Evidence map›Paper›PMID 36376097›Full record

ArticleNeurology(R) neuroimmunology & neuroinflammation2023

Serum GFAP and NfL Levels Differentiate Subsequent Progression and Disease Activity in Patients With Progressive Multiple Sclerosis.

Christian Barro, Brian C Healy, Yanqing Liu, Shrishti Saxena, Anu Paul, Mariann Polgar-Turcsanyi, Charles R G Guttmann, Rohit Bakshi, Harald Kropshofer, Howard L Weiner and 1 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neurology(R) neuroimmunology & neuroinflammation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 109 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
109citing papers in PubMed, 5 pooled it
21.7field-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.

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

109 citing papers in PubMed, 5 syntheses or guidelines pooled it, 156 citations in OpenAlex.

  1. Pooled it
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  4. Rituximab in secondary progressive multiple sclerosis: a meta-analysis.Annals of clinical and translational neurology · 2024
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  17. A framework for blood biomarker discovery in MS.Multiple sclerosis (Houndmills, Basingstoke, England) · 2026
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49 more citing papers are in PubMed but not listed here.

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 at 1 institution in 1 country.

Christian BarroFrom the Harvard Medical School (C.B., B.C.H., M.P.-T., C.R.G.G., R.B., H.L.W., T.C.); Ann Romney Center for Neurologic Diseases (C.B., B.C.H., Y.L., S.S., A.P., M.P.-T., C.R.G.G., R.B., H.L.W., T.C.), Brigham and Women's Hospital; Brigham Multiple Sclerosis Center (R.B., H.L.W., T.C.), Department of Neurology, Brigham and Women's Hospital; Center for Neurological Imaging (C.R.G.G.), Department of Radiology, Brigham and Women's Hospital; Biostatistics Center (B.C.H.), Massachusetts General Hospital, Boston, MA; and Novartis Pharma AG (H.K.), Basel, Switzerland.
Brian C HealyFrom the Harvard Medical School (C.B., B.C.H., M.P.-T., C.R.G.G., R.B., H.L.W., T.C.); Ann Romney Center for Neurologic Diseases (C.B., B.C.H., Y.L., S.S., A.P., M.P.-T., C.R.G.G., R.B., H.L.W., T.C.), Brigham and Women's Hospital; Brigham Multiple Sclerosis Center (R.B., H.L.W., T.C.), Department of Neurology, Brigham and Women's Hospital; Center for Neurological Imaging (C.R.G.G.), Department of Radiology, Brigham and Women's Hospital; Biostatistics Center (B.C.H.), Massachusetts General Hospital, Boston, MA; and Novartis Pharma AG (H.K.), Basel, Switzerland.
Yanqing LiuFrom the Harvard Medical School (C.B., B.C.H., M.P.-T., C.R.G.G., R.B., H.L.W., T.C.); Ann Romney Center for Neurologic Diseases (C.B., B.C.H., Y.L., S.S., A.P., M.P.-T., C.R.G.G., R.B., H.L.W., T.C.), Brigham and Women's Hospital; Brigham Multiple Sclerosis Center (R.B., H.L.W., T.C.), Department of Neurology, Brigham and Women's Hospital; Center for Neurological Imaging (C.R.G.G.), Department of Radiology, Brigham and Women's Hospital; Biostatistics Center (B.C.H.), Massachusetts General Hospital, Boston, MA; and Novartis Pharma AG (H.K.), Basel, Switzerland.
Shrishti SaxenaFrom the Harvard Medical School (C.B., B.C.H., M.P.-T., C.R.G.G., R.B., H.L.W., T.C.); Ann Romney Center for Neurologic Diseases (C.B., B.C.H., Y.L., S.S., A.P., M.P.-T., C.R.G.G., R.B., H.L.W., T.C.), Brigham and Women's Hospital; Brigham Multiple Sclerosis Center (R.B., H.L.W., T.C.), Department of Neurology, Brigham and Women's Hospital; Center for Neurological Imaging (C.R.G.G.), Department of Radiology, Brigham and Women's Hospital; Biostatistics Center (B.C.H.), Massachusetts General Hospital, Boston, MA; and Novartis Pharma AG (H.K.), Basel, Switzerland.
