People with multiple sclerosis had a smaller interthalamic adhesion, or IA, on average than matched controls, and the difference became more pronounced across the MS phenotypes studied, according to a prospective MRI cohort. The IA was the brain structure at the centre of measurements of presence, subtype and volume, alongside cognitive testing. The study's main signal was in the structure's size and subtype, not simply whether it was present.
The difference was in size, not simple presence
The proportion with an IA was reported as 81.9% in MS and 74.7% in controls, and the study stated that prevalence did not differ between groups. The more notable finding was the amount of IA volume measured among participants, rather than simply whether the structure was detected.
The study included 32 people with clinically isolated syndrome or early MS, 31 with relapsing-remitting MS, 31 with primary-progressive MS and 103 matched controls. Participants underwent anatomical 3-tesla MRI and comprehensive cognitive testing. Two blinded readers assessed IA presence, subtype and volume, while thalamic and other brain structures were segmented automatically.
Investigators compared IA subtypes and volumes across groups, analyzed possible predictors and explored cognitive associations with multivariate regressions. Mean IA volume was 146.8 cubic millimetres in the MS groups, with a standard deviation of 117.9, compared with 230.2 cubic millimetres, with a standard deviation of 138.2, in controls. The reported comparison had a p-value below 0.0001. The MS groups also shifted toward a short IA subtype, with worsening across phenotypes.
The associations narrowed at the thalamus and in cognition
Lower IA volume was independently associated with the volumes of medial and posterior thalamic nuclei. It was not associated, in the reported analysis, with white matter lesion load or global atrophy. The authors say this pattern links IA volume reduction to the vulnerability of adjacent thalamic nuclei and supports IA as a marker of thalamic neurodegeneration. That interpretation does not establish cause and effect: the observational design cannot show that MS caused the volume reduction or that the reduction caused thalamic damage.
Cognition showed a narrower link. Among the domains assessed, smaller IA volume was independently associated only with executive dysfunction. The reported odds ratio was 0.89, with a bracketed range of 0.77 to 0.99 and p = 0.021. The supplied analysis does not identify the interval type or list the model covariates, so the result should be read as an association in this cohort, not as a clinical prediction.
An automated tool may widen the next studies
The team also developed a deep-learning-based tool to segment the IA automatically and externally validated it on 30 new patients. It showed good agreement with manual delineation: the median Dice coefficient, an overlap measure for two outlines, was 0.64, and the volume correlation was 0.89. The authors say the tool will enable larger and longitudinal investigations, although the validation sample was limited to the 30 new patients described in the analysis.
The findings still need testing over time
The study does not establish IA volume as a validated diagnostic, prognostic or treatment-response biomarker. It also does not show that automated segmentation is superior to manual delineation or has established clinical utility. Whether IA volume changes track future MS progression, thalamic damage or cognitive decline remains unknown, as does whether the tool generalizes across larger, more diverse cohorts and imaging settings.
The paper is a published version-of-record journal article. The authors report no conflicts of interest, and the study data are available from the corresponding author on reasonable request. Funding came from the University of Bordeaux France 2030 IMPACT program, the French National Research Agency, the TRAIL laboratory of excellence, Genzyme, Roche and a Spanish science ministry project.
Paper data and sources
Original title: Interthalamic adhesion alterations in multiple sclerosis: associations with thalamic damage and cognition.
Authors: Arthur Fournet, Fanny Munsch, Ismail Koubiyr et al.
Journal/Repository: Journal of neurology
Status: Peer-reviewed
First online: 2026-08-20
DOI: 10.1007/s00415-026-14069-5
Original paper · Full text