Evidence map›Paper›PMID 41989606›Full record

SynthesisJournal of neurology2026

Iron accumulation in multiple sclerosis and implications for cognitive and clinical progression: a systematic review of advanced neuroimaging studies.

Carla Susinna, Giovanni Restuccia, Gabriele Triolo, Giulia Marafioti, Simona Cammaroto, Edoardo Sessa, Giangaetano D'Aleo, Angelo Quartarone, Viviana Lo Buono

Abstract readSystematic Review
In one paragraph

Synthesis in Journal of neurology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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.

Carla SusinnaIRCCS Centro Neurolesi "Bonino-Pulejo", S. S. 113 via Palermo C. da Casazza, 98124, Messina, Italy.ORCID http://orcid.org/0009-0008-2507-6606
Giovanni RestucciaIRCCS Centro Neurolesi "Bonino-Pulejo", S. S. 113 via Palermo C. da Casazza, 98124, Messina, Italy. giovanni.restuccia@irccsme.it.ORCID http://orcid.org/0009-0003-8609-7324
Gabriele TrioloIRCCS Centro Neurolesi "Bonino-Pulejo", S. S. 113 via Palermo C. da Casazza, 98124, Messina, Italy.ORCID http://orcid.org/0009-0000-4999-1683
Giulia MarafiotiIRCCS Centro Neurolesi "Bonino-Pulejo", S. S. 113 via Palermo C. da Casazza, 98124, Messina, Italy.ORCID http://orcid.org/0009-0001-5971-1400
Simona CammarotoIRCCS Centro Neurolesi "Bonino-Pulejo", S. S. 113 via Palermo C. da Casazza, 98124, Messina, Italy.ORCID http://orcid.org/0000-0002-4215-8426
Edoardo SessaIRCCS Centro Neurolesi "Bonino-Pulejo", S. S. 113 via Palermo C. da Casazza, 98124, Messina, Italy.
Giangaetano D'AleoIRCCS Centro Neurolesi "Bonino-Pulejo", S. S. 113 via Palermo C. da Casazza, 98124, Messina, Italy.
Angelo QuartaroneIRCCS Centro Neurolesi "Bonino-Pulejo", S. S. 113 via Palermo C. da Casazza, 98124, Messina, Italy.ORCID http://orcid.org/0000-0003-1485-6590
Viviana Lo BuonoIRCCS Centro Neurolesi "Bonino-Pulejo", S. S. 113 via Palermo C. da Casazza, 98124, Messina, Italy.ORCID http://orcid.org/0000-0001-8027-6098

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND AND

aimsIron-related alterations are frequently implicated in multiple sclerosis (MS) neurodegeneration, but its relationship with clinical symptoms and cognitive impairment remains unclear. We systematically reviewed evidence linking iron-sensitive susceptibility-based magnetic resonance imaging (MRI) metrics to cognitive outcomes, in order to evaluate their potential role as diagnostic and prognostic biomarkers of cognitive decline in MS. MATERIALS AND

methodsA systematic review was conducted using the PRISMA guidelines. 600 studies were identified by searching PubMed, Scopus, Web of Science, and Embase in October 2025. After screening, 12 studies fulfilled the eligibility criteria and were included.

resultsTwo main patterns emerged: (i) higher basal ganglia susceptibility/iron-related metrics are consistently linked to worse cognitive performance, particularly information processing speed and executive control; and (ii) thalamic findings are more variable in direction and clinical meaning, with susceptibility often capturing a mixed signal that overlaps with thalamic atrophy.

conclusionsIron-sensitive quantitative MRI captures clinically relevant deep gray matter (DGM) pathology associated with cognitive impairment in MS, with basal ganglia measures showing the strongest linkage with cognitive and clinical outcomes. Future studies should include harmonized methodology and a longitudinal component.

Indexed as

BrainCognitive DysfunctionIronMultiple SclerosisNeuroimagingDisease ProgressionHumansMagnetic Resonance ImagingIronBrain iron depositionCognitive impairmentDeep gray matterDisease clinical progressionMultiple sclerosisQuantitative susceptibility mapping

Identifiers

PMID41989606
PMCPMC13086898

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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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 OpenQuestion graph.