Anu PaulFrom the Harvard Medical School (C.B., B.C.H., M.P.-T., C.R.G.G., R.B., H.L.W., T.C.); Ann Romney Center for Neurologic Diseases (C.B., B.C.H., Y.L., S.S., A.P., M.P.-T., C.R.G.G., R.B., H.L.W., T.C.), Brigham and Women's Hospital; Brigham Multiple Sclerosis Center (R.B., H.L.W., T.C.), Department of Neurology, Brigham and Women's Hospital; Center for Neurological Imaging (C.R.G.G.), Department of Radiology, Brigham and Women's Hospital; Biostatistics Center (B.C.H.), Massachusetts General Hospital, Boston, MA; and Novartis Pharma AG (H.K.), Basel, Switzerland.
Mariann Polgar-TurcsanyiFrom the Harvard Medical School (C.B., B.C.H., M.P.-T., C.R.G.G., R.B., H.L.W., T.C.); Ann Romney Center for Neurologic Diseases (C.B., B.C.H., Y.L., S.S., A.P., M.P.-T., C.R.G.G., R.B., H.L.W., T.C.), Brigham and Women's Hospital; Brigham Multiple Sclerosis Center (R.B., H.L.W., T.C.), Department of Neurology, Brigham and Women's Hospital; Center for Neurological Imaging (C.R.G.G.), Department of Radiology, Brigham and Women's Hospital; Biostatistics Center (B.C.H.), Massachusetts General Hospital, Boston, MA; and Novartis Pharma AG (H.K.), Basel, Switzerland.
Charles R G GuttmannFrom the Harvard Medical School (C.B., B.C.H., M.P.-T., C.R.G.G., R.B., H.L.W., T.C.); Ann Romney Center for Neurologic Diseases (C.B., B.C.H., Y.L., S.S., A.P., M.P.-T., C.R.G.G., R.B., H.L.W., T.C.), Brigham and Women's Hospital; Brigham Multiple Sclerosis Center (R.B., H.L.W., T.C.), Department of Neurology, Brigham and Women's Hospital; Center for Neurological Imaging (C.R.G.G.), Department of Radiology, Brigham and Women's Hospital; Biostatistics Center (B.C.H.), Massachusetts General Hospital, Boston, MA; and Novartis Pharma AG (H.K.), Basel, Switzerland.
Rohit BakshiFrom the Harvard Medical School (C.B., B.C.H., M.P.-T., C.R.G.G., R.B., H.L.W., T.C.); Ann Romney Center for Neurologic Diseases (C.B., B.C.H., Y.L., S.S., A.P., M.P.-T., C.R.G.G., R.B., H.L.W., T.C.), Brigham and Women's Hospital; Brigham Multiple Sclerosis Center (R.B., H.L.W., T.C.), Department of Neurology, Brigham and Women's Hospital; Center for Neurological Imaging (C.R.G.G.), Department of Radiology, Brigham and Women's Hospital; Biostatistics Center (B.C.H.), Massachusetts General Hospital, Boston, MA; and Novartis Pharma AG (H.K.), Basel, Switzerland.
Harald KropshoferFrom the Harvard Medical School (C.B., B.C.H., M.P.-T., C.R.G.G., R.B., H.L.W., T.C.); Ann Romney Center for Neurologic Diseases (C.B., B.C.H., Y.L., S.S., A.P., M.P.-T., C.R.G.G., R.B., H.L.W., T.C.), Brigham and Women's Hospital; Brigham Multiple Sclerosis Center (R.B., H.L.W., T.C.), Department of Neurology, Brigham and Women's Hospital; Center for Neurological Imaging (C.R.G.G.), Department of Radiology, Brigham and Women's Hospital; Biostatistics Center (B.C.H.), Massachusetts General Hospital, Boston, MA; and Novartis Pharma AG (H.K.), Basel, Switzerland.
Howard L WeinerFrom the Harvard Medical School (C.B., B.C.H., M.P.-T., C.R.G.G., R.B., H.L.W., T.C.); Ann Romney Center for Neurologic Diseases (C.B., B.C.H., Y.L., S.S., A.P., M.P.-T., C.R.G.G., R.B., H.L.W., T.C.), Brigham and Women's Hospital; Brigham Multiple Sclerosis Center (R.B., H.L.W., T.C.), Department of Neurology, Brigham and Women's Hospital; Center for Neurological Imaging (C.R.G.G.), Department of Radiology, Brigham and Women's Hospital; Biostatistics Center (B.C.H.), Massachusetts General Hospital, Boston, MA; and Novartis Pharma AG (H.K.), Basel, Switzerland.
Tanuja ChitnisFrom the Harvard Medical School (C.B., B.C.H., M.P.-T., C.R.G.G., R.B., H.L.W., T.C.); Ann Romney Center for Neurologic Diseases (C.B., B.C.H., Y.L., S.S., A.P., M.P.-T., C.R.G.G., R.B., H.L.W., T.C.), Brigham and Women's Hospital; Brigham Multiple Sclerosis Center (R.B., H.L.W., T.C.), Department of Neurology, Brigham and Women's Hospital; Center for Neurological Imaging (C.R.G.G.), Department of Radiology, Brigham and Women's Hospital; Biostatistics Center (B.C.H.), Massachusetts General Hospital, Boston, MA; and Novartis Pharma AG (H.K.), Basel, Switzerland. tchitnis@rics.bwh.harvard.edu.
Harvard University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND AND

