Objective: The primary goal of this study is to define the safety and efficacy of combined systemic and intrathecal (IT) B cell-depleting therapy (i.e. anti-CD20, rituximab) in patients with secondary-progressive multiple sclerosis (SP-MS). The secondary goals of this study are to collect longitudinal data to help identify the most sensitive outcome measures and trial design for future Phase II trials for SP-MS patients and to investigate the mechanism of action of rituximab on the human immune system.