Abstract

Multiple sclerosis (MS) is commonly regarded as an inflammatory disease, but it also has a neurodegenerative component, which represents an additional target for treatment. The use of MRI to evaluate the inflammatory disease component in 'proof-of concept' clinical trials is well established, but no systematic assessment of imaging outcomes to evaluate neuroprotection or repair in MS has been performed. In this Review, we examine the potential of traditional and novel imaging parameters to serve as primary outcomes in phase II clinical trials of neuroprotective and reparative strategies in MS. We present the conclusions of an international meeting of imaging, clinical and statistical experts, as well as a review of relevant literature. The available imaging techniques are appraised in five categories of performance: pathological specificity, reproducibility, sensitivity to change, clinical relevance, and response to treatment. At present, the three most promising primary outcomes in phase II trials of neuroprotective and/or reparative strategies in MS are: changes in whole-brain volume to gauge general cerebral atrophy; T1 hypointensity and magnetization transfer ratio to monitor the evolution of lesion damage; and optical coherence tomography findings to evaluate the anterior visual pathway. Power calculations show that these outcome measures can be applied with attainable sample sizes.

Author affiliations

1. Department of Radiology and Amsterdam MS Center, VU University Medical Center, Amsterdam, The Netherlands.
2. Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, USA.
3. Department of Neuroinflammation and NMR Research Unit, Institute of Neurology, University College London, London, UK.
4. National MS Society and Scientific and Clinical Review Associates, LLC, New York, NY, USA.

Correspondence to: F. Barkhof, Department of Radiology, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam, The Netherlands
Email: f.barkhof@vumc.nl