Evidence map›Paper›PMID 34878197›Full record

Observational studyAnnals of neurology2022

Spinal Cord Atrophy Predicts Progressive Disease in Relapsing Multiple Sclerosis.

Antje Bischof, Nico Papinutto, Anisha Keshavan, Anand Rajesh, Gina Kirkish, Xinheng Zhang, Jacob M Mallott, Carlo Asteggiano, Simone Sacco, Tristan J Gundel and 24 more

Open access · greenAbstract readObservational Study
PubMed Full text at PMC Publisher
In one paragraph

Observational study in Annals of neurology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
69citing papers in PubMed, 3 pooled it
8.8field-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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

69 citing papers in PubMed, 3 syntheses or guidelines pooled it, 111 citations in OpenAlex.

  1. Spinal cord imaging in multiple sclerosis: A vital component we can no longer overlook.Multiple sclerosis (Houndmills, Basingstoke, England) · 2026
    Pooled it
  2. Pooled it
  3. Pooled it
  4. Trial
  5. Review
  6. Review
  7. Article
  8. Article
  9. Charting Cervical Spinal Cord Morphometry Across the Lifespan.bioRxiv : the preprint server for biology · 2026
    Article
  10. Review
  11. Observational
  12. Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Review
  20. Article

9 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

34 authors at 1 institution in 2 countries.

Antje BischofWeill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA.ORCID 0000-0003-3862-5738
Nico PapinuttoWeill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA.
Anisha KeshavanWeill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA.
Anand RajeshWeill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA.
Gina KirkishWeill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA.
Xinheng ZhangWeill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA.
Jacob M MallottWeill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA.ORCID 0000-0001-7309-3605
Carlo AsteggianoWeill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA.
Simone SaccoWeill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA.
Tristan J GundelWeill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA.
Chao ZhaoWeill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA.
William A SternWeill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA.
Eduardo CaverzasiWeill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA.ORCID 0000-0002-0350-0460
Yifan ZhouWeill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA.
Refujia GomezWeill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA.
Nicholas R RaganWeill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA.
Adam SantanielloWeill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA.
Alyssa H ZhuWeill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA.
Jeremy JuwonoWeill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA.
Carolyn J BevanWeill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA.
Riley M BoveWeill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA.
Elizabeth CrabtreeWeill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA.
Jeffrey M GelfandWeill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA.
Douglas S GoodinWeill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA.
Jennifer S GravesWeill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA.ORCID 0000-0003-1539-1940
Ari J GreenWeill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA.
Jorge R OksenbergWeill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA.
Emmanuelle WaubantWeill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA.ORCID 0000-0001-5188-0157
Michael R WilsonWeill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA.
Scott S ZamvilWeill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA.ORCID 0000-0003-2720-9915
University of California, San Francisco MS-EPIC TeamWeill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA.
Bruce A C CreeWeill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA.ORCID 0000-0001-7689-2533
Stephen L HauserWeill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA.ORCID 0000-0002-4932-4001
Roland G HenryWeill Institute for Neurosciences, Department of Neurology, University of California, 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
Correlating Multiple Sclerosis Phenotypes with GenotypesK23NS048869 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CREE, BRUCE C · 2005 to 2009
$807k
National Institute of Neurological Diseases and Stroke R35NS111644National Institute of Neurological Diseases and Stroke RO1NS26799NIAID NIH HHS R01 AI131624NINDS NIH HHS K23 NS048869NINDS NIH HHS R01 NS026799NINDS NIH HHS R35 NS111644
6 · The paper itself

Abstract

objectiveA major challenge in multiple sclerosis (MS) research is the understanding of silent progression and Progressive MS. Using a novel method to accurately capture upper cervical cord area from legacy brain MRI scans we aimed to study the role of spinal cord and brain atrophy for silent progression and conversion to secondary progressive disease (SPMS).

methodsFrom a single-center observational study, all RRMS (n = 360) and SPMS (n = 47) patients and 80 matched controls were evaluated. RRMS patient subsets who converted to SPMS (n = 54) or silently progressed (n = 159), respectively, during the 12-year observation period were compared to clinically matched RRMS patients remaining RRMS (n = 54) or stable (n = 147), respectively. From brain MRI, we assessed the value of brain and spinal cord measures to predict silent progression and SPMS conversion.

resultsPatients who developed SPMS showed faster cord atrophy rates (-2.19%/yr) at least 4 years before conversion compared to their RRMS matches (-0.88%/yr, p < 0.001). Spinal cord atrophy rates decelerated after conversion (-1.63%/yr, p = 0.010) towards those of SPMS patients from study entry (-1.04%). Each 1% faster spinal cord atrophy rate was associated with 69% (p < 0.0001) and 53% (p < 0.0001) shorter time to silent progression and SPMS conversion, respectively.

interpretationSilent progression and conversion to secondary progressive disease are predominantly related to cervical cord atrophy. This atrophy is often present from the earliest disease stages and predicts the speed of silent progression and conversion to Progressive MS. Diagnosis of SPMS is rather a late recognition of this neurodegenerative process than a distinct disease phase. ANN NEUROL 2022;91:268-281.

Indexed as

AdultAtrophyBrainDisease ProgressionFemaleForamen MagnumHumansMagnetic Resonance ImagingMaleMiddle AgedMultiple Sclerosis, Relapsing-RemittingPredictive Value of TestsPrognosisProspective StudiesSpinal Cord

Identifiers

PMID34878197
PMCPMC8916838
OpenAlexW4200514971

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.