Evidence map›Paper›PMID 25888557›Full record

ArticleNeurology2015

Gadolinium-based MRI characterization of leptomeningeal inflammation in multiple sclerosis.

Martina Absinta, Luisa Vuolo, Anuradha Rao, Govind Nair, Pascal Sati, Irene C M Cortese, Joan Ohayon, Kaylan Fenton, María I Reyes-Mantilla, Dragan Maric and 4 more

Registry-linked trialOpen access · bronzeAbstract readEditorial
In one paragraph

Article in Neurology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02659956 (The Pathological Basis of MRI Signal Changes in Multiple Sclerosis), which is not on this map. Cited by 160 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
160citing papers in PubMed, 4 pooled it
19.3field-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.

NCT02659956 recruitingnot on this mapstarted 2016, after this paper: background citation

The Pathological Basis of MRI Signal Changes in Multiple Sclerosis: A Longitudinal In Vivo-to-Postmortem Study

TypeobservationalSponsorNational Institute of Neurological Disorders and Stroke (NINDS)Ran2016 to 2080Enrolled250ConditionsMultiple Sclerosis
3 · Its place in the literature

Who cites it

160 citing papers in PubMed, 4 syntheses or guidelines pooled it, 301 citations in OpenAlex.

  1. Pooled it
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  3. Pooled it
  4. Pooled it
  5. Trial
  6. Article
  7. Article
  8. ODC1 restricts meningeal B cell age-associated-like phenotype and function in multiple sclerosis: A human and experimental study.Proceedings of the National Academy of Sciences of the United States of America · 2026
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  11. Review
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  16. First-year treatment response predicts the following 5-year disease course in patients with relapsing-remitting multiple sclerosis.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025
    Article
  17. Article
  18. Review
  19. Imaging Outcomes for Phase 2 Trials Targeting Compartmentalized Inflammation.Multiple sclerosis (Houndmills, Basingstoke, England) · 2024
    Review
  20. Article

100 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 2 institutions in 2 countries.

