Evidence map›Paper›PMID 41041831›Full record

ArticleAnnals of neurology2026

From Diagnosis to Disease Staging: Multisite Validation of Cerebrospinal Fluid Molecular Tests in Multiple Sclerosis.

Laura Ghezzi, Peter Kosa, Mark Greenwood, Enrique Alvarez, C L Freedman, Anne H Cross, Francesca Pace, Mark S Freedman, Joanna Kocot, Laura Piccio and 1 more

Abstract readMulticenter StudyValidation Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Annals of neurology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

11 authors.

Laura Ghezzi *Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy.ORCID 0000-0001-8180-9730
Peter Kosa *Neuroimmunological Diseases Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.ORCID 0000-0002-1392-0629
Mark GreenwoodDepartment of Mathematical Sciences, Montana State University, Bozeman, MT, USA.ORCID 0000-0001-6933-1201
Enrique AlvarezDepartment of Neurology, Rocky Mountain Multiple Sclerosis Center at the University of Colorado, Aurora, CO, USA.ORCID 0000-0001-5854-9643
C L FreedmanUniversity of Ottawa, Department of Medicine and the Ottawa Hospital Research Institute, Ottawa, ON, Canada.
Anne H CrossDepartment of Neurology, Washington University School of Medicine, St Louis, MI, USA.ORCID 0000-0003-0829-7569
Francesca PaceDepartment of Neurology, Washington University School of Medicine, St Louis, MI, USA.
Mark S FreedmanUniversity of Ottawa, Department of Medicine and the Ottawa Hospital Research Institute, Ottawa, ON, Canada.ORCID 0000-0003-1255-9701
Joanna KocotNeuroimmunological Diseases Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Laura Piccio *Charles Perkins Centre and Brain and Mind Centre, Neuroscience, School of Medical Sciences, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.ORCID 0000-0002-8760-109X
Bibiana Bielekova *Neuroimmunological Diseases Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.ORCID 0000-0002-0959-9430

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveThe growing demand for personalized treatment in multiple sclerosis (MS) highlights the need for more precise biomarkers that can outperform magnetic resonance imaging and clinical assessment in patient stratification. Advances in multiplex proteomic technologies suggest that cerebrospinal fluid (CSF) analysis at MS onset may not only improve diagnostic accuracy, but also offer prognostic and staging information, as well as insight into molecular therapeutic targets.

methodsThis multicenter study retrospectively analyzed cryopreserved CSF samples from 160 individuals undergoing diagnostic evaluation for possible neuroimmunological disorder, and among these, followed a cohort of 96 people with confirmed MS for at least 3 years. The goal was to externally validate previously published CSF-based diagnostic and prognostic classifiers.

resultsUpon unblinding, the CSF-based molecular diagnostic test distinguished 96 people with confirmed MS from 30 individuals with other inflammatory neurological diseases, and 34 individuals with non-inflammatory neurological diseases, achieving an area under the receiver operating characteristic curve of 0.94 (p = 4.7 × 10

interpretationThis multicenter external validation study demonstrates that CSF-based molecular tests can robustly distinguish MS from other neurological conditions, stratify MS subtypes, and predict future disability progression in real-world settings. These results lay the groundwork for development of next-generation molecular tools to personalize care in MS. ANN NEUROL 2026;99:328-340.

Indexed as

Multiple SclerosisAdultBiomarkersDisease ProgressionFemaleHumansMaleMiddle AgedMultiple Sclerosis, Relapsing-RemittingProteomicsRetrospective StudiesBiomarkers

Identifiers

PMID41041831
PMCPMC12894485

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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.