Evidence map›Paper›PMID 30851128›Full record

ArticleAnnals of neurology2019

Silent progression in disease activity-free relapsing multiple sclerosis.

University of California, San Francisco MS-EPIC Team, Bruce A C Cree, Jill A Hollenbach, Riley Bove, Gina Kirkish, Simone Sacco, Eduardo Caverzasi, Antje Bischof, Tristan Gundel, Alyssa H Zhu and 20 more

2 registry-linked trialsOpen access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Annals of neurology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 259 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
259citing papers in PubMed, 4 pooled it
30.3field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT04466150 phase4active not recruitingnot on this mapstarted 2020, after this paper: background citation

Impact of Ocrelizumab on Cerebrospinal Fluid Biomarkers at Multiple Sclerosis Onset

TypeinterventionalSponsorUniversity of California, San FranciscoRan2020 to 2027Enrolled30ConditionsRelapsing Multiple Sclerosis, Clinically Isolated SyndromeArmsOcrelizumab
NCT05937802 naunknown statusnot on this mapstarted 2023, after this paper: background citation

Exploratory Trial of Forza™️, a Novel Nutraceutical From Actinidia Deliciosa Plants Bioengineered to Bio-encapsulate the Osmotin Plant Protein as Adjuvant for the Treatment of Progressive Multiple Sclerosis

TypeinterventionalSponsorOspedale Policlinico San MartinoRan2023 to 2025Enrolled50ConditionsProgressive Multiple SclerosisArmsOsmotin
3 · Its place in the literature

Who cites it

259 citing papers in PubMed, 4 syntheses or guidelines pooled it, 437 citations in OpenAlex.

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  18. Impact of age, BMI, and renal function adjustment on interpretation of serum NfL and GFAP in multiple sclerosis progression: a scoping review.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026
    Article
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199 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

30 authors at 1 institution in 1 country.

University of California, San Francisco MS-EPIC Team
Bruce A C CreeUCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA.
Jill A HollenbachUCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA.
Riley BoveUCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA.
Gina KirkishUCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA.
Simone SaccoUCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA.
Eduardo CaverzasiUCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA.ORCID 0000-0002-0350-0460
Antje BischofUCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA.ORCID 0000-0003-3862-5738
Tristan GundelUCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA.
Alyssa H ZhuUCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA.
Nico PapinuttoUCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA.
William A SternUCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA.
Carolyn BevanUCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA.
Andrew RomeoUCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA.
Douglas S GoodinUCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA.
Jeffrey M GelfandUCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA.
Jennifer GravesUCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA.
Ari J GreenUCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA.
Michael R WilsonUCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA.
Scott S ZamvilUCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA.
Chao ZhaoUCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA.
Refujia GomezUCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA.
Nicholas R RaganUCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA.
Gillian Q RushUCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA.
Patrick BarbaUCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA.
Adam SantanielloUCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA.
Sergio E BaranziniUCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA.
Jorge R OksenbergUCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA.
Roland G HenryUCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA.
Stephen L HauserUCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA.
University of California, San Francisco · US

Funding

The Role of B cells in the Origin and Progression of Multiple SclerosisR35NS111644 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI STEPHEN L HAUSER · 2019 to 2026
$9.1M
GENE LINKAGE STUDY OF MULTIPLE SCLEROSIS SIBLING PAIRSR01NS026799 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI HAUSER, STEPHEN L, OKSENBERG, JORGE R. · 1989 to 2018
$6.8M
Repertoire selection of AQP4-specific T cells that cause CNS autoimmunediseaseR01AI131624 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ZAMVIL, SCOTT S · 2019 to 2023
$2.2M
Friends of the Multiple Sclerosis Research Group at UCSFNIAID NIH HHS R01 AI131624NINDS NIH HHS R01 NS026799NINDS NIH HHS R35 NS111644Valhalla Foundation
6 · The paper itself

Abstract

objectiveRates 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.

methodsDisability 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*15:01 as covariates.

resultsRelapses 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).

interpretationLong-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;85:653-666.

Indexed as

Disease ProgressionAdultCohort StudiesFemaleFollow-Up StudiesHumansLongitudinal StudiesMaleMiddle AgedMultiple Sclerosis, Relapsing-RemittingProspective Studies

Identifiers

PMID30851128
PMCPMC6518998
OpenAlexW2922528121

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.