Evidence map›Paper›PMID 40725145›Full record

Observational studyInternational journal of molecular sciences2025

Combining CSF and Serum Biomarkers to Differentiate Mechanisms of Disability Worsening in Multiple Sclerosis.

Enric Monreal, José Ignacio Fernández-Velasco, Susana Sainz de la Maza, Mercedes Espiño, Noelia Villarrubia, Ernesto Roldán-Santiago, Yolanda Aladro, Juan Pablo Cuello, Lucía Ayuso-Peralta, Alexander Rodero-Romero and 17 more

Abstract readObservational StudyMulticenter Study
In one paragraph

Observational study in International journal of molecular sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed, 1 pooled it
–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

4 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Review
  3. Article
  4. Article
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

27 authors.

Enric MonrealDepartment of Neurology, Hospital Universitario Ramón y Cajal, Red Española de Esclerosis Múltiple (REEM), Red de Enfermedades Inflamatorias (REI), IRYCIS, Universidad de Alcalá, 28034 Madrid, Spain.ORCID 0000-0003-3293-0125
José Ignacio Fernández-VelascoDepartment of Immunology, Hospital Universitario Ramón y Cajal, Red Española de Esclerosis Múltiple (REEM), Red de Enfermedades Inflamatorias (REI), IRYCIS, Universidad de Alcalá, 28034 Madrid, Spain.ORCID 0000-0001-9148-671X
Susana Sainz de la MazaDepartment of Neurology, Hospital Universitario Ramón y Cajal, Red Española de Esclerosis Múltiple (REEM), Red de Enfermedades Inflamatorias (REI), IRYCIS, Universidad de Alcalá, 28034 Madrid, Spain.ORCID 0000-0001-8605-0049
Mercedes EspiñoDepartment of Immunology, Hospital Universitario Ramón y Cajal, Red Española de Esclerosis Múltiple (REEM), Red de Enfermedades Inflamatorias (REI), IRYCIS, Universidad de Alcalá, 28034 Madrid, Spain.
Noelia VillarrubiaDepartment of Immunology, Hospital Universitario Ramón y Cajal, Red Española de Esclerosis Múltiple (REEM), Red de Enfermedades Inflamatorias (REI), IRYCIS, Universidad de Alcalá, 28034 Madrid, Spain.ORCID 0000-0002-2114-8632
Ernesto Roldán-SantiagoDepartment of Immunology, Hospital Universitario Ramón y Cajal, Red Española de Esclerosis Múltiple (REEM), Red de Enfermedades Inflamatorias (REI), IRYCIS, Universidad de Alcalá, 28034 Madrid, Spain.
Yolanda AladroDepartment of Neurology, Hospital Universitario Getafe, Universidad Europea de Madrid, 28905 Madrid, Spain.
Juan Pablo CuelloDepartment of Neurology, Hospital Universitario Gregorio Marañón, 28007 Madrid, Spain.ORCID 0000-0003-0209-8227
Lucía Ayuso-PeraltaDepartment of Neurology, Hospital Universitario Príncipe de Asturias, 28805 Alcalá de Henares, Spain.
Alexander Rodero-RomeroDepartment of Immunology, Hospital Universitario Ramón y Cajal, Red Española de Esclerosis Múltiple (REEM), Red de Enfermedades Inflamatorias (REI), IRYCIS, Universidad de Alcalá, 28034 Madrid, Spain.ORCID 0009-0004-3816-2715
Juan Luís Chico-GarcíaDepartment of Neurology, Hospital Universitario Ramón y Cajal, Red Española de Esclerosis Múltiple (REEM), Red de Enfermedades Inflamatorias (REI), IRYCIS, Universidad de Alcalá, 28034 Madrid, Spain.ORCID 0000-0001-6557-912X
Fernando Rodríguez-JorgeDepartment of Neurology, Hospital Universitario Ramón y Cajal, Red Española de Esclerosis Múltiple (REEM), Red de Enfermedades Inflamatorias (REI), IRYCIS, Universidad de Alcalá, 28034 Madrid, Spain.ORCID 0000-0002-4567-0177
Ana Quiroga-VarelaNeuroimmunology and Multiple Sclerosis Unit, Neurodegeneration and Neuroinflammation Research Group, Girona Biomedical Research Institute (IDIBGI), Dr. Josep Trueta University Hospital, 17001 Catalonia, Spain.
Eulalia Rodríguez-MartínDepartment of Immunology, Hospital Universitario Ramón y Cajal, Red Española de Esclerosis Múltiple (REEM), Red de Enfermedades Inflamatorias (REI), IRYCIS, Universidad de Alcalá, 28034 Madrid, Spain.
Belén Pilo de la FuenteDepartment of Neurology, Hospital Universitario Getafe, Universidad Europea de Madrid, 28905 Madrid, Spain.
Guillermo Martín-ÁvilaDepartment of Neurology, Hospital Universitario Getafe, Universidad Europea de Madrid, 28905 Madrid, Spain.
María Luisa Martínez-GinésDepartment of Neurology, Hospital Universitario Gregorio Marañón, 28007 Madrid, Spain.
José Manuel García-DomínguezDepartment of Neurology, Hospital Universitario Gregorio Marañón, 28007 Madrid, Spain.ORCID 0000-0002-5205-3652
Lluïsa RubioDepartment of Neurology, Hospital Universitario Príncipe de Asturias, 28805 Alcalá de Henares, Spain.
Sara LlufriuNeuroimmunology and Multiple Sclerosis Unit, Laboratory of Advanced Imaging in Neuroimmunological Diseases, Hospital Clinic Barcelona, Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS) and Universitat de Barcelona, 08036 Barcelona, Spain.ORCID 0000-0003-4273-9121
Manuel ComabellaServei de Neurologia, Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebrón (VHIR), Hospital Universitari Vall d'Hebrón, Universitat Autònoma de Barcelona, 08907 Barcelona, Spain.ORCID 0000-0002-2373-6657
Xavier MontalbanServei de Neurologia, Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebrón (VHIR), Hospital Universitari Vall d'Hebrón, Universitat Autònoma de Barcelona, 08907 Barcelona, Spain.ORCID 0000-0002-0098-9918
Gary Álvarez-BravoNeuroimmunology and Multiple Sclerosis Unit, Neurodegeneration and Neuroinflammation Research Group, Girona Biomedical Research Institute (IDIBGI), Dr. Josep Trueta University Hospital, 17001 Catalonia, Spain.
José Luís Veiga-GonzálezDepartment of Immunology, Hospital Universitario Ramón y Cajal, Red Española de Esclerosis Múltiple (REEM), Red de Enfermedades Inflamatorias (REI), IRYCIS, Universidad de Alcalá, 28034 Madrid, Spain.
Jaime MasjuanDepartment of Neurology, Hospital Universitario Ramón y Cajal, Red Española de Esclerosis Múltiple (REEM), Red de Enfermedades Inflamatorias (REI), IRYCIS, Universidad de Alcalá, 28034 Madrid, Spain.ORCID 0000-0003-1329-0943
Lucienne Costa-FrossardDepartment of Neurology, Hospital Universitario Ramón y Cajal, Red Española de Esclerosis Múltiple (REEM), Red de Enfermedades Inflamatorias (REI), IRYCIS, Universidad de Alcalá, 28034 Madrid, Spain.ORCID 0000-0002-6512-4413
Luisa María VillarDepartment of Immunology, Hospital Universitario Ramón y Cajal, Red Española de Esclerosis Múltiple (REEM), Red de Enfermedades Inflamatorias (REI), IRYCIS, Universidad de Alcalá, 28034 Madrid, Spain.ORCID 0000-0002-9067-3668

