Understanding multiple sclerosis as a disease spectrum: above and below the clinical threshold.

Purpose Of Review: Research in multiple sclerosis (MS) has long been predicated on clinical groupings that do not reflect the underlying biologic heterogeneity apparent within patient populations. This review explicates the various levels of explanation through which the spectrum of disease is described and investigated both above and below the clinical threshold of detection, as framed by the topographical model of MS, to help advance a cogent mechanistic framework.

Recent Findings: Contemporary evidence has amended the view of MS as consisting of sequential disease phases in favor of a spectrum of disease with an admixture of interdependent and dynamic pathobiological axes driving tissue injury and progression.

Treatment transitions in neuromyelitis optica spectrum disorder increase risk for disease advancement.

Background: People with neuromyelitis optica spectrum disorder (PwNMOSD) commonly switch between disease modifying therapies, yet the consequence of transitions remains unknown. We aimed to understand if treatment transitions due to medical, non-medical, and tolerability reasons were related to disease progression.

Methods: A retrospective study of medical records for PwNMOSD was performed between 2008 and 2022.

Hiding in plain sight: The magnitude of unused disease modifying therapies in multiple sclerosis and strategies for reducing the economic burden of care.

Background: The rising costs associated with multiple sclerosis (MS) disease modifying therapies (DMTs) creates challenges for patients and the healthcare system in the United States (U.S.).

The topographical model of MS: Empirical evaluation of the recapitulation hypothesis.

Objective: Using the topographical model of multiple sclerosis (MS) to evaluate a longitudinal cohort we (1) test the recapitulation hypothesis, positing that patients' "disease topography" predicts the clinical pattern of disability accumulation; and (2) identify leading indicators of progression.

Methods: 10 patients who transitioned from relapsing-remitting MS to secondary progressive MS (SPMS) were evaluated. Neurologic exams were analyzed from relapses, at time of SPMS diagnosis, and most recent visit.

The topographical model of multiple sclerosis: A dynamic visualization of disease course.

Relapses and progression contribute to multiple sclerosis (MS) disease course, but neither the relationship between them nor the spectrum of clinical heterogeneity has been fully characterized. A hypothesis-driven, biologically informed model could build on the clinical phenotypes to encompass the dynamic admixture of factors underlying MS disease course. In this medical hypothesis, we put forth a dynamic model of MS disease course that incorporates localization and other drivers of disability to propose a clinical manifestation framework that visualizes MS in a clinically individualized way.