Targeting Central Nervous System B Cells in Progression of Multiple Sclerosis: Is Intrathecal Anti-CD20 a Therapeutic Option?

Abstract

Multiple sclerosis (MS) is an immune-mediated chronic disease of the central nervous system (CNS). In most patients, MS starts with a relapsing-remitting (RR) disease course followed by a secondary progressive (SP) phase with slowly accumulating disability, often in the absence of acute exacerbations. Few patients develop a primary progressive (PP) disease course with no circumscribable relapses from the very beginning. A recently proposed new classification of the clinical course of MS puts active and progressive disease as the 2 main phenotypes in the focus. While the pathophysiological correlate of relapses is assumed to be a concerted infiltration by systemic leukocytes resulting in a magnetic resonance imaging–detectable focal inflammatory CNS white matter lesion, the mechanisms behind the slowly progressing aspect of MS are not well understood. Emerging evidence suggests that, besides focal white matter lesions, widespread diffuse inflammation throughout otherwise “normal-appearing” white mat