ArticleNeurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics2026
Heterogeneous Deep Gray Matter Iron Deposition Patterns across Multiple Sclerosis Subgroups Defined by the Clinico-Radiological Paradox.
Article in Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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.
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.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The clinico-radiological paradox in multiple sclerosis (MS) describes the disconnect between white matter lesion load and clinical disability. This study investigated the role of deep gray matter (DGM) iron deposition in this paradox, specifically regarding cognitive impairment. We classified 134 MS patients into subgroups based on T2-lesion volume (LV) and disability (EDSS): LL/LD, HL/LD, LL/HD, HL/HD, comparing them to 46 healthy controls (HCs). Using quantitative susceptibility mapping (QSM) and volumetric analysis, we assessed iron content and atrophy in DGM nuclei, alongside cognitive testing (MoCA, SDMT). Subgroups with high lesion burden (HL/LD, HL/HD) showed significantly increased iron and atrophy in the globus pallidus, putamen, and caudate versus HCs. A critical group-by-volume interaction on susceptibility was found in the putamen for HL/LD (β=-0.55) and HL/HD (β=-0.35) subgroups. Mediation analysis revealed that putamen volume mediates the effect of iron on cognition, with significant indirect effects on SDMT (β=-0.18) and MoCA (β=-0.14) across all patients. In the HL/HD subgroup, this pathway accounted for 45.8 % of iron's total effect on processing speed (SDMT). Our findings demonstrate heterogeneous DGM iron deposition and identify putaminal iron-induced atrophy as a key mechanistic pathway for cognitive deficits, offering a novel explanation for the paradox and a potential biomarker for cognitive risk stratification.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.