Magnetic resonance imaging in the study of clinically isolated syndromes suggestive of multiple sclerosis

In this thesis I used magnetic resonance imaging (MRI) to study patients with clinically isolated syndromes (CIS) suggestive of multiple sclerosis (MS). Asymptomatic T2 lesions were present in the brain in 71% and in the spinal cord in 36% of CIS patients at presentation and their presence increased the risk of early clinical MS. Contrast-enhancing lesions, present in 31% of patients, were the most predictive finding for early clinical MS from a single MRI. More robust overall prognostic data was provided by a combination of T2 lesions at baseline and new T2 lesions after 3 months. Quantitative MRI studies found evidence for mild CNS atrophy, but MR spectroscopy and magnetisation transfer imaging detected tissue damage in lesions and not the widespread damage that has been described in established MS. The relationship between MRI and disability was assessed in 71 CIS patients who had been followed-up for a mean of 14 years. Clinically definite MS had developed in 88% who had cerebral T2 lesions at presentation, compared to only 19% with a normal MRI. Disability, measured on the expanded disability status score (EDSS), in the MS patients was generally mild (median EDSS 3.25), although 15 (32%) had an EDSS > 6, 3 of whom had died as a result of the disease. The EDSS at 14 years correlated moderately with T2 lesion volume at presentation (r = 0.48), but more strongly with T2 lesion volume at 5-years (r = 0.60) and with increase in T2 lesion volume over the first 5 years (r = 0.61). Serial MRI findings in CIS patients identified those at greatest risk of developing MS and disability. A 3-month follow-up MRI was the best predictor of early clinical MS and lesion volume increase in the first 5 years correlated strongly with long-term disability. Early MRI findings are important for prognosis and for selection into therapeutic trials. They also suggest a potential for therapies that suppress MRI lesion formation to have long-term benefits if given early in the course of MS