Evidence map›Paper›PMID 35575778›Full record

Observational studyJAMA neurology2022

Association of Brain Atrophy With Disease Progression Independent of Relapse Activity in Patients With Relapsing Multiple Sclerosis.

Alessandro Cagol, Sabine Schaedelin, Muhamed Barakovic, Pascal Benkert, Ramona-Alexandra Todea, Reza Rahmanzadeh, Riccardo Galbusera, Po-Jui Lu, Matthias Weigel, Lester Melie-Garcia and 34 more

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

Observational study in JAMA neurology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 papers.

0numbers the graph read from it
0cells of the map it votes in
101citing papers in PubMed
22.3field-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.

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

101 citing papers in PubMed, 161 citations in OpenAlex.

  1. Trial
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  8. Observational
  9. Article
  10. Integrating Anatomical Priors Into a Causal Diffusion Model.IEEE transactions on medical imaging · 2026
    Article
  11. Article
  12. Article
  13. Brain atrophy rates vary with age in relapsing-remitting multiple sclerosis.Journal of neurology, neurosurgery, and psychiatry · 2026
    Article
  14. Article
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  16. Article
  17. Review
  18. Observational
  19. Observational
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41 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

44 authors at 8 institutions in 2 countries.

Alessandro CagolTranslational Imaging in Neurology (ThINK) Basel, Department of Biomedical Engineering, Faculty of Medicine, University Hospital Basel, University of Basel, Basel, Switzerland.
Sabine SchaedelinClinical Trial Unit, Department of Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland.
Muhamed BarakovicTranslational Imaging in Neurology (ThINK) Basel, Department of Biomedical Engineering, Faculty of Medicine, University Hospital Basel, University of Basel, Basel, Switzerland.
Pascal BenkertClinical Trial Unit, Department of Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland.
Ramona-Alexandra TodeaTranslational Imaging in Neurology (ThINK) Basel, Department of Biomedical Engineering, Faculty of Medicine, University Hospital Basel, University of Basel, Basel, Switzerland.
Reza RahmanzadehTranslational Imaging in Neurology (ThINK) Basel, Department of Biomedical Engineering, Faculty of Medicine, University Hospital Basel, University of Basel, Basel, Switzerland.
Riccardo GalbuseraTranslational Imaging in Neurology (ThINK) Basel, Department of Biomedical Engineering, Faculty of Medicine, University Hospital Basel, University of Basel, Basel, Switzerland.
Po-Jui LuTranslational Imaging in Neurology (ThINK) Basel, Department of Biomedical Engineering, Faculty of Medicine, University Hospital Basel, University of Basel, Basel, Switzerland.
Matthias WeigelTranslational Imaging in Neurology (ThINK) Basel, Department of Biomedical Engineering, Faculty of Medicine, University Hospital Basel, University of Basel, Basel, Switzerland.
Lester Melie-GarciaTranslational Imaging in Neurology (ThINK) Basel, Department of Biomedical Engineering, Faculty of Medicine, University Hospital Basel, University of Basel, Basel, Switzerland.
Esther RuberteTranslational Imaging in Neurology (ThINK) Basel, Department of Biomedical Engineering, Faculty of Medicine, University Hospital Basel, University of Basel, Basel, Switzerland.
Nina SiebenbornTranslational Imaging in Neurology (ThINK) Basel, Department of Biomedical Engineering, Faculty of Medicine, University Hospital Basel, University of Basel, Basel, Switzerland.
Marco BattagliniDepartment of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy.
Ernst-Wilhelm RadueTranslational Imaging in Neurology (ThINK) Basel, Department of Biomedical Engineering, Faculty of Medicine, University Hospital Basel, University of Basel, Basel, Switzerland.
Özgür YaldizliTranslational Imaging in Neurology (ThINK) Basel, Department of Biomedical Engineering, Faculty of Medicine, University Hospital Basel, University of Basel, Basel, Switzerland.
Johanna OechteringNeurologic Clinic and Policlinic, MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel, University of Basel, Basel, Switzerland.
Tim SinneckerTranslational Imaging in Neurology (ThINK) Basel, Department of Biomedical Engineering, Faculty of Medicine, University Hospital Basel, University of Basel, Basel, Switzerland.
Johannes LorscheiderNeurologic Clinic and Policlinic, MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel, University of Basel, Basel, Switzerland.
Bettina Fischer-BarnicolNeurologic Clinic and Policlinic, MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel, University of Basel, Basel, Switzerland.
Stefanie MüllerDepartment of Neurology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland.
Lutz AchtnichtsDepartment of Neurology, Cantonal Hospital Aarau, Aarau, Switzerland.
Jochen VehoffDepartment of Neurology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland.
Giulio DisantoNeurology Department, Neurocenter of Southern Switzerland, Lugano, Switzerland.
Oliver FindlingDepartment of Neurology, Cantonal Hospital Aarau, Aarau, Switzerland.
Andrew ChanDepartment of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Anke SalmenDepartment of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Caroline PotDivision of Neurology, Department of Clinical Neurosciences, Lausanne University Hospital (CHUV), University of Lausanne, Lausanne, Switzerland.
Claire BridelDivision of Neurology, Department of Clinical Neurosciences, Faculty of Medicine, Geneva University Hospitals, Geneva, Switzerland.
