Evidence map›Paper›PMID 25253748›Full record

ArticleNeurology2014

A type 2 biomarker separates relapsing-remitting from secondary progressive multiple sclerosis.

Alex M Dickens, James R Larkin, Julian L Griffin, Ana Cavey, Lucy Matthews, Martin R Turner, Gordon K Wilcock, Benjamin G Davis, Timothy D W Claridge, Jacqueline Palace and 2 more

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PubMed Full text at PMC Publisher
In one paragraph

Article in Neurology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
54citing papers in PubMed, 1 pooled it
5.5field-weighted citation impact, top 4% 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

54 citing papers in PubMed, 1 synthesis or guideline pooled it, 75 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Article
  4. β-oxidation-mediated differentiation of effector CD4Journal of neuroinflammation · 2026
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  7. PlasmaNeurology(R) neuroimmunology & neuroinflammation · 2025
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  8. Article
  9. Review
  10. Article
  11. Review
  12. Article
  13. Article
  14. Review
  15. Article
  16. NMR-based metabolomics of human cerebrospinal fluid identifies signature of brain death.Metabolomics : Official journal of the Metabolomic Society · 2021
    Article
  17. Review
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 1 institution in 2 countries.

Alex M DickensFrom the CR-UK/MRC Gray Institute for Radiation Oncology and Biology (A.M.D., J.R.L., N.R.S.), Department of Pharmacology (A.M.D., D.C.A.), Department of Chemistry (A.M.D., B.G.D., T.D.W.C.), Nuffield Department of Clinical Neurosciences (A.C., L.M., M.R.T.), and Nuffield Department of Medicine (G.K.W.), University of Oxford; and the Department of Biochemistry (J.L.G., J.P.), University of Cambridge, UK.
James R LarkinFrom the CR-UK/MRC Gray Institute for Radiation Oncology and Biology (A.M.D., J.R.L., N.R.S.), Department of Pharmacology (A.M.D., D.C.A.), Department of Chemistry (A.M.D., B.G.D., T.D.W.C.), Nuffield Department of Clinical Neurosciences (A.C., L.M., M.R.T.), and Nuffield Department of Medicine (G.K.W.), University of Oxford; and the Department of Biochemistry (J.L.G., J.P.), University of Cambridge, UK.
Julian L GriffinFrom the CR-UK/MRC Gray Institute for Radiation Oncology and Biology (A.M.D., J.R.L., N.R.S.), Department of Pharmacology (A.M.D., D.C.A.), Department of Chemistry (A.M.D., B.G.D., T.D.W.C.), Nuffield Department of Clinical Neurosciences (A.C., L.M., M.R.T.), and Nuffield Department of Medicine (G.K.W.), University of Oxford; and the Department of Biochemistry (J.L.G., J.P.), University of Cambridge, UK.
Ana CaveyFrom the CR-UK/MRC Gray Institute for Radiation Oncology and Biology (A.M.D., J.R.L., N.R.S.), Department of Pharmacology (A.M.D., D.C.A.), Department of Chemistry (A.M.D., B.G.D., T.D.W.C.), Nuffield Department of Clinical Neurosciences (A.C., L.M., M.R.T.), and Nuffield Department of Medicine (G.K.W.), University of Oxford; and the Department of Biochemistry (J.L.G., J.P.), University of Cambridge, UK.
Lucy MatthewsFrom the CR-UK/MRC Gray Institute for Radiation Oncology and Biology (A.M.D., J.R.L., N.R.S.), Department of Pharmacology (A.M.D., D.C.A.), Department of Chemistry (A.M.D., B.G.D., T.D.W.C.), Nuffield Department of Clinical Neurosciences (A.C., L.M., M.R.T.), and Nuffield Department of Medicine (G.K.W.), University of Oxford; and the Department of Biochemistry (J.L.G., J.P.), University of Cambridge, UK.
Martin R TurnerFrom the CR-UK/MRC Gray Institute for Radiation Oncology and Biology (A.M.D., J.R.L., N.R.S.), Department of Pharmacology (A.M.D., D.C.A.), Department of Chemistry (A.M.D., B.G.D., T.D.W.C.), Nuffield Department of Clinical Neurosciences (A.C., L.M., M.R.T.), and Nuffield Department of Medicine (G.K.W.), University of Oxford; and the Department of Biochemistry (J.L.G., J.P.), University of Cambridge, UK.
Gordon K WilcockFrom the CR-UK/MRC Gray Institute for Radiation Oncology and Biology (A.M.D., J.R.L., N.R.S.), Department of Pharmacology (A.M.D., D.C.A.), Department of Chemistry (A.M.D., B.G.D., T.D.W.C.), Nuffield Department of Clinical Neurosciences (A.C., L.M., M.R.T.), and Nuffield Department of Medicine (G.K.W.), University of Oxford; and the Department of Biochemistry (J.L.G., J.P.), University of Cambridge, UK.
Benjamin G DavisFrom the CR-UK/MRC Gray Institute for Radiation Oncology and Biology (A.M.D., J.R.L., N.R.S.), Department of Pharmacology (A.M.D., D.C.A.), Department of Chemistry (A.M.D., B.G.D., T.D.W.C.), Nuffield Department of Clinical Neurosciences (A.C., L.M., M.R.T.), and Nuffield Department of Medicine (G.K.W.), University of Oxford; and the Department of Biochemistry (J.L.G., J.P.), University of Cambridge, UK.
Timothy D W ClaridgeFrom the CR-UK/MRC Gray Institute for Radiation Oncology and Biology (A.M.D., J.R.L., N.R.S.), Department of Pharmacology (A.M.D., D.C.A.), Department of Chemistry (A.M.D., B.G.D., T.D.W.C.), Nuffield Department of Clinical Neurosciences (A.C., L.M., M.R.T.), and Nuffield Department of Medicine (G.K.W.), University of Oxford; and the Department of Biochemistry (J.L.G., J.P.), University of Cambridge, UK.
Jacqueline PalaceFrom the CR-UK/MRC Gray Institute for Radiation Oncology and Biology (A.M.D., J.R.L., N.R.S.), Department of Pharmacology (A.M.D., D.C.A.), Department of Chemistry (A.M.D., B.G.D., T.D.W.C.), Nuffield Department of Clinical Neurosciences (A.C., L.M., M.R.T.), and Nuffield Department of Medicine (G.K.W.), University of Oxford; and the Department of Biochemistry (J.L.G., J.P.), University of Cambridge, UK.
Daniel C AnthonyFrom the CR-UK/MRC Gray Institute for Radiation Oncology and Biology (A.M.D., J.R.L., N.R.S.), Department of Pharmacology (A.M.D., D.C.A.), Department of Chemistry (A.M.D., B.G.D., T.D.W.C.), Nuffield Department of Clinical Neurosciences (A.C., L.M., M.R.T.), and Nuffield Department of Medicine (G.K.W.), University of Oxford; and the Department of Biochemistry (J.L.G., J.P.), University of Cambridge, UK. Daniel.Anthony@pharm.ox.ac.uk.
Nicola R SibsonFrom the CR-UK/MRC Gray Institute for Radiation Oncology and Biology (A.M.D., J.R.L., N.R.S.), Department of Pharmacology (A.M.D., D.C.A.), Department of Chemistry (A.M.D., B.G.D., T.D.W.C.), Nuffield Department of Clinical Neurosciences (A.C., L.M., M.R.T.), and Nuffield Department of Medicine (G.K.W.), University of Oxford; and the Department of Biochemistry (J.L.G., J.P.), University of Cambridge, UK.
MACOM (United States) · US

