Evidence map›Paper›PMID 40939291›Full record

ReviewEBioMedicine2025

Smouldering disease in paediatric-onset multiple sclerosis.

Massimo Filippi, Monica Margoni, Brenda Banwell, Tanuja Chitnis, Russell Dale, Giulia Fadda, Yael Hacohen, Lauren B Krupp, Paolo Preziosa, E Ann Yeh and 2 more

Abstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in EBioMedicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Review
  2. Review
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

12 authors.

Massimo FilippiNeuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy; Neurology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy; Neurorehabilitation Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy; Neurophysiology Service, IRCCS San Raffaele Scientific Institute, Milan, Italy. Electronic address: filippi.massimo@hsr.it.
Monica MargoniNeuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy; Neurology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy; Neurorehabilitation Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Brenda BanwellDepartment of Pediatrics, Johns Hopkins University, Baltimore, MD, USA.
Tanuja ChitnisDepartment of Paediatric Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Russell DaleKids Neuroscience Centre, Children's Hospital at Westmead Clinical School, University of Sydney, Sydney, NSW, 2145, Australia.
Giulia FaddaDepartment of Medicine, University of Ottawa, Ottawa Hospital Research Institute, Ottawa, ON, Canada.
Yael HacohenDepartment of Neurology, Great Ormond Street Hospital for Children, London, UK; Department of Neuroinflammation, UCL Institute of Neurology, University College London, London, UK.
Lauren B KruppDepartment of Neurology, NYU Grossman School of Medicine, New York, NY, United States.
Paolo PreziosaNeuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy; Neurology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy.
E Ann YehDivision of Neurology, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, ON, Canada.
Emmanuelle WaubantDepartment of Neurology, University of California San Francisco, San Francisco, CA, USA.
Maria A RoccaNeuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy; Neurology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Smouldering disease in multiple sclerosis (MS) refers to chronic central nervous system processes that occur beyond acute inflammation, driving long-term disability. Although current therapies effectively reduce relapse rates and MRI lesions, many individuals experience progression independent of relapse activity. While clinical progression is uncommon during childhood or adolescence, growing evidence suggests that subclinical progressive disease biology is already active even in this young age group, warranting early intervention to preserve function. Conventional MRI, while critical for diagnosis, lacks sensitivity for subtle damage. Advanced MRI techniques, including detection of chronic active lesions, global and focal brain damage, hold promise for early identification. Fluid biomarkers, such as neurofilament light chain and glial fibrillary acidic protein, provide non-invasive measures of neuroaxonal injury and ongoing chronic inflammation. This review summarises the role of MRI and fluid biomarkers in detecting smouldering disease in paediatric-onset MS and their application in supporting therapeutic decision-making.

Indexed as

Multiple SclerosisAge of OnsetBiomarkersBrainChildDisease ProgressionHumansMagnetic Resonance ImagingBiomarkersChronic active lesionsConfirmed disability accrualFluid biomarkersGrey matterMRINeurofilamentsPaediatric-onset multiple sclerosisProgression independent of relapse activityRepairSmouldering diseaseSpinal cordTreatment

Identifiers

PMID40939291
PMCPMC12571582

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.