Chiara ZeccaNeurology Department, Neurocenter of Southern Switzerland, Lugano, Switzerland.
Tobias DerfussNeurologic Clinic and Policlinic, MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel, University of Basel, Basel, Switzerland.
Johanna M LiebDivision of Diagnostic and Interventional Neuroradiology, Clinic for Radiology and Nuclear Medicine, University Hospital Basel, University of Basel, Basel, Switzerland.
Luca RemondaDepartment of Radiology, Cantonal Hospital Aarau, Aarau, Switzerland.
Franca WagnerDepartment of Diagnostic and Interventional Neuroradiology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Maria I VargasDepartment of Radiology, Faculty of Medicine, Geneva University Hospital, Geneva, Switzerland.
Renaud Du PasquierDivision of Neurology, Department of Clinical Neurosciences, Lausanne University Hospital (CHUV), University of Lausanne, Lausanne, Switzerland.
Patrice H LaliveDivision of Neurology, Department of Clinical Neurosciences, Faculty of Medicine, Geneva University Hospitals, Geneva, Switzerland.
Emanuele PravatàNeurology Department, Neurocenter of Southern Switzerland, Lugano, Switzerland.
Johannes WeberDepartment of Radiology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland.
Philippe C CattinCenter for Medical Image, Analysis, and Navigation, Department of Biomedical Engineering, University of Basel, Allschwil, Switzerland.
Claudio GobbiNeurology Department, Neurocenter of Southern Switzerland, Lugano, Switzerland.
David LeppertNeurologic Clinic and Policlinic, MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel, University of Basel, Basel, Switzerland.
Ludwig KapposTranslational Imaging in Neurology (ThINK) Basel, Department of Biomedical Engineering, Faculty of Medicine, University Hospital Basel, University of Basel, Basel, Switzerland.
Jens KuhleNeurologic Clinic and Policlinic, MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel, University of Basel, Basel, Switzerland.
Cristina GranzieraTranslational Imaging in Neurology (ThINK) Basel, Department of Biomedical Engineering, Faculty of Medicine, University Hospital Basel, University of Basel, Basel, Switzerland.
University of Basel · CHLaboratory for Biomedical Neurosciences · CHKantonsspital Aarau · CHKantonsspital St. Gallen · CHUniversity Hospital of Geneva · CHUniversity of Bern · CHUniversity of Lausanne · CHUniversity of Siena · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Importance: The mechanisms driving neurodegeneration and brain atrophy in relapsing multiple sclerosis (RMS) are not completely understood. Objective: To determine whether disability progression independent of relapse activity (PIRA) in patients with RMS is associated with accelerated brain tissue loss. Design, Setting, and Participants: In this observational, longitudinal cohort study with median (IQR) follow-up of 3.2 years (2.0-4.9), data were acquired from January 2012 to September 2019 in a consortium of tertiary university and nonuniversity referral hospitals. Patients were included if they had regular clinical follow-up and at least 2 brain magnetic resonance imaging (MRI) scans suitable for volumetric analysis. Data were analyzed between January 2020 and March 2021. Exposures: According to the clinical evolution during the entire observation, patients were classified as those presenting (1) relapse activity only, (2) PIRA episodes only, (3) mixed activity, or (4) clinical stability. Main Outcomes and Measures: Mean difference in annual percentage change (MD-APC) in brain volume/cortical thickness between groups, calculated after propensity score matching. Brain atrophy rates, and their association with the variables of interest, were explored with linear mixed-effect models. Results: Included were 1904 brain MRI scans from 516 patients with RMS (67.4% female; mean [SD] age, 41.4 [11.1] years; median [IQR] Expanded Disability Status Scale score, 2.0 [1.5-3.0]). Scans with insufficient quality were excluded (n = 19). Radiological inflammatory activity was associated with increased atrophy rates in several brain compartments, while an increased annualized relapse rate was linked to accelerated deep gray matter (GM) volume loss. When compared with clinically stable patients, patients with PIRA had an increased rate of brain volume loss (MD-APC, -0.36; 95% CI, -0.60 to -0.12; P = .02), mainly driven by GM loss in the cerebral cortex. Patients who were relapsing presented increased whole brain atrophy (MD-APC, -0.18; 95% CI, -0.34 to -0.02; P = .04) with respect to clinically stable patients, with accelerated GM loss in both cerebral cortex and deep GM. No differences in brain atrophy rates were measured between patients with PIRA and those presenting relapse activity. Conclusions and Relevance: Our study shows that patients with RMS and PIRA exhibit accelerated brain atrophy, especially in the cerebral cortex. These results point to the need to recognize the insidious manifestations of PIRA in clinical practice and to further evaluate treatment strategies for patients with PIRA in clinical trials.

Indexed as

Central Nervous System DiseasesMultiple SclerosisMultiple Sclerosis, Relapsing-RemittingNervous System MalformationsNeurodegenerative DiseasesAdultAtrophyBrainDisability EvaluationDisease ProgressionFemaleGray MatterHumansLongitudinal StudiesMagnetic Resonance ImagingMale

Identifiers

PMID35575778
PMCPMC9112138
OpenAlexW4280614108

What OpenQuestion holds

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Registered trials

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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.