Funding

Cancer Research UK 16945Cancer Research UK C5255/A12678Medical Research Council G0401438Medical Research Council G0901996Medical Research Council MC_UP_A090_1006Medical Research Council MR/K01014X/1Motor Neurone Disease Association TURNER/JAN13/944-795
6 · The paper itself

Abstract

objectiveWe tested whether it is possible to differentiate relapsing-remitting (RR) from secondary progressive (SP) disease stages in patients with multiple sclerosis (MS) using a combination of nuclear magnetic resonance (NMR) metabolomics and partial least squares discriminant analysis (PLS-DA) of biofluids, which makes no assumptions on the underlying mechanisms of disease.

methodsSerum samples were obtained from patients with primary progressive MS (PPMS), SPMS, and RRMS; patients with other neurodegenerative conditions; and age-matched controls. Samples were analyzed by NMR and PLS-DA models were derived to separate disease groups.

resultsThe PLS-DA models for serum samples from patients with MS enabled reliable differentiation between RRMS and SPMS. This approach also identified significant differences between the metabolite profiles of each of the MS groups (PP, SP, and RR) and the healthy controls, as well as predicting disease group membership with high specificity and sensitivity.

conclusionsNMR metabolomics analysis of serum is a sensitive and robust method for differentiating between different stages of MS, yielding diagnostic markers without a priori knowledge of disease pathogenesis. Critically, this study identified and validated a type II biomarker for the RR to SP transition in patients with MS. This approach may be of considerable benefit in categorizing patients for treatment and as an outcome measure in future clinical trials. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that serum metabolite profiles accurately distinguish patients with different subtypes and stages of MS.

Indexed as

AdultAgedAlzheimer DiseaseAmyotrophic Lateral SclerosisBiomarkersCase-Control StudiesCohort StudiesDiscriminant AnalysisFemaleHumansMagnetic Resonance SpectroscopyMaleMetabolomicsMiddle AgedMultiple Sclerosis, Chronic ProgressiveMultiple Sclerosis, Relapsing-RemittingBiomarkers

Identifiers

PMID25253748
PMCPMC4222850
OpenAlexW2165481371

What OpenQuestion holds

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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.