Effects of Current Medical Therapies on Reparative and Neuroprotective Functions in Multiple Sclerosis

Abstract

Multiple sclerosis (MS) is most frequently clinically characterized by an initial relapsing-remitting phase that evolves into a secondary progressive course; these phases can also be ongoing concurrently. Each of these clinical disease aspects re fl ects distinctive pathologic substrates, each of which may require its own therapeutic strategies. The pathologic correlate of clinical relapses is the development of new demyelinating lesions within the CNS that feature an in fl ammatory in fi ltrate comprised of cells of the adaptive (lymphocytes) and innate (myeloid cells) systems that have transgressed the blood-brain barrier (BBB) and/or the subarachnoid space/ brain barrier (Kivisakk et al. 2003 ) . Axonal transections are a further feature of the acute lesions (Trapp et al. 1998 ) . Magnetic resonance imaging (MRI) studies indicate that multiple such lesions can occur without apparent clinical symptoms (Engell 1989 ). Recovery from relapses re fl ects the combined effects of multiple factors including resolution of in fl ammation, axonal adaptation to demyelination, remyelination, and cerebral reorganization. The pathologic correlates of the later progressive disease phase are even more complex involving changes both within initial