The mechanisms of lesion genesis in multiple sclerosis?

Dr M. A. Lee and colleagues at the Centre for Functional Magnetic Resonance Imaging of the Brain and the Department of Clinical Neurology of the Radcliffe Hospital and Infirmary in Oxford, the Montreal Neurologic Institute, the Institute of Neurology in London, and the Neuroimaging Research Unit of the University of Milan have collaborated to provide us with interesting and provocative new data that challenges evolving dogma on the evolution if not the pathogenesis of individual plaques in multiple sclerosis. Their data are presented, in rather convincing fashion, in this issue in their paper ‘Spatial mapping of T2 and gadolinium-enhancing T1 lesion volumes in multiple sclerosis: evidence for distinct mechanisms of lesion genesis? (Lee et al., 1999). The introduction of MRI to the study of multiple sclerosis has substantially altered our understanding of the dynamics of MRI-defined lesion formation in this disease. Increasingly the natural history of lesion formation as monitored by MRI is reshaping our concepts of therapeutic management. Management is now focused especially on approaches to prevent future lesion development, with the, as yet, only partially supported hope of retarding the generally relentless progression of neurologic impairment and disability that clinically characterize multiple sclerosis (Ebers et al., 1998). Since the introduction of the use of gadolinium to define regional alterations of the blood–brain barrier that reflect active inflammatory change, there has been the increased expectation that the vast majority of lesions which can be seen with advanced MRI techniques follow a relatively stereotyped course. It is now generally accepted, based on serial observations, that the pathogenesis of individual lesions begins with a regional breach in the blood–brain barrier that is rapidly followed by alterations on T2-weighted images (Miller et al., 1998). However, while more frequent imaging intervals generally reduce any discrepancy between the presence of a new gadolinium enhancement and the finding of a new lesion on T2-weighted sequences, some gap has always remained (Miller et al., 1993). In addition, several groups of investigators, using a variety of different techniques, have suggested that regional changes are evident in otherwise MRI-defined normal-appearing white matter that may anticipate the development of an enhancement associated with a new T2-defined lesion (Filippi et al., 1998), and that these regions may even be abnormal before lesions develop without recognized prior enhancement (Narayana et al., 1998).