Martina AbsintaFrom the Translational Neuroradiology Unit (M.A., L.V., A.R., G.N., P.S., D.S.R.), Neuroimmunology Clinic (I.C.M.C., J.O., K.F.), and Flow Cytometry Core Facility (D.M.), National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD; Neuroimaging Research Unit (M.A.), Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan; Department of Neurology and Radiology (L.V.), University of Florence, Italy; Department of Neurology (M.I.R.-M., P.A.C., C.A.P.), Johns Hopkins School of Medicine, Baltimore; and Diagnostic Radiology Department (J.A.B., D.S.R.), Clinical Center, NIH, Bethesda, MD.
Luisa VuoloFrom the Translational Neuroradiology Unit (M.A., L.V., A.R., G.N., P.S., D.S.R.), Neuroimmunology Clinic (I.C.M.C., J.O., K.F.), and Flow Cytometry Core Facility (D.M.), National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD; Neuroimaging Research Unit (M.A.), Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan; Department of Neurology and Radiology (L.V.), University of Florence, Italy; Department of Neurology (M.I.R.-M., P.A.C., C.A.P.), Johns Hopkins School of Medicine, Baltimore; and Diagnostic Radiology Department (J.A.B., D.S.R.), Clinical Center, NIH, Bethesda, MD.
Anuradha RaoFrom the Translational Neuroradiology Unit (M.A., L.V., A.R., G.N., P.S., D.S.R.), Neuroimmunology Clinic (I.C.M.C., J.O., K.F.), and Flow Cytometry Core Facility (D.M.), National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD; Neuroimaging Research Unit (M.A.), Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan; Department of Neurology and Radiology (L.V.), University of Florence, Italy; Department of Neurology (M.I.R.-M., P.A.C., C.A.P.), Johns Hopkins School of Medicine, Baltimore; and Diagnostic Radiology Department (J.A.B., D.S.R.), Clinical Center, NIH, Bethesda, MD.
Govind NairFrom the Translational Neuroradiology Unit (M.A., L.V., A.R., G.N., P.S., D.S.R.), Neuroimmunology Clinic (I.C.M.C., J.O., K.F.), and Flow Cytometry Core Facility (D.M.), National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD; Neuroimaging Research Unit (M.A.), Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan; Department of Neurology and Radiology (L.V.), University of Florence, Italy; Department of Neurology (M.I.R.-M., P.A.C., C.A.P.), Johns Hopkins School of Medicine, Baltimore; and Diagnostic Radiology Department (J.A.B., D.S.R.), Clinical Center, NIH, Bethesda, MD.
Pascal SatiFrom the Translational Neuroradiology Unit (M.A., L.V., A.R., G.N., P.S., D.S.R.), Neuroimmunology Clinic (I.C.M.C., J.O., K.F.), and Flow Cytometry Core Facility (D.M.), National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD; Neuroimaging Research Unit (M.A.), Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan; Department of Neurology and Radiology (L.V.), University of Florence, Italy; Department of Neurology (M.I.R.-M., P.A.C., C.A.P.), Johns Hopkins School of Medicine, Baltimore; and Diagnostic Radiology Department (J.A.B., D.S.R.), Clinical Center, NIH, Bethesda, MD.
Irene C M CorteseFrom the Translational Neuroradiology Unit (M.A., L.V., A.R., G.N., P.S., D.S.R.), Neuroimmunology Clinic (I.C.M.C., J.O., K.F.), and Flow Cytometry Core Facility (D.M.), National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD; Neuroimaging Research Unit (M.A.), Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan; Department of Neurology and Radiology (L.V.), University of Florence, Italy; Department of Neurology (M.I.R.-M., P.A.C., C.A.P.), Johns Hopkins School of Medicine, Baltimore; and Diagnostic Radiology Department (J.A.B., D.S.R.), Clinical Center, NIH, Bethesda, MD.
Joan OhayonFrom the Translational Neuroradiology Unit (M.A., L.V., A.R., G.N., P.S., D.S.R.), Neuroimmunology Clinic (I.C.M.C., J.O., K.F.), and Flow Cytometry Core Facility (D.M.), National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD; Neuroimaging Research Unit (M.A.), Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan; Department of Neurology and Radiology (L.V.), University of Florence, Italy; Department of Neurology (M.I.R.-M., P.A.C., C.A.P.), Johns Hopkins School of Medicine, Baltimore; and Diagnostic Radiology Department (J.A.B., D.S.R.), Clinical Center, NIH, Bethesda, MD.
Kaylan FentonFrom the Translational Neuroradiology Unit (M.A., L.V., A.R., G.N., P.S., D.S.R.), Neuroimmunology Clinic (I.C.M.C., J.O., K.F.), and Flow Cytometry Core Facility (D.M.), National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD; Neuroimaging Research Unit (M.A.), Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan; Department of Neurology and Radiology (L.V.), University of Florence, Italy; Department of Neurology (M.I.R.-M., P.A.C., C.A.P.), Johns Hopkins School of Medicine, Baltimore; and Diagnostic Radiology Department (J.A.B., D.S.R.), Clinical Center, NIH, Bethesda, MD.
María I Reyes-MantillaFrom the Translational Neuroradiology Unit (M.A., L.V., A.R., G.N., P.S., D.S.R.), Neuroimmunology Clinic (I.C.M.C., J.O., K.F.), and Flow Cytometry Core Facility (D.M.), National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD; Neuroimaging Research Unit (M.A.), Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan; Department of Neurology and Radiology (L.V.), University of Florence, Italy; Department of Neurology (M.I.R.-M., P.A.C., C.A.P.), Johns Hopkins School of Medicine, Baltimore; and Diagnostic Radiology Department (J.A.B., D.S.R.), Clinical Center, NIH, Bethesda, MD.
Dragan MaricFrom the Translational Neuroradiology Unit (M.A., L.V., A.R., G.N., P.S., D.S.R.), Neuroimmunology Clinic (I.C.M.C., J.O., K.F.), and Flow Cytometry Core Facility (D.M.), National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD; Neuroimaging Research Unit (M.A.), Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan; Department of Neurology and Radiology (L.V.), University of Florence, Italy; Department of Neurology (M.I.R.-M., P.A.C., C.A.P.), Johns Hopkins School of Medicine, Baltimore; and Diagnostic Radiology Department (J.A.B., D.S.R.), Clinical Center, NIH, Bethesda, MD.
Peter A CalabresiFrom the Translational Neuroradiology Unit (M.A., L.V., A.R., G.N., P.S., D.S.R.), Neuroimmunology Clinic (I.C.M.C., J.O., K.F.), and Flow Cytometry Core Facility (D.M.), National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD; Neuroimaging Research Unit (M.A.), Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan; Department of Neurology and Radiology (L.V.), University of Florence, Italy; Department of Neurology (M.I.R.-M., P.A.C., C.A.P.), Johns Hopkins School of Medicine, Baltimore; and Diagnostic Radiology Department (J.A.B., D.S.R.), Clinical Center, NIH, Bethesda, MD.
John A ButmanFrom the Translational Neuroradiology Unit (M.A., L.V., A.R., G.N., P.S., D.S.R.), Neuroimmunology Clinic (I.C.M.C., J.O., K.F.), and Flow Cytometry Core Facility (D.M.), National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD; Neuroimaging Research Unit (M.A.), Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan; Department of Neurology and Radiology (L.V.), University of Florence, Italy; Department of Neurology (M.I.R.-M., P.A.C., C.A.P.), Johns Hopkins School of Medicine, Baltimore; and Diagnostic Radiology Department (J.A.B., D.S.R.), Clinical Center, NIH, Bethesda, MD.
Carlos A PardoFrom the Translational Neuroradiology Unit (M.A., L.V., A.R., G.N., P.S., D.S.R.), Neuroimmunology Clinic (I.C.M.C., J.O., K.F.), and Flow Cytometry Core Facility (D.M.), National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD; Neuroimaging Research Unit (M.A.), Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan; Department of Neurology and Radiology (L.V.), University of Florence, Italy; Department of Neurology (M.I.R.-M., P.A.C., C.A.P.), Johns Hopkins School of Medicine, Baltimore; and Diagnostic Radiology Department (J.A.B., D.S.R.), Clinical Center, NIH, Bethesda, MD.
Daniel S ReichFrom the Translational Neuroradiology Unit (M.A., L.V., A.R., G.N., P.S., D.S.R.), Neuroimmunology Clinic (I.C.M.C., J.O., K.F.), and Flow Cytometry Core Facility (D.M.), National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD; Neuroimaging Research Unit (M.A.), Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan; Department of Neurology and Radiology (L.V.), University of Florence, Italy; Department of Neurology (M.I.R.-M., P.A.C., C.A.P.), Johns Hopkins School of Medicine, Baltimore; and Diagnostic Radiology Department (J.A.B., D.S.R.), Clinical Center, NIH, Bethesda, MD. daniel.reich@nih.gov.
Johns Hopkins University · USUniversity of Florence · IT

