Progressive multifocal leukoencephalopathy (PML) has been identified in patients taking natalizumab (NMAB) for the treatment of multiple sclerosis (MS). This patent application provides a novel method of patient screening and monitoring intended to decrease the risk of PML and other opportunistic central nervous system (CNS) diseases in patients undergoing MS therapy with NMAB, and proposes a novel method of screening and monitoring intended to decrease the risk of opportunistic disease processes of the CNS during the treatment of other medical disorders with NMAB.