Funding

Instituto de Salud Carlos III PI21/00828La Red Española de Enfermedades Inflamatorias (REI) RD21/0002/0053La Red Española de Esclerosis Múltiple (REEM) RD16/0015/0001La Red Española de Esclerosis Múltiple (REEM) RD16/0015/0002La Red Española de Esclerosis Múltiple (REEM) RD16/0015/0003La Red Española de Esclerosis Múltiple (REEM) RD16/0015/0006
6 · The paper itself

Abstract

The combined use of serum and CSF biomarkers for prognostic stratification in multiple sclerosis (MS) remains underexplored. This multicenter observational study investigated associations between serum neurofilament light chain (sNfL), glial fibrillary acidic protein (sGFAP), and CSF lipid-specific IgM oligoclonal bands (LS-OCMB) with different forms of disability worsening, such as relapse-associated worsening (RAW), active progression independent of relapse activity (aPIRA), and non-active PIRA (naPIRA). A total of 535 patients with MS were included, all sampled within one year of disease onset. Biomarkers were quantified using single-molecule array and immunoblotting techniques, and CSF cell subsets were analyzed by flow cytometry. High sNfL z-scores and LS-OCMB positivity were independently associated with increased risk of RAW and aPIRA, collectively termed inflammatory-associated worsening (IAW), while elevated sGFAP levels predicted naPIRA. Patients with both high sNfL and LS-OCMB positivity had the highest risk of IAW. Among LS-OCMB-positive patients, higher regulatory T cell percentages were associated with lower sNfL levels, suggesting a protective role. Conversely, in LS-OCMB-negative patients, sNfL levels correlated with CSF C3 concentrations. These findings support the complementary role of sNfL, sGFAP, and LS-OCMB in identifying distinct mechanisms of disease worsening and may inform early personalized management strategies in MS.

Indexed as

BiomarkersMultiple SclerosisAdultDisease ProgressionFemaleGlial Fibrillary Acidic ProteinHumansMaleMiddle AgedNeurofilament ProteinsOligoclonal BandsPrognosisBiomarkersGlial Fibrillary Acidic Proteinneurofilament protein LNeurofilament ProteinsOligoclonal Bandsglial fibrillary acidic proteinintrathecal IgM synthesismultiple sclerosisneurofilament light chainprogression

Identifiers

PMID40725145
PMCPMC12295370

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.