Funding

Multimodal MRI in Multiple SclerosisZIANS003119 · NINDS · NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE · PI REICH, DANIEL · 2010 to 2025
$53.4M
Intramural NIH HHS
6 · The paper itself

Abstract

objectiveTo determine the frequency and nature of leptomeningeal contrast enhancement in multiple sclerosis (MS) via in vivo 3-tesla postcontrast T2-weighted, fluid-attenuated inversion recovery (FLAIR) MRI and 7-tesla postmortem MRI-pathology correlation.

methodsBrain MRI, using the postcontrast T2-weighted, FLAIR technique, was prospectively collected in 299 MS cases and 37 age-matched neurologically healthy controls. Expert raters evaluated focal gadolinium enhancement in the leptomeningeal compartment. Two progressive MS cases came to autopsy after in vivo MRI characterization. Pathologic and immunohistochemical examination assessed the association of enhancement with leptomeningeal inflammation and adjacent cortical demyelination.

resultsFocal contrast enhancement was detected in the leptomeningeal compartment in 74 of 299 MS cases (25%) vs 1 of 37 neurologically healthy controls (2.7%; p = 0.001). Enhancement was nearly twice as frequent (p = 0.009) in progressive MS (39/118 cases, 33%) as in relapsing-remitting MS (35/181, 19%). Enhancing foci generally remained stable throughout the evaluation period (up to 5.5 years). Pathology showed perivascular lymphocytic and mononuclear infiltration in the enhancing areas in association with flanking subpial cortical demyelination.

conclusionLeptomeningeal contrast enhancement occurs frequently in MS and is a noninvasive, in vivo marker of inflammation and associated subpial demyelination. It might therefore enable testing of new treatments aimed at eliminating this inflammation and potentially arresting progressive MS.

Indexed as

GadoliniumHumansMagnetic Resonance ImagingMeningesMeningitisMultiple Sclerosis, Relapsing-RemittingGadolinium

Identifiers

PMID25888557
PMCPMC4501940
OpenAlexW2169159041

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