Evidence map›Paper›PMID 40187193›Full record

ArticleNeuroImage. Clinical2025

Thalamic iron in multiple sclerosis: Waning support for the early-rise late-decline hypothesis.

Fahad Salman, Niels Bergsland, Michael G Dwyer, Jack A Reeves, Abhisri Ramesh, Dejan Jakimovski, Bianca Weinstock-Guttman, Robert Zivadinov, Ferdinand Schweser

Abstract read
In one paragraph

Article in NeuroImage. Clinical, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. 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

9 authors.

Fahad SalmanBuffalo Neuroimaging Analysis Center, Department of Neurology at the Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, The State University of New York, Buffalo, NY, United States; Department of Biomedical Engineering, University at Buffalo, The State University of New York, Buffalo, NY, United States.
Niels BergslandBuffalo Neuroimaging Analysis Center, Department of Neurology at the Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, The State University of New York, Buffalo, NY, United States.
Michael G DwyerBuffalo Neuroimaging Analysis Center, Department of Neurology at the Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, The State University of New York, Buffalo, NY, United States; Center for Biomedical Imaging, Clinical and Translational Science Institute, University at Buffalo, The State University of New York, Buffalo, NY, United States.
Jack A ReevesBuffalo Neuroimaging Analysis Center, Department of Neurology at the Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, The State University of New York, Buffalo, NY, United States.
Abhisri RameshBuffalo Neuroimaging Analysis Center, Department of Neurology at the Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, The State University of New York, Buffalo, NY, United States.
Dejan JakimovskiWynn Hospital, Mohawk Valley Health System, Utica, NY, United States.
Bianca Weinstock-GuttmanJacobs Neurological Institute, Buffalo, NY, United States.
Robert ZivadinovBuffalo Neuroimaging Analysis Center, Department of Neurology at the Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, The State University of New York, Buffalo, NY, United States; Center for Biomedical Imaging, Clinical and Translational Science Institute, University at Buffalo, The State University of New York, Buffalo, NY, United States.
Ferdinand SchweserBuffalo Neuroimaging Analysis Center, Department of Neurology at the Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, The State University of New York, Buffalo, NY, United States; Center for Biomedical Imaging, Clinical and Translational Science Institute, University at Buffalo, The State University of New York, Buffalo, NY, United States. Electronic address: schweser@buffalo.edu.

Funding

University of Buffalo Clinical and Translational Science Institute - Supplement SchulyerUL1TR001412 · NCATS · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI MURPHY, TIMOTHY F · 2015 to 2024
$33.8M
Deep Gray Matter Iron and Disease Progression in Multiple SclerosisR01NS114227 · NINDS · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI SCHWESER, FERDINAND · 2021 to 2024
$1.5M
NCATS NIH HHS UL1 TR001412nihNINDS NIH HHS R01 NS114227nsf
6 · The paper itself

Abstract

backgroundStudies of thalamic iron levels in multiple sclerosis (MS) have yielded variable findings, potentially due to differences in study cohorts. For example, studies in relatively young cohorts (average ages below 40 years) have reported elevated susceptibility in people with MS (pwMS), whereas studies in older cohorts (above 40 years) found decreased susceptibility.

objectiveTo test the "early-rise late-decline" hypothesis, which posits that age differences in study cohorts are responsible for conflicting findings regarding thalamic susceptibility in MS.

methodsWe chose to replicate one of the previous studies that showed evidence of elevated thalamic iron concentrations in younger pwMS (Rudko et al., 2014). We also replicated a study involving older pwMS (Pudlac et al., 2020) to serve as a control. We assessed thalamic susceptibility using the QSM processing and analysis methodology outlined by Rudko et al.

resultsAlthough cohort characteristics, QSM processing, and analytical methods were closely matched, we found significantly lower thalamic susceptibility in the younger pwMS compared to controls (-1.1 ± 7.8 vs. 5.4 ± 6.1 ppb; effect sizes: -0.35 to -0.91). Study outcomes were robust across a wide range of regularization parameters, with effect size differences influenced by background field removal regularization. A similar pattern was observed in the older cohort, where thalamic susceptibility was again lower in pwMS compared to controls (4.0 ± 9.5 vs. 9.6 ± 10.7 ppb; effect size: -0.55).

conclusionsOur findings contradict the "early rise" hypothesis of thalamic iron levels in pwMS. The consistency of our results across multiple analyses suggests that QSM processing artifacts are unlikely to explain previous reports of increased thalamic iron. Instead, these variations may stem from demographic or clinical differences, such as geographical factors and treatment regimens.

Indexed as

IronMultiple SclerosisThalamusAdultAgedCohort StudiesFemaleHumansMagnetic Resonance ImagingMaleMiddle AgedIronDeep gray matterIron metabolismMultiple sclerosisquantitative susceptibility mapping (QSM)ReproducibilityThalamus

Identifiers

PMID40187193
PMCPMC12002950

What Socratic holds

Textmetadata
LicenceCC BY
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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 Socratic graph.