Brain atrophy and lesion load measures over 1 year relate to clinical status after 6 years in patients with clinically isolated syndromes
- M Di Filippo1,2,4,
- V M Anderson1,2,
- D R Altmann1,5,
- J K Swanton1,2,
- G T Plant6,
- A J Thompson1,3,
- D H Miller1,2
- 1NMR Research Unit, UCL Institute of Neurology, London, UK
- 2Department of Neuroinflammation, UCL Institute of Neurology, London, UK
- 3Department of Brain Repair and Rehabilitation, UCL Institute of Neurology, London, UK
- 4Multiple Sclerosis Centre, Section of Neurology, University of Perugia, Perugia, Italy
- 5Medical Statistical Unit, London School of Hygiene and Tropical Medicine, London, UK
- 6Neuro-ophthalmology Clinic, Moorfields Eye Hospital, London, UK
- Correspondence to Dr M Di Filippo, Multiple Sclerosis Centre, Section of Neurology, S Maria della Misericordia Hospital, University of Perugia, Perugia, Italy;
- Received 2 January 2009
- Revised 17 May 2009
- Accepted 20 June 2009
- Published Online First 10 September 2009
Background Conventional MRI lesion measures modestly predict long term disability in some clinically isolated syndrome (CIS) studies. Brain atrophy suggests neuroaxonal loss in multiple sclerosis (MS) with the potential to reflect disease progression to a greater extent than lesion measures.
Objective To investigate whether brain atrophy and lesion load, during the first year in patients presenting with CIS, independently predict clinical outcome (development of MS and disability at 6 years).
Methods 99 patients presenting with CIS were included in the study. T1 gadolinium enhanced and T2 weighted brain MRI was acquired at baseline and approximately 1 year later. Percentage brain atrophy rate between baseline and follow-up scans was analysed using SIENA.
Results Mean annual brain atrophy rates were −0.38% for all patients, −0.50% in patients who had developed MS at 6 years and −0.26% in those who had not. Brain atrophy rate (p = 0.005) and baseline T2 lesion load (p<0.001) were independent predictors of clinically definite MS. While brain atrophy rate was a predictor of Expanded Disability Status Scale (EDSS) score in a univariate analysis, only 1 year T2 lesion load change (p = 0.007) and baseline gadolinium enhancing lesion number (p = 0.03) were independent predictors of EDSS score at the 6 year follow-up. T1 lesion load was the only MRI parameter which predicted Multiple Sclerosis Functional Composite score at the 6 year follow-up.
Conclusions The findings confirm that brain atrophy occurs during the earliest phases of MS and suggest that 1 year longitudinal measures of MRI change, if considered together with baseline MRI variables, might help to predict clinical status 6 years after the first demyelinating event in CIS patients, better than measurements such as lesion or brain volumes on baseline MRI alone.
Funding VMA is supported by the Multiple Sclerosis Society of Great Britain and Northern Ireland.
Competing interests MDF received a travel grant from Biogen to attend an international congress. VMA, DRA, JKS and GTP have no competing interests. AJT receives honoraria from Novartis (PPMS Advisory Group) and Eisai (Advisory Board, Clinical Neuroscience), and has received honorarium and support for travel from Serono Symposia (invited lecturer). DHM has received grant support from Biogen Idec, Elan, Bayer Schering, Novartis and GlaxoSmithKline for performance of MRI analyses in clinical trials, as well as honoraria for advisory or consultancy work, lectures and related travel expenses from Aventis, Biogen Idec, Bristol Myers Squibb, GlaxoSmithKline, Bayer Schering, Merck Serono, UCB Pharma and Wyeth.
Ethics approval Ethics approval was obtained from the Joint Medical Ethics Committee of the Institute of Neurology and National Hospital for Neurology and Neurosurgery, University College London and Moorfields Eye Hospital Ethics Committee.
Provenance and peer review Not commissioned; externally peer reviewed.