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Silent progression in disease activity-free relapsing multiple sclerosis.
Cree, Bruce A C; Hollenbach, Jill A; Bove, Riley; Kirkish, Gina; Sacco, Simone; Caverzasi, Eduardo; Bischof, Antje; Gundel, Tristan; Zhu, Alyssa H; Papinutto, Nico; Stern, William A; Bevan, Carolyn; Romeo, Andrew; Goodin, Douglas S; Gelfand, Jeffrey M; Graves, Jennifer; Green, Ari J; Wilson, Michael R; Zamvil, Scott S; Zhao, Chao; Gomez, Refujia; Ragan, Nicholas R; Rush, Gillian Q; Barba, Patrick; Santaniello, Adam; Baranzini, Sergio E; Oksenberg, Jorge R; Henry, Roland G; Hauser, Stephen L.
Affiliation
  • Cree BAC; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA.
  • Hollenbach JA; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA.
  • Bove R; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA.
  • Kirkish G; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA.
  • Sacco S; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA.
  • Caverzasi E; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA.
  • Bischof A; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA.
  • Gundel T; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA.
  • Zhu AH; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA.
  • Papinutto N; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA.
  • Stern WA; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA.
  • Bevan C; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA.
  • Romeo A; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA.
  • Goodin DS; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA.
  • Gelfand JM; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA.
  • Graves J; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA.
  • Green AJ; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA.
  • Wilson MR; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA.
  • Zamvil SS; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA.
  • Zhao C; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA.
  • Gomez R; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA.
  • Ragan NR; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA.
  • Rush GQ; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA.
  • Barba P; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA.
  • Santaniello A; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA.
  • Baranzini SE; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA.
  • Oksenberg JR; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA.
  • Henry RG; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA.
  • Hauser SL; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA.
Ann Neurol ; 85(5): 653-666, 2019 05.
Article in En | MEDLINE | ID: mdl-30851128
ABSTRACT

OBJECTIVE:

Rates of worsening and evolution to secondary progressive multiple sclerosis (MS) may be substantially lower in actively treated patients compared to natural history studies from the pretreatment era. Nonetheless, in our recently reported prospective cohort, more than half of patients with relapsing MS accumulated significant new disability by the 10th year of follow-up. Notably, "no evidence of disease activity" at 2 years did not predict long-term stability. Here, we determined to what extent clinical relapses and radiographic evidence of disease activity contribute to long-term disability accumulation.

METHODS:

Disability progression was defined as an increase in Expanded Disability Status Scale (EDSS) of 1.5, 1.0, or 0.5 (or greater) from baseline EDSS = 0, 1.0-5.0, and 5.5 or higher, respectively, assessed from baseline to year 5 (±1 year) and sustained to year 10 (±1 year). Longitudinal analysis of relative brain volume loss used a linear mixed model with sex, age, disease duration, and HLA-DRB1*1501 as covariates.

RESULTS:

Relapses were associated with a transient increase in disability over 1-year intervals (p = 0.012) but not with confirmed disability progression (p = 0.551). Relative brain volume declined at a greater rate among individuals with disability progression compared to those who remained stable (p < 0.05).

INTERPRETATION:

Long-term worsening is common in relapsing MS patients, is largely independent of relapse activity, and is associated with accelerated brain atrophy. We propose the term silent progression to describe the insidious disability that accrues in many patients who satisfy traditional criteria for relapsing-remitting MS. Ann Neurol 2019;85653-666.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Disease Progression / Multiple Sclerosis, Relapsing-Remitting Type of study: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limits: Adult / Female / Humans / Male / Middle aged Language: En Journal: Ann Neurol Year: 2019 Document type: Article Affiliation country:
Fulltext
Add to My VHL
Print
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PubMed Links
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Disease Progression / Multiple Sclerosis, Relapsing-Remitting Type of study: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limits: Adult / Female / Humans / Male / Middle aged Language: En Journal: Ann Neurol Year: 2019 Document type: Article Affiliation country: