Evidence map›Paper›PMID 35096143›Full record

ReviewTherapeutic advances in neurological disorders2022

Smouldering multiple sclerosis: the 'real MS'.

Gavin Giovannoni, Veronica Popescu, Jens Wuerfel, Kerstin Hellwig, Ellen Iacobaeus, Michael B Jensen, José Manuel García-Domínguez, Livia Sousa, Nicola De Rossi, Raymond Hupperts and 8 more

Open access · goldAbstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Therapeutic advances in neurological disorders, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 144 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
144citing papers in PubMed, 3 pooled it
32.4field-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

144 citing papers in PubMed, 3 syntheses or guidelines pooled it, 239 citations in OpenAlex.

  1. Effects of natalizumab on oligoclonal bands in the cerebrospinal fluid of patients with multiple sclerosis: a systematic review and meta-analysis.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025
    Pooled it
  2. Pooled it
  3. Pooled it
  4. Trial
  5. Trial
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Review
  13. Observational
  14. Observational
  15. Article
  16. Review
  17. Article
  18. Article
  19. Review
  20. Article

84 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

18 authors at 17 institutions in 12 countries.

Gavin GiovannoniBlizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, 4 Newark St., Whitechapel, London E1 2AT, UK.ORCID https://orcid.org/0000-0001-9995-1700
Veronica PopescuUniversitair MS Centrum, Hasselt, Belgium; Noorderhart Hospital, Pelt, Belgium; Hasselt University, Hasselt, Belgium.
Jens WuerfelMIAC AG, Department of Biomedical Engineering, University of Basel, Basel, Switzerland; Charité - University Medicine Berlin, Berlin, Germany.
Kerstin HellwigKatholisches Klinikum Bochum, Klinikum der Ruhr-Universität, Bochum, Germany.
Ellen IacobaeusKarolinska University Hospital, Stockholm, Sweden.
Michael B JensenDepartment of Neurology, Nordsjællands Hospital, Hillerød, Denmark.
José Manuel García-DomínguezHGU Gregorio Marañón, Madrid, Spain; HM Hospitales, Madrid, Spain.
Livia SousaCentro Hospitalar e Universitário de Coimbra, Faculdade de Medicina, Universidade de Coimbra, Coimbra, Portugal.
Nicola De RossiSpedali Civili of Brescia, Brescia, Italy.
Raymond HuppertsZuyderland Medisch Centrum, Sittard-Geleen, The Netherlands; Maastricht University Medical Center, Maastricht, The Netherlands.
Giuseppe FenuDepartment of Neurology, Brotzu Hospital, Cagliari, Italy.
Benedetta BodiniParis Brain Institute, Sorbonne University, Paris, France; Department of Neurology, APHP, Saint-Antoine Hospital, Paris, France.
Hanna-Maija KuusistoDepartment of Neurology, Tampere University Hospital, Tampere, Finland; Department of Customer and Patient Safety, University of Eastern Finland, Kuopio, Finland.
Bruno StankoffParis Brain Institute, Sorbonne University, ICM, CNRS, Inserm, Paris, France; APHP, Saint-Antoine Hospital, Paris, France.
Jan LyckeInstitute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden.ORCID https://orcid.org/0000-0002-7891-8466
Laura AirasUniversity of Turku, Turku, Finland.
Cristina GranzieraNeurologic Clinic and Policlinic, Departments of Medicine, Clinical Research and Biomedical Engineering, University Hospital Basel and University of Basel, Basel, Switzerland.
Antonio ScalfariCentre for Neuroscience, Department of Medicine, Charing Cross Hospital, Imperial College London, London, UK.
University of Basel · CHAzienda Ospedaliera G. Brotzu · ITAzienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia · ITCentre National de la Recherche Scientifique · FRCharing Cross Hospital · GBHasselt University · BEHM Hospitales · ESHospitais da Universidade de Coimbra · PTKarolinska University Hospital · SEKatholisches Klinikum Bochum · DEMaastricht University · NLNordsjællands Hospital · DKQueen Mary University of London · GBSorbonne Université · FRUniversity of Eastern Finland · FIUniversity of Gothenburg · SEUniversity of Turku · FI

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Using a philosophical approach or deductive reasoning, we challenge the dominant clinico-radiological worldview that defines multiple sclerosis (MS) as a focal inflammatory disease of the central nervous system (CNS). We provide a range of evidence to argue that the 'real MS' is in fact driven primarily by a smouldering pathological disease process. In natural history studies and clinical trials, relapses and focal activity revealed by magnetic resonance imaging (MRI) in MS patients on placebo or on disease-modifying therapies (DMTs) were found to be poor predictors of long-term disease evolution and were dissociated from disability outcomes. In addition, the progressive accumulation of disability in MS can occur independently of relapse activity from early in the disease course. This scenario is underpinned by a more diffuse smouldering pathological process that may affect the entire CNS. Many putative pathological drivers of smouldering MS can be potentially modified by specific therapeutic strategies, an approach that may have major implications for the management of MS patients. We hypothesise that therapeutically targeting a state of 'no evident inflammatory disease activity' (NEIDA) cannot sufficiently prevent disability accumulation in MS, meaning that treatment should also focus on other brain and spinal cord pathological processes contributing to the slow loss of neurological function. This should also be complemented with a holistic approach to the management of other systemic disease processes that have been shown to worsen MS outcomes.

Indexed as

multiple sclerosisprogression independent of relapse activityprogressive multiple sclerosissmouldering multiple sclerosis

Identifiers

PMID35096143
PMCPMC8793117
OpenAlexW4226087203

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.