The pathology of MS - New insights and potential clinical applications

Background: The pathological hallmarks of the multiple sclerosis (MS) lesion consist of focal demyelination, inflammation, scar formation, and variable axonal destruction. Despite years of classical histopathological study and more recent intensive use of magnetic resonance technology, the MS lesion is incompletely understood. How it is initiated, how it changes over time, how it correlates with clinical symptoms and other markers of disease activity, and how it is impacted by therapeutic intervention are all largely unknown. As the site of disease pathology, the MS lesion remains the target of attack for therapy. Therefore it is essential we better understand MS lesion evolution and its clinical as well as paraclinical correlates. Review Summary: In this review, we focus on what can be learned about MS from detailed pathological analysis. We discuss the literature on both the traditional and more recent changing concepts about MS pathogenesis. We also review the work of the Multiple Sclerosis Lesion Project, an international collaborative effort to study the pathologic, clinical, and radiologic correlates of the MS lesion. Conclusions: The introduction of new technologies has contributed to a better appreciation regarding the complexity of the MS lesion. The discovery of heterogeneity in demyelinating lesions has suggested that different mechanisms may be involved in MS pathogenesis. This observation may be important for future studies on the etiology and therapy of the disease. However the potential to apply these findings to the clinic will rely on the development of technologies that allow the stratification of MS subtypes without being dependent on brain biopsies.