK was funded by the MS Society of Great Britain and Northern Ireland. OC was funded by the Wellcome Trust and receives anhonorarium for work as Clinical Editor of Current Medical Literature—Multiple Sclerosis. MC was funded by the Italian Ministry of Health (grant number PS05.5B) and has received travel expenses and/or honoraria for lectures or educational activities not funded by industry. DHM has received honoraria from UCB Pharma, Schering, Biogen Idec, GSK and Wyeth for consulting services, speaking and serving on a scientific advisory board. He has received reimbursement for work as co-chief Editor of Journal of Neurology and a research grant support from the MS Society of Great Britain and Northern Ireland, Wellcome Trust, Medical Research Council UK, Biogen Idec, Novartis, GlaxoSmithKline and Schering. AJT has received honoraria and support for travel for consultancy, serving on advisory boards or speaking from Novartis, Eisai, Weleda/Society for Clinical Research, Hoffman La Roche, UCB Pharma, Serono Foundation, Sanofi-Aventis and the MS Society of GB. He is editor-in-chief of Multiple Sclerosis, for which he receives an honorarium from Sage Publications. This work was undertaken at UCLH/UCL, who received a proportion of funding from the Department of Health's NIHR Biomedical Research Centres funding scheme. The MS NMR Research Unit is supported by the MS Society of Great Britain and Northern Ireland.
Competing interests None
Patient consent Obtained.
Ethics approval Ethics approval was provided by the Joint Medical Ethics Committee of the National Hospital for Neurology and Neurosurgery and the Institute of Neurology, London.
Provenance and peer review Not commissioned; externally peer reviewed.