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August 2021; 11 (4) ReviewOpen Access

Multiple Sclerosis Phenotypes as a Continuum

The Role of Neurologic Reserve

Timothy L. Vollmer, Kavita V. Nair, Ian M. Williams, Enrique Alvarez
First published January 29, 2021, DOI: https://doi.org/10.1212/CPJ.0000000000001045
Timothy L. Vollmer
Department of Neurology (TLV, KVN, EA), University of Colorado, and Rocky Mountain Multiple Sclerosis Center at the University of Colorado, Aurora; Department of Clinical Pharmacy (KVN), Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora; and Oxford PharmaGenesis (IMW), United Kingdom.
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Kavita V. Nair
Department of Neurology (TLV, KVN, EA), University of Colorado, and Rocky Mountain Multiple Sclerosis Center at the University of Colorado, Aurora; Department of Clinical Pharmacy (KVN), Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora; and Oxford PharmaGenesis (IMW), United Kingdom.
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Ian M. Williams
Department of Neurology (TLV, KVN, EA), University of Colorado, and Rocky Mountain Multiple Sclerosis Center at the University of Colorado, Aurora; Department of Clinical Pharmacy (KVN), Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora; and Oxford PharmaGenesis (IMW), United Kingdom.
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Enrique Alvarez
Department of Neurology (TLV, KVN, EA), University of Colorado, and Rocky Mountain Multiple Sclerosis Center at the University of Colorado, Aurora; Department of Clinical Pharmacy (KVN), Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora; and Oxford PharmaGenesis (IMW), United Kingdom.
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Citation
Multiple Sclerosis Phenotypes as a Continuum
The Role of Neurologic Reserve
Timothy L. Vollmer, Kavita V. Nair, Ian M. Williams, Enrique Alvarez
Neurol Clin Pract Aug 2021, 11 (4) 342-351; DOI: 10.1212/CPJ.0000000000001045

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Abstract

Purpose of Review This review presents the hypothesis that loss of neurologic reserve explains onset of progressive multiple sclerosis (PrMS).

Recent Findings Evidence supporting the separate classification of PrMS and relapsing multiple sclerosis (RMS) is limited and does not explain PrMS or the response of these patients to therapy.

Summary We argue that multiple sclerosis (MS) progresses along a continuum from RMS to PrMS, with differing levels of neurologic reserve accounting for phenotypic differences. In early MS, inflammation causes brain atrophy with symptoms buffered by neurologic reserve. As brain loss from normal aging and MS continues, reserve is depleted and effects of subclinical MS disease activity and aging are unmasked, manifesting as PrMS. Most therapies show limited benefit in PrMS; patients are older, have fewer inflammatory events, and the effects of aging cause continued loss of neurologic function, even if inflammation is terminated. Loss of neurologic reserve means patients with PrMS cannot recover function, unlike patients with RMS.

Footnotes

  • Funding information and disclosures are provided at the end of the article. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/cp.

  • The Article Processing Charge was funded by the authors.

  • Editorial, page 271

  • Received May 6, 2020.
  • Accepted December 10, 2020.
  • Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

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