| Primary progressive multiple sclerosis is the central theme of this thesis which includes the first randomised controlled trial to be specifically designed for this group. The difficulties in diagnosis, classification and choice of outcome measures for therapeutic trials in this group are considered, and the role of magnetic resonance imaging (MRI) in monitoring disease progression is explored. Two recently developed and more pathologically specific MRI techniques, magnetisation transfer ratio (MTR) and 1H magnetic resonance spectroscopy (MRS), are evaluated in cross-sectional studies. To investigate the marked discrepancy between focal cerebral lesions and disability in primary progressive multiple sclerosis, these techniques are applied to normal appearing white matter (NAWM) and provide evidence for the hypothesis that intrinsic changes, including axonal damage, are occurring in NAWM. Consideration is also given to methodological issues in serial MRI measurement and studies of reproducibility of spinal cord area measurement and of physiological variation in MRS are presented. Finally, the first randomised controlled study of a beta interferon in primary progressive multiple sclerosis is presented. This is an exploratory study and its objectives are to explore the safety of and look for hint of efficacy of interferon beta-1a in primary progressive multiple sclerosis and to identify potentially useful outcome measures in this group. This study demonstrates that it is entirely feasible to carry out therapeutic trials in primary progressive multiple sclerosis and appropriate outcome measures are available. Overall this thesis provides evidence to facilitate continuing increase in interest and research activity in primary progressive multiple sclerosis. |
