The goal of this project is to use magnetic resonance imaging (MRI) to examine the natural history and effectiveness of experimental therapies in multiple sclerosis (MS). Emphasis has been placed on investigation of the early MS lesion which is characterized by enhancement on T1- weighted MRI images following administration of gadolinium-DTPA (Gd). Results from initial studies have indicated that MS can be an active disease, even during periods of remission in the early, relapsing-remitting phase of the illness. Disease activity MRI has been correlated with clinical disease. Episodes of worsening tend to occur during periods of increased disease activity as evidenced by increased frequency or area of enhancing lesions. The clinical symptoms and signs generally are due to lesions occurring in the spinal cord or brain stem concurrently with the increased activity in the cerebrum. Examination of the pathological changes occurring in conjunction with Gd enhancement indicate an acute inflammatory process with prominent perivascular cuffs of lymphocytes. These findings support the hypothesis that Gd enhancement represent the initial step in lesion development. The ability to use MRI as an outcome measure in clinical trials has been examined in a baseline, versus treatment trial design studying IFN- beta1B. The results of this study indicate that IFN-beta1B has a dramatic effect on the occurrence of gadolinium-enhancing lesions; the frequency of gadolinium-enhancing lesions was dramatically reduced in patients on treatment as compared with lesion frequency prior to treatment. Additional information relating to the natural history of MS has been derived from a study of a 68-patient cohort studied for a minimum of three months by serial MRI. Results of this study indicate approximately two-thirds of patients with early-mild, relapsing-remitting MS have active disease on MRI, again indicating the disease process is active, even during this early-remitting phase. In addition to the occurrence of gadolinium-enhancing lesions, assessment of changes in the overall magnitude of the disease on MRI as measured by the volume of T2 lesions, indicates progression in a population of patients with mild, relapsing- remitting MS.
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