1. New Insights into Multiple Sclerosis Clinical Course from the Topographical Model and Functional Reserve 
Stephen C. Krieger, MD, James Sumowski, PhD 
Neurologic Clinics 
Volume 36, Issue 1, Pages (February 2018)
DOI: /j.ncl
Copyright © 2017 The Author(s) Terms and Conditions

2. Fig. 1 The 4 classic disease course phenotypes in multiple sclerosis.
(Adapted from Lublin FD, Reingold SC. Defining the clinical course of multiple sclerosis: results of an international survey. Neurology 1996;46:907–11.)
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3. Fig. 2
Archetypal clinical course for multiple sclerosis (MS) incorporating clinical relapses, lesions, and the loss of neurologic reserve in tandem with accelerated brain atrophy. PPMS, primary progressive multiple sclerosis; SPMS, secondary progressive multiple sclerosis.
(Courtesy of Dr Tim Vollmer, Aurora, CO; with permission.)
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4. Fig. 3
The topographical model of multiple sclerosis (MS), clinical (A) and subclinical (B) views. (A) Water is opaque, only above-threshold peaks are visible. (a) Above-threshold topographical peaks depict relapses and quantified Expanded Disability Status Scale (EDSS)/functional system disability measures. Each peak yields localizable clinical findings; the topographical distribution defines the clinical picture for an individual patient. (b) Water level at outset reflects baseline functional capacity and may be estimated by baseline brain volume. (c) Water level decrease reflects loss of functional reserve and may be estimated by metrics of annualized brain atrophy. (B) Subclinical view. The water is translucent, both clinical signs and subthreshold lesions are visible. (d) Subthreshold topographical peaks depict T2 lesion number and volume. (e) The tallest peaks (ie, the most destructive) in the cerebral hemispheres are shown capped in black as T1 black holes.
(Data from Krieger SC, Cook K, De Nino S, et al. The topographical model of multiple sclerosis: a dynamic visualization of disease course. Neurol Neuroimmunol Neuroinflamm 2016;3:e279.)
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5. Fig. 4
Representative disease course archetype at 5 and 20 of years disease duration. 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. This archetypal disease course is shown at years 5 and 20. In progressive multiple sclerosis, several subthreshold lesions denote underlying early disease activity, which cross the clinical threshold as functional reserve declines yielding gradual accumulation of disability.
(Data from Krieger SC, Cook K, De Nino S, et al. The topographical model of multiple sclerosis: a dynamic visualization of disease course. Neurol Neuroimmunol Neuroinflamm 2016;3:e279.)
Neurologic Clinics  , 13-25DOI: ( /j.ncl )
Copyright © 2017 The Author(s) Terms and Conditions