Figure 4 Four representative disease-course archetypes

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Figure 4 Four representative disease-course archetypes Four representative disease-course archetypes The model conceptualizes relapsing and progressive contributions to disease course along a continuum: an individual's disease course can be driven predominantly by relapses, or predominantly by progression, and those with very mild or stable disease may demonstrate neither. Each archetypal disease course is shown at year 5 and year 20. (A) Relapsing-remitting MS with early secondary progressive disease: relapsing disease transitions to secondary progressive MS with disability being driven in the early years by relapse (“base effects”) and in the later years primarily by the declining threshold (“surface effects”). (B) Relapsing-remitting MS with highly active disease is characterized topographically by extensive clinical and subclinical inflammatory activity. Here, several lesions in the spinal cord and brainstem do not resolve below the clinical threshold, demonstrating lesions with high severity and low recovery capacity. (C) Primary progressive MS: several subthreshold lesions denote underlying disease activity, which do not cross the clinical threshold until functional reserve declines. Disability is driven here by the dropping threshold. (D) Mild course: no demonstrable disability is accumulated at 20 years of disease. All relapses resolve below the clinical threshold—demonstrating lesions with a high recovery capacity—and there is little depletion of functional reserve beyond that of normal aging. MS = multiple sclerosis. Stephen C. Krieger et al. Neurol Neuroimmunol Neuroinflamm 2016;3:e279 © 2016 American Academy of Neurology