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From the Institute of Neurology (Drs. Paolillo, Molyneux, Gawne–Cain, MacManus, Barker, and Miller), NMR Research Unit, National Hospital, Queens Square, London; the Department of Neurology (Drs. Coles and Compston), Addenbrooke’s Hospital, University of Cambridge; and the ED Adrian Building (Dr. Compston), University Forvie Site, Robinsons Way, Cambridge, UK.
Address correspondence and reprint requests to Dr. D.H. Miller, NMR Research Unit, Institute of Neurology, National Hospital, Queens Square, London WC1N 3BG; e-mail: d.miller{at}ion.ucl.ac.uk
BACKGROUND: To assess the long-term effect of the lymphocyte-depleting humanized monoclonal antibody Campath 1H on MR markers of disease activity and progression in secondary progressive MS patients.
METHODS: Twenty-five patients participated in a crossover treatment trial with monthly run-in MR scans for 3 months, followed (after a single pulse of Campath 1H) by monthly MR scans from months 1 to 6 and again from months 12 to 18. MR analysis was performed to provide measurements of the number and volume of gadolinium (Gd)-enhancing lesions as well as the hypointense lesion volume on a T1-weighted sequence. In addition, serial measurements of T2 brain lesion volume, brain volume, and spinal cord cross-sectional area were made over the duration of the study. The relationship between clinical and MR measures of disease evolution was also assessed.
RESULTS: Treatment was associated with a reduction in the number and volume of Gd-enhancing lesions (p < 0.01). Despite this, a decrease in brain volume was seen in 13 patients during the 18 months post-treatment. The mean pretreatment Gd-enhancing lesion volume was predictive of subsequent reduction in brain volume (r = 0.77, p = 0.002). Reduction in brain volume also correlated with the change in T1 hypointense lesion volume after treatment (r = 0.53, p < 0.01). A reduction in spinal cord area was also seen throughout the study duration, and this correlated with an increase in disability (r = 0.65, p = 0.01).
CONCLUSION: Campath 1H treatment was associated with a sustained and marked reduction in the volume of Gd enhancement, indicating suppression of active inflammation. Nevertheless, many patients developed increasing brain and spinal cord atrophy, T1 hypointensity, and disability. This study highlights the potential role for novel MR techniques in monitoring the effect of treatment on the pathologic process in MS.
Key words: Quantitative MRI—Secondary progressive MS—Monoclonal antibody—Campath 1H.
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