Walsh & Hoyt: Treatment of Multiple Sclerosis and Clinically Isolated Syndromes

Charcot recognized two clinical phenomena in patients with MSexacerbations and progression. Although some patients with MS have an illness that is slowly progressive from onset (PPMS) and others have an acute, rapidly progressive disease (acute MS), most cases of MS begin with a relapsing-remitting course (RRMS). The earliest form of RRMS is the clinically isolated syndrome, which most often manifests as acute optic neuritis, a brainstem syndrome, or spinal cord syndrome. Although not all patients with RRMS develop a progressive course, secondary progressive MS is a long-term sequela of RRMS for many. Patients with RRMS have clearly defined relapses with a lack of disease progression during inter-relapse intervals; however, SPMS is characterized by disease progression and worsening of neurologic baseline following an initially relapsing-remitting course. Like the clinical course of MS, the pathogenesis of MS also is heterogeneous, with prominent components of inflammation, demyelination, and axonal loss. Treatments therefore not only must be targeted toward reducing inflammatory responses and numbers of exacerbations in patients with MS but ideally should minimize disease progression and axonal loss.