objectivesNeurodegeneration and astrocytic activation are pathologic hallmarks of progressive multiple sclerosis (MS) and can be quantified by serum neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP). We investigated sNfL and sGFAP as tools for stratifying patients with progressive MS based on progression and disease activity status.

methodsWe leveraged our Comprehensive Longitudinal Investigation of MS at the Brigham and Women's Hospital (CLIMB) natural history study, which includes clinical, MRI data and serum samples collected over more than 20 years. We included patients with MS with a confirmed Expanded Disability Status Scale (EDSS) score ≥3 that corresponds with our classifier for patients at high risk of underlying progressive pathology. We analyzed sNfL and sGFAP within 6 months from the confirmed EDSS score ≥3 corresponding with our baseline visit. Patients who further developed 6-month confirmed disability progression (6mCDP) were classified as progressors. We further stratified our patients into active/nonactive based on new brain/spinal cord lesions or relapses in the 2 years before baseline or during follow-up. Statistical analysis on log-transformed sGFAP/sNfL assessed the baseline association with demographic, clinical, and MRI features and associations with future disability.

resultsWe included 257 patients with MS who had an average EDSS score of 4.0 and a median follow-up after baseline of 7.6 years. sNfL was higher in patients with disease activity in the 2 years before baseline (adjusted β = 1.21; 95% CI 1.04-1.42; DISCUSSION: Higher levels of sGFAP correlated with subsequent progression, particularly in nonactive patients, whereas sNfL reflected acute disease activity in patients with MS at high risk of underlying progressive pathology. Thus, sGFAP and sNfL levels may be used to stratify patients with progressive MS for clinical research studies and clinical trials and may inform clinical care.

Indexed as

Glial Fibrillary Acidic ProteinMultiple Sclerosis, Chronic ProgressiveNeurofilament ProteinsBiomarkersDisease ProgressionHumansMagnetic Resonance ImagingBiomarkersGlial Fibrillary Acidic Proteinneurofilament protein LNeurofilament Proteins

Identifiers

PMID36376097
PMCPMC9749933
OpenAlexW4308963383

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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.