Stevenson, Valerie L; (1999) The natural history of primary progressive multiple sclerosis: Serial clinical and MRI evaluation and application of new spinal imaging techniques. Doctoral thesis (M.D), UCL (University College London).

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Abstract

This thesis describes the clinical and Magnetic Resonance Imaging (MRI) characteristics of patients with primary progressive multiple sclerosis (PP MS). These patients make up less than 10% of the MS population and because of their relative rarity, few studies have looked at this group and only three small therapeutic trials have been undertaken to date. By definition their course is purely progressive and therefore they are an ideal group to study disease progression independent from the effect of relapses. In a cohort of 60 patients, cross sectional analysis revealed that patients with PP MS have lower T2 and T1 hypo-intensity lesion loads than other patient groups. Serial analysis revealed that despite these low lesion loads, measurable changes were seen after relatively short time periods. Both brain and cord atrophy was also shown to develop. These results have implications for trial design particularly in the choice of appropriate outcome measures. As many of these patients have a predominant spinal cord syndrome which is responsible for much of their locomotor disability, the development of several techniques aimed at optimising spinal cord imaging are described. These include two new MR sequences, fast FLAIR and 3-dimensional fast spin echo (3D FSE). Although the 3D FSE sequence did increase lesion detection, the relationship between spinal cord lesion load and disability remained poor. The fast FLAIR sequence failed to detect lesions in the cord despite increased lesion detection in the brain, thus indicating differences in lesion composition dependent on lesion site. This was confirmed by the subsequent quantification of T1 and T2 relaxation times in both lesions and normal appearing white matter in MS. This work is important in improving our understanding of the pathological processes responsible for disease progression in MS and aids in the choice of appropriate outcome measures for monitoring change, particularly important in therapeutic trials.

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