Primary progressive multiple sclerosis: a distinct syndrome?

Multiple sclerosis (MS) has long been recognised to have both a relapsing-remitting and progressive course. More recently patients with progressive disease have been further sub-divided into those with a progressive course from onset (primary progressive MS) and those with progressive decline following an initially relapsing-remitting period (secondary progressive MS). Diversity in MS may not however be restricted to clinical course. There is growing evidence that the subgroups of MS also differ with respect to clinical features, epidemiology, pathogenesis, genetics and neuroimaging appearances. In this review we outline the criteria variously applied in the classification of MS patients, addressing the need for a clear nomenclature. We evaluate the proposition that primary progressive MS has a profile distinct from other MS categories, contrasting the separate differential diagnoses and examining the implications for future therapeutic trials.